Medicine Up To Now

Pregnancy, skin and connective tissue diseases, and malignancies

noreply@blogger.com (Unknown) — Sun, 12 Mar 2023 17:21:00 +0300

PREGNANCY AND CONNECTIVE TISSUE DISEASES

systemic lupus erythematosus (SLE)

• SLE improves in 1:3 pregnancies, remains unchanged in 1:3 and worsens in 1:3 pregnancies. Pregnancy outcomes depend primarily on the severity of the underlying renal disease.

Fetal heart block and fetal bradycardia may occur due to the myocardium and conduction system being affected by antibodies.

• Preeclampsia risk is high in patients with lupus nephritis and preeclampsia develops more frequently in patients with positive antiphospholipid antibodies.

• Perinatal complication risks are significantly increased in pregnant women with lupus. Among them; preterm labor, IUGR, stillbirth, and neonatal lupus syndrome.

Due to the myocardium and conduction system being affected by antibodies

(especially anti SS-A and anti SS-B) fetal heart block and fetal bradycardia may occur.

Differential Diagnosis of Active Lupus and Preeclampsia Syndrome
	Lupus	preeclampsia
Clinical findings	Fatigue, headache. extrarenal findings (rash, serositis, arthritis)	Headache, confusion, visual symptoms, convulsion
Blood pressure	normal or high	High
Anemia	hemolytic anemia	no
proteinuria	There is	There is
creatinine	normal or high	normal or high
Transaminases	Normal	normal or high
complement	decreased	Normal

Rheumatoid Arthritis

• Pregnancy is protective against rheumatoid arthritis and improves the clinical picture.

However, the risk of relapse increases 6 times in the first 3 months after birth. Rheumatoid arthritis does not have a negative effect on pregnancy outcomes.

Systemic Sclerosis (Scleroderma)

• Disease is usually stable during pregnancy if basal functions are good

however, exacerbations occur in 1/3 of the cases.

• Maternal and fetal outcomes depend on the severity of the underlying disease. The risk of superimposed preeclampsia is increased in patients with renal failure and malignant hypertension. There is an increased risk of preterm birth, very low birth weight infants, IUGR and perinatal mortality.

PREGNANCY AND SKIN DISEASES

pregnancy specific dermatoses
	Frequency	Characteristic lesion	Adverse effects on pregnancy	Treatment
Pregnancy Cholestasis	Widespread	No primary skin lesion, Secondary excoriation due to scratching	Perinatal morbidity increases	Antipruritic, Cholestyramine, Ursodeoxycholic acid
Itchy urticarial papules and plaques of pregnancy	Widespread	Erythematous pruritic papule or plaque Patchy or generalized involvement Occurs on abdomen, thighs, buttocks and especially striae. But the belly is preserved	no	Antipruritic, Emollient topical steroid, Oral steroid
Atopic eruptions of pregnancy: Pregnancy eczema	Widespread	Dry, red scaly patches, Flexor surfaces of extremities, neck and face	no	Antipruritic, Emollient topical steroid, Oral steroid
pregnancy prurigo	Widespread	1-5 mm, pruritic red papules, Extensor surfaces of extremities, trunk	*	*
itchy folliculitis of pregnancy	Rare	Small, red papule, sterile pustule on trunk	*	*
Pemphigoid gestationalis	Rare	Erythematous pruritic papule. plaques, vesicles and bullae, Abdomen (often including umbilicus), extremities	Preterm birth, IUGG, Transient neonatal lesion	Antipruritic, Emollients topical steroid, Oral steroid

Course of Systemic Diseases in Pregnancy
Diseases worsened by pregnancy	Diseases cured by pregnancy	Diseases not affected by pregnancy
hepatitis E	rheumatoid arthritis	ulcerative colitis
Depression	peptic ulcer	Crohn's disease
aplastic anemia	multiple sclerosis	ITP
sickle cell anemia	Hashimoto	myasthenia gravis
Autoimmune Hemolytic Anemia	Fox-Fordyce Disease	Hereditary spherocytosis
Paroxysmal Nocturnal Hemoglobinuria	Hidradenitis suppurativa	sarcoidosis
Reflux esophagitis
Epilepsy (increases 20-30%)

Diseases with 1/3 rule in pregnancy; Asthma and SLE

PREGNANCY AND MALIGN DISEASES

• Breast, cervix, hematological malignancies and melanoma are among the most common cancers in pregnancy.

The most common cancer in pregnancy is stated differently in different sources (breast, cervix or lymphoma).

The most common surgical procedure during pregnancy is laparoscopy. During laparoscopy, hypercarbia and acidosis occur and uteroplacental perfusion decreases. The cerebrospinal fluid pressure increases.

Pregnancy and blood diseases

noreply@blogger.com (Unknown) — Sun, 12 Mar 2023 17:11:00 +0300

Anemia

• Hb concentration below 12 g/dl in a non-pregnant woman; your pregnancy

1st and III. 11 g/dl in trimesters of II. If it is below 10.5 g/dl in the third trimester, it is called anemia.

• The first of the 2 most common causes of anemia in pregnancy and puerperium is iron deficiency and the second is acute blood loss.

Causes of acquired anemia in pregnancy---------Causes of congenital anemia in pregnancy

Iron deficiency anemia--------------thalassemias

Anemia due to acute blood loss-------------Sickle cell hemoglobinopathies Anemia due to inflammation and malignancy-------------Other hemoglobinopathies Megaloblastic anemia-------- ---Hereditary hemolytic anemia

Acquired hemolytic anemia-----------------------

Aplastic or hypoplastic anemia-------------------

Iron Deficiency Anemia

► Serum ferritin level decreases physiologically during pregnancy, but 10-15 mg/L makes the diagnosis of iron deficiency anemia. A pregnant woman diagnosed with iron deficiency anemia should be given 200 mg of elemental iron daily.

Megaloblastic Anemia

► Folic acid deficiency is almost always the cause of megaloblastic anemia in pregnant women. Because the fetus and placenta absorb folic acid effectively, maternal anemia does not cause fetal anemia.

Hemolytic Anemias

► · Autoimmune Hemolytic Anemias: Hemolysis becomes significantly more pronounced during pregnancy.

► Paroxysmal Nocturnal Hemoglobinuria: Venous thrombosis is seen in approximately 40% of the cases. Pregnancy can lead to serious consequences in these patients and maternal mortality is 10-20%. Maternal complications are more common postpartum and postpartum venous thrombosis is seen in 50% of cases.

► Hemolytic Anemia Due to Bacterial Toxins: Clostridium perfringens and group A beta hemolytic streptococci cause the most severe acquired hemolytic anemia during pregnancy.

► Hereditary Spherocytosis: Generally, the course of the disease is not affected during pregnancy. Folic acid replacement is recommended for cases. The disease can lead to abortion and preterm birth.

Aplastic Anemia

► Anemia and thrombocytopenia may deepen in pregnant women with aplastic anemia. The greatest risk in these pregnant women is bleeding and infection. The risk of preterm birth, preeclampsia, IUGR and stillbirth also increases.

Hemoglobinopathies

Sickle Cell Anemia

► Pregnancy creates a significant burden for these patients; because infections and . pulmonary complications are more common. Maternal mortality rate in cases

While it is 1%, one in three fetuses may have abortion, stillbirth, IUGR and perinatal death. The risk of preeclampsia/eclampsia, ablatio placentae, preterm labor is increased.

Thalassemias: Pregnancy is well tolerated in cases of thalassemia minor.

Polycythemia Vera: Maternal thrombotic sequelae and fetal loss rate are increased. Pregnancy outcomes can improve with aspirin therapy. Women with a history of venous thrombosis should be given prophylaxis with low molecular weight heparin.

Platelet Disorders

Immune Thrombocytopenic Purpura (ITP)

► Pregnancy does not increase the risk of relapse of ITP, nor does it aggravate the clinical course in the active period. Anti-platelet autoantibodies in IgG structure can cross the placenta and cause fetal thrombocytopenia. Fetal death is also common due to the resulting hemorrhage. The risk of preterm labor also increases. Fetuses with severe thrombocytopenia are at increased risk of intracranial hemorrhage at the time of delivery. Cesarean section does not prevent fetal complications.

thrombocytosis

► The platelet count is > 450,000/ul. The most common causes of reactive thrombocytosis in pregnancy are; iron deficiency, infections, inflammatory diseases and malignancies. There is an increased risk of arterial and venous thrombosis. The risk of spontaneous abortion, fetal loss and preeclampsia increases during pregnancy.

thrombocytopenia

► Thrombocytopenia is relatively common during pregnancy and is defined as <150,000/ul platelet count. The cause of 75% is gestational thrombocytopenia, another common cause is HELLP syndrome.

Hereditary Coagulation Disorders

• The most common inherited bleeding disorder is Von Willebrand's Disease. Pregnancy outcomes are generally good; however, 50% postpartum bleeding is seen.

Pregnancy and kidney disease

noreply@blogger.com (Unknown) — Sun, 12 Mar 2023 16:56:00 +0300

PREGNANCY AND ENAL DISEASES

Asymptomatic Bacteriuria (ABU)

·• Asymptomatic bacteriuria during pregnancy may progress to pyelonephritis with a higher rate (20-30%) compared to non-pregnant women. E.coli is the most common causative agent.

Acute Pyelonephritis

• Urosepsis is the most common cause of septic shock during pregnancy. Factors; Escherichia cali (75-80%), Klebsiella pneumoniae (10%), Enterobacter and Proteus (10%).

Chronic renal failure

• Pregnancy outcomes depend on renal functions and the presence and severity of hypertension. The degree of proteinuria does not correlate with pregnancy outcomes.

Complications due to chronic kidney failure

Complications ---------------------------------------------Incidence (%)

maternal

Chronic hypertension ---------------------------------25 - 70

Gestational hypertension------------------------20- 75

Renal dysfunction -----------8 - 43

Temporary pause in kidney functions ----4 - 35

Fetal

Preterm labor ------------7 - 73

IUGG --------------------------8 - 57

Perinatal mortality ------5 - 14

Pregnancy and digestive diseases

noreply@blogger.com (Unknown) — Sun, 12 Mar 2023 16:24:00 +0300

Hyperemesis Gravidarum

• It is the name given to severe nausea and vomiting that will cause weight loss, dehydration, acidosis due to fasting ketosis, alkalosis and hypokalemia due to HCl loss in pregnancy. It is thought that the formation of this clinical picture is caused by rapidly increasing chorionic gonadotropin or estrogen or both. It is less common in obese patients.

• Prerenal acute renal failure, Mallory Weiss tears, esophageal rupture, pneumothorax and pneumomediastinum have been reported in very severe cases. In many cases, it causes nutritional disorders and especially

Deficiency of both vitamins causes serious complications. Cases developing Wernicke's encephalopathy due to thiamine deficiency have been reported (E 11J. Cases of coagulopathy and epistaxis have also been reported due to vitamin K deficiency. K

Vitamin deficiency can cause embryopathy.

• Effective and safe first-line treatment in these cases is vitamin B6 + doxylamine. If this treatment fails, intravenous crystalloids should be added. Antiemetics (promethazine, chlorpromazine, prochlorperazine, metoclopramide) can also be used safely. There is no evidence to suggest that glucocorticoids are beneficial in hyperemesis gravidarum.

From Inflammatory Bowel Disease (Ulcerative Colitis, Crohn's Disease)

• Pregnancy does not increase the possibility of exacerbation of inflammatory bowel disease, but if there is an exacerbation, it is quite severe. Complications of preterm birth, low birth weight, IUGR and cesarean delivery are 1.5-2 times more common; however, there is no increase in perinatal mortality despite these complications.

Intestinal Obstruction

• Its incidence does not increase in pregnant women and the cause of more than 50% of the cases is adhesions due to previous pelvic surgeries (including cesarean section). Maternal mortality (6%) and fetal mortality (26%) rates are quite high in these cases due to the late diagnosis of the picture.

Appendicitis

• Suspicion of appendicitis is one of the leading reasons for performing laparotomy during pregnancy. However, it is difficult to diagnose appendicitis in case of pregnancy, and therefore, delay in cases causes more rupture of appendicitis and more generalized peritonitis in pregnant women.

Intrahepatic Cholestasis

• The exact cause of obstetric cholestasis is unknown; however, whatever the reason is, bile acids cannot be completely cleared and increase in plasma. Bilirubin and alkaline phosphatase levels are also elevated. In most of the patients, the complaint of itching starts in the following weeks of pregnancy. Jaundice can be seen in 10% of cases.

• Measurement of fasting serum bile acid level is used in the diagnosis (normal level

< 10µmol/L). Elevated AST and ALT levels may also accompany.

• The cause of itching is increased bile acids. Antihistamines are sufficient for this. Cholestyramine is also effective in 50-70% of cases; however, since it reduces the absorption of the fat-soluble vitamin, the already decreased vitamin K may be further reduced with this drug and bleeding may occur (it may lead to fetal coagulopathy and intracranial hemorrhage). Ursodeoxycholic acid relieves itching immediately and also lowers serum transaminases.

• 38-39. week of birth should be considered.

Acute Fatty Liver

• It is the most common cause of acute liver failure during pregnancy. The main causes are fulminant viral hepatitis, drug toxicity and acute fatty liver disease of pregnancy.

• In acute fatty liver, the picture almost always becomes evident in the later stages of pregnancy (usually the third trimester). The disease is more common in nulliparous and pregnant women with male fetuses. 15% of cases occur in multiple pregnancies.

• The picture is very similar to preeclampsia. It presents with fatigue, anorexia, nausea, vomiting, polyuria/polydipsia, epigastric pain, and progressive jaundice. Persistent vomiting is the major finding in most patients. Hypoglycemia, leukocytosis, increase in urea and creatinine levels, increase in transaminases, ascites, encephalopathy and coagulopathy (PT and aPTT prolong, fibrin degradation products and D-Dimer increase) can be added to the picture. Fetal mortality is 10%-1S.

• Emergency delivery should be planned for treatment. Liver functions improve rapidly with birth and the picture improves.

The most useful laboratory test in distinguishing HELLP Syndrome from acute fatty liver of pregnancy is blood glucose measurement (N-17).

Viral Hepatitis

• Hepatitis A: The clinic of hepatitis A is not exacerbated during pregnancy. Hepatitis A virus is not teratogenic and there is no transplecental transmission to the fetus.

• Hepatitis B: The clinic of hepatitis B is not exacerbated during pregnancy. Transplacental transmission of the virus is very rare and the main transmission occurs during breastfeeding.

• Hepatitis C: The clinic of hepatitis C during pregnancy is not exacerbated and does not cause perinatal complications. However, the most important thing is that hepatitis C can be transmitted vertically to the fetus (3-6%). Prenatal screening for hepatitis C is not recommended, as there is currently no method to prevent the transmission of hepatitis C to the fetus.

• Hepatitis E: Hepatitis E progresses more severely during pregnancy . The disease can be transmitted to the fetus transplacental at a high rate.

Cholelithiasis and Cholecystitis

• In pregnancy i. After the third trimester, the volume of the gallbladder is fasting and following a meal.

doubles after contraction. Incomplete emptying of the gallbladder leads to the accumulation of cholesterol crystals and the formation of cholesterol stones. Acute cholecystitis in pregnancy occurs due to these gallstones and surgical treatment may be required.

pancreatitis

• While acute pancreatitis develops as a result of 45% gallstones and 35% alcohol use in non-pregnant women; gallstones in pregnancy are almost always the only cause . The accompanying hypocalcemia, hypovolemia, hypoxia and acidosis in the cases cause high fetal loss. The risk of fetal mortality and preeclampsia increases in acute pancreatitis.

Pregnancy, lung diseases and nervous system diseases

noreply@blogger.com (Unknown) — Sun, 12 Mar 2023 16:05:00 +0300

PREGNANCY AND NEUROLOGICAL DISEASES

Headache and Migraine

• The most common neurological complaint during pregnancy is headache; however, there is a decrease in the prevalence of all types of headache in nulliparous pregnant women, especially in the third trimester. Ergotamines are vasoconstrictors that should be avoided during pregnancy.

Cerebrovascular Diseases

• Relatively rare during pregnancy; but its mortality is high. 0/oSO of the cases are postpartum, 40% are intrapartum and 10% are antepartum. The most common risk factor associated with pregnancy is pregnancy-induced hypertensive diseases.

Convulsive (Epileptic) Diseases

• Despite the recurrence of seizures during pregnancy in 20-30% of epilepsy patients, if seizures have not been experienced for more than 2 years before conception, it is foreseen to discontinue the drugs.

• Seizures cause maternal hypoxemia resulting in fetal damage. In addition, some pregnancy complications are slightly increased in women with epilepsy, including spontaneous abortion, bleeding, hypertensive diseases, preterm birth, IUGR and cesarean delivery. The risk of maternal mortality increases 10 times in women with epilepsy, and postpartum depression is also more common.

• The cause of congenital malformations found to be increased in cases with epilepsy is not due to the disease but to the anticonvulsants used. Therefore, monotherapy should be preferred.

Multiple Sclerosis (MS)

• Relapse rate decreases by 70% during pregnancy; however, the postpartum relapse rate increases markedly. Uncomplicated MS cases generally do not have a negative effect on pregnancy. The delivery method of the cases is vaginal, cesarean section is not necessary. If necessary, epidural analgesia is recommended, not spinal anesthesia, due to the risk of autonomic dysreflexia.

Myasthenia Gravis

• The course of the disease is unpredictable during pregnancy, but it remains stable during pregnancy in most women with stable disease. Exacerbations occur in 1/3 of the cases.

• This disease generally does not have a negative effect on pregnancy. Since myasthenia gravis does not affect the smooth muscles, the patient's labor progresses normally. All kinds of curare effective drugs (magnesium, muscle relaxants, aminoglycoside) should be avoided in patients. There is no indication for cesarean section in patients; however, forceps or vacuum can be applied in the second stage of labor since the patient cannot exert pushing effort.

PREGNANCY AND LUNG DISEASES

Asthma

• The most common lung disease in pregnancy is asthma. There is a 1/3 rule about the course of asthma in pregnancy. Asthma does not change 1/3 during pregnancy, 1/3 decreases, 1/3 increases. 20% of asthma exacerbations occur intrapartum, and cesarean delivery increases the risk of exacerbation of asthma 18 times compared to vaginal delivery.

• As the severity of asthma increases, preeclampsia, preterm labor, IUGR, low birth weight, detachment, premature rupture of membranes, gestational diabetes and perinatal mortality can be seen.

Prostaglandin F2 alpha and ergonovine are contraindicated in pregnant women with asthma as they cause significant bronchospasm.

pneumonia

• Hypoxia and acidosis are poorly tolerated by the fetus and often trigger preterm labor after the second trimester. Every pregnant woman with suspected pneumonia should have a chest X-ray. When pneumonia is encountered during pregnancy, oseltamivir should be added to empirical antibiotherapy.

Strep is the most common cause of bacterial pneumonia.

pneumoniae.

Viral causes are the most common cause of pneumonia in pregnancy. Influenza A pneumonia is the most common viral pneumonia. In order to prevent the disease, influenza vaccine should be applied to all cases (regardless of the gestational week) who become pregnant during periods when influenza is common.

Tuberculosis

• It increases the risk of active tuberculosis, preterm birth, low birth weight, IUGR, preeclampsia and perinatal mortality. Breastfeeding is not prohibited during the treatment of tuberculosis.

sar o oz

• Sarcoidosis does not usually progress negatively during pregnancy. Sarcoidosis in pregnancy usually does not lead to adverse perinatal outcomes, but the risk of preeclampsia, preterm labor and thromboembolism increases.

• Cystic fibrosis is not affected by pregnancy. If the pre-pregnancy FEV is less than 60%, the risk of preterm birth, pulmonary complications, and maternal death within a few years of birth is increased.

Pregnancy, cardiovascular disease, and thromboembolism

noreply@blogger.com (Unknown) — Sun, 12 Mar 2023 15:47:00 +0300

PREGNANCY AND CARDIOVASCULAR DISEASES

Congenital heart diseases constitute 50% of maternal heart diseases. The most common diseases in this group are bicuspid aorta, ASD and VSD.

The second most common heart disease is rheumatism! are heart diseases and the most common disease of this group is mitral stenosis (1:- GOJ.

Mortality of Heart Diseases in Pregnancy

• Diseases without an increase in mortality compared to normal (WHO class I)

► Uncomplicated, mild or moderate; pulmonary stenosis, VSD, PDA, mitral valve prolapse

► Successfully repaired; secundum ASD, VSD, PDA, total pulmonary venous return anomaly

• Diseases that increase mild maternal mortality (WHO class province)

► Uncomplicated; non-operated ASD, repaired tetralogy of Fallot, most arrhythmias

• Individual situation dependent (WHO class II or III}

► Mild left ventricular dysfunction

► Hypertrophic cardiomyopathy

► Natural heart valve diseases

► Marfan syndrome without aortic dialatation

► Heart transplantation

• Diseases that significantly increase maternal mortality (WHO class III}

► Mechanical cover

► Cyanotic heart diseases

► Patients who have undergone Fontan surgery

► Repaired transposition

• Quite a lot of mortal heart diseases (WHO class IV}

► Pulmonary hypertension (highest}

► Severe systemic ventricular dysfunction

► Previous peripartum cardiomyopathy with sequelae of left ventricular failure

► Severe left heart obstruction

► Marfan syndrome with aortic dilatation

PREGNANCY AND THROMBOEMBOLIC DISEASES

• The risk of venous thrombosis and pulmonary embolism increases during pregnancy and puerperium. While deep vein thrombosis alone is more common antepartum, solitary pulmonary embolism is more common in the first 6 weeks postpartum.

• Obstetric risk factors that increase the risk of thromboembolism during pregnancy: Cesarean section (most common), diabetes, bleeding and anemia, hyperemesis, immobility - prolonged bed rest, multiple pregnancy, multiparity, preeclampsia, puerperal infection, stillbirth and operative vaginal delivery

thrombophilia

• Thrombophilias are responsible for 50% of thromboembolism encountered during pregnancy.

• The most common thrombophilia III• Activated protein C resistance (aPCR}

• The most common cause of aPCR III• Factor V Leiden mutation

• Most common hereditary thrombophilia III • Heterozygous Factor V Leiden mutation

• The most thrombogenic thrombophilia III • Antithrombin III deficiency

Protein S and homocysteine levels decrease in normal pregnancy.

• Empirical aspirin and/or low molecular weight heparin is recommended for hereditary thrombophilia prophylaxis.

Deep Vein Thrombosis (DVT)

• Most DVTs during pregnancy occur in the left leg, and the first-line test used in the diagnosis of DVT is compression ultrasonography of the lower extremities. Invasive contrast venography is the gold standard for excluding the diagnosis of lower extremity DVT.

• D-Dimer level; increases with gestational age in normal pregnancy, so its use in pregnancy is uncertain. However, a negative D-Dimer test excludes thromboembolism.

• Heparin is used in women with a previous history of DVT and in the treatment of acute thromboembolism. Heparin does not cross the placenta and is therefore not teratogenic. Treatment throughout pregnancy and postpartum 6-12. It should last up to a week.

Pulmonary Embolism PE)

• 70% of the patients have DVT in lower extremity Doppler ultrasonography, and in patients with leg DVT finding, Doppler ultrasonography should be performed first.

• Chest X-ray should be taken in patients without leg findings, and CT, which is the gold standard method for definitive diagnosis, should be performed in patients with abnormal findings on chest X-ray.

pulmonary angiography (CTPA} is performed J J. Ventilation perfusion scintigraphy (V/Q) should be performed in patients with normal chest X-ray.

• A therapeutic dose of heparin (25,000-40,000 U) is indicated in women with a previous history of PE. Unfractionated (normal) heparin is suitable for the treatment of acute thromboembolism. Treatment throughout pregnancy and postpartum 6-12. It should last up to a week. Oral anticoagulants are used after delivery. Alternative treatments (thrombolysis, embolectomy, vena cava filters) are not preferred because they are associated with high complications in pregnancy.

PREGNANCY AND THYROID DISEASES

noreply@blogger.com (Unknown) — Sun, 12 Mar 2023 15:04:00 +0300

Hyperthyroidism (Thyrotoxicosis)

• The most common cause of hyperthyroidism during pregnancy is Graves' disease (95%) (. Since thyroid stimulating antibodies in the circulating IgG structure can cross the placenta, there is a risk of developing hyperthyroidism in the fetus (2-10%).

Pregnancy Outcomes in Women with Thyrotoxicosis

-----------------------Treated and Euthyroid Pregnants------- Uncontrolled Pregnants

Maternal Complications

- Preeclampsia ---------------- 10%------------- 17%

-Heart failure ----------------1 ---------------8%

-Death o 1

Perinatal Complications

-Preterm birth -------------16% ----------32%

-IUGG--------------------------- %11-----------17%

-stillbirth-------------------- 0 ---------------18%

• While propylthiouracil is primarily preferred in treatment; methimazole may cause aplasia cutis, esophageal and choanal atresia (methimazole embryopathy). However, in case of long-term use of propylthiouracil, it is recommended to use propylthiouracil in the first trimester and methimazole from the second trimester due to its hepatotoxicity.

• Radioactive iodine treatment is absolutely contraindicated during pregnancy. Surgical treatment is avoided if possible during pregnancy, but if it is mandatory, the best time is II. trimester.

hypothyroidism

• The most common cause of hypothyroidism during pregnancy is Hashimoto's thyroiditis.

Pregnancy Outcomes in Women with Hypothyroidism
Complications	Pregnant women with significant hypothyroidism	pregnant women with subclinical hypothyroidism
Birth weight < 2000 g 33%	33%	32%
Preeclampsia 32%	32%	8%
stillbirth 9%	9%	3%
Abrupt placenta 8%	8%	1%
cardiac dysfunction	3%	2%

• Levothyroxine treatment is started and TSH value should be kept between 0.5-2.5 mU/L.

Postpartum Thyroiditis

• Transient autoimmune thyroiditis is detected in 5-10% of women during the first year after delivery. The tendency to thyroiditis exists before pregnancy and is directly related to the serum thyroid autoantibody level. Postpartum thyroiditis develops in 16% of pregnant women with type 1 diabetes.

• For diagnosis, TSH abnormality (suppressed or low) must be present within one year following birth, excluding thyroid-stimulating antibody positivity (except Graves') or presence of toxic nodules.

• Lymphocytic infiltration is observed and has two defined clinical phases:

► Destructive-induced thyrotoxicosis stage: Due to excessive hormone secretion as a result of glandular destruction

► Hypothyroidism stage: It takes place in 4-8 months postpartum.

• There is an annual risk of 3.6% progression and 30% permanent hypothyroidism. in the next pregnancy There is a 69% risk of recurrence.

PREGNANCY AND DIABETES

noreply@blogger.com (Unknown) — Sun, 12 Mar 2023 14:51:00 +0300

• It is the most common medical complication of pregnancy.

Classification

• Today, the Modified White Classification is used less frequently, and instead the classification focusing on whether diabetes is diagnosed before pregnancy or during pregnancy has been put into use.

• According to this, the presence of diabetes before pregnancy is called pregestational diabetes, and glucose intolerance that occurs for the first time during pregnancy or is diagnosed for the first time during pregnancy is called gestational diabetes.

Modified White classification
Class	Beginning	Fasting Blood Sugar	blood sugar in the 2nd hours after food	Treatment
A1	gestational	<105 mg/dL	<120 mg/dL	Diet
A2	gestational	> 105 mg/dL	>120 mg/dL	insulin
Class	starting age	Duration (year)	Vascular disease	Treatment
B	>20	<10	no	insulin
C	10---9	10---9	no	insulin
D	<10	>20	Benign retinopathy	insulin
F	It doesn't matter	It doesn't matter	nephropathy	insulin
R	It doesn't matter	It doesn't matter	Proliferative retinopathy	insulin
H	It doesn't matter	It doesn't matter	Heart	insulin

Screening and Diagnosis

overt DM Screening and Diagnosis

► Overt DM diagnostic criteria:

0 Glucose value > 200 mg/dl in randomized plasma and classical symptoms such as polydipsia, polyuria, unexplained weight loss, or

0 Fasting blood sugar :::: Above 126 mg/dl. The reason for limiting this value is that the risk of retinopathy increases significantly above this value.

0 Hemoglobin Alc > 6.5%

Gestational DM Screening and Diagnosis

► All pregnant women 24-28. gestational diabetes screening is recommended.

► There is some controversy regarding the diagnostic criteria, and two-stage or single-stage screening and diagnostic tests are recommended.

► One-step approach:

0 75 g two-hour OGTT is used as a screening and diagnostic test.

0 Gestational diabetes is diagnosed when at least one of the fasting, first hour and second hour glucose values is above the threshold value.

► Two-stage approach:

0 50 g 1-hour glucose screening test is used as a screening test. If the screening test is positive, a 100-gram OGTT is performed for diagnosis.

0 In the two-stage approach, universal all pregnant women or selective screening can be performed. Therefore, the risk of gestational DM should be determined at the first prenatal visit. Low-risk pregnant women may not be screened. High-risk pregnant women should have a glucose screening test as soon as possible.

0 Low Risk: Routine glucose screening is not required if all of the following are present.

- Ethnicity with a low prevalence of gestational DM (GDM)

- No DM in first degree relatives

- Age< 25

- Normal pre-pregnancy weight

- Normal birth weight

- No history of abnormal glucose metabolism

- No history of poor obstetric outcome

0 Medium Risk: 24-28. Glucose screening test is done between weeks.

0 High Risk: Glucose screening test is performed as soon as possible if one or more of the following is present. If the test is normal, 24-28. It should be repeated every few weeks or whenever there are signs or symptoms indicative of hyperglycemia.

- Severe obesity

- Strong family history for type 2 DM

- Large baby birth history

- History of unexplained fetal loss

- History of GDM, impaired glucose metabolism or glycosuria in previous pregnancies

Recommended Approaches for Gestational DM Complete and Screening

1. One-Stage Approach (75 g Oral Glucose Tolerance Test)

- Fasting glucose -------->= 92

- 1st hour glucose ----->= 180 -------GDM diagnosis is made if the single value is high.

- 2nd hour glucose ------>=153

2. The Two-Stage Approach

a. 50 g Oral Glucose Tolerance Test

- 1st hour glucose --->=135 or 140 -------100 g OGTT should be done.

b. 100 g Oral Glucose Tolerance Test

- Fasting glucose ----->=95

- 1st hour glucose ---->0180------ If two values are higher, the diagnosis of GDM is made.

- 2nd hour glucose 2:: 155

- 3rd hour glucose 2:: 140

Pregestational Diabetes

• The probability of achieving successful pregnancy outcomes in pregestational diabetes depends to some extent on blood sugar control, but more importantly on the degree of underlying cardiovascular or kidney disease. In the White classification, the probability of good pregnancy outcomes decreases as the alphabetical classification progresses.

• Effects of pregestational diabetes on pregnancy outcomes: Macrosomia (45%), gestational hypertension and preeclampsia (28%), preterm birth (28%), fetal growth retardation (5%), perinatal death (1.7%), stillbirth (1%) )

Fetal Complications

► Increased risk of spontaneous abortion: Early pregnancy loss is associated with poor glycemic control, and the risk is markedly increased, especially in women with HbAlc > 12% and persistent postprandial glucose > 120 mg/dl.

► The risk of preterm birth increases. Beta-mimetics should not be preferred as tocolytics in diabetic women because they disrupt glucose regulation.

► The risk of congenital major malformation increases by 2 times: The incidence of major malformation is 11% and it constitutes half of the perinatal mortality. More than half of congenital anomalies are cardiac anomalies. Cardiac defect risk increased 4 times and non-cardiac defect risk increased 2 times.

Most Common Major Congenital Anomalies in Newborns of Diabetic Women (A total of 36, 345 pregnancies were examined)
systems	Type 1 diabetic pregnant women (n=482)	Type 2 diabetic pregnant women (n=4166)	gestational diabetic pregnant women (n=31.700)
cardiac system	38	272	1129
Musculoskeletal system	1	31	231
urinary system	3	28	260
Central nervous system	1	13	64
gastro-intestinal system	1	30	164
Other	11	80	355
Total	55	454	2203

The most common congenital system anomaly in patients with pregestational type 1 diabetes is cardiac anomalies.

The anomalies with the highest incidence in those with pregestational diabetes are caudal regression and situs inversus, respectively.

► The risk of severe malformations is associated with poor glycemic control before and during pregnancy. Those with lower glycosylated hemoglobin (HbAlc) levels during conception have a lower risk of anomaly. Due to hyperglycemia, cellular lipid metabolism, production of toxic superoxide radicals and programmed cell death increase, leading to the development of malformations.

Diabetes fetal chromosome! does not increase the risk of anomaly (eg Down syndrome) .

► May cause fetal growth changes:

0 Macrosomia: If the mean maternal glucose level is > 130 mg/dl, the incidence of macrosomia increases significantly and is seen especially in the second half of pregnancy. Since there is more fat accumulation in the shoulders and trunk, it increases the risk of shoulder dystocia and cesarean delivery.

0 IUGG: IUGG can be seen in pregnant women with pregestational diabetes who have vascular complications as a result of a decrease in the substrate passed to the fetus.

► Risk of fetal mortality is increased 3-4 times: Unexplained fetal death rate is increased in women with pregestational diabetes, and stillbirth without an identifiable cause is unique to pregestational DM. unexplained stillbirths

. is associated with poor glycemic control, and lactic acid levels were often found to be high in these fetuses. Villous edema (hydropic) occurs with the induction of maternal hyperglycemia and osmosis. Hence the placenta! transport is broken. They are typically large for gestational age and are usually lost before labor at 35 weeks or later.

0 There is also an increase in the frequency of explainable stillbirth due to placental insufficiency in pregestational DM. It is increased in women with advanced diabetes and vascular complications and is usually associated with preeclampsia. Fetal death may also occur due to ketoacidosis.

amniotic fluid diseases

0 Hydramnios: Pregestational diabetes is often complicated by hydramnios. It occurs with polyuria due to fetal hyperglycemia and is associated with poor maternal glucose control.

0 Oligohydramnios: Oligohydramnios can be seen in pregestational diabetic women with vascular complications.

Neonatal mortality and morbidity

The risk of preterm birth increases.

0 Increased risk of respiratory distress syndrome. Lung maturation is delayed in diabetic pregnant women.

0 Neonatal hypoglycemia, hypocalcemia, hyperbilirubinemia and polycythemia

0 Cardiomyopathy: Hypertrophic cardiomyopathy may be seen and the interventricular septum is usually involved.

0 Inheritance of diabetes: While the risk is 3-5% in children of parents with Type I diabetes; In those with type II diabetes, the risk is 40%.

Maternal Complications

- Maternal mortality increases (0.5%): Factors that increase maternal mortality; ketoacidosis, hypoglycemia, hypertension, preeclampsia, infection.

- Diabetic nephropathy: Pregnancy does not generally worsen diabetic nephropathy. Although progression is not observed in patients with mild renal failure, there may be an acceleration in progression during pregnancy in patients with moderate and severe renal impairment. However, the risk of preeclampsia is significantly increased in pregnant women with nephropathy (class F) (risk 40%).

- Diabetic retinopathy: Progression can be seen in early pregnancy in 25% of women with Type 1 diabetes and 14% of women with Type 2 diabetes. The level of retinopathy before pregnancy is the only independent risk factor that determines the progression. Other risk factors associated with progression are hypertension, elevated IGF-I, and macular edema in early pregnancy. Therefore, routine retinal evaluation should be performed in pregnant women with pregestational diabetes following the first prenatal visit.

Pregnancy does not affect the long-term course of diabetes, except for diabetic retinopathy.

- Diabetic neuropathy: Peripheral symmetrical sensorimotor diabetic neuropathy is rare in pregnant women. However, diabetic gastropathy increases the risk of morbidity and poor perinatal outcome during pregnancy.

- The risk of preeclampsia increases: The risk of preeclampsia is increased 3-4 times in those with pregestational diabetes, and the risk increases 12 times in diabetics with accompanying hypertension. Preeclampsia risk is increased in diabetic women with any vascular complications or pre-existing proteinuria, whether they are hypertensive or not. Hypertension caused or exacerbated by pregnancy is the most important complication leading to preterm delivery in diabetic pregnant women. As the White classification increases, the risk of preeclampsia also increases , and the risk of preeclampsia is associated with glucose control.

- Diabetic ketoacidosis: It is mostly seen in Type 1 diabetes and its incidence is 1%. However, it can also be seen in type II diabetes and gestational diabetes. Ketoacidosis is a predictor of poor prognosis in pregnancy. The fetal loss rate is 20% in ketoacidosis. Predisposing factors; hyperemesis gravidarum, use of beta mimetics for tocolysis, infections, steroid use for lung maturation.

- Infections: Most infections increase in diabetic pregnant women. The most common infections; candida vulvovaginitis, urinary system infection, respiratory system infection, puerperal pelvic infection and wound infection after cesarean section.

Treatment Approach

Pre-Pregnancy Care

► Optimal glycemic control should be provided to prevent early pregnancy losses and congenital malformations. Target glucose levels using pre-pregnancy insulin; FBC: 70 - 100 mg/dl, postprandial 2nd hour peak value; 100-120 mg/dl and daily average glucose value; It is <110 mg/dl.

► In order to evaluate early metabolic control, glycosylated hemoglobin (HbAlc) showing the last 4-8 weeks glucose average should be measured and should be :56.5. The most important risk for malformations is values exceeding 10% (increased 4 times).

► 400 ug/day Folic acid should be given before pregnancy and early pregnancy to reduce the risk of NTD. If indicated, diabetic complications such as retinopathy or nephropathy should be treated.

First Trimester

0 Oral antidiabetics should not be used and insulin therapy should be given.

0 Diet: A diet consisting of a mixture of carbohydrates, proteins and fats but containing a minimum of 175 g/day carbohydrates should be taken.

0 Diabetes tends to be unstable, especially in the first trimester, and maternal hypoglycemia is most common in 10-15 days. monitored for weeks. Glucose control targets during pregnancy;

- AKŞ ►:5 95 mg/dl

- Pp 1st hour ► ::5 140 mg/dl

- Pp 2nd hour ►:5 120 mg/dl

- HbAlc ►:5 % 6%

Second Trimester

0 16-20. Maternal serum AFP level should be measured in terms of anomalies and NTD between gestational weeks and ultrasonography should be performed. Fetal echocardiography should be performed in the second trimester as the risk of cardiac anomaly is increased.

0 Diabetes is more stable in the second trimester and after the 24th week, the need for insulin begins to increase due to the anti-insulinergic effect of pregnancy hormones. The period with the highest insulin requirement is the second half of pregnancy (increases by 3 times).

Third Trimester and Birth

► 32-34. Tests that determine fetal well-being (fetal movement count, fetal heart monitoring, biophysical profile, and CST if necessary) should be started between weeks and weeks.

► Birth should be planned at 38 weeks. If the fetus is not very large and the cervix is suitable, labor induction can be attempted. Estimated birth weight

Cesarean section is preferred for babies weighing �4500 gr. Cesarean section rates are high (80%) in diabetic women to reduce birth trauma due to macrosomic babies.

0 Long-term insulin dose should be reduced or discontinued on the day of delivery. Because the need for insulin decreases markedly after delivery.

puerperium

► There is no need for insulin in the first 24 hours postpartum, and it varies in the following days.

Gestational Diabetes

• It is glucose intolerance of varying degrees that is diagnosed or manifested for the first time during pregnancy. Its incidence is 5-6% and the prevalence varies according to race, age, body composition and screening criteria.

• The probability of fetal death in properly treated gestational diabetes is general.

not different from the population.

• The most important perinatal concern is macrosomia, which causes maternal and fetal birth trauma.

The adverse side effects of gestational diabetes differ from pregestational diabetes and the incidence of fetal anomaly has not increased.

Fetal Complications

The risk of fetal mortality is increased: This risk is lower in diet-regulated gestational diabetes. In addition, unexplained fetal death rate increased in pregnant women with high fasting blood sugar, similar to pregestational diabetes. FAC > 105 mg/dl in the last 4-8 weeks of pregnancy is associated with an increased risk of fetal death.

► Macrosomia: Babies with a birth weight of over 4500 g are macrosomic.

0 Maternal hyperglycemia causes fetal insulinemia, which leads to stimulation of excessive somatic growth, especially in the second half of pregnancy.

0 Factors associated with macrosomia; insulin (C peptide}, IGF I (strong relationship with birth weight), epidermal growth factor, leptin and adiponectin.

0 Maternal obesity is a more important and independent risk factor for fetal macrosomia than glucose intolerance. The risk of gestational diabetes is increased, especially in women with truncal obesity.

Treatment Approach

► The incidence of preeclampsia, shoulder dystocia and macrosomia is significantly lower in treated gestational diabetic pregnant women.

► Pregnant women with gestational diabetes are divided into two functional classes according to whether the blood glucose target can be achieved with diet or not. Target glucose values in gestational diabetes are FPG <95 mg/dl and postprandial 2nd hour <120 mg/dl.

0 Take class if goal can be achieved with diet

0 Class A2 if dietary target cannot be achieved; Treatment is usually switched to insulin.

► Diet: Daily calorie intake should be 30-35 kcal/kg/day; however, it should be restricted to 25 kcaljkg/day in those with BMI>30. 40% of daily calorie needs should be adjusted as carbohydrates, 40% protein and 20% fat.

► Exercise: It reduces the need for insulin in obese patients with gestational DM.

► Glucose monitoring: Postprandial monitoring is more important than preprandial for gestational DM. Glucose monitoring is recommended 4 times a day, with fasting and satiety being measured at the 1st or 2nd hour.

► Insulin: If FAC persists > 95 mg/dl despite diet, insulin is started. Insulin should also be started if the 1st hour of postprandion is > 140 mg/dl or the 2nd hour of the postprandion is > 120 mg/dl.

► Oral hypoglycemic agents; In case of persistent hyperglycemia in gestational diabetes, insulin is the first choice, but there is increasing evidence supporting the safety and efficacy of Glyburide and metformin.

► Prenatal follow-up: Premature birth and other interventions are rarely necessary in gestational diabetics who do not need insulin. Pregnant women using insulin due to fasting hyperglycemia should be followed closely antepartum and managed like pregestational DM.

► Delivery: Induction of labor is not recommended before 39 weeks in gestational diabetic women who do not use insulin. In patients using insulin, delivery at 38 weeks is recommended. In order to avoid brachial plexus injury in macrosomic fetuses, cesarean section should be preferred if the estimated fetal weight is 2= 4500 g.

► Postpartum follow-up: The risk of developing DM in 20 years in women with gestational DM is 0/oSO. For this reason, 75 g OGTT and annual fasting glucose measurement should be performed between 6 and 12 weeks postpartum, postpartum 1 year, every 3 years and before the next pregnancy.

Follow-up Recommendations for Women with Gestational Diabetes After Pregnancy

Time -------------------------------------------Recommended Test

• Postpartum (Day 1-3)-----• Fasting or instant plasma glucose measurement

• Early postpartum (6-12 weeks)----------• 75 g OGTT

• Postpartum 1st year -------• 75 g OGTT

• Annually----• Fasting plasma glucose measurement

• Every three years-------• 75 g OGTT

• Pre-pregnancy----------• 75 g OGT

- Normal ........ ➔ FPS <100, ...... 2hr<140, ..... HbA1c<5.7%

- Impaired glucose tolerance .... ➔ FCA 100-125, .... 2h 140-199, ... HbA1c 5.7-6.4%

- Overt DM .............. ➔ FCA >=126, ........ 2nd hour >=200, ...... HbA1c >= % 6.5

► Since they can be associated with dyslipidemia, hypertension and abdominal obesity (metabolic syndrome), they also carry a risk in terms of cardiovascular complications.

► The risk of recurrence in the next pregnancy is 48%.

HYPERTENSIVE DISEASES IN PREGNANCY

noreply@blogger.com (Unknown) — Sun, 12 Mar 2023 12:59:00 +0300

• Hypertensive states of pregnancy occur in 5% to 10% of all pregnancies and are examined in five groups:

Chronic Hypertension

• It can be diagnosed in two ways;

- Blood pressure => 140 / 90 mmHg before pregnancy or before 20 weeks of gestation not attributable to gestational trophoblastic disease

- Hypertension diagnosed after the 20th week for the first time and continuing after the postpartum 12th week

If the diastolic pressure is consistently above 100 mmHg in those who do not have other health problems, antihypertensive treatment should be started. The most reliable agent in the antihypertensive treatment of chronic hypertensive pregnant women is a-methyldopa.

• Low-dose aspirin is recommended for pregnant women with chronic hypertension. (from 12 weeks to birth).

e Women with chronic hypertension, with or without treatment, have an increased risk of fetal congenital anomalies (especially cardiac anomalies).

Gestational Hypertension

• Diagnostic criterion is 2!140 / 90 mmHg blood pressure two times after the 20th week of pregnancy; however, the definitive diagnosis can be made after the blood pressure returns to normal before the postpartum 12th week.

preeclampsia

Diagnostic criteria;

► Having a blood pressure >= 140 / 90 mmHg for the first time after the 20th week of pregnancy, and

► Any of the following criteria accompanying hypertension

0 Detection of new onset pathological proteinuria (>= 300 mg/day or >=1 in spot urine + protein/creatinine in dipstick or spot urine >= 0.3

0 Platelet count less than 100,000/l

0 Creatinine over 1.1 mg/dl

0 Serum transaminases exceeding 2 times normal

0 Headache, visual disturbances, convulsions

0 Pulmonary edema

Peripheral edema is not a diagnostic criterion.

Eclampsia

• Convulsions that cannot be explained by any other reason in a preeclamptic pregnant

is to accompany.

Preeclampsia Developing on the Background of Chronic Hypertension

• If new-onset pathological proteinuria or other preeclampsia diagnostic criteria are present in a chronic hypertensive patient, a diagnosis of superimposed preeclampsia is made.

• Typically, after the 24th week, blood pressure values begin to rise. It tends to occur earlier and progress worse than pure preeclampsia. It is usually accompanied by IUGR.

PREECAMPSIA

Risk factors

• Those exposed to chorionic villi for the first time (nulliparity)

• Those exposed to chorionic villi more than normal (multiple pregnancy, molar pregnancy)

• Those with previous vascular disease (chronic HT, collagen tissue diseases, DM, kidney diseases, CVS diseases)

• Race and ethnicity genetically predisposed to develop hypertension in pregnancy

• Those with a history of hypertensive disease in a previous pregnancy

• Obesity

• Maternal age > 35

• Hyperhomocystinemia

• Metabolic syndrome

• Antiphospholipid antibody syndrome

• Factor 5 leiden mutation

• Pregnancies of women born with SGA

Smoking reduces the risk of preeclampsia. (Increases placental adrenomedullin expression)

Trisomy 13 is the only aneuploidy with an increased risk of preeclampsia.

Preeclampsia does not increase the risk of fetal cardiac anomaly.

etiopathogenesis

• For the development of preeclampsia, chorionic villi, not the fetus, must be present (can be seen in complete moles). However, chorionic villi are not necessarily intrauterine. It can also be seen in ectopic pregnancies greater than 18 weeks.

• The cause of preeclampsia is not known exactly, but the factors that trigger preeclampsia cause ischemic and thrombotic sequelae affecting the whole system by causing two main pathologies regardless of etiology.

► Generalized Vasospasm: (E-98) Increased resistance as a result of vasospasm causes hypertension. In addition, due to decreased blood flow, ischemia, necrosis, bleeding and end-organ disorders occur in all surrounding tissues.

► Endothelial Cell Activation: Unknown but possibly placenta! These factors are secreted into the maternal circulation and cause vascular endothelial dysfunction. As a result of this;

0 Endothelial cell damage

0 Decreased nitric oxide production, increased endothelin-1 synthesis

0 Disruption of prostaglandin balance

0 Atherosis and lipid-laden macrophages (foam cell)

0 Microvascular coagulation (thrombocytopenia)

0 Increased capillary permeability (proteinuria and edema)

While prostacyclin decreases in preeclamptic pregnant women, thromboxan A2 increases, and vasospasm occurs when resistance to angiotensin II disappears.

► There may be incomplete trophoblastic invasion in preeclampsia. While invasion occurs in decidual spiral arterioles, invasion is not observed in myometrial spiral arterioles. Thus, high resistance and small diameter vessels

consists of. Incomplete invasion of spiral arterioles is associated with severe preeclampsia.

► Another theory is the absence or dysregulation of maternal immune tolerance to placental and fetal antigens of paternal origin. A decrease in the amount of HLA-G expressed by extravillous trophoblasts has been shown in preeclamptic pregnant women in the early period. This can cause abnormal trophoblastic invasion. While the Th1/Th2 ratio is in favor of Th2 in normal pregnancies, this ratio changes in favor of Th1 in preeclampsia. Thl causes an increase in inflammatory cytokines. Microparticles secreted from the placenta are also thought to initiate these inflammatory reactions.

► Preeclampsia risk doubles in pregnant women whose daily ascorbic acid intake is below 85 mg, since antioxidant production is reduced.

► It is recommended to use low-dose aspirin to reduce the recurrence of preeclampsia.

► Genetic predisposition: Preeclampsia is a multifactorial, polygenic disease. First-degree relatives are at increased risk.

► Changes in arteries at the implantation site in preeclampsia: Endothelial damage, penetration of plasma components into the vessel wall, proliferation of myointimal cells and medial necrosis. Fat accumulation in myointimal cells is called atherosis. An infarct can be seen in the placenta.

Clinic

• It can be in a spectrum ranging from symptoms that are difficult to notice clinically to multiorgan involvement that threatens the life of the mother and the baby. Therefore, gestational hypertensive diseases are clinically examined in two groups as mild and severe.

• Presence of one of the following findings makes the diagnosis of severe gestational hypertensive disease.

Mild to severe preeclampsia criteria
	Light	Severe
Diastolic pressure	< 110 mmHg	>= 110 mmHg
systolic pressure	<160 mmHg	160mmHg
headache	no	There is
Visual disturbances (scotoma)	no	There is
epigastric pain	no	There is
oliguria	no	There is
Convulsion (eclampsia)	no	There is
Serum creatinine	Normal	increased
thrombocytopenia	no	There is
Serum transaminase elevation	Very little	Evident
Fetal growth restriction	no	Evident
pulmonary edema	no	There is
Onset of preeclampsia	start in the coming weeks	Early weeks start

Presence or degree of proteinuria is NOT a criterion for severe preeclampsia.

Renal System

► Glomerulocapillary endotheliosis {classical pathological lesion)

► Decreased renal perfusion

► Decrease in glomerular filtration rate (GFR)

► Decreased uric acid clearance

► Increased plasma uric acid concentration (one of the earliest laboratory findings)

► Increase in creatinine level

► Proteinuria

► Sodium uptake increases

► Urine sodium concentration increases

► Decreased urinary calcium excretion

► Oliguria (Excessive fluid therapy should not be applied.)

► Acute renal failure (acute tubular necrosis); rare unless there is severe haemorrhage

► Renal cortical necrosis (rare)

Hematological System

► Thrombocytopenia (most common hematological finding)

► Microangiopathic hemolysis; LDH increases

► Reduction in coagulation factors

► Increase in fibrin degradation products

► Increase in D-Dimer, fibrinopeptide A and B levels

► Decrease in antithrombin, protein C and S levels

► Disseminated intravascular coagulation {DIC)

► HELLP syndrome

Induction of microangiopathic hemolysis of severe vasospasm and activation and aggregation of platelets leads to thrombocytopenia in cases, which is a sign of worsening preeclampsia.

In pregnant women with preeclampsia, the level of fibronectin, a glycoprotein associated with the endothelial basement membrane and indicating endothelial damage, is increased.

Cardiovascular System

► Increased peripheral vascular resistance results in increased cardiac afterload. In this case, cardiac output decreases.

► Hemoconcentration (especially in cases with severe preeclampsia and eclampsia) leads to a decrease in preload.

► Decreased blood volume (normal in gestational hypertension)

► In preeclampsia, ventricular remodeling (in response to increased afterload) occurs in the myocardium. Diastolic dysfunction is present in 40% of patients.

► Since there is no normal hypervolemia of pregnancy, even normal blood loss is less tolerated than normal pregnancies.

Endocrine Changes

► Renin, angiotensin and aldosterone decrease compared to normal pregnancy, but they are still above normal values compared to non-pregnant women.

► Deoxycorticosterone (DOC) increases. This explains the sodium retention in preeclamptic pregnant women.

► Vasopressin levels do not change.

► Atrial natriuretic peptide (ANP) increases.

► So-called antiangiogenic soluble endolgin (sEng) and soluble Fms like tyrosine kinase 1 (sflt-1) increase in preeclampsia. While sflt-1 causes endothelial dysfunction; soluble endolgin reduces nitric oxide dependent vasodilation.

Fluid - Electrolyte Changes

► Extracellular fluid volume increases; Due to endothelial damage, proteinuria and decrease in plasma oncotic pressure, the passage of intravascular fluid into the interstitial space is increased. Thus, edema is seen.

► Electrolyte concentrations do not change.

► After an eclamptic convulsion, serum pH and bicarbonate concentration decrease.

Liver

► Periportal hemorrhage, infarction, necrosis, hepatic failure

► Increased transaminases

► Subcapsular hematoma and rupture (The risk increases especially in those with HELLP syndrome.)

► HELLP syndrome

0 Epigastric and right upper quadrant pain in patients occurs as a result of stretching Glisson's capsule due to hepatocellular necrosis, ischemia, and edema. These findings are preliminary signs of liver infarction or rupture of a subcapsular hematoma.

0 Hemolysis, elevated liver enzymes and thrombocytopenia are present in HELLP syndrome.

Neurology System

► Intracranial petechial hemorrhages (especially in eclampsia)

► Changes in cerebral perfusion and perivascular edema (reversible posterior leukoencephalopathy): The development of generalized edema in the brain is dangerous; because fatal transtentorial herniation can develop.

► Hyperreflexia

► Convulsions (grand mal type): excitatory neurotransmitter release increases (especially glutamate)

► Headache and scotoma

► Visual disturbances: Often, scotoma, blurred vision, diplopia occur due to edema in the occipital lobe and usually resolve spontaneously. Temporary blindness of 4-6 hours (amorosis) may occur. It may rarely be permanent blindness due to retinal ischemia, necrosis or detachment (Purtscher retinopathy).

► Neurocognitive sequelae are detected in eclamptic patients in the long term (comprehension decreases).

Theroplacental Perfusion

► Increases perinatal morbidity and mortality

► Uteroplacental insufficiency (IUGR and intrauterine fetal death)

► Detachment placenta

Screening and Prophylaxis

• There is no reliable and valid screening test. It has been shown that salt restriction in the diet, the use of diuretics, and the intake of antioxidants such as calcium, fish oil, vitamin C and E have no effect.

• It is recommended to use low-dose aspirin from the 12th week of pregnancy until delivery in high-risk pregnant women to reduce the recurrence of preeclampsia.

Treatment

• The only real treatment for preeclampsia is termination of pregnancy. Management varies according to mild or severe preeclampsia.

Mild Preeclampsia

► Inpatient treatment or outpatient follow-up is appropriate. Mild preeclampsia can be followed until lung maturation is achieved. Physical activity restriction is helpful; however, absolute bed rest is not necessary. Coagulation tests do not need to be routinely performed during follow-up.

► If diastolic blood pressure is >100 mgHg in mild preeclampsia, antihypertensive treatment

recommended.

► Mode and timing of delivery: Induction vaginal delivery is the first choice after lung maturity is achieved.

Severe Preeclampsia

The purpose of the treatment of severe preeclampsia;

Control of Maternal Blood Pressure (Antihypertensive Treatment):

0 Purpose; To prevent complications such as hypertension-related cerebrovascular hemorrhage, encephalopathy, convulsions, congestive heart failure and detachment without reducing uteroplacental blood flow. Most of these complications occur when blood pressure is above 160/110 mmHg.

0 Agents used in antihypertensive therapy:

- Oral nifedipine: Nifedipine sublingual is not recommended. The blood pressure lowering effect is faster. May cause headache and tachycardia. Increases renal blood flow.

- Hydralazine: Hydralazine is a direct-acting arteriolar vasodilator. Hydralazine is the most commonly used drug in gestational hypertension and significantly reduces cerebral hemorrhage. The aim is to bring the diastolic pressure to 90-110 mmHg. Placenta if dropped even more! perfusion is affected. May cause maternal tachycardia. Increases renal blood flow.

- Labetalol: May cause maternal hypotension and bradycardia.

- Nitroprusside or Nitroglycerin: It is a direct-acting arteriolar and venous vasodilator. If there is no response to the first group of drugs, it should be evaluated. Fetal cyanide toxicity should not be forgotten.

- Verapamil, Nimodipine

- Ketanserine

Diuretics are used only for antepartum pulmonary edema. Other than that, the placenta! They are not used because they reduce perfusion. ACE inhibitors are NOT to be used as they are teratogenic.

Prevention of Convulsions (Magnesium Prophylaxis)

0 Since it is excreted by the kidneys, they can be used in patients with normal kidney functions. Dose adjustment should be made in patients with impaired renal function. It should not be given in complete anuria:

0 The therapeutic dose range is 4-7 mEq/L or 4.8-8.4 mg/dl; however, routine measurement of magnesium level is not recommended. Clinical follow-up is performed by the follow-up of deep tendon reflexes and the first sign of magnesium toxicity is loss of DTR. Calcium gluconate should be used as an antidote.

0 Magnesium sulfate should be given during labor and 24 hours postpartum.

Magnesium sulfate is not used for antihypertensive therapy.

Initiation of Birth:

0 Severe preeclampsia requires immediate delivery. Steroids should be administered between 24-34 weeks.

0 Type and timing of birth; vaginal delivery is the first choice.

ECLAMPSY

• Convulsions that cannot be explained by another reason in a preeclamptic pregnant woman. The incidence is 1/2000 births. Seizures are tonic-clonic in character and can be seen antepartum, intrapartum or postpartum. Eclampsia is most common in the third trimester.

and the frequency increases as the term approaches. Postpartum convulsions are seen less than 10%

and usually occurs in the first 48 hours.

Complications

• Ablation placenta-------10%

• Neurological deficits-----7%

• Aspiration pneumonia--------- 7%

• Pulmonary edema-------5%

• Cardiopulmonary arrest------ 4%

• Acute renal failure--------4%

• Maternal death------ 1%

Clinic

• An aura that precedes the seizure is often absent and is in the form of a generalized tonic-clonic convulsion. Fever is rare; however, it is a poor prognostic factor in its presence (a sign of hemorrhage in CNS). Pulmonary edema may develop following the seizure, due to aspiration pneumonitis. Retinal detachment and visual loss due to occipital lobe ischemia-edema may develop in 10% of cases following the seizure. cases Persistent coma may develop in up to 5% of patients due to diffuse cerebral edema and transtentorial uncal herniation. In some severe cases of eclampsia, sudden death may occur due to massive cerebral hemorrhage developing during convulsions. Very rarely, psychosis and related aggression may be seen in the patient after the attacks.

• Sometimes, uterine contractions may begin or intensify during seizures. Maternal hypoxemia and lactic acidemia due to convulsions cause fetal bradycardia. This condition usually resolves in 3-5 minutes; however, if it lasts longer than 10 minutes, other factors should also be considered, such as detachment.

• Epilepsy, encephalitis, meningitis, cerebral tumor, cysticercosis and ruptured cerebral aneurysm should be considered in the differential diagnosis. However, all pregnant women with convulsions should be considered eclampsia until other causes are excluded.

Treatment

• Control of convulsions and prevention of recurrence: Magnesium sulfate is the most effective and safe. Other agents that can be preferred in the control of convulsions in eclampsia; amobarbital, thiopental, midazolam, lorazepam

• Antihypertensive treatment

• Initiation of labor: It is the definitive form of treatment. First of all, vaginal delivery should be preferred. Usually, labor begins spontaneously or labor can be successfully induced.

Prognosis

• Preeclampsia and eclampsia always improve after delivery (except for complications such as SVO). Diuresis (4 L/day) is the best indicator of recovery. Proteinuria and edema return to normal within 1 week after delivery in eclampsia. Fetal prognosis mostly depends on gestational age at birth and problems are related to prematurity.

• The risk of recurrence in subsequent pregnancies is increased (25%). The earlier it is diagnosed, the greater the risk of recurrence. If diagnosed before the 30th week, 40% will recur. The risk of recurrence is also significantly higher in those with HELLP syndrome and thrombophilia.

• Long-term risks of women who have had any hypertensive processes during pregnancy:

► Morbidity and mortality due to cardiovascular diseases increase: The risk of ischemic heart disease, stroke, venous thromboembolism, chronic hypertension and type II DM increases.

► Increased risk of kidney failure

► It has been determined that lesions in the white matter of the brain persist in those who have had eclamptic convulsions in the long term, and some cognitive functions may be impaired (impaired attention, decreased cognition).

RISKY PREGNANCY

noreply@blogger.com (Unknown) — Sat, 11 Mar 2023 19:47:00 +0300

Amniotic fluid diseases

Normal amniotic fluid dynamics

• Before the eighth week, the amniotic fluid is formed by the fluid transuded from the amniotic and fetal skin. During the second trimester, the fetus begins urinating, swallowing, and inspiring amniotic fluid, but before the second trimester, the major source of amniotic fluid is not fetal urine. In the third trimester of pregnancy, while the main mechanism in amniotic fluid production is fetal urine, fetal swallowing plays a fundamental role in resorption {

• Normally, amniotic fluid volume becomes 30 ml at the 10th week, 200 ml at the 16th week, and 800 ml in the middle of the third trimester. It decreases after 36 weeks of gestation and decreases below 200 ml at 42 weeks of gestation.

functions of amniotic fluid

1. Protecting the fetus from external trauma

2. Protecting the umbilical cord from compression

3. Ensuring the development of the fetal musculoskeletal system by allowing fetal movements

4. Contributing to fetal pulmonary development

5. Lubricating fetal skin

6. Protect from chorioamnionitis and fetal infection due to its bacteriostatic property

7. Aiding fetal temperature control

• Measurement of amniotic fluid:

► Amniotic fluid index (ASI): The uterus is divided into 4 equal quadrants and the largest vertical depth in each quadrant is measured and summed. ASI: If S is 5 cm, oligohydramnios; If ASI 2:: 25 cm, hydramnios is diagnosed.

► Measurement of the deepest single amnion pocket: The normal value of the deepest vertical pocket is 2-8 cm

between.

hydramnios

etiology

► The degree and prognosis of hydramnios are dependent on the etiological factor. Hydramnios is most commonly observed as idiopathic (50%). Cases of hydramnios with determined causative agents are usually associated with fetal malformations, especially CNS and GIS.

0 Common reasons·

- GIS anomalies (esophageal atresia)

- CNS anomalies (anencephaly, spina bifida)

- Maternal diabetes

- Non-immune hydrops fetalis and isoimmunization

- Chromosomal anomalies; Trisomy 18 should be considered in case of IUGR and polyhydramnios.

- Thoracic anomalies (cystic adenomatoid malformation, pulmonary sequestration and diaphragmatic hernia)

- Skeletal system anomalies

- Cardiac malformations

- Multiple pregnancies (twin to twin transfusion syndrome)

0 Rare causes:

- Pseudohypoaldosteronism, fetal Batter syndrome (hyperprostaglandin E syndrome), fetal nephrogenic diabetes insipidus, placental chorioangioma, fetal sacrococcygeal teratoma, maternal substance abuse, congenital infections (parvovirus, CMV, syphilis and toxoplasma), fetal mesoblastic nephroma.

Complications

► Edema of lower extremities, vulva and abdominal wall

► Dyspnea

► Ureteral pressure

► Ablation placenta (detachment)

► Uterine atony

► Increased cesarean rate as a result of malpresentations

► Preterm action

► Cord prolapse

► Increase in perinatal mortality

Treatment

► Mild hydramnios rarely requires treatment. Antepartum treatment options are limited. Indomethacin reduces the amount of fetal urine; however, it causes premature closure of the ductus arteriosus, so it cannot be used after 34 weeks.

► Removal of fluid with amnioreduction is only temporarily effective. Controlled amniotomy during labor can reduce the incidence of complications resulting from rapid decompression (ablation placenta, cord prolapse, etc.).

Oligohydramnios

etiology

► Oligohydramnios is almost always present in cases of obstruction of the fetal urinary system and renal agenesis.

Fetal Causes

- Chromosome anomalies

- Congenital anomalies

- IUGG

- intrauterine death

- Postterm pregnancy

- Premature rupture of membranes

0 Maternal Causes

- Uteroplacental insufficiency

- hypertension

- Preeclampsia

- Overt diabetes

- AFAS

0 Placental Causes

- Ablation placenta (detachment)

- Twin-to-twin transfusion

0 Drugs

- Prostaglandin synthesis inhibitors

- ACE inhibitors

- Trastuzumab

0 idiopathic

15-25% of oligohydramnios cases are associated with congenital anomalies.

Anhydramnios resulting from bilateral renal agenesis leading to extremity contractures, facial compression and pulmonary hypoplasia is called Potter's syndrome.

Complications

► Amniotic band syndrome

► Musculoskeletal deformities due to uterine compression (such as clubfoot)

► Increase in umbilical cord compression and cesarean section rate

► Pulmonary hypoplasia

Treatment

► It should be evaluated in terms of fetal anomalies and fetal growth retardation. Morbidity is increased in IUGR cases complicated with oligohydramnios. Antepartum treatment options are limited, but inutero surgery may have a chance to correct some structural defects (such as posterior urethral valve repair in male fetuses).

► Timing of delivery depends on gestational age, fetal well-being and etiology. Infusion of crystalloid solution into the amniotic cavity during labor

Cord compression can be prevented, the risk of cesarean section can be reduced and the risk of neonatal meconium aspiration can be minimized by performing (amnioinfusion). Amnioinfusion is not recommended in the treatment of oligohydramnios other than labor.

PLACENTA AND CORD ANOMALIES

Abnormal Placenta Types

• Bilobular Placenta {Plasenta Bipartita): The placenta is almost in the form of two equal lobes.

• Multilobile Placenta: It is a placenta with three or more lobes.

• Placenta Su centriata: It is the presence of one or more small accessory lobes connected to the main placenta with the fetal vessels on the membranes. It is more common in twin pregnancy. It may cause postpartum hemorrhage due to the fact that the accessory lobe remains in the uterus after delivery. It can also cause fetal bleeding by causing vasa previa. It may be related to abortions.

• Membranous Placenta: Most or all of the fetal membranes are covered with functioning villi.

• Annular Placenta The placenta is annular and sometimes the placental tissue forms a complete ring. The probability of antepartum and postpartum bleeding is increased and is associated with IUGR.

Penned Placenta {Planta Fenestrata) The disc-shaped placenta has no middle part, but often the defect contains only villous tissues and the chorionic plate remains intact.

• Extrachorial Placenta: The chorionic layer on the fetal surface of the placenta, the placenta on the maternal side! It is the condition that the peripheral surface of the placenta cannot be covered because it remains smaller than the basal layer. There are two types:

Circumvallate placenta: It is the presence of a central collapsed area on the fetal face surrounded by a thick, gray-white, degenerate decidua and fibrin-containing chorion and a double folded ring formed by the amnion. There is an increased risk of antepartum hemorrhage (both abruption and fetal hemorrhage), preterm delivery, perinatal mortality, and congenital anomalies.

Circummarginate placenta is the absence of a central collapsed area between the membrane folds in this ring. Poor clinical outcomes are less.

placentomegaly

• Etiology

► Maternal diabetes

► Severe fetal anemia

► Fetal hydrops

► Placental hemorrhage

► Erythroblastosis fetalis

► Intrauterine infections (syphilis, toxoplasmosis, CMV and parvovirus infection)

► Chromosome! anomalies

► Molar pregnancies

► Severe maternal anemia

Placental Tumors

• Gestational trophoblastic neoplasms

• Chorioangioma: It is the only benign tumor of the placenta. It may be associated with antepartum hemorrhage, preterm labor, amniotic fluid abnormalities, and IUGR, polyhydramnios, fetal anemia, and fetal heart failure.

• Metastatic tumors: Tumors that most commonly metastasize to the placenta; melanoma, leukemia, lymphoma and breast cancer. Metastatic cells are located in the intervillous space. The most common tumor that metastasizes to the fetus is melanoma.

Single Umbilical Artery

• It is due to secondary atrophy of the previously normal umbilical artery. Cases of increased incidence; diabetes, epilepsy, preeclampsia, antepartum hemorrhage, oligohydramnios, hydramnios, pregnancies with chromosomal anomalies, twin pregnancies.

• It is an isolated finding in most cases, but 1/3 of the cases have additional anomalies (most frequently cardiovascular and genitourinary anomalies). In addition, there is no increase in the risk of aneuploidy unless other structural anomalies are accompanied.

• It may also be associated with IUGR and perinatal mortality.

Cord insertion Anomalies

Marginal insertion (Battledore placenta)

► It is the insertion of the cord into the edge of the placenta. It is common in multiple pregnancies and ivf pregnancies. Marginal insertion rarely causes problems.

Valemento (membranous) insertion

► Umbilical vessels separate from the umbilical cord away from the edge of the placenta and reach the placenta only surrounded by the amniotic remnant. The incidence increases in placenta previa and multiple pregnancies. The risk of vasa previa is high. A low apgar score may be associated with stillbirth, preterm birth, and SGA.

ANTEPARTUM BLEEDINGS

• Bleeding in the genital system after the 28th week. It is one of the important causes of maternal mortality.

Causes of antepartum bleeding

Obstetrical Causes (95%)---------------------Non-obstetrics (5%)

Ablation placenta (30-50%)------------------- Cervicitis, cervical erosion and polyps

Placenta previ-a (-10-15%)-------------------- Vaginal laceration, trauma and varicose veins

Yasa previa / Velamentous insertion---------- Vaginal malignant/benign neoplasms

Uterine rupture------------------------------------Cervical malignant/-ben-ign neoplasms -

--------------------------------------------------------Coagulation disorders

The most common cause of antepartum hemorrhages is detachment.

Detachment (Ablation - Abruptio Placenta)

• It is the early separation of the placenta from the implantation site before the birth of the fetus. Separation can be total or partial. 37-39 of pregnancy most. observed between weeks.

Risk factors

Ablation Placenta Risk Factors Relative Risk

1. Ablation history -------------------------------► 10-188

2. Low birth weight-----------------------► 14

3. Multiple pregnancies ---------------------------------► 2 - 8

4. Hydramnios-----------------------------------------► 2 - 8

5. Preterm premature rupture of membranes -------------------- 2.4 - 4.9

6. Preeclampsia--------------------------------► 2.1- 4.0

7. Single umbilical artery------------------------------► 3,4

8. Chorioamnionitis------------------------------------------- 3

9. Chronic hypertension------------------------► 1.8 - 3

1 O. Advanced age (> 35) and multiparity -----------------► 1.3- 2.3

11. Smoking ------------------------------------------------► 1.4- 1.9

12. Cocaine -------------------------------------------► -

13. Leiomyoma (at implantation site)-------------► -

The most increasing risk in the etiology of detachment: history of detachment

Pathology

► It begins with bleeding into the decidua basalis. The decidua then separates, leaving a thin layer adjacent to the myometrium. The result is a decidual hematoma. Retroplacental hematoma enlarges and causes separation of the adjacent placenta.

► Bleeding is almost always maternal (because the separation occurs in the maternal decidua), but fetal bleeding may also occur in traumatic cases (from the placental damaged area).

Clinic

► Vaginal bleeding: Accumulated blood can separate the membranes from the uterine wall and external bleeding may occur (78%) (overt bleeding) or remain completely inside the uterus (occult bleeding). While there is overt bleeding and the fetus may not be in danger, there may be no overt bleeding and the fetus may be lost.

► Courvelaire uterus (uteroplacental apoplexy): Widespread extravasation to the uterine musculature and below the serosa. It may rarely cause uterine atony and is not an indication for hysterectomy.

► There is uterine tenderness, frequent uterine contractions and hypertonicity (uterus tetanic and contracted) (66%). For this reason, preterm labor may be misdiagnosed (20%) until fetal distress develops.

► Fetal distress is common (60%) and fetal death may occur.

► In severe cases, hypovolemic shock, acute renal failure and Sheehan's syndrome may occur due to bleeding. Detachment is the most common cause of acute cortical necrosis in pregnancy.

► The most common cause of DIC due to obstetric causes is detachment. The risk is greater in occult separation and is less common when the fetus is alive. It develops as a result of tissue thromboplastins passing into the maternal circulation.

Diagnosis and Differential Diagnosis

► In live pregnancies with vaginal bleeding, placenta previa and other causes of bleeding should be excluded by ultrasonography. However, the diagnosis of abruptio placentae, especially in the early period, can be made rarely (2%) by ultrasonography. MR imaging is very successful in the diagnosis of detachment.

► Painful uterine bleeding should suggest detachment and painless bleeding should suggest previa; however, it should not be forgotten that painful bleeding may occur in preterm labor accompanied by placenta previa.

► Depending on the level of bleeding, anemia and thrombocytopenia can be observed among the laboratory findings. While fibrinogen and coagulation factors decrease, fibrin degradation products may increase. Coagulation tests are helpful in diagnosis.

Treatment

► In the presence of a history of detachment, delivery should be planned at 37-38 weeks. In other patients, treatment should be tailored to the gestational age and the condition of the mother and fetus.

0 Approach in term pregnant: If the fetus is not live and vaginal delivery is not close, emergency cesarean section is preferred.

0 Approach in preterm pregnancy: Obvious placenta! Tocolysis is contraindicated in separations.

► Mode of delivery: If the fetus is alive but in distress, it should be delivered by cesarean section. Vaginal delivery is usually preferred if separation is severe enough to kill the fetus. Vaginal delivery is contraindicated in the presence of severe bleeding and other obstetric complications that cannot be overcome even with intensive blood replacement.

Complications

► Maternal complications:

0 Increased maternal mortality (0.5%-5%) (hemorrhage, heart and kidney failure). Clinically significant coagulopathy (DIC) may be seen in 10% of cases.

► Fetal complications:

0 Perinatal morbidity and mortality increase. Fetal mortality in severe detachments is 50%-SO. Causes of high mortality; placenta! separation, preterm birth, and an increase in the incidence of IUGG. Survivors have an increased risk of significant neurological sequelae.

0 Increase in congenital anomalies

The incidence of malpresentation does not increase in ablation.

PLACENTA PREVIA

• It is the placement of the placenta on or very close to the internal cervical os. Incidence of l'dit per 300 births

• Classification of placenta previa;

► Placenta previa: Internal cervical os completely {total) or partially

It is closed with a (partial) placenta.

► Lower placed placenta: The internal cervical os is not covered by the placenta, but the tip of the placenta is closer than 2 cm to the internal cervical os.

Risk factors

► History of placenta previa

► advanced maternal age; Incidence after 35 years 1:100

► Multiparity

► Multiple pregnancy (40%)

► previous cesarean section history (the higher the number, the higher the risk;)

► Cigarettes (increase 2 times)

► Uterine leiomyomas

► History of curettage

► Assisted reproductive techniques

Clinic

► It is characterized by painless, red vaginal bleeding and the bleeding is of maternal origin. Bleeding is not usually seen until the end of the second trimester or later. Bleeding can range from mild to severe but usually stops spontaneously to recur.

► Coagulation disorders are very rare, even with excessive separation; because tissue thromboplastins are expelled with bleeding.

► Bleeding may continue after the placenta is removed. It may even be associated with placental invasion defects.

The risk of placental invasion anomalies (acreta, increta, percreta) increases in pregnant women with a previous cesarean section history and diagnosed with placenta previa.

► Fetal malpresentation is common because the placenta prevents engagement of the presenting part.

tan

► Placenta previa must be ruled out ultrasonographically in pregnant women who have bleeding in the second half of pregnancy. Placental localization can almost always be determined by ultrasonography i. MRI can be used if a clear diagnosis cannot be made by ultrasonography or in the presence of a posteriorly located placenta. MRI is also helpful in the diagnosis of placenta accreta.

► Placenta previa is observed in 30% of the cases in the first half of pregnancy. In most of these cases, the placenta is pulled upward while the lower uterine segment is formed. Therefore, the diagnosis of placenta previa should be made after the 24th gestational week.

T d vi

► Birth 36-38. should be planned in the week and all cases with placenta previa are cesarean section.

should be born with

► In case of severe bleeding, delivery should be considered regardless of gestational age. In the absence of severe bleeding, the decision is made according to the condition of the fetus. If the fetus is mature; birth should be planned. If the fetus is premature and there is no other indication for delivery, close follow-up can be done. Tocolysis can be performed if necessary during follow-up.

Complications

Maternal complications:

0 Maternal mortality and morbidity have increased. Neonate options:

0 Preterm birth

0 IUGR

0 2.5-fold increase in congenital anomaly risk

Vasa Previa

• It is the presence of fetal vessels on the cervical os, passing through the membranes. It is bleeding from the umbilical vessels and the bleeding is of fetal origin.

• The placenta type with the highest risk of vasa previa is velamentous (membranous) insertion. There is also an increased risk of placenta suxentriata and bilobular placenta. Other conditions that increase the risk are placenta previa (2nd trimester), IVF pregnancies and multiple pregnancies.

• Fetal mortality is 75% due to fetal blood loss. 34-35 in case of prenatal diagnosis. Elective cesarean section should be performed during the gestational week. The diagnosis can also be made in case of heavy bleeding in light red color with the discharge of amniotic fluid following amniotomy during labor. In this case, an emergency cesarean section should be performed.

EARLY MEMBRANE RUPTURE AND PRETERM ACTION

Fetal Lung Maturation

• Respiratory distress syndrome (RDS) occurs due to pulmonary surfactant deficiency. Surfactant prevents alveolar collapse and consists mainly of phospholipids (dipalmitoyl-lecithin, phosphatidyl glycerol (PG) and phosphatidyl inositol

{Pi). Fetal cortisol stimulates surfactant synthesis, while insulin inhibits it.

• Amniotic fluid taken by amniocentesis is used in fetal lung maturation tests.

Lung maturation tests

► Lecithin / sphingomyelin ratio: 32-34 of pregnancy. After the first week, the lecithin level starts to rise rapidly and if the L/S ratio is above 2, the lungs are highly mature.

► Phosphatidylglycerol (PG): Phosphatidylglycerol is not seen in the amnion until the 35th gestational week, then its amount increases. In PG amniocentesis fluid (+), the lungs are mature, (-) they are immature.

► Fluorescent polarization test: Amniotic fluid is put into an automatic device without centrifugation and 30 min. It gives results according to the surfactant/albumin ratio. When the ratio is above 55, 100% lungs are mature. It gives better results than any of the other tests. It is also successful in diabetic women and those with blood contamination.

► Foam stability (shaking) test: It is based on the ability of the surfactant to form stable foam with 1 ml of amniotic fluid + 1 ml of 95% ethanol.

► Coverslip cell count: It is a fast and effective method.

Lung maturation induction

► 24-34. Corticosteroids should be administered to increase lung maturation (surfactant synthesis) in cases where delivery is expected in gestational weeks. Steroid administration can also be considered in pregnancies at 23 weeks of expected delivery. The benefit of using steroids after 34 weeks is controversial. Some authors 34-37. recommends a single dose of steroids, if it has not been done before, between weeks.

► Corticosteroids; RDS, intraventricular hemorrhage, necrotizing enterocolitis,

and reduces neonatal mortality. steroid therapy bronchopulmonary dysplasia

does not reduce the incidence

► Useful even 4 hours after application; however, preferably 48 hours are desired. Betamethasone or dexamethasone is used as iM. Repeated doses are not recommended as they may slightly increase the risk of cerebral palsy. Prednisone is not given for this purpose as it does not cross the placenta.

Premature Membrane Rupture (EMR)

• It is the rupture of membranes before labor starts after 37 weeks of pregnancy. If membrane rupture occurs before 37 weeks of gestation, it is called preterm premature rupture of membranes. Spontaneous rupture of membranes occurs physiologically at the end of the first stage of labor.

• Active labor often begins immediately after the arrival of the amniotic fluid. If there is still no delivery 12-24 hours after the waters come, the possibility of intrauterine infection increases significantly.

etiology

► Idiopathic (most common)

► History of premature rupture of membranes

► Intraamniotic infections (considered as the most important risk factor)

► Unexplained vaginal bleeding

► Low socioeconomic level

► Low body mass index (< 19.8)

► Nutritional disorders

► Smoking

tan

► It is placed clinically. Vaginal fluid accumulation and turning the litmus (nitrazine) paper blue of the vaginal fluid is valuable in sterile speculum examination. The pH of the vaginal secretions is 4.5-6.0, while the pH of the amniotic fluid is 7.1-7.3. The microscopic ferning pattern (which crystallizes when dry) is also significant. Decreased amniotic fluid index in abdominal ultrasonography also supports the diagnosis (I).

Complications

eona I o m ions depend on the severity of prematurity and oligohydramnios. These include RDS, intraventricular hemorrhage, periventricular leukomalacia, sepsis, convulsions, pulmonary hypoplasia (only at or below 23 weeks), cord prolapse, extremity deformities (related to the duration and severity of oligohydramnios).

Matern I complications: Chorioamnionitis and postpartum endometritis.

► Chorioamnionitis when one or more of the following clinical findings are present

diagnosis is made.

Fever above 0 38°C (the most important and only reliable finding suggesting the development of chorioamnionitis)

0 Maternal leukocytosis (> 18,000/mm3) (Unreliable alone.)

0 Foul-smelling vaginal discharge

0 Maternal (100 beats/min) and/or fetal tachycardia (more than 160 beats/min)

0 Uterine tenderness

0 CRP increase in amniotic fluid, leukocyte increase, IL-6 increase, glucose decrease, positive Gram staining and culture/catalase positivity (N ı ı J

Routine amniocentesis is not recommended to detect infection, but a negative result on Gram staining of amniotic fluid excludes the presence of bacteria in 99% amniotic fluid. In addition, culture negativity is the most reliable method to exclude the presence of bacteria.

► Risk factors for chorioamnionitis;

0 prolonged EMR

0 prolonged action

0 Multiple vaginal exams

0 low parity

0 Internal fetal monitoring

0 Bacterial vaginosis

► In all cases with clinical diagnosis of chorioamnionitis, emergency delivery is the basis of treatment to minimize the infectious morbidity of mother and baby, regardless of gestational age . If there are no signs of fetal distress in monitoring with NST, labor is induced and the patient is delivered vaginally. However, if there are signs of fetal distress, cesarean section is preferred.

► Broad-spectrum antibiotics are given to the mother in the intrapartum and postpartum period.

Group B and D streptococci are most commonly isolated in amniotic fluid culture in chorioamnionitis.

Treatment

EMR'de tedavi yaklasım
Gestasyonel yaş	treatment approach
34 hafta ve üstü	Birth; Induction if no contraindications Group B streptococcal prophylaxis between 34-37 weeks; Corticosteroids can be used if it has not been done before.
24 ile 33 haftalar arası	Follow-up until lung maturity (34 weeks) Group B streptococcal prophylaxis corticosteroid Tocolysis (if needed) Between 24-31 weeks; magnesium, sulfate for neuroprotection (if delivery is planned
24. haftanın alti	Follow-up or termination under 24 weeks should be based on the family's decision. Corticosteroid and group B streptococcal prophylaxis are not recommended, but antibiotic use can be started from the 20th week.

In premature rupture of membranes; ampicillin + erythromycin (7 days), ampicillin

± sulbactam (3-7 days) or erythromycin can be used. Amoxicillin + clavulanate should not be used because it increases the risk of NEC.

Preterm Action

• It is the onset of labor before 37 weeks of gestation. 34-36 days of labor. It is called late preterm labor and it constitutes 70-75% of all preterm labors. Preterm labor is the most common cause of perinatal morbidity and mortality.

Causes of preterm birth

► There are 4 main causes directly related to preterm birth:

0 Unexplained (idiopathic) spontaneous preterm birth without membrane rupture (40-45%)

0 Preterm premature rupture of membranes (30-35%)

0 Preterm births due to maternal or fetal indication (30-35%)

0 Multiple pregnancies

Risk factors

► History of preterm labor; It is a major risk factor and the risk increases 3 times.

► Intrauterine infections (25-40%)

► Bacterial vaginosis

► Abortion imminens

► Smoking, illegal drug use

► Young or advanced maternal age

► Low socioeconomic level, insufficient weight gain, vitamin C deficiency, obesity

► Heavy working conditions

► Psychological factors such as depression, anxiety, chronic stress

► Physical trauma

► Black race and short stature

► Chronic periodontal diseases

► Congenital anomalies

► < 18th month or >59th of pregnancy interval. be the moon

The most frequently isolated microorganisms in amniotic fluid in cases of preterm labor are; Ureaplasma urealyticum, Gardnerella vaginalis, Fusobacterium and Mycoplasma hominis

Diagnosis

► For a definitive diagnosis, uterine contractions (4 in 20 minutes or 8 in 60 minutes), cervical dilation (more than 1 cm) and cervical effacement (80% and above) are required.

► Another approach is to measure the cervical canal length by ultrasonography.

While it is normal to be >35 mm at the 24th gestational week; If it is <25 mm, cervical length is shortened. Funneling of the cervix on ultrasound is a harbinger of preterm labor.

► Detection of fetal fibronectin, a glycoprotein secreted from the amnion, in the cervicovaginal fluid before the 37th week of pregnancy is also a powerful method for diagnosing preterm labor.

prophylaxis

► Prophylaxis can be successful in selected patients. For this purpose, progesterone or

cervical cerclage can be used.

0 Progesterone can be given IM or vaginally between 16-36 weeks in pregnant women with a history of spontaneous preterm delivery.

0 In patients with a cervical length of <25 mm and a history of preterm birth, cervical cerclage should be applied in addition to progesterone.

Treatment

► Tocolytic agents; They do not significantly prolong the gestation period. and they are used to temporarily stop uterine contractions and to gain 48 hours for corticosteroids to take effect.

► Routine antibiotic use has no place in the treatment of preterm labor.

Preterm marriage treatment approach

Gestational grief -----------Treatment

34th week and above: Fetal monitoring and fetal follow-up, between 34-37 weeks; Never done job corticosteroid

24 to 33 weeks: Group B streptococcal prophylaxis, Corticosteroid, 24-31 weeks; magnesium sulfate for neuroprotection (if delivery is planned), Tocolysis

Below 24 weeks: Pregnancy is terminated

Tocolytics and their maternal-fetal effects

MgSO4

Maternal effect:

hypermagnesemia

pulmonary edema

cardiac arrest

hot flashes

diplopia

Fetal effect:

Protects against cerebral palsy (neuroprotective between 24-31 weeks)

Ca channel blockers

Maternal effect: None

Fetal effect: Reliable

Pg inhibitors (Indomethacin)

Maternal effect:

Oligohydramnios

Fetal effect:

Closure of the ductus arteriosus

Necrotizing enterocolitis

Intraventricular bleeding

Beta-mimetics (Ritodrin, Terbutaline)

Maternal effect:

Sodium and water retention

hypokalemia

pulmonary edema

cardiac arrhythmia

Maternal sepsis

hyperglycemia

Fetal effect:

Myocardial necrosis

Oxytocin antagonist (Atosiban)

Maternal effect: none

Fetal effect: increased neonatal morbidity

Oral terbutaline has no tocolytic effect.

· Beta mimetics should not be preferred in diabetics as they disrupt glucose regulation

POSTTERM PREGNANCY

• It is the name given to the fact that the birth has not occurred despite the completion of the 42nd week (294th day) of the pregnancy.

• The most effective method in determining or confirming the gestational age is the first trimester ultrasonographic measurement. If available, the last menstrual period and first trimester ultrasonographic measurements are compared. The only exception to this is the pregnancies that occur with assisted reproductive techniques, and the embryo age or transfer date is used to determine the gestational age in these pregnancies.

Risk factors

• Postterm pregnancy history (the situation that increases the risk the most}

• Those with a body mass index of 25 and above

• Nulliparity

• Fetal anencephaly

• Fetal adrenal hypoplasia

• X-dependent placenta! sulfatase deficiency

Complications

• Oligohydramnios

• Macrosomia

• Fetal distress

• Placenta! failure

• Meconium aspiration

• Increase in cesarean section rate

Treatment

• If there is no hypertension, oligohydramnios or decreased fetal movements, normal pregnancy follow-up is performed until the 42nd week is completed. If labor has not started yet, an induction delivery is performed.

FETAL DEVELOPMENT DISORDERS

Normal Fe I growth

• Cellular hyperplasia in the first 16 weeks of fetal growth during pregnancy, 16-32. Cellular hyperplasia and hypertrophy are effective in weeks, and cellular hypertrophy is effective from 32 weeks to delivery.

• Those that are effective in fetal growth; insulin, IGF 1-11, leptin. Leptin increases during the first two trimesters of pregnancy and correlates with birth weight.

Developmental Retardation

• Fetal weight below the 10th percentile (2 standard deviations) for gestational age is defined as small for gestational age (SGA), and perinatal morbidity and mortality increase significantly below the 3rd percentile. A history of IUGG increases the risk of recurrence by 20%.

• Intrauterine growth restriction is classified as symmetrical and asymmetrical.

► Symmetrical growth retardation (20%): Both cell number and cell size decrease due to factors in early pregnancy weeks. This results in a proportional reduction in both head and body size. It can be seen in the presence of chemical exposure, viral infections or aneuploidy.

► Asymmetric growth retardation (80%): As a result of uteroplacental insufficiency due to factors in late pregnancy, cell size is affected, not cell number. Accordingly, while normal brain and head development continues (brain protective effect), abdominal circumference (liver size) measurements are delayed.

Risk factors

► Non-pathological factors affecting birth weight include maternal and paternal height and weight, parity, ethnicity, geographical location and fetal sex.

0 Fetal Causes

- Genetic factors: Autosomal trisomies (t18, t13, t22, t21), Turner syndrome, osteogenesis imperfecta and chondrodystrophies

- Fetal structural anomalies: Gastroschisis

- Multiple pregnancies

Trisomy 18 can cause severe IUGR, while Klinefelter syndrome does not.

Uteroplacental Causes

- Preeclampsia, chronic vascular diseases, chronic hypertension, placenta previa, chronic ablation placenta, placenta! infarct, placenta circumvallata, chorioangioma, marginal or velamentous location of umbilical cord, umbilical artery thrombosis

0 Maternal Causes

- History of giving birth to a baby with IUGR

- The mother is small

- Malnutrition

- A history of infertility

- AFAS

- Infections (Rubella, CMV infection, hepatitis A, hepatitis B, listeria, tuberculosis, syphilis, toxoplasma, malaria)

- Teratogens (anticonvulsants, antineoplastics, smoking, alcohol, opiates, cocaine, caffeine)

- Diseases (CKD, hypertension-related chronic nephropathy, asthma, cyanotic heart diseases, sickle cell anemia, pregestational diabetes)

- Living at high altitude

physiopathology

► As a result of the effect on uteroplacental blood flow, insufficient nutrients (glucose, amino acids) pass to the fetus. First, subcutaneous tissue, liver stores, skeletal system development stops, then vital organs (brain, heart, kidney) stop their development.

► As a result, hypoxia, acidosis and death develop in the fetus.

GLUT-3 expression in the placenta increases in intrauterine growth retardation.

Diagnosis

► The most important factor in the diagnosis of growth retardation is the correct calculation of the gestational age. Ultrasonography performed in the early period (10-12 weeks) is more valuable than the last menstrual period in determining the gestational age.

► In the ultrasonographic determination of gestational age, the head-rump distance (CRL) in the first trimester gives the most valuable information. Abdominal circumference (AC) is the most valuable parameter for fetal growth and weight. It is recommended to use the HC/AC ratio in the determination of symmetric-asymmetric growth retardation.

► In ultrasonography, amniotic fluid index and Doppler flow velocity should also be evaluated. Perinatal mortality increases as the amniotic fluid index decreases (oligohydramnios).

► End-diastolic flow loss and reverse flow pattern are associated with developmental delay in Doppler USG.

► According to the severity of the retardation in the Doppler flow pattern, the affected vessels are respectively; umbilical artery, middle cerebral artery (MCA), aorta, pulmonary artery and ductus venosus. Defects in the ductus venosus doppler indicate myocardial damage and acidemia.

The most important cardiovascular parameter in predicting newborn outcomes

ductus venosus Doppleri.

Treatment

► IUGR near term (>=34th week):

0 If there is oligohydramnios or NST disorder over the 34th week, or if there is a defect in the umbilical artery Doppler examination, delivery is performed. Except in these situations, follow-up is recommended.

IUGR far from term (< 34 weeks):

0 If there is NST disorder or reverse flow in umbilical artery Doppler before 34 weeks, delivery is performed. If the NST, biophysical profile and Doppler are normal and the fetus continues to grow, follow-up is continued until fetal maturity is achieved.

,. Labor and birth:

The incidence of cesarean section has increased in 0 IUGR pregnancies. Because the placenta! insufficiency becomes evident in labor and if oligohydramnios is present, the risk of cord compression is increased.

macrosomia

• Fetal macrosomia is defined as an absolute birth weight of 4.500 g and above. Fetal macrosomia affects all organs of the fetus except the brain. f, J0J

Risk factors

► Obesity

► Diabetes {gestational and Type 2)

► Postterm pregnancy

► Multiparity

► Large parents and gaining a lot of weight during pregnancy

► Advanced maternal age

► History of previous macrosomic birth

► Racial and ethnic factors

Complications

► Macrosomic fetuses have a high risk of birth trauma, especially shoulder dystocia and brachial plexus paralysis.

► Increased maternal morbidity due to the delivery of a macrosomic baby is mainly related to the incidence of cesarean section. Other maternal complications are postpartum hemorrhage, perineal trauma and puerperal infection.

Treatment

► In order to prevent shoulder dystocia, elective cesarean section should be performed when the estimated birth weight is 5000 g and above (for diabetics, it should be 4500 g and above).

HYDROPS FETALIS

• It is edema of the fetus. There is abnormal accumulation of fluid in multiple fetal extravascular compartments such as the abdomen, thorax, and skin. It is often accompanied by hydramnios and a hydropic thickened placenta.

• Prenatal diagnosis can be made in 60% of cases with effusion in two or more regions (pleural, pericardial, or ascites) or anasarca-like edema accompanying effusion in one region on ultrasonography.

Non-immune Hydrops Fetalis

• It constitutes 90% of all hydrops. It is hydrops that develops without an immune etiology. While the most common cause of non-immune hydrops fetalis is cardiac anomalies (22%), the most common infection causing non-immune hydrops is parvovirus B-19 infection.

• Etiology

► Cardiovascular anatomical and functional causes (21%): Structural defects (Ebstein anomaly, tetralogy of Fallot, hypoplastic left and right heart, premature closure of ductus arteriosus), arteriovenous malformations (vein of galena aneurysm), cardiomyopathies, tachyarrhythmias, bradycardia (heterotaxy syndrome, maternal SLE)

► Chromosomal anomalies (13%): Turner syndrome, triploidy, trisomy 21,18 and 13

► Hematological causes (10%): α-thalassemia, erythrocyte enzyme and membrane diseases, fetomaternal hemorrhage, erythrocyte aplasia/dyserythropoiesis, decrease in erythrocyte production (myeloproliferative diseases)

► Lymphatic anomalies (8%): Cystic hygroma, systemic and pulmonary lymphangiectasia

► Infections (7%): Parvovirus, syphilis, cytomegalovirus, toxoplasmosis, Rubella, Enterovirus, Varicella, HSV, Coxacivirus, Listeriosis, Leptospirosis, Chagas disease, Lyme disease

► Syndromes (5%): Arthrogryposis multiplex congenita, lethal multiple pterygium, congenital lymphedema, myotonic dystrophy type I, Neu-Laxova, Noonan, Pena-Shokeir syndrome

► Thoracic anomalies (5%): Cystic adenomatoid malformation, pulmonary sequestration, diaphragmatic hernia, hydro and chylothorax, congenital airway obstructions, mediastinal tumors, skeletal dysplasias with small thorax

► Placental, cord and twinning-related anomalies (5%): Placenta! chorioangioma, twin-to-twin transfusion syndrome, TRAP sequence, twin anemia polycythemia sequence, thrombosis of cord vessels

► Other rare diseases (5%): Neonatal metabolic diseases (Gaucher's disease, galactosidosis, GM1 gangliosidosis, sialidosis, mucopolysaccharidosis, mucolipidosis), tumors (sacrococcygeal teratoma, Kassabach-Merritt Syndrome accompanied by hemangioendothelioma)

► Renal and urinary system causes (2%): Renal malformations, bladder outlet obstruction, congenital nephrosis, Bartter syndrome, mesoblastic nephroma

► Gastrointestinal causes (1%); Meconium peritonitis, gastrointestinal tract obstruction

► Idiopathic (18%)

• The frequencies of the factors change according to the period of diagnosis;

► In cases diagnosed prenatally, the most common factors are aneuploidies (20%), cardiac anomalies (15%) and infections (14%).

► About half of the cases diagnosed before the 24th gestational week are accompanied by chromosomal anomalies, the most common being Turner syndrome (45XO) and often cystic hygroma is present.

• The prognosis varies according to the etiology, while it is quite poor in alpha thalassemias; those due to infection, chylothorax and tachyarrhythmias can be cured with treatment;

Immune Hydrops Fetalis (RH Isoimmunization)

• Also known as erythroblastosis fetalis. It constitutes 10% of hydrops. Immune hydrops occurs when fetal erythrocytes carry a protein not found in maternal erythrocytes, and protein D is the most antigenic structure on erythrocytes. It is also known as the Rhesus factor.

• Most cases of severe fetal anemia occur against the Kell, D, c or E antigen. Other antigens that can cause severe alloimmunization include group A Duffy, MNS and Kidd antigens. Lewis, I and group B Duffy antigen

It does not cause hemolytic disease.

• If the Rh (-) mother encounters Rh (+) erythrocytes, first IgM and then IgG response develops against these foreign proteins. IgG antibodies formed can cross the placenta and hemolyze fetal erythrocytes, which may cause fetal anemia and high-output cardiac failure. Therefore, Rh incompatibility affects the next pregnancies; however, it can also be seen in first pregnancies since sensitization may occur for reasons other than pregnancy.

etiology

Conditions that may cause fetomaternal hemorrhage that may cause sensitization in the mother

Cordocentesis (state with the greatest risk of immunization)

Abortion (spontaneous or elective)

Chorionic villus sampling

amniocentesis

ectopic pregnancy

Fetal death (in any trimester)

Normal vaginal or cesarean delivery (most common cause of immunization)

external cephalic version

Ablation placenta, placenta previa and vasa previa

Abdominal trauma

Unexplained vaginal bleeding during pregnancy

Molar pregnancy evacuation

Manual removal of the placenta

Determination of fetal risk

► If the expectant mother is Rh (+), there is no fetal risk. In order to determine the fetal risk in the pregnancy of a woman with Rh (-), the father's blood group is checked first, and if Rh (-) there is no fetal risk.

► If the mother candidate is Rh (-) and the father candidate is Rh (+); Analyzing ONA-based zygosity for prenatal paternal D antigen is helpful in determining risk. If the father is homozygous positive, there is absolute fetal risk; If the father is heterozygous positive, fetal blood group determination by amniocentesis (from amniocytes by PCR) or free fetal DNA method in maternal blood should be recommended for fetal antigenic structure. If the fetal blood group is Rh (+), there is a risk; however, if Rh (-) there is no fetal risk.

► Cell-free ONA test can also be used to determine the fetal Rh status in cases with Rh incompatibility.

Diagnosis

► Antibody screening in blood type and Rh (-) patients is recommended in the first prenatal examination for all pregnant women.

► Indirect Coombs (IDC) test is a test used for the determination of free antibodies in maternal blood (E-92, E 93). In cases with positive indirect Coombs test, the titer of specific anti-D antibodies in the IgG structure is checked. The critical titer for these antibodies is 1/16 and higher titer of positivity. In cases with positivity below the critical value, the titer should be repeated every 4 weeks (S-19).

Once the critical value is exceeded, repetition is of no use and further examination is required. requires.

► Direct Coombs test is performed in fetal blood with cordocentesis for the determination of antibodies on erythrocytes in fetal circulation .

► Kleihauer-Betke test; it is a quantitative test to calculate the amount of fetal erythrocytes that have entered the maternal circulation . As hemoglobin F is resistant as a result of acid elution, fetal erythrocytes do not undergo hemolysis, while maternal erythrocytes are hemolyzed and appear in silhouette.

► The deep anemia caused by the sinusoidal heartbeat tracing in fetal monitoring leads to Ultrasonography shows placentomegaly.

Physiopathology and clinical

► The primary factor that determines the severity of acid formed in hydrops is the severity and duration of anemia. Extramedullary hemopoiesis, liver dysfunction and hypoproteinemia occur due to deep anemia and hypoxia. Colloid oncotic pressure decreases due to hypoproteinemia and capillary endothelial leakage occurs. As a result, heart failure develops due to hypoxia and decreased intravascular volume.

► Although the mother's liver has the ability to metabolize excess bilirubin, after birth the fetus, maternal and placenta! Since he is deprived of help, he cannot clear excess bilirubin from his blood and runs the risk of kernicterus (bilirubin encephalopathy) (E-02).

prophylaxis

► When there is a risk of fetomaternal hemorrhage, maternal immune response does not develop if sufficient doses of antibodies are given to the maternal circulation. If the Rh (-} mother is indirect Coombs negative, anti-D IgG must be administered at 28 weeks and within the first 72 hours after birth.Half-life is 16-24 days, with a standard dose of 300 µg, 15 ml Rh (+) fetal erythrocytes and 30 ml Contains enough IgG to neutralize fetal blood

► In only 0.2-0.3% of pregnancies, the amount of fetomaternal bleeding is more than 30 ml. In these patients, a single dose of anti-D IgG may not be sufficient. Therefore, all D-negative women should be screened at birth with the rosette test (a qualitative test that indicates the presence of fetal D-positive cells in the circulation of a D-negative woman). If the test is positive afterwards, the amount of bleeding should be determined by a quantitative test (Kleihauer-Betke Test or flow cytometry) in order to calculate the required dose of anti-D immunoglobulin.

► If the spouse of a pregnant woman with Rh (-) is Rh (+) and the pregnant woman has an indirect Coombs test (-), anti-D IgG must be performed in any situation that may cause sensitization (such as amniocentesis, chorionic villus sampling).

Treatment

► Today, amniocentesis and Liley X-rays are out of practice and replaced by fetal middle cerebral artery (MCA} Doppler examination.Detection of increased systolic velocity (> 1.5 MoM) in fetal MCA with Doppler ultrasonography, which is a completely noninvasive method, establishes the diagnosis of anemia.

► In cases with severe anemia findings (increased systolic velocity in MCA Doppler or development of hydrops findings), treatment is planned according to gestational age and fetal well-being. In order to determine the severity of anemia in preterm fetuses and to determine whether intrauterine transfusion is required, Hb and hematocrit should be measured in fetal blood sample by cordocentesis. Transfusion is recommended if fetal hematocrit is <30%.

► Intrauterine transfusion O-negative, CMV-negative, burned, irradiated and

It is performed with erythrocytes with 80% hematocrit. Today, more intravascular

transfusion is used (intraperitoneal use has decreased).

· Mirror syndrome; It is the presence of maternal edema with fetal hydrops. Edema in the mother, fetus and placenta is called triple edema.

WITH MULTIPLE PREGNANCY

ZIGOSITY

dizygotic twin

► It occurs as a result of maturation of two oocytes and fertilization by two different sperms during a single ovulatory cycle. Therefore, they are not identical. 80% of multiple pregnancies are dizygotic.

► The frequency of dizygotic twins is significantly affected by race, heredity, maternal age, parity and infertility treatments.

monozygotic twin

► It occurs as a result of the division of a single fertilized oocyte into two separate structures. Monozygotic twinning occurs with a constant frequency throughout the world (1/250 births).

► Monozygotic twinning frequency is independent of race, heredity, age and parity. Assisted reproductive techniques can increase the rate of monozygotic twinning.

· Superfecondation: It is the fertilization of two ova in the same cycle in different coituses.

Superfetation: It is the fertilization of two different ova, which are excreted in different cycles, in different coituses. This situation does not occur spontaneously in humans.

Chorionicity

• Chorionicity reflects the arrangement of membranes in multiple pregnancies. Determination of chorionicity is helpful in determining obstetric risks and in the management of multiple pregnancies.

Chorionicity in dizygotic twins

► Dizygotic twins are always dichorionic diamniotic.

Chorionicity in monozygotic scars

► Chorionicity of monozygotic twins changes according to the day of zygotic division.

0 If division occurs within the first 72 hours after fertilization; dichorionic diamniotic monozygotic twin pregnancy occurs.

0 If division occurs 4-8 days after fertilization; monochorionic diamniotic monozygotic twin pregnancy occurs. It is the most common type of monozygotic twins.

0 If division occurs 8-13 days after fertilization; monochorionic monoamniotic monozygotic twin pregnancy occurs (E J 6).

0 If division occurs after 2 weeks, the division of the embryonic disc is incomplete

and conjoined twins occur. It is the type with the highest mortality and the latest onset.

Monochorionic twins are always monozygotic.

► While chorionicity can be detected with an accuracy of 98% by ultrasonographic examination in the first trimester; In the second trimester, more than 10% of wrong evaluations can be made.

► Fetuses of different sexes are almost always dizygotic, therefore dichorionic.

► The presence of two separate placentas and a separating membrane with a thickness of >=2 mm establishes the diagnosis of dichorionicity.

► In the case of a single placenta and same-sex presence, the membranes are placenta! Examination of the starting point on the surface is helpful in diagnosis. Observing the thick chorion between the membranes establishes the diagnosis of dichorionic and indicates the fusion of the two placentas. (Twin peak finding = Lambda finding). Membrane thickness <2 mm and placenta! If the starting point on the face is thin and right-angled (T sign), it is monochorionic.

Risk factors

• Race: Caused by racial variations in FSH levels.

• Heredity: The maternal ancestry is more important and four potential gene regions have been identified. Among these, the most frequent association was seen on the long arm of the 6th chromosome, and the other gene regions were on the 7,9 and 16 chromosomes.

• Maternal age: It is the age with the highest rate of dizygotic twin pregnancies between the ages of 15-37. The incidence of twin pregnancy increases with advancing maternal age. Although there is a relationship with paternal age, its perceptible effect is quite low.

• Parity: The risk increases with increasing parity and is an independent risk factor.

• Nutrition: Those with better nutritional conditions are at increased risk. Tall and overweight women are at greater risk. The incidence may increase slightly in those with folic acid intake.

• Pituitary gonadotropin level: It is associated with high gonadotropin level. The rate of dizygotic twins increased in women who became pregnant within the first month following the discontinuation of oral contraceptive use.

• Infertility treatment: Ovulation induction significantly increases the rate of multiple ovulation (25-30%).

• Assisted reproductive techniques: The more embryos transferred, the higher the risk.

Maternal hCG, AFP and estriol levels are higher in multiple pregnancies than in singleton pregnancies.

Obstetric Complications

Spontaneous abortion

► The probability of spontaneous abortion is increased in multiple pregnancies, and the risk is higher in monochorionic twins and pregnancies with assisted reproductive techniques.

malformations

► The rate of congenital malformations is significantly increased in multiple pregnancies, and the risk is higher in monochorionic twins and pregnancies with assisted reproductive techniques. Cardiac anomaly risk is 73% higher in twin pregnancies compared to singleton pregnancies.

low birth weight

► They are more likely to have low birth weight due to IUGR and preterm labor. The degree of growth restriction is greater in monozygotic twins.

Siscordance

► Explained by more than 25% difference in estimated fetal weights between fetuses or a difference in abdominal circumferences >20 mm

Gestational hypertension and preeclampsia

► Pregnancy-related hypertensive diseases tend to be more frequent, earlier and more severe in multiple pregnancies. BMI>=30 and oocyte donation are independent risk factors for the development of preeclampsia. The risk of preeclampsia increases as the number of fetuses and placental mass increase. There is no relationship between the type of zygosity and the risk of developing preeclampsia.

preterm action

► As the number of fetuses increases, the duration of pregnancy decreases. The most important cause of neonatal morbidity and mortality in twin pregnancies is preterm birth and is seen in 50% of twin pregnancies.

Long-term effects on infant development

► There is no difference in cognitive results and general intelligence levels, but the risk of cerebral palsy is higher.

Specific Fetal Complications

cord entanglement

► It is seen in monochorionic monoamniotic twins (Ş-20).

conjoined twins

► It is seen in monozygotic twins and the most common one is thoracopagus.

twin to twin transfusion syndrome

► It is seen in monochorionic twins and originates from placental vascular anastomoses. In twin-to-twin transfusion syndrome, as a result of arteriovenous anastomosis, blood donor passes from twin to recipient with one-way flow. Recipient fetus; It is larger, has heart failure, hypertensive, polycythemic, polyhydramniotic appearance and hydrops may develop. donor fetus; growth retarded, anemic, dehydrated, hypovolemic and oligohydramniotic (stuck twin).

► Diagnosis: It is made according to two criteria;

0 Monochorionic diamniotic twin pregnancy

0 Polyhydramnios in one twin (largest vertical amniotic fluid measurement >8 cm) and oligohydramnios in the other (largest vertical amniotic fluid measurement)

<2 cm)

► Quintero Classification is used in its evaluation.

Quintero classification of twin-to-twin transfusion syndrome

• Stage I: There is discordant amniotic fluid; but the donor has urine in the bladder.

Stage II: There is no urine in the donor bladder.

Stage III: Accompanied by abnormal Doppler finding in umbilical artery, vein or ductus venosus

Stage IV: Accompanied by ascites or significant hydrops in one of the twins

· Stage V: Death of one of the twins.

► Treatment: Amnioreduction, septostomy, laser ablation of vascular anastomoses and selective fetocide

Both donor and recipient twins have an increased risk of brain injury, and cardiac functions of the recipient twin are associated with fetal outcomes.

TRAP (Twin reversed arterial perfusion)

► It is seen in monochorionic twins and originates from placental vascular anastomoses. It is caused by a large artery-to-artery and often accompanying vein-to-vein shunt.

► A donor twin with signs of heart failure and developing normally and his heart (acardia)

and other superstructures are recipient twins.

death of one of the twins

► At birth, a dead fetus may be recognized and markedly crushed (fetus compressus).

In others, the fetus may be markedly flattened (fetus papyraceous).

► The prognosis of the surviving twin depends on the gestational week at which the other twin died, the chorionicity, and the length of time between death and delivery of the living fetus. After intrauterine loss of one fetus in twin pregnancies, the risk of neurological damage such as cerebral palsy in the other baby born alive is increased.

► Risk of loss of living twin following the death of one of the twins

It is highest in monochorionics.

vanishing twin syndrome

► It is the twin syndrome lost in the early period and is seen before the second trimester in 10-40% of all twins. It is observed more frequently in pregnancies using assisted reproductive techniques. The prognosis is generally good. The neurologic prognosis of the survivor is dependent on chorionicity and the risk is greater in monochorionics. The death of one of the fetuses in late pregnancy can theoretically lead to the development of DIC, but it is rare.

Multiple pregnancy risks

Perinatal and neonatal complications ------------Maternal complications

• Preterm birth------------------------------------------ Postpartum atony bleeding

• Very low birth weight (<1500 g)--------• Preeclampsia

• Abortion------------------------------------------------ ------• Hyperemesis

• IUGG------------------------------------------------ ---------- Urinary infection

• Anomaly of presentation ---------------------------- Polyhydramnios

• Congenital anomalies---------------------------------• Abrupt placenta

• Hypoxia and trauma--------------------------------------- Placenta previa

• stillbirth----------------------------------------------- ---• Gestational diabetes

• ------------------------------------------------- ---------------------- Anemia

•------------------------------------------------ -----------------------• Depression

Antenatal Follow-up

• The need for calories, protein, minerals, vitamins and essential fatty acids has increased. Folic acid and iron replacement should be done. Serial sonographic measurements, amniotic fluid volume monitoring, NST and fetal biophysical follow-up should be performed.

• Bed rest, tocolytics, progesterone, pessary and prophylactic cervical cerclage have no significant effect for the prophylaxis of preterm labor. Side effects of tocolytics (especially 3-mimetics) to be used in the treatment of preterm labor

(tachycardia, pulmonary edema) is more common in multiple pregnancies.

The method of administration of steroids for lung maturation is the same as in singleton pregnancies.

If cervical length is >25 mm at 24 weeks and fetal fibronectin is negative

The risk of delivery before 32 weeks is low.

labor and birth

• The recommended mode of delivery depends on the presentation of the twins, gestational age (or expected birth weight), and maternal and fetal well-being. Time of delivery in multiple pregnancies;

► 38th week in uncomplicated dichorionic twins,

► Between 34-37 weeks in uncomplicated monochorionic diamniotic twins

► 32-34 in monochorionic monoamniotic twins. week between birth is recommended.

• Head-to-head presentation is most common in term twin pregnancies (fF 9 i). Cesarean section is recommended in twins with non-vertex presentation of the first presenting fetus and in multiple pregnancies with more than two numbers.

Locking at birth: If the first baby is breech and the second baby is head, the jaws can be locked at birth

Multifetal reduction (fetocyte): It can be done in multichorionic multiple pregnancies, and it is often used between the 10th and 13th days of pregnancy to reduce perinatal risks due to prematurity. It is the reduction of the number of fetuses that are 3 or more between weeks of pregnancy and mostly by the transabdominal route by injecting KCI. The ideal is to achieve a twin or singleton pregnancy. The most common complication is premature rupture of membranes (13%). Because of the vascular anastomoses in monochorionic multiple pregnancy, multifetal reduction can only be performed if there is a dichorionic placenta.

INTRAUTERINE FETAL DEATH

• 20 weeks or more (or 350 g and more) is the loss of the fetus before it is born.

Risk Factors -------------------roactive risk

Renal diseases------------------------------------------------ --------------------► 2.2-30.0

SLE ------------------------------------------------ --------------------------------------► 6.0-20.0

Diabetes (insulin) ---------------------------------------------- ----------------------► 1. 7 -7

Thrombophilia ------------------------------------------------ -----------------------------► 2.8-5.0

IUGG in previous pregnancy ----------------------------------------------- ------------► 2.0-4.6

severe preeclampsia ------------------------------------------------ --------------► 1.8-4.4

Pregnancy cholestasis ------------------------------------------------ -------------------► 1.8-4.4

Mild preeclampsia ------------------------------------------------ ------------------► 1.2-4.0

Triplet pregnancy ------------------------------------------------ --------------------------► 2. 8-3. 7

Maternal age > 40 ----------------------------------------------- --------------------------► 1.8-3.3

Fetal death in previous pregnancy---------------------------------------------- ------► 1.4-3.2

Thyroid diseases------------------------------------------------ -------------------► 2.2-3.0

Smoking (> 10/day) ------------------------------------------ -----------------------► 1. 7-3

BMI (> 30 ) --------------------------------------------- --------------------------------► 2.1-2.8

Chronic hypertension------------------------------------------------ --------------► 1.5-2. 7

black race------------------------------------------------ --------------------------------► 2.0-2.2

Maternal age 35-39 --------------------------------------------- -----------------------► 1.8-2.2

Diabetes (diet)---------------------------------------------- --------------------------► 1.2-2.2

Education (< 12 years)---------------------------------------------------------- --------------------------► 1.6-2.0

Diagnosis

• Decreased beta-hCG levels in early pregnancy may help in diagnosis.

• Absence of fetal heartbeats in ultrasonography is the gold standard for today .

• Microarray analysis is recommended in case of fetal chromosome examination in stillbirths.

Treatment

• Since the risk of DIC is increased in cases of intrauterine fetal death, pregnancy should be terminated and the safest method to terminate the pregnancy after the 20th week is to induce labor.

• Pregnant women with a history of fetal death in their previous pregnancy are considered risky pregnancies. Fetal monitoring is started 2 weeks before the previous week of death and elective labor induction is performed at the 39th gestational week.

OBSTETRIC REASONED CONSUMPTION COAGULOPATHY (E-06)

• Placental abruption (most common obstetric cause)

• Fetal death and delayed delivery

• Amniotic fluid embolism

• Sepsis

• Abortion

• Preeclampsia

Puerperium And Puerperal Diseases

noreply@blogger.com (Unknown) — Sat, 11 Mar 2023 11:29:00 +0300

PUERPERIUM

• Uterine involution: This process mostly occurs as a result of reduction in myometrial cell sizes. Immediately after birth, the uterus is at the level of the navel. It descends to the symphysis pubis level in the 1st week postpartum and to the pelvis in the 2nd week. Uterine involution approximately postpartum

It is completed in the 6th week.

• Endometrium: While regeneration occurs in the stroma and glands in the decidua basalis, the decidua superficialis is excreted as lochia. It contains erythrocytes, fragmented decidua, epithelial cells, bacteria and leukocytes. It is called lochia rubra in the first few days, lochia serosa after 3 or 4 days, and lochia alba after the 10th day, and the total lochia lasts 24-36 days.

• Cervix: Complete healing and reepithelialization postpartum 6-12. It will be a week later.

• Vagina: The vagina returns to its antepartum state in the 3rd week. Torn hymen mucosa! It heals as fibrous nodules and is called caruncle mirtiformis.

• Urinary system: Blood urea nitrogen increases in the puerperium.

• Hormones: Placenta right after birth! blood levels of hormones decrease. Maternal serum levels of hPL decrease to undetectable levels at the end of the 1st day. hCG, postpartum 11-16. disappears completely in a day. Plasma prolactin level decreases during the 2nd week after delivery and returns to the pre-pregnancy level; however, in lactating women, an increase in its level is observed during lactation. FSH and LH levels rise to normal levels in the 2nd week.

PUERPERAL DISEASES

Puerperal Fever

• Having a fever of 38 °C after birth. Fever in the first 24 hours postpartum

While 20% are due to pelvic infections, the most common cause of persistent postpartum fever is genital tract infections.

• The most common cause of virulent pelvic infection that causes fever in the first 24 hours postpartum is group A streptococci. Other causes are breast engorgement, pyelonephritis and respiratory complications after cesarean section.

Breast Engagement

• Occurs due to vascular and lymphatic stasis. The breasts are heavy, hard, painful, warm and tender on palpation. The patient may have a fever of 37.8-39°C but rarely lasts more than 4-16 hours. 2-4 days after birth. It is seen especially in women who do not breastfeed during the day. It can occur at any time during the periods when breastfeeding is interrupted.

• It is treated with conservative methods such as tight bra, cold application, analgesics. Lactation suppression is not recommended in breast engorgement.

mastitis

• It is a regional infection of the breast parenchyma. Usually the causative Staph. aureus and the source is usually the baby's nose and throat flora. More than 50% of cases occur in primiparous cases and are almost always unilateral. It is characterized by fever, chills, focal unilateral breast erythema, edema, and tenderness. Usually 3-4 postpartum. seen in weeks.

• In treatment, resolution of ductal obstruction (breastfeeding, pumping), analgesics, antibiotics (dicloxacillin 10-14 days) are applied. of patients

Abscess formation is seen in 10% of them. Mastitis usually responds to treatment in 48-72 hours, if not, breast abscess should be considered.

Postprtum Endometritis

• Polymicrobial infection of the endometrium and often includes the underlying myometrium. The most common puerperal infection is endometritis.

• Streptococcus is the most common cause in those seen in the early postpartum period.

Chlamydia is the most common cause of late endometritis. Vaginal

seen less than 5% after birth; The risk increases 5-10 times with cesarean section.

Endometritis risk factors

1. Cesarean section (most important risk factor)

2. Premature rupture of membranes

3. Multiple vaginal exams

4. Manual removal of the placenta

5. Internal fetal monitoring

6. Prolonged labor

7. Multiple pregnancy

8. Birth at a young age

9. Nulliparity

10. Obesity

11. Prolonged induction 12. Cesarean section with meconium contamination

13. General anesthesia

• Fever (the most important finding in the diagnosis), uterine tenderness, foul-smelling vaginal discharge and increase in vaginal bleeding are seen. It is most commonly seen 5-10 days after birth. Placenta! D&C is applied if fragment retention is considered. Broad-spectrum antibiotics (clindamycin + gentamicin + ampicillin) are used until the patient recovers clinically and is afebrile for 24 hours.

• If the fever does not decrease or the general condition of the patient does not improve despite antibiotic treatment, MRI or CT should be performed for differential diagnosis. In patients treated for endometritis, the most common cause of persistent fever exceeding 48-72 hours despite antibiotic therapy is wound infection. Incisional abscess after cesarean section causes fever from the 4th day.

• Conditions to be considered in cases resistant to antibiotic therapy:

► Wound infection and incision abscess

► Parametrial phlegmon (dense cellulite area)

► Pelvic abscess

► Infected hematoma

► Septic pelvic thrombophlebitis

Septic Pelvic Thrombophlebitis (SPT)

• Bacterial infection of the placenta can lead to thrombosis and thrombophlebitis in the myometrial veins. Clinically, fever, sweating and chills and abdominal pain are observed. It is detected more frequently after cesarean sections. It is considered if the picture of endometritis does not regress despite antibiotic treatment and no abscess formation is observed in ultrasonography.

• Pelvic veins adjacent to uterus accompany the picture. It causes 30-40% septic pulmonary embolism. The most common involvement is ovarian veins (v.ovarica dextra).

• Diagnosis is made by pelvic computed tomography and magnetic resonance imaging. Today, the use of heparin in treatment is controversial.

Necrotizing Fasciitis

• It is a necrotic infection of the superficial fascia spreading to the abdominal wall, hips and thighs. Group A streptococci and anaerobes are the most common agents. Diabetes, obesity and hypertension are important risk factors for necrotizing fasciitis.

• Although the skin is normal, there is extensive necrosis in the superficial fascia and subcutaneous tissue. True gangrene occurs with skin edema, blue-brown discoloration, loss of sensation or hyperesthesia. It can cause septicemia and shock. Maternal mortality is close to 50%. Early diagnosis, aggressive surgical debridement and broad-spectrum antibiotics should be used.

Obstetric Neuropathy

• Nulliparity can be seen due to prolongation of the second stage of labor and prolonged straining in the semifowler position. The most common obstetric neuropathy is lateral femoral cutaneous neuropathy. In addition, common fibular nerve damage may occur due to external compression in long-term deliveries.

Postpartum Urinary Retention

• The patient should urinate within 4 hours after birth. Risk factors for retention; primiparity, perineal lacerations, oxytocin induction delivery, operative vaginal delivery, urinary catheterization during delivery, and delivery time exceeding 10 hours.

BREAST-FEEDING

• Conditions in which breastfeeding is contraindicated: Alcohol use, HIV infection, tuberculosis without active treatment, breast cancer treatment, presence of galactosemia in the baby, maternal infectious mononucleosis (if the fetus is preterm) and human T-cell leukemia virus Type 1 and 2 infection, maternal cocaine, heroin and marijuana use.

• Situations where breastfeeding is not contraindicated: CMV in the mother (if asymptomatic infection and fetus is term), HBV

(if the baby was given immunoglobulin) and HCV infection.

ABNORMAL BIRTH ACTION AND OPERATIVE BIRTH

noreply@blogger.com (Unknown) — Fri, 10 Mar 2023 18:34:00 +0300

ABNORMAL BIRTH ACTION (DISTOCIA)

• dystocia; In short, it means difficult birth. The expression nonprogressive action is also used to describe dystocia.

Dystocia due to uterine dysfunction

• Abnormalities in action are basically divided into 2 parts; prolongation of action and cessation of action. However, in order for these diagnoses to be made, the cervical opening must be at least 6 cm and the membranes must be ruptured. In addition, the cervical dilation should not progress, although the contraction force obtained in every 10-minute periods in the last 4 hours is 2: 200 Montevideo units.

• Epidural analgesia prolongs both the 1st and 2nd stages of labor and slows down the fetal descent.

Abnormal labor diagnoses and approaches
action pattern	Nullipar	multiparous	Recommended Treatment	Alternative Treatment
Prolongation of the latent phase	> 20 hours	> 14 hours	Rest cure	Oxytocin or C/S in an emergency
prolongation of active phase	<1.2 cm/hour	<1.5 cm/hour	Wait	C/S on BPU
elongation of descent	1 cm/hour	2 cm/hour	Wait	C/S on BPU
Prolonged deceleration - Dilatation arrest - Descent arrest	>3 hours >2 hours >1 hour	>1 hour >2 hours >1 hour	C/S if no BPU oxytocin if BPU	C/S

Prolongation of the second stage of labor

► The second stage of labor lasts an average of 2 hours in nulliparous and 1 hour in multiparas. Epidural anesthesia prolongs these periods by 1 hour. Exceeding these times requires intervention.

Dystocias of the Birth Tract

• They are dystocias originating from the bony pelvis and soft tissues.

Bone Pelvis Dystocia

► Pelvic entrance, mid pelvis and pelvic outlet dystocias can be seen.

Soft Tissue Dystocias

► Tumoral formations or congenital anomalies occupying space in the birth canal cause dystocia by making more presentation anomalies.

Fetal Dystocia (Malpresentations)

• Situs and presentation anomalies

• Big baby

• Malformed baby (hydrocephalus, anencephaly, meningomyelocele, sacrococcygeal teratoma)

• conjoined twins

• Locked in twin birth

Complications of Dystocia

• Chorioamnionitis

• Postpartum pelvic infections

• Postpartum bleeding due to atony

• Uterine rupture

• Vesicovaginal, vesicocervical, rectovaginal fistulas

• Pelvic floor damage (prolapse, urinary-anal incontinence)

• Peroneal nerve damage

• Increased risk of cesarean section

• Increased risk of peripartum fetal sepsis

• Cephal hematoma

• Caput succedanum (edema in vertex)

• Molding; is the movement of the skull bones over each other.

Vesicovaginal fistulas are the most common of the urinary fistulas and the most common cause of vesicovaginal fistula is dystocia.

MALPRESENTATIONS

• The most common malpresentation is breech presentation (3-4%). It is followed by transverse arrivals (1/340), compound arrivals (1/1.000), hundred arrivals (1/2.000) and forehead arrivals (1/10.000).

Breech Arrivals

• It is the most common presentation anomaly (3-4%). While it is seen in 45% at the 24th week of pregnancy; After the 36th week, the rate drops below 5%.

Risk factors

1. Premature (most common cause)

2. Hydramniosis

3. Oligohydramnios

4. Multiple pregnancies

5. Grand multiparity

6. Hydrocephalus

7. Anencephaly

8. History of previous breech birth

9. Uterine anomalies 10. Placenta previa

11. Pelvic tumors

12. History of previous cesarean section

complications (in persistent breech presentation)

1. Cord prolapse: The risk increases in small fetuses and impure breech presentations.

2. Placenta previa

3. Congenital anomalies

4. Uterine anomalies and tumors

5. Difficult childbirth

6. Increased maternal morbidity and mortality

a. Increased rate of invasive delivery and cesarean section

b. genital tract injuries

c. Uterine rupture during version

D. Uterine atony and postpartum bleeding

to. increased risk of infection

7. Increased perinatal morbidity and mortality

a. Prematurity

b. Congenital anomalies

c. Birth traumas

I. Humerus, clavicle, femur fractures

ii. Separation of epiphyses in scapula, humerus, femur

iii. Upper extremity paralysis (due to brachial plexus injury)

iv. Skull, neck fractures

v. Testicular damage, anorchia

D. mortality

I. concussion

ii. Brain damage➔ The breech is one of the most frequently injured organs at birth.

iii. Intracranial hemorrhage

iv. cord prolapse; more common than cephalic presentations.

v. Intrapartum asphyxia

Hip dislocations are more common in breech presentations than vertex presentations; but this is not due to the mode of birth.

Indications for cesarean section in breech presentation

1. Large fetus (3800-4000 g)

2. Preterm fetus

3. Fetus with severe IUGR

4. History of a child lost due to previous birth trauma

5. Stenosis in the bony pelvis

6. Head in hyperextension

7. History of previous cesarean delivery

8. Incomplete breech presentation or foot presentation

9. Fetal anomaly not suitable for vaginal delivery 10. The patient's request for cesarean section

11. Inexperienced physician

Cesarean section should be planned for breech presentations that have entered into labor between 24-32 weeks. Vaginal delivery can be planned if the estimated birth weight is >2500 g in breech presentations that enter labor between 32-37 weeks.

Vaginal Birth Types

1. Spontaneous breech birth: It is spontaneous birth without any intervention.

2. Partial breech extraction: No intervention up to the umbilicus level

3. Total breech extraction: The operator performs the entire delivery.

• In breech descent, descent and engagement occur with a bitrochanteric diameter.

Maneuvers used in Vaginal Birth

1. Pinard maneuver (total breech extraction): It is to remove the feet of the pure breech from the vagina.

2. Mauriceau maneuver (recovering the head from behind with the baby's back forward)

3. Modified Praque maneuver (recovering the head from behind if the baby's back is not turned forward)

4. Dührssen incision (freeing the stuck head): An incision is made in the cervix at the level of 2 and 10 o'clock.

5. Zavanelli maneuver (pushing the implanted head of the fetus into the uterine cavity and saving it with C/S)

Piper forceps or Laufe forceps can be used to save the head coming from behind.

The external cephalic version is a maneuver aimed at reversing the breech presentation. As a rule, the pregnancy should be past the 36th week and the labor should not have started. If the mother is Rh negative, anti-D Rh immunoglobulin should be administered after administration. Use of tocolytic agent before the procedure, polyhydramnios, multiparity,

The absence of engagement and the placement of the placenta on the posterior wall increase the chances of success.

External cephalic version contraindications

• Placenta previa

• Unreliable fetal well-being and fetal distress

• Membrane rupture

• Uterine malformation (unicornuate uterus etc.)

• Multiple pregnancy

• Recent uterine bleeding

• Previous cesarean section

• Fetal length cord on ultrasound

• Overt head-pelvis incompatibility,

• Oligohydramnios

IUGR

• History of abruptio placentae

Deflection Arrival

• It is the entry of the presenting fetal head into the birth canal in a position where it is not sufficiently flexed,

► Sinciput: The anterior fontanelle or bregma is the most anterior

► Get

► Face: It is full extension and the most advanced deflection.

face to face

► It is the most forward deflection of the head. Anencephalic fetuses usually present with a facial presentation . In addition, prematurity, an extremely thick neck, a cord in the neck, fetal malformations, hydramnios, pelvic stenosis, excessively large fetus and grand multiparity may also cause facial presentations.

► The position is determined according to the relationship of the chin with the symphysis and can be mentum anterior (60-80%) or mentum posterior (20-25%). Vaginal delivery is possible in mentum anterior presentations as long as there is no pelvic stenosis. In mentum posterior presentations, vaginal delivery is impossible and cesarean delivery is strictly indicated. Rotating the mentum posterior to the mentum anterior with vacuum or forceps is contraindicated.

come and go

► It is the rarest presenting anomaly. The reasons are the same as for face comings.

► Since the head comes with one of the largest diameters, the birth progresses slowly and takes a long time. Pregnancy is followed closely and it is expected that the head will return to the occiput or face. If there is no rotation, she must be delivered by cesarean section. The use of vacuum and forceps is strictly contraindicated.

Transverse Arrivals

• The leading part in transverse situs is the shoulder.

• Risk factors:

► Grand multiparity

► Preterm fetus

► Placenta previa

► Uterine anomaly

► Hydramnios

► Pelvic stenosis

• It is not possible for a transverse delivery to be delivered vaginally at term and a transverse delivery in labor is always delivered by cesarean section. If neglected, prolapse of the arm and subsequent uterine rupture develops.

• In cases where the fetus is small (800g and below) and the pelvis is wide, it is possible for the fetus to be born folded. This is called conduplicato corpore

Combined Presentation

It is the coming of an extremity next to the presenting part. The hand is most often next to the head. In the second frequency, the upper extremity comes next to the breech. The most common cause is prematurity.

• Concomitant cord prolapse in 10-20% of cases. (the most important cause of fetal loss). In the birth of compound presentations, if the extremity next to the incoming part does not prevent the descent, it is not intervened. If it hinders the descent, try to gently push the extremity in. If the extremity cannot be pushed in, a cesarean section should be planned.

BIRTH INDUCTION

General Information

• Initiation of contractions in the inactive uterus. In all cases where labor induction is planned, first of all, it should be evaluated whether the pelvis is suitable for vaginal delivery by examination.

Indications and Contraindications of Labor Induction

indications

1. Premature rupture of membranes ➔ Most common indication for induction

2. Gestational hypertension

3. Oligohydramnios

4. Postterm pregnancy

5. Chronic hypertension and diabetes

6. Serious IUGR

7. Isoimmunization

8. Pregnancy cholestasis

9. Fetal death

contraindications

1. Previous uterine surgical incision (metroplasty, classical cesarean section)

2. Contracted pelvis, deformed pelvis

3. Placenta previa

4. Active genital herpes

5. Cervical cancer

6. Macrosomia (normally >5000 g, in diabetics >4500 g)

7. Severe hydrocephalus

8. Malpresentation (transverse presentation, mentum posterior facial presentation, incomplete breech presentation)

9. Unsafe fetal condition

10. History of uterine rupture

11. Cord prolapse

Complications:

► Increasing cesarean rate

► Chorioamnionitis

► Rupture from existing uterine incision

► Uterine atony and postpartum bleeding

► Uterine rupture

► Postpartum hysterectomy

• There are some factors that increase the success of induction. These include young age, multiparity, BMI below 30, cervical compliance, and birth weight below 3500 g.

• It is a prerequisite that the cervix is mature in inducing labor. Bishop scoring is used to determine this. 5 parameters are used to determine the Bishop score:

► Dilatation (cm)

► Efesman (deletion){%}

► Level (from -3 to +2)

► The consistency of the cervix

► Position of the cervix

Bishop scoring system
Point	0	1	2	3
Cervical dilation (cm)	0	1--2	3--4	>=5
Cervical effacement (%)	0-30	40-50	60-70	>=80
Level	3	2	-1	3
the consistency of the cervix	Hard	Middle	Soft	-
position of the cervix	Back	Middle	Front

• If the Bishop score is 9 and above, the probability of being successful in induction is high. If the score is below 4, induction cannot be started. In these cases, cervical ripening methods should be applied before induction. The aim is to minimize induction failures and reduce rates of interventional births.

Cervical Maturation and Induction Methods

Pharmacological Methods

► Prostaglandin E2 (Dinoprostone): Local application intracervically is a frequently used method.

► Prostaglandin E1 (Misoprostol): When used orally or vaginally, it increases cervical ripening and induces labor. Vaginal PgE1 is more effective in labor induction and cervical ripening than PgE/.

► Oxytocin: It is the most effective and widely used method of induction of labor and is also an effective cervical ripening agent when used in low doses. Oxytocin has a half-life of 3-5 minutes and is used by IV infusion. The amino acid structure of oxytocin is similar to arginine vasopressin. Therefore, it has a pronounced antidiuretic effect. When used in high doses (20 mU/min), the renal clearance of water decreases and water intoxication and convulsions related to it and even death may occur. It rarely causes hypotension, myocardial ischemia and chest pain if undiluted IV is used. If fetal heartbeat changes and fetal distress develop, it can be discontinued and restarted if the picture returns to normal.

Mechanical Methods

► Transcervical Catheter: It is the process of applying downward traction with a Foley catheter placed in the cervical canal. It is used for both cervical ripening and labor induction.

► Hygroscopic Dilators: They swell by absorbing cervical secretions and provide mechanical dilatation. There are natural (laminaria} or synthetic (polyvinyl alcohol polymer, hydrogel) forms.

► Amniotomy: Following the artificial rupture of the membranes, there is an increase in endogenous prostaglandins, which induces labor.

OPERATIVE BIRTHDAYS

episiotomy

• An episiotomy is an incision applied to the perineum and is actually a second degree perineal laceration. It should not be used routinely. Episiotomy not only reduces anterior perineal injury, but increases the risk of anal sphincter injury, rectal injury, and gas/fecal incontinence.

• Indications include shoulder dystocia, breech delivery, macrosomic fetus, occiput posterior delivery, forceps and vacuum application, too short perineal length. It is applied mediolaterally or medianly.

Episiotomy differences
	median	mediolateral
surgical repair	Easy	Difficult
erroneous healing	Rare	common
Postoperative pain	Little	very
anatomical results	Very good	Bad
blood loss	LITTLE	very
dyspareunia	Rare	Sometimes
Prolongation of the episode	common	Rare

The most common cause of episiotomy dehiscence is infections. Other risk factors are coagulation disorders, smoking, HPV infection.

Forceps and vacuum applications

• The most common cause of operative deliveries is fatigue and prolongation of the second stage of labor.

• Indications:

► Maternal indications

0 Maternal heart disease

0 Maternal pulmonary disease

0 Intrapartum infection

0 Some neurological problems

0 Mother's fatigue

0 Prolongation of the second stage of birth

► Fetal indications

0 Premature separation of placenta

0 Unreliable fetal heart rate tracing

• Conditions:

► Experienced operator

► Head must be engaged

► Membranes must be ruptured

► Presentation should be vertex development (forceps can be attached to the mentum anterior face, but vacuum cannot be inserted)

► Cervical opening must be complete (10 cm)

► Head position must be known exactly

► There should be no head-pelvis incompatibility

► Fetal weight estimation should be made

► The bladder must be emptied

► There should be no fetal coagulopathy and bone mineralization disorder

• Factors reducing success in operative deliveries; persistent occiput posterior presentation, birth weight >= 4000 g.

Forceps Application

► In forceps application in the occiput anterior position, forceps are placed on the occipitomental diameter and applied.

Vacuum Application

► It is a method of assisting the delivery with uterine contractions and traction of the fetus by attaching a bell with vacuum power to the fetal head. Silastic bells are easier to apply and safer for scalp injuries than metal bells.

► Vacuum-specific conditions: The fetus must be at least 34 weeks old and fetal scalp blood sampling has not been performed recently.

Comparison of vacuum and forceps complications
Complications	Vacuum	Forceps
intracranial hemorrhage Brachial plexus injury facial nerve damage Defecation problems (Fecal incontinence) 3-4. degree perineal lacerations Obstetric bleeding shoulder dystocia Cephal hematoma Neonatal jaundice Retinal hemorrhage	1:860 0.4% % 12 % 12 Little 15% 37% More More	1:664 0.5% 0.9-9.2% 38% 29% More 6% 19% Little Little

Cesarean (C/S)

• It is the delivery of the fetus by abdominal route (laparotomy). Pfannenstiel incision; The skin, subcutaneous tissue of the anterior abdominal wall and the fascia of the rectus abdominis muscle are cut transversely, the rectus abdominis muscle is separated manually without cutting in the vertical plane, and the abdomen is entered by making a vertical incision into the peritoneum. Kerr (lower uterine segment transverse) requires an incision to be made into the uterus through the incision (hysterotomy). Planned cesarean deliveries are performed after the 39th week of pregnancy.

• Indications:

► Maternal

0 Previous cesarean section (most common)

0 Abnormal placentation

0 Maternal demands

0 Previous classical cesarean section (vertical uterine incision)

0 Unknown uterine scar

0 Opening the uterine incision

0 Previous full-thickness myomectomy

0 Mass in the genital tract obstructing the birth canal

0 invasive cervical cancer

0 Previous trachelectomy

0 Permanent cerclage

0 Prior pelvic reconstructive surgery

0 Pelvic deformity

0 Presence of HSV or HIV infection

0 Cardiac or pulmonary disease

0 Cerebral aneurysm or arterio-venous malformation

0 Pathological conditions requiring additional intraabdominal surgery

0 Perimortem cesarean section requirement

► Maternal - Fetal

0 Head pelvis incompatibility (most common)

0 Forceps fail in vacuum

0 placenta previa

0 Placental abruption

► Fetal

0 Unsafe fetal condition (most common)

0 Malpresentation (most common)

0 Macrosomia

0 Congenital anomaly

0 Impaired umbilical cord Doppler examination

0 Thrombocytopenia

0 History of neonatal birth trauma

Comparison of vaginal and cesarean delivery complications
Complications	Caesarean section (%)	Vaginal (%)
General morbidity Postpartum hysterectomy Anesthesia complications cardiac arrest Venous thromboembolism Puerperal infection wound opening Wound hematoma Blood transfusion requirement hypovolemic shock death in hospital	2.73 0.09 0.53 0.19 0.06 0.60 0.09 1.30 0.02 0.01 0.00	0.90 0.01 0.21 0.04 0.03 0.21 0.05 0.27 0.07 0.02 0.002

• Situations where peripartum hysterectomy may be required:

► Abnormal placentation (Most common)

► Atony

► Uterine rupture

► Cervical laceration

► Postpartum uterine infection

► Myoma uteri

► Invasive cervical cancer

► Ovarian neoplasia

Obstetric Analgesia and Anesthesia

• Maternal deaths due to anesthesia during cesarean section are more common in general anesthesia than in regional anesthesia. The most common complication in regional anesthesia for cesarean section is hypotension. The first and second stages of labor last longer and the need for more vacuum-forceps application arises in pregnant women who receive regional anesthesia compared to those who receive intravenous meperidine analgesia.

COMPLICATIONS OF BIRTH

noreply@blogger.com (Unknown) — Fri, 10 Mar 2023 10:51:00 +0300

POSTPARTUM BLEEDING

• Postpartum bleeding over 1000 ml and accompanying symptoms.

Early Postpartum bleeding

► Bleeding before 24 hours. Most postpartum hemorrhages fall into this group.

Uterine Atony

0 Bleeding from the implantation site of the placenta due to insufficient uterine contractility following delivery.

0 The most common cause of maternal mortality and early postpartum hemorrhage due to bleeding is uterine atony.

0 Etiology:

- Excessive distension of the uterus (hydramnios, multiple pregnancy, fetal macrosomia)

- Grand multiparity

- Rapid (precipitate) or prolonged action

- History of previous uterine atony

- Use of uterine relaxant agents (terbutaline, magnesium, halothane anesthesia, conduction analgesia)

- Induction and augmentation of labor with oxytocin or prostaglandin

- Chorioamnionitis

0 Treatment: After exclusion of uterine rupture and placental retention, bimanual massage and/or compression is applied. Subsequently, medical uterotonic treatment is applied. In cases where there is no response, bacri balloon application, uterine compression sutures (B-lynch sutures), uteroovarian vessel ligation, hypogastric artery ligation, angiographic uterine artery embolization can be performed. If there is no response, hysterectomy is performed.

0 Uterotonics used in medical treatment:

- Oxytocin rapid infusion (contraindicated in hypotension)

- Methyl ergonovine (contraindicated in hypertension) (E-91J

- Prostaglandin F2 alpha (carboprost)

- Prostaglandin E1 (misoprostol)

- Prostaglandin E2 (dinoprostone)

Lower Genital Tract (cervix, vagina, perineum) lacerations

0 It should be suspected in case of vaginal bleeding despite adequate contraction and contraction of the uterus.

Lower genital tract lacerations

Grade 1 laceration-------- Laceration of vaginal epithelium or perineal skin only

2nd degree laceration-------- Laceration involving perineal muscles (bulbospongiosis and superficial transverse perineal muscle)

Grade 3 laceration-------- Laceration involving the anal sphincter;

- 3a: < 50% external anal sphincter laceration

- 3b: > 50% external anal sphincter laceration

- 3c: Laceration of external anal sphincter + internal anal sphincter

Grade 4 laceration ------- Laceration involving the perineal body, the entire anal sphincter complex, and the anorectal mucosa1

Among the risk factors for 0 3rd and 4th degree lacerations; median episiotomy, nulliparity, persistent occiput posterior presentation, operative delivery, Asian race, short perineal length, and macrosomia. Mediolateral episiotomy is protective.

0 Primary is repaired. If it is insufficient, measures such as compression, hypogastric artery ligation, embolization are taken.

Uterine Rupture

0 It is a rare complication and may be complete or incomplete. While all uterine layers are ruptured in complete rupture; In incomplete rupture, only the visceral peritoneum is intact.

0 The most common cause of uterine rupture is separation of the previous cesarean section scar. The risk also varies according to the uterine incision patterns during cesarean section.

cesarean scars and rupture risks: (risk increases with incisions involving the upper segment)

Classical incision------4-9%

T incision--------4-9%

lower segment vertical-----1-7%

Belonging segment transverse ----0.2-1.5%

previous lower segment uterine rupture scar---6%

previous upper segment uterine rupture scar ----32%

0 Risk factors:

- Previous cesarean section {highest risk factor}

- Previous myometrial surgeries (curettage, perforation, myomectomy, metroplasty)

- Overstretched uterus (hydramnios, multiple pregnancy, etc.) Muitiparity

- Hyperstimulation (especially prolonged use of oxytocin in multiparous patients), PGE1 use

- Difficult childbirth

- Intrauterine manipulation (internal version-extraction)

- focal weakness in the myometrium; Connective tissue diseases such as uterine anomalies, leiomyoma, adenomyosis, choriocarcinoma and Ehlers Danlos syndrome.

Clinical: Classical findings in spontaneous rupture developing in labor are suprapubic pain and tenderness, sudden disappearance of labor pains, regression of the fetal part presenting with impaired fetal heartbeat, and vaginal bleeding. Subsequently, signs of hypovolemic shock and hemoperitoneum may develop.

The most common finding in the cases is severe deceleration in fetal heart beats.

0 Prognosis and Treatment: The risk of fetal mortality is 50-75% and if the fetus is alive at the time of rupture, the only chance is emergency laparotomy. Survivors are at risk for hypoxic ischemic encephalopathy. Maternal mortality due to rupture is rare (0.2%). Hysterectomy is the preferred treatment. The rupture can be repaired in cases with a desire to have children; however, the chance of recurrence of rupture in the next pregnancy is 20%.

Uterine Inversion

0 It is a rare painting. Among the risk factors, fundal implantation of the placenta, uterine atony, placenta! umbilical cord traction and placental adhesion anomalies without separation are included.

0 There is acute pain and shock (30%) and life-threatening bleeding. The uterus can be seen protruding from the vagina. The treatment is emergency manual replacement accompanied by tocolysis, surgical replacement or hysterectomy if it is not possible (push in the uterus).

Placenta Implantation Disorders

0 Variations in which trophoblastic tissues invade the myometrium at different depths. In these cases there is little or no decidua basalis and no physiological separation line (Nitabuch layer) along the spongy layer of the decidua. Therefore, the cotyledons are firmly attached to the myometrium.

- P. accreta: The villi adhere to the superficial myometrium (80%); is the most common type.

- P. increta: The villi invade the myometrium (15%).

- P. percreta: The villi completely penetrate the myometrium and reach the serosa (5%).

etiology

- Placenta previa (1/3 of cases)

- Caesarean section history (1/4 of the cases)

- History of curettage (1/4 of the cases)

- Multiparity

- advanced maternal age; The risk increases 3 times over the age of 35

- Cigarette

Clinical and diagnosis: Antepartum hemorrhage is common, usually due to the accompanying placenta previa. Color flow Doppler ultrasonography has a very high diagnostic value. If the diagnosis is in doubt, MRI can be used in addition to ultrasonography.

Treatment: The placenta is tried to be removed, in case of heavy bleeding, postpartum hysterectomy may be required.

coagulopathy

0 The most common causes are von Willebrand disease and ITP.

0 Acquired causes are anticoagulation and consumption coagulopathy.

Late Postpartum Bleeding

► Bleeding after 24 hours before 12 weeks

► Etiology:

0 Placental fragment retention (most common cause); Risk factors include stillbirth, premature birth and a history of cesarean section.

0 Infections (endometritis)

0 Coagulopathy (von Willebrand disease)

0 Subinvolution of placenta

cord prolapse and cord presentation

• Following the opening of the fetal membranes, the presence of the umbilical cord in the lower uterine segment, next to the presenting fetal part (hidden) or in front of the birth canal is called cord prolapse.

• If the umbilical cord is between intact membranes in the cervical os and the fetal head, it is called cord presentation.

• Risk factors include malpresentation, hydramnios, prematurity (<34 weeks), pelvic tumors, inferior placenta, head-pelvic incompatibility, occiput posterior position, multiple pregnancy, rupture of membranes during prematurity. Among malpresentations, the most common risk factor is transverse situs (20%), followed by foot (15%). The risk also increases in breech presentations.

• Perinatal mortality is 20% in cord prolapse. When the umbilical cord prolapses, emergency cesarean section should be performed to reduce perinatal morbidity and mortality.

BIRTH INJURIES IN THE NEWBORN

• Cranial injuries: Skull fractures, mandible fractures, intracranial hemorrhages, epidural hemorrhages, subdural hemorrhages, cerebral palsy.

► Intracranial hemorrhages; It is more common in premature babies. While it is least observed in spontaneous deliveries and elective cesarean sections; It is more common in operative deliveries and emergency cesarean sections in active labor.

► The risk factor that increases the risk of cerebral palsy the most is preterm birth (between 23-27 weeks).

• Spinal cord injuries: Caused by excessive stretching. Facial paralysis, brachial plexus injury,

• Bone fractures: Clavicle, humerus, femur, mandible fractures

• Muscle injuries: Torticollis

• Soft tissue injuries: Subcapsular hepatic hematoma, scrotal hematoma

Shoulder dystocia

• It is the situation where the time between the birth of the head and the birth of the body lasts longer than 60 seconds. 75% of the cases occur in fetuses over 4000 g and the risk increases as the fetus weight increases.

• Risk factors:

► Obesity

► Multiparity

► Diabetes mellitus

► Exceeding term (postterm pregnancy)

► History of shoulder dystocia; recurrence risk 1-13%

• Prevention: Most are unpredictable and unavoidable. However, if the estimated birth weight is ?: 4500 g in women with diabetes and ?: 5000 g in non-diabetic women, elective cesarean section should be performed.

• Management scheme in shoulder dystocia:

► A wide episiotomy should be opened.

► The first thing to do is Mc Robert maneuver and suprapubic compression (N�J3J. Fundal compression alone should not be done.

► The second group of maneuvers that can be performed in case of failure are: Woods screw maneuver (rotating the shoulder 180 degrees), delivery of the posterior shoulder and Rubin maneuver (reducing the distance between each twin shoulder by pushing the fetal shoulder towards the anterior surface of the rib cage).

► What to do if no result is obtained; fracture of the clavicle, Zavanelli maneuver (pushing the head back in) and symphysiotomy.

AMNION fluid EMBOLI

• Risk factors:

► Advanced maternal age, placenta previa, abruptio placentae, preeclampsia, forceps vacuum or cesarean delivery, meconium stained amnion, precipitated labor, postterm pregnancy, labor induction, lacerations in the great pelvic veins, polyhydramnios

► Hypertonus due to oxytocin is the condition that increases the risk of amniotic fluid embolism the least; because strong contractions prevent the amniotic fluid from entering the uterine veins.

• Clinical: Hypotension, pulmonary edema, ARDS, cardiopulmonary arrest, cyanosis, coagulopathy (DIC), dyspnea, convulsions

Amniotic Fluid Embolism Diagnostic Criteria

Sudden onset of hypotension and respiratory failure

Documentation of overt disseminated intravascular coagulation not associated with bleeding

Onset of symptoms at birth or within 30 minutes of delivery of the placenta

Fever not 38 degrees or higher

Diagnosis; It is a clinical diagnosis and the definitive diagnosis is made only with the presence of fetal cells in the maternal circulation and maternal mortality is 60-90%.

NORMAL BIRTH ACTION

noreply@blogger.com (Unknown) — Thu, 9 Mar 2023 14:37:00 +0300

BONE PELVIS

• the base consists of the sacrum, os coccyx and os coxae (os ilium, os ischium, os pubis). It is divided into true (small) and false (large) pelvis by the linea terminalis . The important thing in obstetrics is the true pelvis, and it is divided into three planes as pelvis inlet, mid pelvis and pelvis outlet in terms of delivery.

PELVIC TYPES

• Pelvis types according to the Caldwell-Moloy classification:

Gynecoid pelvis: It is the type in which the spinae are faint and the interspinous distance is > 10 cm. Symphysis pubis angle is 90° or more. It is the most suitable pelvis type for delivery.

Android pelvis: It is the type in which the spines are prominent and the pubis arch is narrow.

Andropoid pelvis: It is the type in which the anteroposterior diameter of the pelvic inlet is larger than the transverse diameter.

Platipelloid pelvis: It is the type in which the anteroposterior diameter of the pelvic inlet is smaller than the transverse diameter. It is the most unfavorable type of pelvis for childbirth.

PELVIC DIAMETER

Pelvis Inlet Diameters

► Transverse diameter (13.5 cm): It is the distance between the linea terminalis.

► Conjugata vera diagonalis (12.5 cm): It is the diameter between the promontorium and the lower edge of the symphysis. It can be measured clinically.

► Conjugata vera anatomica (11 cm): It is the diameter between the promontorium and the upper edge of the symphysis. It cannot be measured clinically. It is calculated by subtracting 1.5 cm from Conjugata vera diagonalis.

► Conjugata vera obstetrica (10.5 cm): It is the diameter between the promontorium and the most protruding inner surface of the symphis. It is approximately 10.5 cm. Not clinically measurable; however, it is calculated by subtracting 2 cm from the conjugata vera diagonalis. It is the narrowest diameter of the pelvic inlet.

Middle Pelvis Diameters

Transverse diameter (10 cm): Interspinous distance. It is the narrowest diameter of the middle pelvis.

Anteroposterior diameter (11.5 cm)

The transverse diameter of the middle pelvis (interspinous distance) is the narrowest part of the bony pelvis.

Pelvis Outlet Diameters

► Transverse diameter (11 cm): It is the distance between the tuber ischiadicum.

► Anteroposterior diameter (9.5-11.5 cm): It is the distance between the symphysis pubis and the sacrum.

FETAL HEAD DIAMETER

• Bitemporal diameter (8 cm): It is the longest distance between two temporal sutures. your fetal head

• Biparietal diameter (9.5 cm): It is the longest distance between the two parietal bones. It is the largest transverse diameter of the fetal head.

• Suboccipitobregmatic diameter (9.5 cm): It is the distance between the great fontanelle and the occipital bone. It is the diameter (32 cm) that makes up the smallest circumference of the head.

• Occipitofrontal diameter (11.5 cm): It is between the top of the nasal root and the most protruding part of the occipital bone. It is the diameter (34.5 cm) that forms the greatest circumference of the head.

• Occipitomental-Diameter (12.5 cm): It is the distance between the chin and the most protruding point of the occiput. It is the largest diameter of the fetal head.

STATUS SHAPES OF FETUS

Habitus

► Defines the intrauterine posture of the fetus (flexion or deflection). It is often in the habit of flexion.

situs

► It expresses the relationship of the long axis of the fetus to the long axis of the mother. It can be longitudinal (99%), transverse and oblique (1%).

In longitudinal situs; It may be vertex, sinciput, occiput, forehead, face or breech presentation.

presentation

► It refers to the structure that enters the birth canal in the front. Cephalic (95%), breech (4%) or Shoulder (1%) or rarely cord presentation may be present.

Position

► Indicates the position of the leading part relative to the right or left of the birth path. Occiput in vertex presentations, chin in facial presentations, sacrum in breech presentations and acromion in transverse (shoulder) presentations are the defining points. (N-1 IJ These can have right and left shapes. In most deliveries, the fetal head enters the pelvis in a transverse position, and left occiput transverse (LOT) is most common.

► Leopold maneuvers are used to determine fetal presentation and position.

Leopold 1------Fundus fetal part is determined (cephalic-podalic)

Leopold 2------The position of the fetal back is determined (fetal situs)

Leopold 3-----The premier (presentation) and engagement is determined

Leopold 4-----Level of the leading part is determined

engagement

Biparietal diameter decreases below the linea terminalis line in occiput arrivals.

In this case, the vertex, which is the most anterior part of the fetus, It comes to the interspinous line. It usually occurs within the last 2 weeks in primigravidas, and usually at the beginning of labor in multiparas.

Level

► It is the distance of the presenting part to the spina ischiadics. Its distance from the pelvic inlet is measured in cm (-) values (-5, -4, -3, -2, -1), while its distance from the outlet is measured in cm (+) values (+1, +2, +3, +4 , +5). Reaching the linea terminalis level of the leading part is expressed as -5, reaching the spina ischiadicas as O (engagement) and being seen at the hatch is expressed as +5 level.

synclitism

► It is the situation where the biparietal diameter is parallel to the pelvic inlet anteroposterior diameter or the sagittal suture is parallel to the transverse diameter. Anterior or posterior lateral deflections are called asynclitism. If the sagittal suture is close to the sacrum, the anterior parietal bone of the fetus is felt first, and this is called anterior asynclitism. If the sagittal suture is close to the symphysis, the posterior parietal bone is palpated first, which is called posterior asynclitism. Moderate ones of asynclitism can be born through the normal vaginal route. However, in severe posterior asynclitism cases, cesarean delivery may be required.

CARDINAL MOVEMENTS OF BIRTH

• These are the movements necessary for the adaptation of the presenting fetal part to the bony pelvis. It is necessary for the fetus to pass through the narrowest pelvis segment (mid pelvis) with the smallest circumference (suboccipitobregmatic diameter). For this purpose, birth takes place with the following cardinal movements in order.

► Engagement: The biparietal diameter plane crosses the pelvic inlet. It can happen in the last weeks of pregnancy or with the onset of labor.

► Descent: In nulliparous, the engagement is usually before the start of labor, while in multiparas, the descent usually begins with the engagement. Although the descent is maximum in the second stage of labor, it can also be in the deceleration phase.

► Flexion: The fetal head flexes when it encounters pelvic resistance. Thus, the long occipitofrontal diameter is replaced by the suboccipitobregmatic diameter, which constitutes the smallest circumference.

► Internal Rotation: With this movement, the occiput turns forward slowly and the nuchal symphysis is placed behind the pubis. In this way, it enters the middle pelvis, which is the narrowest part of the pelvis, with the head biparietal diameter in the interspinous space. Internal rotation is completed when the fetal head reaches the pelvic floor in 95% of cases.

► Extension: When the fetal occiput comes into contact with the lower part of the pubis, due to the fact that the pelvic outlet is up and forward, the uterus is contracted and the head is protruded only by extension, when the patient is strained.

► External Rotation: After the head comes out, the shoulders rotate in such a way that they come to the anterior posterior diameter of the pelvic outlet, thus giving birth to the shoulders.

occiput posterior position

• Fetus is born in occiput posterior position in 2% to 10% of deliveries in vertex presentation. This is not a deflection, but a rotational disorder.

• Risk factors include epidural analgesia, nulliparity, increased fetal weight and occiput posterior birth, anthropoid pelvis and narrow subpubic angle.

• All birth-related complications are more common than occiput anterior. In occiput posterior births, the 2nd stage of labor may be significantly prolonged and 3-4th stage of labor may be prolonged. degree perineal lacerations are more common.

• Manual occiput anterior rotation can be attempted or forceps vacuum can be used during delivery. Cesarean section should be performed even if the head does not pass the pelvic inlet.

parturition

• Parturition is examined in 4 phases and these phases are different from the stages of birth. The stages of birth take place in the third phase of parturition.

► Phase 1 (Silent phase}: Non-contractile uterus, rigid and closed cervix

► Phase 2 (Preparation phase}: Preparation for action begins with cervical and myometrial changes.

► Phase 3 (Birth phase}: It is the phase where the birth takes place.

► Phase 4 (Puerperium phase}: It is the phase where involution takes place.

Phase 1 (silence phase)

• Almost with implantation, a period of silence begins in the myometrium. This period of silence continues until the end of pregnancy. Sometimes there may be weak contractions of the uterus in the later weeks of pregnancy. Braxton Hicks refers to these contractions that do not cause action.

contractions or pseudo-actions. They can be seen in the first 30 weeks and are contractions of 5-25 mmHg in intensity.

	real action	lying action
rhythm of contractions	Regular	Irregular
Intervals of contractions	It gets shorter	Constant
severity of contractions	It increases more and more	Constant
Location of discomfort	back and abdomen	lower abdomen
Response to sedations	no effect	Usually lighter
cervical opening	THERE IS	NONE

PHASE 2 (PREPARATION PHASE)

• In the last 6-8 weeks of pregnancy, mobility begins in the uterus. During this phase, the myometrial and cervical changes necessary for action occur.

• Myometrial changes: Oxytocin receptors increase, gap-junction proteins such as connexin-43 increase, Pg F receptors increase. All of these increase the response to uteotonins. Again in this phase, the lower segment of the uterus begins to form and the leading part of the fetus descends.

• Cervical maturation: Hyaluronic acid increases, dermatan sulfate, which binds collagen fibers, decreases, and as a result, collagen fibers are destroyed and the cervix softens. Although the mechanisms triggering cervical ripening are not fully known, progesterone antagonists (mifepristone}, PgE and PgF20 are known to accelerate cervical ripening.

PHASE I (BIRTH PHASE)

• The 3rd phase of parturition includes 3 phases of birth:

First Stage (Cervical Erasing and Opening Stage)

► It covers the time taken to complete the dilatation of the cervix (10 cm) required for the fetus to pass through the passage. It lasts about 12 hours (the latent phase averages 8 hours, the active phase averages 4 hours).

► Depending on the amount of cervical dilatation, this phase is also divided into phases:

0 latent phase

Active phase: The active phase of labor begins when the cervical dilation is 6 cm. Cervical opening and fetal descent are observed. It is divided into three parts:

- Acceleration phase

- Maximum peak phase

- Deceleration phase

► Uterine contractions that start in labor are completely involuntary contractions and although nerve blockage is provided with epidural analgesia, the frequency and amplitude of the contractions do not decrease. Mechanical stretching of the cervix also triggers uterine contractions (Ferguson's reflex). ;.

The best evidence of adequacy of uterine activity is cervical effacement and patency.

► Contractions are not of the same intensity in the whole uterus. The more active part of the uterus is the upper segment, and the passive part is the lower segment. The junction of the thick upper part and the thin lower segment is the physiological retraction ring. If the thinning in the lower segment is severe, this ring becomes prominent and is called the pathological retraction ring (Bandl ring). Uterine rupture is expected immediately after this development.

Second Stage (Fetus Expulsion Stage)

► This stage includes the period from the completion of dilatation of the cervix until the delivery of the fetus. It is expected to take an average of 50 minutes, a maximum of 2 hours (up to a maximum of 3 hours with regional anesthesia) in nulliparous patients, and an average of 20 minutes, a maximum of 1 hour (2 hours with regional anesthesia) in multiparas.

► Delayed cord clamping is recommended after the fetus is born, except in cases where emergency intervention is required. Delaying cord clamping for 30-60 seconds in preterm and term newborns increases hemoglobin levels and iron stores. It also accelerates neurodevelopment. While this practice reduces the need for blood transfusion, intraventricular bleeding and necrotizing enterocolitis, especially in preterm newborns, the only negative side is that it can cause hyperbilirubinemia.

► Cord entanglement is observed in the neck in 25% of births and it does not normally cause any harm. If the cord is loosely coiled, the shoulders are delivered after the fetal head is released. If the cord is too tightly wrapped, the shoulders should be delivered after the cord is clamped and cut with two clamps.

Third stage (Expulsion of the Placenta)

► This stage covers the time between the expulsion of the fetus and the expulsion of the placenta and fetal membranes and usually lasts less than 10 minutes. If there is no excessive bleeding, it is considered normal for up to 1 hour and waited without intervention. If the placenta is not separated, halas is done by hand.

PHASE 4 (PUERPERIUM PHASE)

• Postpartum hemorrhage is prevented by the contraction of the myometrium within 1 hour following the birth. At the same time, with the arrival of the mother's milk, the baby begins to be breastfed and the oxytocin released by the sucking reflex also helps myometrial contractions.

REGULATION OF MYOMETRIAL CONTRACTIONS IN PARTURITION

• Basically, 5 mechanisms control myometrial contractions in parturation:

► Increased actin-myosin interaction

► Increased oxytocin receptors in myometrium

► Increased intracellular Ca level in the myometrium and/or increased extracellular Ca entry into the cell

► Increased gap junction formation in the myometrium

► Increased production of Connexin 43 protein

• While estrogen from steroid hormone activity activates all the regulatory mechanisms required for myometrial contractions, progesterone inhibits these mechanisms. Parturition occurs during pregnancy, as progesterone dominates estrogen.

It waits in the first phase, that is, the silent phase, but towards the end of the pregnancy, with the decrease in progesterone efficiency, estrogen becomes relatively dominant over progesterone and the parturition passes to the second phase, that is, the preparatory phase.

• Progression of parturition occurs with the loss of activity of progesterone by different mechanisms rather than a decrease in the amount of progesterone (N-04, N 11).

• CRH plasma levels rise dramatically in the last 6-8 weeks of pregnancy and play an important role in parturition physiology. The placenta secretes large amounts of CRH. Maternal CRH level peaks in labor and falls rapidly with birth. Unlike hypothalamic CRH release, placenta! CRH secretion is not under the negative feedback effect of glucocorticoids, but on the contrary, cortisol stimulates CRH secretion from the placenta with a positive feedback effect. Increasingly, CRH directly stimulates myometrial contractility. In addition, increased secretion of cortisol also increases myometrial contractility by increasing prostaglandin synthesis from fetal membranes. Another effect is increased steroidogenesis. CRH increases the production of DHEA-S from the fetal adrenal gland and aromatizes into estrogens in them, resulting in the predominance of estrogen, which is necessary for myometrial contractility, over progesterone.

• Uterotonins that initiate labor. The most well-known among these are oxytocin, prostaglandins, endothelin-1, serotonin, histamine, PAF and angiotensin II.

FETAL MONITORING

noreply@blogger.com (Unknown) — Wed, 8 Mar 2023 11:50:00 +0300

ANTEPARTUAL EVALUATION

Fetal Movements

• Perception of fetal movements is an indicator of fetal well-being. If 10 or more significant movements are felt within 2 hours after the 28th week of pregnancy, it indicates that the fetus is good.

Fetal Respiration

• Although this measurement is not alone, it is used as a parameter of the biophysical profile.

Non-Stress Test (NST)

• It is a test in which fetal heart beats increase during fetal movement. Since it shows the maturation of the fetal autonomic nervous system, it is also an indication that the fetus is well.

• It is usually applied once a week. However, it should be repeated more frequently in postterm pregnancies, multiple pregnancies, type 1 diabetes, IUGR or hypertensive conditions (2 times a week or more).

Reactive NST (R-NST)

► Defined as at least two periods of acceleration (acceleration) with normal heart rate (120-160 beats), normal variability, lasting at least 15 seconds within 20 minutes, increasing more than 15 beats from baseline, in NSTs performed after 32 weeks of pregnancy .

► Causes of fetal death following a reactive NST include; meconium aspiration (most common), cord pathologies, intrauterine infections and detachment.

Non-reactive NST (NR-NST)

► It is the absence of 2 defined accelerations within 20 minutes of follow-up. The first conditions to be considered in NR-NST are that the fetus is asleep, the mother is hungry, or the mother has used cigarettes or sedatives. After these conditions are corrected, the NST is repeated.

► Poor perinatal outcomes are obtained in only 20% of NR-NST cases at term. Therefore sometimes NST needs to be extended to 90-120 min. If they remain non-reactive despite being prolonged, this is considered an indication that the fetus is very bad. Placental infarction (most common), oligohydramnios, IUGR, fetal acidosis and mel<onium may be responsible for such NR-NST results.

Contractions (Oxytocin) Stress Test (CST - O T)

• Unlike NST, CST is a test that shows uteroplacental reserve. Uterine contraction placenta! It reduces blood flow by about 20-30%. A fetus without uteroplacental perfusion disorders tolerates it.

• The test is administered spontaneously or with nipple stimulation or oxytocin infusion, with at least 3 contractions lasting at least 40 seconds over a 10-minute period.

• The absence of deceleration in more than 50% of the contractions created is reassuring and is called a negative CST. The presence of severe variable or late deceleration as a result of the contractions created is called positive CST and bad perinatal outcomes occur in 35-40% of these traces.

Biophysics Profile (BPP)

• It is a scoring system consisting of 5 different parameters used to determine fetal well-being. The test is usually 30-60 min. takes. There are 5 basic variables in BPP.

biophysics profile
PARAMETER	2 POINTS	0 POINTS
NST (20-40 min.)	>2 accelerations (within 20-40 minutes)	0-1 acceleration
Fetal respiration (30 min.)	>= 1 breath lasting 30 seconds (within 30 minutes)	Breathing lasting <30 sec
Fetal movement (30 min.)	>= 3 body/extremity movements (within 30 min.)	<3 body/extremity movements
Fetal tone (30-60 min.)	>= 1 extremity extension-flexion	0 limb extension flexion
Amniotic fluid amount (AFI)	At least 2 cm. 2 pockets measured in depth (2x2 cm. cap)	< 2 cm. one deep pocket

Evaluation of the biophysical profile
Point	Comment	Recommended Treatment
10	Normal, nonasphyctic fetus	NO Intervention , test can be repeated weekly
8/ 10 (AFI normal) 8/8 (no NST)	Normal, nonasphyctic fetus	Intervention vok, test can be repeated weekly
8/10 (AFI decreased)	Suspected chronic fetal asphyxia	Birth
6	Possible fetal asphyxia	Birth with reduced AFI, >36. week and delivery if AFl is normal, delivery if < 6 points in test repetition, follow-up if 6 points in repeat test
4	Most likely fetal asphyxia	If the test is repeated on the same day and the score is < 6, delivery
0---2	Definite fetal asphyxia	Delivered quickly (cesarean section)

• NST can be neglected if all four ultrasonographic parameters are normal. If the largest vertical amniotic fluid pocket is 52 cm, further investigation is required regardless of the biophysical profile. Fetal tone is the last parameter to deteriorate in fetal asphyxia.

• Recently, modified BPP based on the measurement of amniotic fluid with NST has been applied. Studies have shown that it is at least as sensitive and specific as classical BPP. It has replaced the classical BPP today as it requires less time.

DOPPLER ULTRASONOGRAPHY

• Doppler ultrasonography is a noninvasive method. While Doppier examinations of the umbilical artery, middle cerebral artery (MCA) and ductus venosus provide information about fetal circulation; Uterine artery Doppler examination gives information about placental circulation.

• Umbilical artery Doppler examination can only be used in IUGR cases.

Middle cerebral artery (MCA) Doppler is a noninvasive examination method in the diagnosis of fetal anemia and in the follow-up of treatment. The Doppler parameter that best predicts perinatal outcomes is the ductus venosus Doppler; however, it is meaningless to use it routinely because it occurs too late.

Intrapartum monitoring

Electronic Fetal Monitoring

• It is used for continuous monitoring of fetal heart beats during birth.

bradycardia

► 110 beats/min. of fetal heart rate. that it is under. Bradycardia does not indicate fetal distress if variability is normal and accelerations are also present. However, if the number of beats falls below 80, it creates an unreliable trace.

Some causes of bradycardia:

0 Fetal heart block due to maternal SLE

0 Maternal hypothermia

0 severe pyelonephritis

0 Severe fetal distress

0 Maternal general anesthesia

0 Head compression due to occiput posterior or transverse position in the second stage of labor

0 Maternal hypoglycemia

0 Maternal CMV infection

tachycardia

► Fetal heart rate is 160 beats/min. that it is above. While the prognosis is good in tachycardias without deceleration; The prognosis is poor when there are late or variable decelerations.

Some causes of tachycardia:

0 Maternal hyperthermia due to maternal infections and chorioamnionitis (most common cause)

0 Early stages of fetal hypoxia

0 Fetal anemia

0 Maternal hyperthyroidism

0 Fetal cardiac tachyarrhythmia

0 Drugs used by the pregnant

- Parasympatholytics (atropine, phenothiazine)

- Sympathomimetics (terbutaline, ritodrine)

Variability

► Variability is an important indicator of cardiovascular function and is under the control of the autonomic nervous system. Therefore, parasympathetic and sympathomimetic effects show ups and downs (oscillations) in basal heart rate with opposite movements.

► Loss of variability, especially with decelerations, is an indication of fetal acidemia and this situation is fatal. Metabolic acidemia depresses the fetal brain and heart.

► Some conditions that lead to reduced variability:

0 Maternal acidemia (diabetic ketoacidosis etc.)

0 Analgesics (meperidine, morphine, etc.)

0 CNS depressants (narcotics, barbiturates, phenothiazines, tranquilizers, diazepam, buprenorphine)

0 Butorphanol

0 General anesthesia

0 Epidural analgesia

0 Magnesium sulfate

0 Corticosteroids

0 Anencephaly

0 Fetal anemia

Decreased or lost baseline variability is the most reliable indication that the fetus is in danger.

accelerations

► Periodic, transient increases in fetal heart rate more than 15 beats lasting longer than 15 seconds. They are mostly related to fetal activity and are always reassuring traces that indicate that the fetus is not acidic.

decelerations

► Periodic and transient decreases in fetal heart rate. They are divided into 3 groups as early, variable and late. This classification is made according to their connection with contractions, form and time.

Early Decelerations (head press)

0 They are the reductions in heartbeats that start simultaneously with the contraction and return to the normal basal rate with the end of the contraction.

0 Unrelated to fetal hypoxia, acidemia and low APGAR score.

They develop as a result of vagal reflex due to increased intracranial pressure as a result of compression of the fetal head. Benign is trace, travail is followed by doing nothing

Late decelerations (uterplacental insufficiency)

0 They are the reductions in heartbeats that begin during or after the peak of contractions and continue for a while after the contraction ends and return to the normal basal rate.

► Causes of Late Deceleration:

0 Maternal hypotension: Especially due to epidural analgesia (most common}

0 Uterine hyperstimulation: Due to oxytocin infusion (most common}

0 Hypertensive diseases

0 diabetes

0 Collagen-vascular diseases

0 Ablation placenta (detachment)

Variable Decelerations (cord compression)

0 Structure and initial variable, not necessarily repetitive, not related to contractions.

0 Variable decelerations 70 beats/min. If it lasts for at least 60 seconds or more, it indicates that the fetus is in absolute danger.

Variable decelerations are traces that occur only as a result of cord compression.

Sinusoidal Trace

► True sinusoidal trace is indicative of severe fetal anemia (E-OOJ.

► Conditions leading to sinusoidal trace:

0 Rh isoimmunization

0 Vasa previa bleeding

0 Feto-maternal hemorrhage

0 Twin-to-twin transfusion syndrome

0 Fetal intracranial hemorrhage

0 Parvovirus infection

0 Severe fetal asphyxia (hypoxia)

0 Chorioamnionitis

0 Fetal distress

0 Umbilical cord compression

0 Using meperidine, morphine, alphaprodine and butorphanol

Fetal cardiac arrhythmias

► The most common fetal arrhythmia is atrial extrasystole (68%) and usually resolves after delivery.

► If tachyarrhythmias (supraventricular tachycardia, atrial flutter) cannot be treated, antiarrhythmic treatment should be given as they may cause cardiac decompensation and hydrops. Digoxin is the first choice and most commonly used antiarrhythmic in treatment.

Fetal heartbeat patterns are examined in 3 categories.

► Category I: These traces are normal. Indicates a normal fetal acid-base status. There is no need to do anything specific.

0 Basal rate: 110-160 beats/min (bpm)

0 Baseline variability: normal

0 Late or variable decelerations: none

0 Early decelerations: present or absent

0 Accelerations: present or absent

► Category II: Does not predict abnormal fetal acid-base status; however, we do not yet have sufficient evidence to classify them as Category I or III. It requires close observation and constant reassessment.

0 Basal rate:

- Bradycardia without loss of baseline variability

- tachycardia

0 Basal variability:

- Minimal baseline variability

Absence of baseline variability without recurrent deceleration

- Significant baseline variability

0 Accelerations:

- Absence of induced accelerations after fetal stimulation

0 Periodic or episodic decelerations:

- Recurrent variable decelerations with minimal or normal baseline variability

- Prolonged decelerations >2 min, < 10 min

- Recurrent late decelerations with normal baseline variability

- Variable decelerations with atypia features

Category 3: These traces are abnormal. Indicates an abnormal fetal acid-base status. It requires detailed evaluation. Depending on the clinical situation, attempts to correct the abnormal rate heart rate pattern include maternal oxygen supply, changing maternal position, cessation of labor induction, and treatment of maternal hypotension.

0 Loss of baseline variability and any of the following:

- Recurrent late deceleration

- Recurrent variable deceleration

- bradycardia

0 Sinusoidal pattern

PRECONCEPTIONAL AND PRENATAL EVALUATION

noreply@blogger.com (Unknown) — Tue, 7 Mar 2023 15:04:00 +0300

PRECONCEPTIONAL EVALUATION

GENERAL CONSULTING

Diet

► During pregnancy, expectant mothers should be warned not to consume raw meat and dairy products and not to consume fish with high mercury content (shark and swordfish, etc.) excessively.

Maternal and paternal age

► In adolescent pregnancies; anemia, preterm labor and preeclampsia are more common.

► Both maternal and fetal mortality increases in pregnancies where the maternal age is >35. The incidence of preterm labor, spontaneous preterm labor, IUGR, fetal aneuploidy and dizygotic twinning increases due to maternal complications such as hypertension and diabetes.

Although there is a significant increase in the risk of trisomy with advanced maternal age; Monosomy-X (Turner Syndrome) is not associated with advanced maternal age.

► Although there is an increase in the risk of genetic diseases with the increase in paternal age, the incidence is very low. There is a slight increase in the risk of Down Syndrome with advanced paternal age, but there is no increase in the risk of other aneuploidies. There is no increase in the risk of IUGR and stillbirth with advanced paternal age.

Obesity

► Significant obesity causes increased maternal and fetal morbidity and mortality. It may also be associated with fetal structural anomalies (neural tube defect, cardiac anomaly).

Adverse Pregnancy Outcomes in Obese Women
Complication	Prevalence (%) in normal weight pregnant women (BMI-18.5-24.9)	Prevalence (%) and Odds Ratio in Obese (BMI 30) Pregnants
gestational diabetes preeclampsia Wound infection or complication macrosomia LGA cesarean section Preoperative or elective caesarean section stillbirth labor induction Postpartum bleeding pelvic infection Preterm birth shoulder dystocia	2.3 2.7 0.4 2 8.7 25.2 6.6 0.3 20.9 6.7 0.6 3.8 2.0	8.6 (4.04) 8.1 (3.17) 1.0 (2.70) 5.1 (2.60) 16.3 (2.04) 39.3 (1.92) 11.5 (1.85) 0.5 (1.71) 29.7 (1.60) 8.7 (1.34) 0.8 (1.34) 4.8 (1.28) 2.3 (1.14)

The obstetric complication with the highest risk in obesity and pregnancy is gestational diabetes.

Assisted Reproductive Techniques

► The rate of major congenital malformations increased in pregnancies with assisted reproductive techniques and was found to be 8.3%. This risk is especially found in intracytoplasmic injection (ICSI) pregnancies.

Questioning Medical Diseases and Drug Use Diabetes Mellitus

► In the follow-up of pregestational diabetic patients, the HbA1C level and malformation rate are directly proportional, and the most important preconceptional goal is to normalize the HbA1c level. In pregestational diabetic women, HbA1C, serum creatinine, urine protein and thyroid function tests should be measured in the preconceptional period.

Epilepsy

► Being pregnant after a seizure-free year reduces the risk of epilepsy by 50-70%, and control should be sought with monotherapy, which is less teratogenic. Preconceptional high-dose folic acid (4 mg) should be started in women using antiepileptic drugs.

Other Medical Diseases and Environmental Factors

► Cardiovascular diseases, chronic hypertension, asthma, thrombophilias, renal diseases, inflammatory bowel diseases, sickle cell anemia (in risk group), thalassemias (in risk group), rheumatoid arthritis, SLE, epilepsy, depression, dermatological diseases, cancers, mercury and lead exposure should be questioned.

Questioning Infections

Infections That Need to be Screened Before Pregnancy

► Rubella (if there is no immunity, vaccinate and use effective contraception for 1 month)

► Varicella (vaccinate if not immune)

► Hepatitis B (vaccinate if not immune)

► HIV (at-risk women should be screened)

► Hepatitis C (should be screened only in high-risk cases)

► Tuberculosis (it should be screened only in high-risk cases)

► Syphilis (should be screened only in high-risk cases)

► Gonorrhea (should be screened only in high-risk cases)

► Chlamydia (should be screened only in high-risk cases)

Infections that do not need to be screened before pregnancy

► Toxoplasma

► Cytomegalovirus

► Herpes simplex virus (HSV); Only asymptomatic women with an affected partner should be screened.

Questioning Genetic Risks

• Genetic diseases are quite common and trisomies constitute about half of all chromosomal anomalies. Chromosomal anomalies are seen in approximately 50% of first trimester spontaneous abortions, 6-8% of stillbirths and early childhood deaths, and 0.4% of live births.

• Major congenital anomalies occur in 2-3% of live births. The most common cause of infant mortality is congenital defects (20%). While the most common congenital defect is cardiac anomalies, the second is neural tube defect.

• The risk of both anomalies increases in those with methylene tetrahydrofolate reductase gene polymorphism and is reduced by preconceptional folic acid supplementation. In order to prevent NTD, it is sufficient to start folic acid use before conception (400-800 µcg) and to use it in the first trimester of pregnancy. In cases with a history of NTD, using a dose of 4 mg reduces the risk.

PRENATAL EVALUATION

Prenatal Follow-up

• Thanks to prenatal care, maternal mortality and the risk of preterm birth, stillbirth and neonatal mortality are reduced.

Recommended follow-up algorithm during pregnancy
Frequency of follow-up	once a month for 28 weeks 28-36. every 2-3 weeks between weeks Once a week after 36 weeks
To be applied at each follow-up	blood pressure measurement Weight measurement Fundus height measurement; The measurement value in cm between 20-34 weeks gives the gestational week. Detection of fetal heartbeat, position, development, activity and amniotic fluid volume
will be applied at the first visit (weeks 0-14)	Risk analysis for genetic, medical, obstetric and psychosocial factors Calculating the estimated date of birth (Naegele formula: month-3, day+7) General physical and obstetric examination hematocrit or hemoglobin blood type and Rh Antibody screening with Indirect Coombs (if required) Pap smear Protein in the urine and urine culture chlamydia culture Rubella, syphilis, hepatitis B, HIV screening Fetal aneuploidy screening (between 11-14 weeks) should be offered to the patient. Cystic fibrosis screening should be offered to the patient. Gonococcal screening (should be performed in high-risk patients)
will be applied at the second visit (weeks 15-28)	Hematocrit or hemoglobin. Glucose screening test (glucose tolerance test if necessary) (between 24-28 weeks) Antibody screening with Indirect Coombs (week 28 if needed) Fetal aneuploidy screening (between 15 and 21 weeks) should be offered to the patient. NTD screening (MS-AFP) (weeks 15-21) should be offered to the patient. If cystic fibrosis screening was not performed at the first visit, it should be offered to the patient.
To be applied at the third visit (weeks 29-41)	Group B streptococcal culture (rectovaginal) (between 35-37 weeks) Gonococcal screening (in high-risk patients) Chlamydia culture and syphilis screening (in high-risk patients) Hepatitis B screening (in high-risk pregnant women, especially when hospitalized for delivery should be checked again) HIV screening (review in high-risk pregnant women)

If there is an indication, tuberculosis screening can be performed with tuberculin skin test or tuberculosis blood test at any gestational week.

Screening Tests

• Every pregnant woman should be offered a screening test in the early stages of pregnancy. Although the risk of Down syndrome increases after the age of 35, 70% of Down syndrome cases are seen in pregnant women younger than 35 years of age, and maternal age alone is a bad screening test.

Screening Tests in the First Trimester (11-14 Weeks of Pregnancy)

► It is a screening test performed between 11-14 weeks of pregnancy using some markers in maternal serum and ultrasonography.

► Pregnancy-related plasma protein-A (PAPP-A) and hCG (or free 13-hCG) levels are checked in maternal serum . In addition to these serum markers, ultrasonographic fetal nuchal translucency (NT) and nasal bone measurement can be added.

Free B-hCG: Increases in Down syndrome, decreases in trisomy 18 and trisomy 13.

0 PAPP-A (pregnancy-associated plasma protein-A): It is a glycoprotein secreted by the placenta. It is released directly into the maternal serum, therefore it is not found in the amniotic fluid. Down syndrome is reduced in trisomy 18 and trisomy 13.

0 Nape thickness (NT) measurement: It is the maximum thickness of the translucent subcutaneous tissue between the skin and the soft tissue on the vertebrae in the nuchal part of the fetus. An increase in nuchal thickness indicates a disorder in lymphatic transformation. It is generally used in combination with serum markers; however, it is used as a stand-alone screening test in multiple pregnancies. In 1/3 of the chromosomal abnormalities, NT is measured as abnormal, and about half of these are Down syndrome. Apart from chromosomal aneuploidies, NT is also increased in genetic syndromes, various birth defects and especially cardiac anomalies. Therefore, chorionic villus sampling and karyotype analysis are primarily recommended for diagnosis when NT is 3 mm or more. If the karyotype analysis is normal, fetal echocardiography should be performed.

0 Nasal bone: In 2/3 of fetuses with Down syndrome, nasal bone is hypoplasic or aplasic by ultrasonography between 11-14 weeks.

First trimester trisomy screening test (11-14 weeks of gestation)
tests	trisomy 21
hCG or free B-hCG	Increases (2 2.0 MOM)
PAPP-A	Decreases (s 0.5 MOM)
NT	Increases (23 mm)
nasal bone	Hypoplasic/ Aplasic

In the first trimester screening test, chorionic villus sampling and karyotype analysis should be applied as a definitive diagnostic test in patients with high risk of aneuploidy.

Screening Tests in the Second Trimester (15-21st Pregnancy Weeks)

► Between the 15th and 21st weeks of pregnancy, a triple screening test is performed by looking for alpha-fetoprotein (AFP), unconjugated estriol (uE3) and hCG (or free B-hCG) in maternal serum. In addition, quadruple screening is performed by looking at the inhibin A level.

► If the risk score obtained with these markers is 1/270 and above, karyotype analysis with amniocentesis should be applied to the patient as a diagnostic test.

0 Free (B-hCG: Levels increase in Down syndrome, decrease in trisomy 18).

Unconjugated estriol (uE3): Decreased in both Down syndrome and trisomy 18.

Inhibin A: The serum level is increased in Down syndrome.

0 Maternal serum alpha-fetoprotein (MS-AFP): Down syndrome and decreased in trisomy 18; increased in neural tube defects.

second trimester trisomy screening test (15-21 weeks of gestation)
Test	trisomy 18	trisomy 21
MS-AFP	Decreases (s 0.6 MOM)	Decreases (s 0.7 MOM)
Unconjugated estriol (uE3)	Decreases (≤ 0.5 MOM)	Decreases (s 0.8 MOM)
hCG or free B-hCG	Decreases (s 0.55 MOM)	Increases (2 2.0 MOM)
Inhibin-A	-	Increases (z 1.8 MOM)

► MS-AFP levels are also used in neural tube defect (NTD) screening. AFP is a glycoprotein synthesized by the fetal yolk sac (vitelline sac), liver and gastrointestinal tract, and is an analogue of albumin . Until the 13th week of pregnancy, AFP rises in both fetal serum and amniotic fluid, then rapidly decreases. On the contrary, it begins to rise in maternal serum after the 12th week.

► MS-AFP level affects maternal weight, gestational week, race/ethnicity, diabetes and multiple pregnancy, and the upper limit value accepted as normal in singleton pregnancies is 2.5 MoM (multiples of median).

► The gestational age is 15-20 after confirmation. AFP (MS-AFP) levels in the maternal erum are checked between gestational weeks, and if the value is found to be 2.5 MoM and above, level II ultrasonography is applied for diagnosis and fetal anatomy is evaluated. If a neural tube defect cannot be demonstrated by ultrasonography, the risk is reduced by 95%. If a neural tube defect cannot be excluded by ultrasonography, amniocentesis can be considered for the measurement of AFP and acetylcholinesterase in amniotic fluid.

Factors affecting MS-AFP levels

Situations where it increases

• Neural tube defects

• Renal anomalies (renal agenesis, polycystic kidney)

• Multiple pregnancies (normal range would be 3.5-4.0 MoM)

• Low birth weight

• Cystic hygroma

• Esophageal and intestinal obstruction

• Urinary obstruction

• Sacrococcygeal teratoma

• Osteogenesis imperfecta

• Preeclampsia

• detachment

• Placental intervillous thrombosis

• Fetal growth restriction

• Oligohydramnios

• Abdomen anterior wall defects (omphalocele, gastroschisis)

• Pilonidal cyst

• Congenital nephrosis

• Congenital skin defects (epidermolysis bullosa)

• Cloacal exstrophy

• Placental chorioangioma

• Liver necrosis

• Fetal death

• Low maternal weight

• Maternal hepatoma, teratoma

• Underestimating the gestational age

Decreased states

• Trisomy 21 or 18

• Gestational trophoblastic diseases

• Fetal death

• Maternal diabetes

• Maternal obesity

• Overestimation of gestational age

screening with free fetal DNA (cell free DNA) in the maternal circulation (noninvasive prenatal test)

► Free fetal DNA from the maternal circulation cell is released from apoptotic placental trophoblasts rather than from true fetal cells. 9 -10. It can be detected in the maternal circulation starting from the second week and is present in the maternal plasma at a rate of 10%. However, it is generally preferred to be used after the 10th week of pregnancy. Unlike intact fetal cells, free fetal DNA is cleared in maternal blood within minutes and decreases to immeasurable levels within two hours.

► The clinical usage areas of this test;

determination of the 0 Rh genotype; It can be used to determine the fetal Rh status in cases with Rh incompatibility.

0 Determination of fetal sex; It can be used to determine maternal steroid therapy in patients at risk for X-linked disease and in fetuses at risk for congenital adrenal hyperplasia.

0 Studies are also underway to detect various single gene diseases with fetal ONA in the maternal circulation (myotonic dystrophy, achondroplasia, Huntington's disease, CAD, cystic fibrosis and thalassemia).

0 Screening for aneuploidy (Noninvasive prenatal test=NIPT}; It is recommended to be used as a screening test for trisomy 21, 18 and 13 in high-risk pregnancies as early as the 10th week of pregnancy. It is not a diagnostic test, but if the result is abnormal, the result should be confirmed with invasive diagnostic tests. Single Its sensitivity in detecting Down syndrome in pregnancies is very high, with a detection rate of 99% and a false positivity of 0.5%.As the fetal DNA fraction increases, the reliability of the test increases.

• Patients at high risk of trisomy for whom screening with maternally circulating DNA is recommended;

- Women who are 35 years or older at birth

- Presence of ultrasonographic findings that increase the risk of fetal aneuploidy

- History of trisomy 21, 18 or 13 in previous pregnancies

- Presence of a balanced translocation involving chromosome 21 or 13 in one of the parents

- Abnormal first or second trimester screening test result

• Placenta! It should be kept in mind that the results may not reflect the fetal karyotype in case of mosaicism, loss of aneuploid twin in early weeks, maternal mosaicism or maternal malignancy.

It is not recommended for use in multiple pregnancies.

Efficacy of Screening Tests in Pregnancy in Detection of Down Syndrome
tests	tokens	Detection rate (%)
NT (11-14 weeks)	NT	64- 70
1st trimester screening test (11-14 weeks)	NT +PAPP-A+hCG	80-84
Quadruple screening test (weeks 15-20)	MS-AFP +hCG + uE3 +Inhibin A	80-82
Integrated Testing	1.Timester test + Quad test	94-96
Cell-free DNA screening test		99

Obstetric ultrasonography

Ultrasonography in the First Trimester

► Components and some indications of ultrasonographic evaluation in the first trimester;

0 Determination of gestational sac diameter, localization and number

0 Identification of embryo and/or yolk sac

0 Detection of number of fetuses, amnionicity, chorionicity in multiple pregnancies

0 cardiac activity

0 Gestational age determination; measurement of head-butt distance

0 NT measurement between 11-14 weeks

0 Detection of advanced anomalies such as anencephaly

0 Investigation of the cause if there is pain, vaginal bleeding

0 Investigation of the maternal uterus and adnexal region for mass

0 As a guide in chorionic villus biopsy and embryo transfer procedures

► With transvaginal ultrasonography, the gestational sac can be seen at the 5th week, the yolk sac in the middle of the 5th week, and the embryo and cardiac activity at the 6th week.

The most accurate result in determining the gestational age up to 13 617 weeks is obtained by measuring the head-rump distance of the embryo/fetus.

Findings That Can Be Detected by Ultrasonography in the First Trimester in Down Syndrome

• NT increase

• Nasal bone hypo/aplasia

• Enlargement of the frontomaxillary angle

• Tricuspid regurgitation

• Abnormal ductus venosus blood flow (monitoring of reverse a wave)

Second and Third Trimester Ultrasonography

► Components and some indications of ultrasonographic evaluation in the second trimester;

0 Fetal cardiac activity

0 Gestational age; head circumference (HC) measurement when biparietal diameter (BPD) cannot be measured

0 Estimated fetal weight, fetal growth (IUGR-macrosomia)

0 Number of fetuses and chorionicity in multiple pregnancies

0 Amniotic fluid amount (8-24 cm) (oligohydramnios - hydramnios)

0 Placental location, proximity to the cervical canal and cord insertion site

0 Other placental anomalies

0 Pathologies related to the umbilical cord

0 Fetal anomalies (NTD, cardiac anomalies etc.); ideally 18-20. between weeks.

0 Presentation

0 Evaluation of uterine adnexa and cervix (cervical canal length)

► Many fetuses with aneuploidy are lost in utero and most of these cases have anomalies that can be detected by ultrasonography in the second trimester. On the other hand, only 25-30% of Down syndrome cases have a major anomaly that can be detected by ultrasound in the second trimester.

Findings that can be detected by ultrasonography in the second trimester in Down syndrome

Increase in nuchal fold (the finding that increases the probability of Down)

short humerus

echogenic gut

echogenic intracardiac focus

short femur

Mild dilatation of the renal pelvis

short ear

Hypoplasia or aplasia of the nasal bone

Brachycephaly or short frontal lobe

Widening at the iliac angle

Clinodactyly (hypoplasia of the middle phalanx of the 5th finger)

flat face image

Single transverse palmar line

sandal gap

single umbilical artery

Aberrant right subclavian artery

The relationship between aneuploidy and defects detected by USG
defect	Aneuploidy Risk (%)	Most Commonly Associated Aneuploidy
cystic hygroma	50-70	45 X (most common in second trimester) t21 (most common in first trimester) t18, t13, triploidy
Omphalocele	30-50	t18, t13, t21, triploidy
Dandy-Walker complex	40	t18, t13, t21, triploidy
holoprosencephaly	30-40	t13, t18, t22, triploidy
Duodenal atresia	30	t21
cardiac defects	10-30	t21, t18, t13, 45 X. 22g11.2 deletion
clubfoot	5-30	t18, t13
Ventriculomegaly	5-25	t13, t18, t21, triploidy
Nonimmune hydrops	10-20	t21, t18, t13, 45X, triploidy
Diaphragmatic hernia	5-15	t18, t13, t21
Cleft palate/lip	5-15	t18, t13
Esophageal atresia	10	t18, t21
gastroschisis	NO INCREASE	no

The malformation most associated with aneuploidy is Cystic Hygroma.

► Sacrococcygeal teratoma: It is the most common neoplasm in the neonatal period and is more common in female babies. Perinatal mortality rate is around 40%. If hydrops or placentomegaly develops in the case, the loss is 100%. One of the causes of death in the postnatal period is malignant invasion. In cases, hydramnios is frequently encountered. High-output heart failure due to increased tumor vascularity or anemia due to intra-tumor hemorrhage causes hydrops in cases. In the antenatal period, masses below 7 cm can be followed ultrasonographically. For masses of 5 cm and above, the delivery method should be absolute cesarean section.

► Fetal renal pelvis dilatation: Renal pelvis dilatation is observed in 1-2% of fetuses and is temporary in 40-90% of the cases and is not associated with any anomaly. An anomaly of the urinary system can be observed in up to 1/3 of the cases, most commonly obstruction or vesicoureteral reflux at the ureteropelvic junction. In the ultrasonographic follow-up of the fetus, the measurement of the renal pelvis is made as anteroposterior diameter in the transverse plane. If the anteroposterior diameter measurement exceeds 4 mm in the second trimester and exceeds 7 mm in the third trimester, the diagnosis of renal pelvis dilatation is made. Mild pyelectasis observed in the second trimester slightly increase the risk of Down syndrome.

Prenatal Invasive Diagnostic Tests

Chorionic Villus Sampling

► Obtaining chorionic villi for cytogenetic analysis in the first trimester (10-13 weeks). The most important advantage is that direct karyotyping can be done without culturing the chorionic villus cells taken. Thus, by obtaining results in the early period, pregnancy termination can be done in earlier weeks of pregnancy.

► The most important disadvantage of this process is that more than 2% mosaicism is detected.

► The risk of discharge of amniotic fluid or infection is around 0.5%. your pregnancy

The incidence of extremity deformities or oromandibular defects increases when applied at 7 weeks of age. The fetal loss rate is similar to amniocentesis and is around 1:400; however, fetal loss rate is higher in procedures performed due to high NT.

Amniocentesis (A/S)

► The most commonly used test for genetic diagnosis is amniocentesis, and the classical application time is 15-20. are weeks of pregnancy.

► It is preferred because the risk of mosaicism is very low. The most important disadvantage of the procedure is the length of the culture phase, which lasts 7-10 days after the procedure.

► Complications of A/S are very few and occur rarely. Spotting or amniotic fluid may occur in 1-2% of cases. Chorioamnionitis risk

when less than 0.1%; fetal loss rate is around 1/500.

Fetal blood sampling (cordocentesis, percutaneous Umbilical Blood Sampling)

► It is the process of taking blood from the umbilical cord.

► Indications

0 Evaluation of fetal anemia due to alloimmunization and blood transfusion (most common indication)

0 Karyotype analysis: Results can be obtained in 24-48 hours.

0 Platelet alloimmunization

0 Fetal metabolic and hematological diseases

0 Acid-base analysis

0 Viral and bacterial cultures

0 For PCR testing in the diagnosis of infections

► Complications

0 Cord bleeding (20-30%)

0 Fetal-maternal hemorrhage (40% if crossed the placenta)

0 Fetal bradycardia (5-10%)

0 Fetal loss (1.4%)

Preimplantation genetic testing

► Preimplantation genetic diagnosis and preimplantation genetic screening are examined in two parts. For genetic analysis; polar body analysis, blastomere biopsy (3 days old and 6-8 cell embryo stage) or trophectoderm biopsy (5-6 days blastocyst stage) are used.

► Preimplantation genetic diagnosis: The aim is to place only healthy embryos intrauterinely by performing genetic analysis before implantation. Its indications include the presence of balanced translocation in the parents, single gene diseases (cystic fibrosis, thalassemia, hemophilia), fetal sex determination for X-linked diseases, detection of mutations such as BRCA-1, and detection of HLA compatibility with sibling for stem cell transplantation.

► preimplantation genetic screening: It is screening for aneuploidy before embryo transfer in couples who do not carry any known genetic abnormality.

DRUG USE AND VACCINES IN PREGNANCY

noreply@blogger.com (Unknown) — Mon, 6 Mar 2023 13:57:00 +0300

DRUG AND SUBSTANCE USE IN PREGNANCY (TERATOGENITY)

• All kinds of agents (chemicals, viruses, environmental factors, physical factors, drugs) that cause permanent loss of structure or function by acting in the embryonic or fetal period are called teratogens.

• The effects of teratogens differ according to the developmental period exposed:

► The first 2 weeks after fertilization is called the "all or nothing period" During this period, the pregnancy is either not affected at all or ends in miscarriage.

► Since there is organogenesis between the first 2 and 8 weeks after fertilization (embryonic period), teratogens taken during this period cause structural malformations.

► Maturation and functional development continue after the 8th week (fetal period). Some organs may also be affected during this period (brain and heart, etc.).

Known teratogens

Alcohol

Leflunomide

acitretin

Lithium

ACE inhibitors

methimazole

Angiotensin receptor blockers

methotrexate

Androgens

misoprostol

bexarotene

mycophenolate

Bosentan, Ambrisentan, Macitentan

paroxetine

Mercury

radioactive iodine

danazol

ribavirin

Diethylstilbesterol (DES)

Cigarette

Efavirenz

cyclophosphamide

phenytoin

tamoxifen

phenobarbital

Thalidomide, Lenalidomide

fluconazole

Tetracycline

Isotretinoin

Toluene

carbamazepine

Topiramate

chloramphenicol

Trastuzumab

Cocaine

Tretinoin

corticosteroids

Valproate

Bullet

warfarin

lamotrigine

Nitrofurantoin and sulfonamides are considered low-risk teratogens, and they can be used in the treatment of urinary infections in the first trimester if there is no alternative.

Anticonvulsants

• The most common fetal malformations in anticonvulsant users are orofacial clefts (the risk of cleft lip and palate increases 10 times), cardiac malformations and neural tube defects. While this risk is slightly lower in monotherapies, the risk may increase considerably in polytherapies.

• Of all anticonvulsants, valproic acid increases the risk of fetal malformations the most (9% major malformation risk, NTD risk 4%), and was associated with significant lower IQ compared with those exposed to other antiepileptics.

Risk of Major Congenital Malformation with Antiepileptic Use in the First Trimester

Antiepileptic ------------------------------------------------ ----Relative Risk

Gabapentin ------------------------------------------------ -------------------► 0.6

Lamotrigine ------------------------------------------------ ---------------------► 1.8

Oxcarbazepine ------------------------------------------------ --------------► 2.0

Levatiracetam ------------------------------------------------ ---------------► 2.2

Phenytoin ------------------------------------------------ -----------------------► 2.6

Carbamazepine ------------------------------------------------ ---------------► 2, 7

Clonazepam ------------------------------------------------ -------------------► 2.8

Topiramate ------------------------------------------------ ---------------------► 3.8

Phenobarbital ------------------------------------------------ -----------------► 5, 1

Valproic acid ------------------------------------------------ ------------------► 9.0

Antihypertensives

• ACE inhibitors are fetotoxic and cause ACE inhibitor fetopathy. Since angiotensin receptor blockers act by the same mechanism, these drugs are considered fetotoxic like ACE inhibitors.

• Both groups of drugs disrupt the renin-angiotensin system, which is necessary for the renal development of the fetus during the fetal period. In addition, they cause renal ischemia, renal tubular dysgenesis and anuria as a result of prolonged fetal hypotension and hypoperfusion. Developing oligohydramnios leads to pulmonary hypoplasia and limb contractures. In addition to its effects on the kidney, hypoperfusion in the fetus causes short limbs, IUGR and calvarium developmental defects (ACE inhibitor fetopathy).

Anti-inflammatory

Non-steroidal Anti-Inflammatory Drugs

► Not considered a major risk factor for birth defects; however, their use in the third trimester causes undesirable fetal side effects.

► Indomethacin causes premature closure of the ductus arteriosus and consequently pulmonary hypertension. It decreases the urine production of the fetus by increasing the sensitivity and amount of vasopressin. Thus, it leads to oligohydramnios (especially when used over 72 hours). All these side effects improve if NSAID use is discontinued after 34 weeks, so they should not be used after 34 weeks (E-08).

► In addition to these, intraventricular hemorrhage, bronchopulmonary dysplasia and necrotizing enterocolitis can be seen in babies born within 48 hours.

Aspirin

► Does not increase the risk of congenital malformation.

Leflunpmid

► Use in pregnancy is contraindicated. In animal studies, it has been shown to cause hydrocephalus, eye anomalies, skeletal anomalies and embryo death.

antimicrobials

antibiotics

► Aminoglycoside (gentamicin, streptomycin, etc.): Although ototoxicity and nephrotoxicity are observed when used in preterm newborns, congenital defects due to exposure to these drugs have not been demonstrated.

► Chloramphenicol: Teratogen. It should be avoided in late pregnancy as it may cause gray baby syndrome when given to preterm newborns.

► Nitrofurantoin: If used in the first trimester, the risk of cleft palate and lip increases 2 times. There are also studies stating that it increases the risk of hypoplastic left heart syndrome. However, the absolute risk remains very low and if there is no alternative, it is suitable to be used in the first trimester.

► Sulfonamides: Although there are studies showing that the use of periconceptional trimethoprim-sulfomethoxazole increases the risk of esophageal atresia or diaphragmatic hernia, the absolute risk remains very low and it is appropriate to use in the first trimester if there is no alternative.

► When tetracyclines are used after the 25th week of pregnancy, they accumulate in the teeth and long bones and cause yellow-brown discoloration.

Antivirals

► Ribavirin is highly teratogenic and causes anomalies in the skull, palate, eye, skeleton and gastrointestinal system.

► Efavirenz causes CNS and ocular anomalies in animals.

Antifungals

► Malformations associated with the use of fluconazole include cleft palate-lip, abnormal face, cardiac anomaly (tetralogy of fallot), skull, long bone and joint abnormalities. These anomalies are observed only in the first trimester, if it is used in chronic and high doses.

Antineoplastics

cyclophosphamide

► The risk of pregnancy loss has increased and the most common fetal anomalies; skeletal anomalies, extremity defects, cleft palate and eye anomalies.

Methotrexate and Aminopterin

► The critical period is between the 8th and 10th weeks and the minimal dose level required is 10 mg.

► Methotrexate-Aminopterin syndrome:

0 Craniosynocytosis (with cloverleaf skull)

0 Wide nose

0 Down-set ears

0 micrognathia

0 Limb anomalies

tamoxifen

► Pregnancy is not recommended either during the treatment or within two months of the end of the treatment, as it may cause DES-like syndrome in the long term.

Trastuzumab

► Not associated with fetal malformations; however, cases of oligohydramnios, anhydramnios and fetal renal failure have been reported. Therefore, they may be associated with pulmonary hypoplasia, limb abnormalities, and neonatal death.

Anticoagulants (Warfarin - Kumadin)

• Embryotoxic and fetotoxic. Its teratogenic effects are dose dependent and occur at doses above 5 mg. Spontaneous abortion occurs in 72% of cases as a result of exposure in the early stages of pregnancy. When exposed between the 6th and 9th weeks of pregnancy, warfarin embryopathy develops in 8% of cases (nasal hypoplasia, vertebral, femoral epiphyseal defects).

• When warfarin is used in the second or third trimester, corpus callosum agenesis, Dandy-Walker malformation (cerebellar vermian agenesis), optic atrophy and microphthalmia may be seen due to inappropriate growth and bleeding. Affected newborns are at risk of blindness, deafness and growth retardation.

Psychiatric Drugs

Lithium

► It causes Ebstein anomaly when used in the first trimester of pregnancy. In addition, it can cause hypothyroidism, diabetes insipidus, cardiomegaly, bradycardia, cyanosis and hypotonia in newborns (N-03, N-06).

SSRIs and SNRLs

► They are not considered teratogens except for paroxetine. Paroxetine increases the risk of cardiac malformation (most commonly ASD and VSD) when used in the first trimester.

antipsychotics

► They are not teratogenic; however, it may have SSRI-like effects in the neonatal period.

Sex Hormones

Testosterone and anabolic steroids

► It causes varying degrees of virilization and ambigius genitalia in female fetuses due to exposure. While labioscrotal fusion is observed as a result of exposure in the first trimester, phallic growth is observed in late fetal exposure.

danazol

► As a result of exposure in early pregnancy, dose-dependent cliteromegaly, labial fusion and urogenital sinus malformations are observed.

Diethylstilbesterol (DES)

► It increases the risk of vaginal clear cell cancer in girls with intrauterine exposure, and the risk of malignancy is not related to dose or timing of exposure. It also causes a 2-fold increase in the risk of vaginal and cervical intraepithelial neoplasia.

► In both sexes, it can cause genital tract anomalies. While hypoplasic uterus causes T-shaped uterine cavity, cervical anomalies (septum, etc.) and tubal anomalies in girls; It can cause hypospadias, epididymal cyst, microphallus, cryptorchidism and testicular hypoplasia in men. In the following years, it slightly increases the risk of early menopause and breast cancer in women.

Immunosuppressives

corticosteroids

► The use of corticosteroids in the first trimester causes a 3-fold increase in the occurrence of cleft palate-lip. However, their use in the following weeks does not cause malformation.

► Since prednisone is inactivated in the placenta, it has no effect on the fetus.

mycophenolate

► In case of exposure in the first trimester, 30% spontaneous abortion and 30% complex birth defects (mycophenolate embryopathy) are observed (Microtia, auditory canal atresia, cleft palate lip, coloboma and other eye anomalies, short fingers with hypoplastic nails, cardiac defects).

Retinoids

• They are derivatives of vitamin A and are the most teratogenic agents in humans (isotretinoin, acitretin and bexaroten). They cause CNS, face, heart and thymus anomalies by preventing neural crest migration during embryogenesis (retinoic acid embryopathy)

• Anomalies specific to retinoic acid embryopathy:

► Craniofacial anomalies: Microtia / anotia, micrognathia, cleft palate, facial bones and cranial deformities

► Cardiac anomalies: Conotruncal defects

► CNS anomalies: Ventriculomegaly

► Thymus anomalies: Aplasia, hypoplasia

Vitamin A:

• There are 2 natural forms of Vitamin A. The first of these is the precursor of vitamin A (Beta-carotene, which is found in fruits and vegetables. It is not teratogenic. The use of the other form, retinol, at a dose of more than 10,000 IU/day in the 1st trimester is associated with cranial neural crest defects.

Bexarotene:

• Use of bexarotene, a retinoid class, during pregnancy causes eye-ear anomalies, cleft palate and ossification defects.

Isotretinoin:

• One of the most patented teratogens. While it causes abortion at a high rate when exposed in the first trimester, malformation is observed in one third of the living fetuses.

Acitretin:

• Although it has a short half-life, it is metabolized to etretinate and, since the half-life of etretinate is 120 days, even discontinuation during the preconceptional period may not protect it from malformation. It is recommended not to become pregnant until 3 years after stopping the drug.

Other Items

Alcohol

► Ethyl alcohol is a strong teratogen and causes preventable developmental disorders (dysmorphic facial appearance, growth retardation, structural brain abnormalities, neurobehavioral disorders). There are no established ultrasonographic criteria for the prenatal diagnosis of fetal alcohol syndrome. There is no safe alcohol level during pregnancy and overdose has been associated with stillbirths. Omphalocele and gastroschisis cases have also been reported with periconceptional alcohol use.

Cocaine

► Congenital anomalies associated with cocaine use include cleft palate, cardiovascular anomalies and urinary system anomalies.

Opiads and narcotics

► They are not considered major teratogens; however, they cause a slight increase in the risk of spina bifida, gastroschisis and cardiac anomalies as a result of periconceptional exposure.

Cigarette

► Smoking is fetotoxic and has many vasoactive effects.

► Congenital anomalies associated with smoking due to vasoactive effects: Poland syndrome, congenital heart diseases, hydrocephalus, microcephaly, gastroschisis and omphalocele, cleft palate and lip, hand anomalies

► Obstetric risks associated with smoking: IUGR, low birth weight, SGA, sudden infant death syndrome, spontaneous abortion, placenta previa, ablatio placenta, premature rupture of membranes, preterm birth, uteroplacental insufficiency, fetal death.

Coffee

► Excessive consumption (5 cups/day or 500 mg of caffeine) every day

slightly increases the risk.

Caffeine, amphetamine, heroin, methadone and marijuana are not teratogens, but they can cause growth retardation.

OTHER TERATOGENS

Thalidomide and Lenalidomide

► 35-50 of pregnancy. Causes 20% malformation when taken on days Its characteristic malformation is the absence of one or more long bones (phocomelia). Cardiac, gastrointestinal, outer ear anomalies, eye anomalies and other extremity reduction defects are other common anomalies.

Radioactive iodine ( Iodine 131 )

► Radioactive iodine is contraindicated in pregnancy. It can cause severe and irreversible fetal and neonatal hypothyroidism by causing ablation of fetal thyroid tissue.

Bullet

► It is associated with fetal growth retardation and behavioral abnormalities.

Mercury

► Associated with microcephaly and severe brain damage.

Ionizing Radiation

► There is no malformation effect of ionizing radiation below 5 rad (0.05 Gy) during pregnancy .

► While microcephaly is the most common fetal anomaly when exposed to high doses of x-rays in the first 8 weeks of pregnancy, the exposure period is 8-15, when radiation-induced mental retardation is most likely. week range.

Phencyclidine and Lysergic acid are not teratogenic.

VACCINES IN PREGNANCY

Vaccines that are absolutely contraindicated

• Mumps

• Measles

• Rubella (Rubella)

• Chickenpox (Varicella zoster)

• Smallpox vaccine

• Anthrax; Theoretically, it is teratogenic.

Vaccines that can be used as needed

• influenza

• Rabies

• Hepatitis B

• Hepatitis A

• pneumococcus

• Meningococcus

• Diphtheria, pertussis and tetanus: 27-36 for each pregnant woman. A single dose is recommended between weeks.

Vaccines that are not routinely recommended but can be given as mandatory

• Oral or subcutaneous polio

• typhoid

• yellow fever

Although teratogenicity has not been observed in HPV vaccines, it is not recommended for use during pregnancy.

MATERNAL PHYSIOLOGY

noreply@blogger.com (Unknown) — Sun, 5 Mar 2023 11:26:00 +0300

GENITAL TRACT

Uterus

• The weight, internal volume and dimensions of the uterus increase compared to the pre-pregnancy period. This uterine growth occurs due to hypertrophy and stretching of muscle cells, and new myocyte formation is limited.

• 6-8 weeks of pregnancy. The fundus is softer than the cervix and the isthmus is compressible and excessively softened (Hegar sign).

• After the 12th week, the uterus enlarges to protrude beyond the pelvis, and the uterus is slightly turned to the right due to the presence of the sigmoid colon on the left. uterine pregnancy It reaches the level of the navel in the 20th week, and reaches the xiphoid in the 36th week. When engaged, it slowly descends.

• In the case of a term pregnant woman lying on her back, venous return to the heart is reduced due to the enlarged uterus's compression on the aorta and inferior vena cava. When a term pregnant woman needs to lie on her back, turning her to her left by 15-30 degrees will prevent supine hypotension.

• Due to the effect of estrogen, progesterone, relaxin and some adipocytokines (Chimerin, visfatin, leptin, resistin, adiponectin) during pregnancy, uteroplacental blood flow gradually increases throughout pregnancy and is 450-650 ml/min at term. . During contractions, the flow is markedly reduced.

In normal pregnancy, there is resistance to the vasopressor effects of angiotensin II and norepinephrine.

cervix

• Cyanosis and softening of the cervix are observed due to increased vascularity, diffuse edema, and hypertrophy and hyperplasia of the cervical glands during pregnancy (Godell's sign). Eversion occurs due to columnar cell metaplasia.

• The cervical canal is covered with a mucus plaque (marker) and this plaque is expelled at the beginning of labor. If the cervical mucus is dried and examined, a fern appearance is not observed due to poor crystallization.

vagina

• Increased vascularization and hyperemia are seen in the vagina, and accordingly the vagina turns purple (Chadwick's sign). Mucosal thickness increases, loosening of connective tissue and hypertrophy of smooth muscle cells occur.

• Vaginal pH is between 3.5-6.0.

ovary

• Ovulation stops during pregnancy in the ovary.

• While the corpus luteum is the main source of progesterone until the sixth and seventh weeks of pregnancy, progesterone secretion decreases after this week. The increase in the level of relaxin in the early weeks of gestation is due to the secretion from the corpus luteum.

SKIN

Hyperpigmentation

• There is increased pigmentation in the areola and genital area. This increase in pigmentation is due to the increase in melanocyte stimulating hormone. Linea alba hyperpigmentation is called linea nigra.

Chloasma (Melasma - Pregnancy Mask)

• They are macular hyperpigmentations on the forehead, cheeks and nasal root. It regresses after birth, but it can also be permanent.

Telangiectasia (Spider Angioma) and Palmar Erythema,

• They occur due to increased estrogen, but disappear in the postpartum period.

Striae Gravidarum

• It is due to collagen breakage that occurs as a result of excessive stretching of the skin. They are red, slightly sunken irregular lines that can be seen on the skin of the abdomen, chest, thighs and buttocks. Once formed, it cannot be recycled.

Hair Changes

• While the anagen phase (growth) is prolonged during pregnancy, the postpartum telogen ratio (resting) increases. Although not exaggerated in most pregnant women, excessive hair loss in the puerperal period is called telogen effluvium.

BREAST

• Breast tenderness and pain are common in the early weeks of pregnancy. From the second month, the breast volume increases and the veins begin to appear on the skin. Nipple enlarged, pigmented and erect! becomes. Colostrum may come after the first months. Hypertrophic sebaceous glands appear in the areola (Montgomery glands). Striae may occur as in the abdomen.

Prolactin plays an important role in lactation and increases throughout pregnancy. However, lactation is constantly suppressed by estrogen, progesterone and hPL so that it does not start before birth. Lactation begins with the sudden drop in the levels of these hormones after birth.

Hormones related to breast development and lactation

Mammogenesis (Breast development)

estrogen

progesterone

prolactin

Growth hormone

epidermal growth factor

Glucocorticoids

insulin

Lactogenesis (Start of milk secretion)

Estrogen reduction

Decreased progesterone

hPL reduction

prolactin

Glucocorticoids

insulin

Galactogenesis (continuation of milk secretion)

Absorption (Oxytocin + Prolactin)

low estrogen

low progesterone

insulin

Growth hormone

T4 and parathyroid hormone

Glucocorticoids

METABOLIC CHANGES

Metabolic Rate

• In the third trimester of pregnancy, the basal metabolic rate increases by approximately 20%.

Weight Gain

• The most striking physiological change in pregnancy is the recommended weight gain of 11.5-16 kg.

Distribution of weight gain in a term pregnancy

Fetus------------------------------------------------ ------------------------------------------ 3400 g

Placenta------------------------------------------------- -----------------------► 650g

amniotic fluid------------------------------------------------ ----------------► 800g

Uterus------------------------------------------------- --------------------------► 970 g

Blood volume increase------------------------------------------------ -----------► 1450 g

Maternal fat deposition------------------------------------------------ --► 3345 g

Extravascular fluid------------------------------------------------ -----► 1480 g

Breast tissue------------------------------------------------ ---------------► 405g

Total------------------------------------------12.5 kg

Protein Metabolism

• Total protein, albumin and colloid pressure decrease during pregnancy. In contrast, the total globulin concentration increases.

• Binding proteins, transferrin, pregnancy-specific proteins, IgM and IgD increase, while IgG decreases.

• The concentration of most amino acids {ornithine, glycine, taurine, proline) is reduced in maternal plasma.

Carbohydrate Metabolism

• Pregnancy is characterized by mild fasting hypoglycemia, postprandial hyperglycemia and hyperinsulinemia. Since the resistance of peripheral insulin increases during pregnancy, latent diabetes becomes evident or worsens if diabetes is present.

• A number of endocrine and inflammatory factors are responsible for the increase in insulin resistance and decrease in insulin sensitivity during pregnancy. These include pregnancy-related hormones {human placental lactogen, progesterone, placental-derived growth factor, prolactin and cortisol}, cytokines {TNF}, and central adipose tissue-derived hormones {leptin} and hormones interacting with prolactin.

• While glomerular filtration of glucose increases during pregnancy, tubular reabsorption decreases minimally. Therefore, physiological glucosuria is seen in half of the pregnant women (150 mg/dl).

Lipid Metabolism

• All lipids increase during pregnancy {triglyceride, T.cholesterol, VLDL, HDL, LDL, apolipoproteins, phospholipids, free fatty acids}. The main mechanism responsible for these changes is increased lipolytic activity and decreased lipoprotein lipase activity in adipose tissue.

• Leptin; It is associated with fetal birth weight because fetal organs have a role in development. Low leptin levels are associated with IUGR. It is secreted mainly from adipose tissue and partially by the placenta. Therefore, there is a significant correlation between placental weight and leptin level. Maternal serum leptin levels increase during pregnancy. Leptin level peaks especially in the second trimester and then plateaus and maintains this level until term. In addition, abnormal leptin elevations have been associated with preeclampsia and gestational diabetes.

• Ghrelin; It is secreted from the placenta and has a role in fetal development.

Water and Mineral Metabolism

• From the early period of pregnancy, tubular reabsorption increases and water retention occurs in the body. As a result, there is an increase of approximately 6.5 liters of extracellular fluid in pregnant women.

Edema is normal in pregnant women, it does not show any pathology

• Glomerular filtration of sodium (Na) and potassium (K) increases during pregnancy, and 1,000 mEq Na and 300 mEq K are uptake during pregnancy. However, Na and K levels are relatively low due to the increase in plasma. (0.5 mEq/L drops). Since the tubular resorption of these electrolytes has increased, their urinary excretion does not change.

Serum osmolarity decreases in pregnant women.

• While the total calcium concentration decreases during pregnancy, the ionized calcium level does not change. On the other hand, the level of both the total and ionized form of magnesium decreases significantly in pregnant women. The phosphate level in the serum does not change.

Folate Metabolism

• The need for folic acid increases during pregnancy and this need becomes 400-800 µg/day.

• Folic acid needs increase in cases such as multiple pregnancy, hemolytic anemia, Crohn's disease, alcoholism and inflammatory skin diseases, children with NTD and family history of congenital heart disease.

Disorders that can be seen in folic acid deficiency

1. Megaloblastic anemia

2. Neural tube defect

3. Preeclampsia

4. Ablation placenta

5. Fetal cardiac anomaly

vitamins

• Diet is sufficient for many vitamins.

• Vit B12 decreases during pregnancy and this decrease is due to the decrease in transcobalamin. Vit 86 support is useless; however, it is beneficial to use it together with doxylamine in the treatment of nausea and vomiting. Vitamin D deficiency is common during pregnancy and 15 ug/day (600 IU) vitamin D intake is sufficient during pregnancy and lactation.

HEMATOLOGICAL CHANGES

Blood Volume

• The blood volume increases by approximately 1600-1700 ml. The increase in blood volume is due to an increase in both plasma and erythrocyte levels, but most of the increase occurs in plasma (1200 ml). Since the erythrocyte volume increases by only 450 ml, there is a physiological anemia with dilutional effect. Therefore, hemoglobin concentration and hematocrit decrease slowly throughout pregnancy. Erythropoietin levels increase during pregnancy and peak in the third trimester. Accordingly, there is mild erythroid hyperplasia in the bone marrow during pregnancy and the reticulocyte count increases slightly during normal pregnancy.

• There is a picture of leukocytosis in pregnancy (15,000/ul). Especially in travay, it can rise up to 25,000.

• Platelet count also decreases during pregnancy.

changes in blood cell content during pregnancy

Neutrophil ► Increases

Erythrocyte ► Increases

Erythrocyte fragility ► Increases

Sedimentation ► Increases

Leukocytes ► Increases

Cover. melt. Volume ► Slightly increases

Lymphocyte ► Unchanged

Cover. melt. Hgb. Conc ► Invariant

Basophil ► Decreases

Hemoglobin ► Decreases

Hematocrit ► Azahr

Platelets ► Decreases

Iron Metabolism

• The need for iron increases during pregnancy and usually this open store cannot be met by iron. From early pregnancy periods, hepcidin levels decrease and accordingly, iron absorption in the intestines increases (up to 40%). However, iron supplementation may be required as the daily requirement is 6-7 mg/day.

• Serum iron and ferritin levels decrease during pregnancy. However, a serum ferritin level of <10-15 mg/L during pregnancy makes the diagnosis of iron deficiency anemia.

• There is no need for iron support for the first 4 months in pregnant women who do not have anemia. The reason for Hb concentration below 11 g/dl in the second half of pregnancy is iron deficiency rather than hypervolemia. Pregnant women should be given 30 mg of elemental iron daily as a supplement.

Coagulation System

• Fibrinogen (factor I) increases. This increase is the most important reason for the increase in sedimentation during pregnancy.

• Plasminogen activator inhibitor 1-2 (PAI-1,2) levels increase during pregnancy and accordingly, the efficiency of tissue plasminogen activator (tPA) decreases. As a result of all these, fibrinolytic activity is insufficient during pregnancy. Therefore, there is hypercoagulability in pregnant women and the risk of thromboembolism in pregnant women is 5 times higher than in normal women.

Coagulation changes in pregnant women

F 1 (Fibrinogen) F 5, F 7, F 8, F9, F10, F12 ---increases

PA1-1 , 2 ► Increases

Plasminogen ► Increases

Thrombin time ► Increases

aPC resistance ► Increases

Activated PTT ► Unchanged

F 11 (prothrombin) ► Does not change

Antithrombin ► Unchanged

F XI, XIl1 ► Decreases

tPA activity ► Decreases

Protein C and S ► Azahr

aPC level------decreases

CARDIOVASCULAR SYSTEM

Heart

• In the last trimester, with the rise of the diaphragm, the heart is pushed upwards, rotates forward and the left margin is displaced laterally. Due to this displacement, the most common change in the ECG is mild left axis deviation.

• Significant changes occur in heart sounds:

► The first heart sound is markedly doubled and its volume increases.

► There is no change in the aortic and pulmonary elements of the second heart sound.

► The third heart sound becomes clear and easily audible.

► Systolic murmur is normal up to 3rd degree.

► Diastolic murmur is not normal and should be investigated

• Cardiac output increases and becomes 6 L/min. The output, which increases by 30-50% during pregnancy, increases the most within 10-30 minutes following birth.

• The increase in heart rate occurs with the inotropic effect of the increased estrogen of pregnancy. If the heart rate rises above 100 beats/min, it should be investigated.

Hemodynamic Functions

Status of hemodynamic parameters in term pregnant (compared to puerperium and non-pregnant)

Heart rate ► Increases

Cardiac output ► Increases

Mean arterial pressure ► Does not change

Pulmonary capillary wedge pressure ► Does not change

Central venous pressure ► Does not change

Left ventricular power index ► Unchanged

Pulmonary vascular resistance ► Decreases

Systemic vascular resistance ► Decreases

Colloid oncotic pressure ► Decreases

Blood pressure

• There is a slight decrease in blood pressure in 24-26 weeks of pregnancy and this decrease is more evident in diastolic pressure. Diastolic pressure decreases slightly in the first two trimesters; however, it returns to its normal level in the pre-pregnancy period at term

• Renin, angiotensin II and aldosterone levels increase.

• PgE2 and Pgl2 increase.

• Atrial natriuretic peptide and brain natriuretic peptide levels do not change.

THE RESPIRATORY SYSTEM

• The increase in basal oxygen consumption during pregnancy, excessive increase in progesterone (resistance in the pulmonary vessels decreases), and the ribs opening outward and the diaphragm rising up to 4 cm create some differences in respiratory functions and capacities during pregnancy.

Changes in the respiratory system

Increases:

1. Tidal volume 150- 200 mL

2. Inspiratory capacity increases by 5-10% (200- 250 mL)

3. Minute ventilatory volume increases by 40% (3,000 mL/min)

4. Minute oxygen uptake

5. Peak expiratory flow rate

6. Oxygen consumption

invariants

1. Lung compliance

2. Vital capacity

3. Respiration rate

4. Inspiratory reserve volume

Descendants

1. Total lung capacity is reduced by 5% (200 ml)

2. Functional residual capacity decreases by 20-30% (400-700 mL) -96)

3. Residual volume decreases by 20-25% (200-400 mL)

4. Expiratory reserve volume decreases by 15-20% (200-300 mL)

• Arterial pCO2 decreases slightly as tidal volume increases. Mild compensated respiratory alkalosis (pH 7.45) occurs due to hyperventilation during pregnancy. In contrast, HCO3 decreases compensatory (20-22 mEg/L).

• This pH increase shifts the oxygen dissociation curve to the left, increasing maternal hemoglobin's affinity for oxygen, thereby reducing the oxygen-freeing capacity of maternal blood. The decrease in pCO2, which develops as a result of maternal hyperventilation, facilitates the passage of CO2 from the fetus to the mother, while at the same time increasing the oxygen transmission to the fetus.

URINARY SYSTEM

• There is a slight increase in kidney size and approximately 30% volume increase in both kidneys during pregnancy. Hydroureter and hydronephrosis can often be seen on the right side due to compression and dextrorotation of the pregnant uterus.

• Asymptomatic bacteriuria occurs in 5% of pregnant women, of which 25-30% causes pyelonephritis. The ureters dilate and the slowing of the urine flow increases the susceptibility to infection.

• In addition to physiological glucosuria during pregnancy, physiological proteinuria is also seen due to the decrease in hyperfiltration and tubular reabsorption, and it is more prominent especially in the second half of pregnancy. The upper limit for physiological proteinuria in pregnancy is 300 mg/day. Hypercalciuria is also observed during pregnancy.

• Daily urine volume increases by 25%, nocturia and frequent urination can be seen. While glomerular filtration rate (GFR) increased by 50% , creatinine clearance Increases by 30%. The serum creatinine level decreases by 25% and at values of 0.9 mg/dl and above, the patient should be investigated for renal pathology. Urea level (25%) and uric acid level also decrease.

In preeclampsia, serum uric acid level is increased due to decreased GFR. The first biochemical marker of preeclampsia may be an increase in uric acid levels.

Relaxin is involved in an increase in GFR and an increase in renal blood flow.

GASTROINTESTINAL SYSTEM

• Nausea and vomiting (emesis gravidarum) is seen in 70% of pregnant women, usually peaks at the 10th week and lasts until the 16th week.

• With the effect of progesterone, relaxation of the smooth muscles of the gastrointestinal tract and, as a result, decrease in intestinal motility, reflux esophagitis (pyrosis) due to relaxation of the lower esophageal sphincter are observed.

• During pregnancy, gastric acid secretion is decreased but mucus secretion is considerably increased, so active peptic ulcer is almost never seen in pregnant women .

• An increase in gastric volume is observed in pregnant women due to increased gastric secretion. There is no slowdown in gastric emptying rate during pregnancy; however, gastric emptying rate slows down when labor begins.

• Relaxation in the colon leads to an increase in water and salt absorption and, as a result, constipation. Hemorrhoids are common in pregnant women due to compression and constipation.

• Gallstone formation becomes easier during pregnancy. The reason for this is the decreased contractility of the gallbladder that occurs with progesterone activity, the condensation of bile and the increase in the residual volume of the gallbladder. Cholesterol stones are the most common gallstones in pregnant women.

• Liver function tests (AST, ALT, GGT) and bilirubin levels are slightly decreased. Serum alkaline phosphatase increases 2-fold (placental synthesis increased). Bromsulfophthalein (BSP) clearance is reduced. Spleen size increases approximately 70% during pregnancy, but hepatomegaly is a potentially pathological finding (A-18).

ENDOCRINE SYSTEM

• The pituitary gland is the most enlarged endocrine gland (135%). While an increase in lactotroph cells and a decrease in gonadotroph and somatotroph cells are observed, the amount of corticotropic and thyrotropic cells does not change. Prolactin levels in pregnant women can increase up to 10 times normal. However, the incidence of prolactinoma does not increase during pregnancy. Even in women who are breastfeeding after giving birth, prolactin levels decrease. However, there are pulsatile increases in secretion in response to breastfeeding in early lactation periods.

• Thyroid gland enlarges anatomically, glandular hyperplasia and vascularity increase. With the effect of high estrogen, thyroxine binding globulin (TBG) increases. Total thyroxine (T4) level increases; however, there is a slight increase in the free thyroxine (T4) level due to the increase in hCG, and then it goes down to normal. Total triiodothyronine (T3) increases; however, there is no significant change in free triiodothyronine (T3) level. Resin T3 uptake (uptake} decreases. TRH level does not change during pregnancy. However, TRH may cross the placenta and stimulate thyrotropin release from fetal pituitary. Although thyrotropin (TSH) level is slightly suppressed during pregnancy, serum level is within normal limits in non-pregnant women.

• Iodine requirement increases in normal pregnancies due to the increase in maternal and fetal thyroid hormone production and renal excretion of iodine during pregnancy.

• The plasma concentration of parathyroid hormone decreases during the first trimester and then increases progressively until the end of pregnancy.

• Serum 1,25-dihydroxyvitamin D3 level in pregnant women increases due to placental PTH or PTH-related protein (PTH-rP), and accordingly, calcium absorption in the gastrointestinal tract increases, especially in the third trimester.

• While the corticotropin (ACTH) level is low in the early weeks of pregnancy; In the following weeks, both ACTH and free cortisol levels increase. Serum total cortisol level increases in pregnant women; however, most of it is bound to increased transcortin (cortisol binding globulin). Although the production of adrenal cortisol does not increase, the reason for the increase in cortisol level is that the metabolic clearance of cortisol is reduced by half.

• Aldosterone level increases during pregnancy and has a role in determining the trophoblast development and placental diameter. Deoxycorticosterone level also increases 15 times during pregnancy. The level of antiduretic hormone (vasopressin) does not change during pregnancy.

• Androstenedione and testosterone levels increase in maternal serum; however, since almost all of them are converted to estrogen in trophoblasts, there are no fetal side effects. DHEA-S levels are decreased in maternal serum and urine.

IMMUNOLOGICAL SYSTEM

• In order not to reject the semiallogeneic fetal graft during pregnancy, some adaptations occur in the humoral and cellular immune system and immune silence is ensured.

• Th2-mediated immune system becomes dominant to Th1-mediated immune system. Suppression of Th1-dependent immunity plays an important role in maintaining pregnancy. This is the main reason why Th1 activity-dependent autoimmune diseases (rheumatoid arthritis, multiple sclerosis, Hashimoto's thyroiditis) go into remission during pregnancy.

• While T lymphocyte counts increase during pregnancy, B lymphocyte count and CD4/CD8 T lymphocyte ratio do not change.

• C-reactive protein level, which is an inflammation marker, increased in pregnant women and continues to increase in labor. Another marker, the erythrocyte sedimentation rate, is also increased during pregnancy (due to increased plasma globulin and fibrinogen). In the second and third trimesters of pregnancy, complement factors C3 and C4 are very high. Procalcitonin levels also increase at the end of the third trimester and in the first few days postpartum.

MUSCLE AND SKELETON SYSTEM

• Normal pregnancy is characterized by progressive lordosis and the center of gravity shifts forward.

• Sacroiliac, sacrococcygeal and pubic joint mobility also increases.

CENTRAL NERVOUS SYSTEM and EYE

• During pregnancy, a decrease is observed in middle and posterior cerebral artery blood flow, especially in the late stages of pregnancy, and mild concentration, attention and memory problems are observed in most pregnancies.

• Intraocular pressure decreases due to the increase in the flow of vitreous fluid. While corneal thickness increases slightly, corneal sensitivity decreases. Brown/red opacities (Krukenberg spindles) may be observed on the posterior surface of the cornea; however, visual functions are not affected during pregnancy.

• Pregnancy causes an increase in sleep disorders and changes in sleep patterns. In the third trimester, Stage 1 non-REM sleep increases, while total sleep time, Stage 3 and 4 non-REM sleep and REM sleep decrease.

FETAL PHYSIOLOGY

noreply@blogger.com (Unknown) — Sat, 4 Mar 2023 19:30:00 +0300

PLACENTAL TRANSPORT AND FETAL NUTRITION

• The intervillous space is the compartment where maternal-fetal transfer takes place. Placental villi form a large (approximately 10 m2) exchange surface at term and placental transfer is of great importance in the nutrition of the fetus.

Passive Diffusion

• Most of the molecules with a molecular weight below 500 daltons pass in this way. Insulin, steroid hormones and thyroid hormones pass through, albeit at a very slow rate.

• Oxygen, carbon dioxide, water, most electrolytes and anesthetic gases pass through the placenta by passive diffusion.

Facilitated Diffusion

• Glucose (GLUT-1 and GLUT-3), lactate (as lactic acid) cross the placenta by facilitated diffusion.

Active Transport

• Essential amino acids, iodine, calcium, phosphorus, ascorbic acid (Vit C), iron and folic acid pass through the placenta by active transport.

Specific Receptor Mediated Endocytosis

• LDL (250,000 DA) and IgG (160,000 DA) cross the placenta by endocytosis.

IgA, IgM, heparin, erythropoietin, TSH, ACTH, triacylglycerol and coagulation factors do not cross the placenta.

FETAL CIRCULATION SYSTEM

• Fetal circulatory system shows some differences from adults. Chief among these is that fetal blood does not need the pulmonary artery system to be oxygenated, and therefore blood from the right ventricle bypasses the lungs. Again, fetal heart chambers work in parallel, not in series, and myocardium and brain receive the most oxygen-rich blood.

• In the 3rd week of pregnancy, blood vessels begin to appear in the chorionic villi. In the 4th week, the cardiovascular system is formed and the real circulation begins.

• Nutrients and oxygen from the placenta are transported to the fetus through a single umbilical vein. The most oxygen-rich blood is located in the ductus venosus, with an oxygen saturation of approximately 85% . The umbilical vein divides into two in the liver: the ductus venosus and the portal sinus. The ductus venosus bypasses the liver and pours directly into the inferior vena cava . Since it does not give blood to other organs, this blood with high oxygen content goes directly to the heart . On the other hand, as the portal sinus gives blood to the liver via hepatic veins, the amount of oxygen in its content decreases. This blood, which is deoxygenated in the liver, is then poured into the inferior vena cava.

Thus, the blood coming to the heart via the inferior vena cava becomes a mixture of well-oxygenated blood carried by the ductus venosus and deoxygenated blood coming from below the level of the liver and diaphragm (oxygen saturation about 70%).

• The well-oxygenated part of the blood in the inferior vena cava pouring into the right atrium goes to the left atrium (oxygen saturation approximately 70%), left ventricle (oxygen saturation approximately 65%) and from there to the brain via the foramen ovale; The deoxygenated part of the blood is poured into the right ventricle and goes to other parts of the body. This different distribution of blood according to oxygen content is provided by the flow of the blood in the inferior vena cava and the structure of the right atrium. Well-oxygenated blood flows in the middle part of the inferior vena cava, while deoxygenated blood flows in the outer part near the vessel wall. Thus, when it is poured into the right atrium, the chambers called crista dividens in the atrium direct the oxygenated blood flowing faster and in the middle part to the foramen ovale; It directs the deoxygenated blood flowing in the outer part close to the vessel wall to the tricuspid valve.

• Less oxygenated blood from the brain, which is poured into the right atrium via the vena cava superior (oxygen saturation about 29%), is also poured into the right ventricle (approximately 55% saturation).

Because of all these flow systems, the oxygen content of the blood in the right ventricle is 15-20% less than in the left ventricle.. 90% of the blood exiting the right ventricle is poured directly into the abdominal aorta (about 60% oxygen saturation) by bypassing the lungs via the ductus arteriosus (oxygen saturation approximately 52%). 10% of the blood goes to the lungs. This deoxygenated blood carried by the abdominal aorta is transported to the placenta via the a.iliaca interna (hypogastric arteries) that separates from the common iliac arteries and the umbilical arteries (oxygen saturation approximately 58-60%).

Some fetal structures and their adult counterparts

• Umbilical artery - Medial umbilical folds

· Umbilical vein - Lig. teres hepatis

· Ductus arteriosus - Lig. arteriosus

• Ductus venosus - Lig. venosum

• Urachus (Allantois) - Median umbilical ligament

FETAL HEMOPOETIC SYSTEM

• Hemopoiesis begins in the embryo at the earliest and first in the yolk sac . Gower 1, Gower 2 and Portland hemoglobins are made here until the gestational week 8-10 . From the 8-10 week onwards, the hematopoiesis passes to the liver. Hemoglobin F (Hbf) is produced in the liver during this period. After the 16th week of pregnancy, the main site of hematopoiesis becomes the bone marrow, and hemoglobin A (HbA) begins to be made from there.

• Since fetal HbF has a high affinity for oxygen, it 'binds more oxygen under the same conditions' than adult HbA. As pregnancy progresses, HbF begins to decrease in the fetus, and at term, 75% of the fetal blood is HbF. After birth, HbF gradually decreases and is replaced by HbA.

• Fetus starts to make procoagulant, fibrinolytic and anticoagulant proteins at the 12th week of intrauterine. These proteins, which are found in high amounts in the mother, cannot cross the placenta.

• While the level of prealbumin, one of the plasma proteins, decreases as pregnancy progresses, other proteins increase.

FETAL IMMUNE SYSTEM

• The transmission of IgG from mother to fetus begins approximately at the 16th week of pregnancy, and the highest transmission occurs in the last 4 weeks of pregnancy. Therefore, IgG levels are even lower in preterm infants. In a normal fetus, very small amounts of IgM are made and IgM cannot cross the placenta. Therefore, high amounts of IgM in the fetus reflect the fetus's own immune response and mostly due to intrauterine fetal infections due to rubella, CMV or toxoplasma.

While IgG production in the fetus starts after the 20th gestational week; IgA, D and E cannot be made in the fetus.

• B lymphocytes are seen in the liver at the 9th week, and in the blood and spleen at the 12th week. T lymphocytes are released from the thymus at 14 weeks.

FETAL NERVOUS SYSTEM

• While the brain and spinal cord are formed from the wall of the neural tube, the ventricular system is developing from its lumen. At the end of the 6th week, the neural tube is closed (cranial end closes on 38th day, caudal end on 40th day according to SAT). By week 6, three primary vesicles (prosencephalon, mesencephalon, and rhombencephalon) appear at the cranial end of the neural tube. In the 7th week, five secondary vesicles develop. The structures that will develop from these vesicles in the future are as follows;

► Telencephalon; cerebral hemisphere

► Diencephalon; Thalamus

► Mesencephalon; midbrain

► Metencephalon; Pons and cerebellum

► Myelencephalon; Medulla oblongata

• Neuronal proliferation peaks at 3-4 months. Neuronal migration also occurs simultaneously and makes picks in the month 3-5.

• The development of the CNS continues throughout pregnancy and until the second postpartum year. The spinal cord reaches S1 level at 24 weeks intrauterine, L3 level at birth and L1 level in adult. Myelination of the spinal cord begins in the 6th month of pregnancy and continues until the end of the 1st year.

FETAL GASTROINTESTINAL SYSTEM

• After the embryological formation of the yolk sac, various extensions (foregut, midgut and hindgut) emerge to form the digestive system.

► Builds evolving from Foregut; Pharynx, lower respiratory tract, esophagus, stomach, proximal duodenum, liver, pancreas and biliary tract

► Structures evolving from Midgut; Distal duodenum, jejunum, ileum, cecum, appendix and right colon

► Structures evolving from Hindgut; Superior part of left colon, rectum and anal canal

• Fetal swallowing starts in the week 10-12 . In the same period, peristalsis appears in the small intestines and glucose absorption can be done. There is no ability to suck before 24 weeks. Meconium passage may occur in the mature fetus with normal intestinal peristalsis or with vagal stimulation due to cord compression. In addition, meconium passage occurs with the stimulation of arginine vasopressin (AVP) release from the pituitary gland of the fetus remaining in the hypoxic environment.

• Fetal liver enzymes are at a very low level compared to adults. For this reason, fetal liver cannot conjugate the already increased bilirubin load due to short-lived erythrocytes, and from the 12th week, unconjugated bilirubin is released into the amnion, from which it passes to the mother via the placenta.

FETAL URINARY SYSTEM

• In the embryo, pronephros is at 2 weeks, mesonephros is at 5 weeks, and metanephros is at 9-12 weeks. starts a week. While the kidneys and ureters develop from the intermediate mesoderm; The bladder and urethra also develop from the urogenital sinus.

• At the 14th week of pregnancy, loops of Henle form and reabsorption begins. Fetal kidneys begin to produce urine at 12 weeks. Fetal urine is hypotonic. Renal functions increase as pregnancy progresses.

FETAL RESPIRATORY SYSTEM

• Fetal respiratory movements can be detected in the 11th week.

• The anatomical development of the lungs occurs in 4 stages.

► Pseudoglandular stage (between 5-17 weeks); An intrasegmental bronchiole tree develops.

► Canalicular stage (between 16-25 weeks); Each terminal bronchiole divides into several respiratory bronchioles, and respiratory bronchioles into numerous saccular ducts.

► Terminal sac period (starts after 25 weeks); Respiratory bronchioles transform into primitive pulmonary alveoli (terminal sac).

► Alveolar stage; Although the complete transition is not certain, it usually starts at 32 weeks.

• Surfactant prevents the collapse of alveoli after birth and type II pneumocytes begin to synthesize surfactant at 24 weeks. 90% of the surfactant is composed of lipids and the remaining 10% is composed of proteins. The major apoprotein in the structure of surfactant is Surfactant Protein A (SP-A).

• Phospholipids provide the basis for the surface tension reducing effect of the surfactant. 80% of glycerophospholipids are phosphatidylcholine (lecithins). The main component responsible for the functionality of the surfactant is a specific lecithin called dipalmitolphosphatidylcholine (DPPC) and it constitutes 50% of all lecithins. Phosphatidylglycerol (PG), the second important component, is present at a rate of 8-15%. Another component is phosphatidylinositol (PI).

FETAL ENDOCRINE SYSTEM

• While the adenohypophysis develops from the oral ectoderm (Rathke's sac) in the embryo, the neurohypophysis develops from the neuroectoderm. The middle pituitary begins to disappear before term (a MSH, beta-endorphin).

• At the 7th week of pregnancy, the fetal pituitary gland begins to make ACTH, at the 13th week, growth hormone and LH begin to be made, and at the end of the 17th week, the production of all pituitary hormones begins. Fetal neurohypophysis 10-12. It begins to secrete oxytocin and arginine vasopressin (AVP).

• Thyroid gland begins to secrete within a week 10-12. TSH, thyroxine and TBG can be detected in fetal serum at 11 weeks. Free T4, free T3 and TBG increase continuously throughout fetal life, and at 36 weeks, when compared to adults, serum TSH concentrations are high, whereas total and free T3 levels are low and T4 levels are normal. This shows that the fetal thyroid gland is not sensitive to feedback mechanisms until term. The fetus retains more iodine than the mother.

• The placenta deiodinates maternal thyroid hormones, preventing their effective transmission to the fetus (converts T4 and T3 to reverse T3, which is ineffective); however, since this is within a limited capacity, the placenta cannot deiodinate all thyroid hormones in the overproduction of maternal thyroid hormones. Thyroid-stimulating immunoglobulins and long-acting thyroid stimulator (LATS) pass directly to the fetus.

• Fetal adrenals are hypertrophic. The reason for this is that the fetal zone, which disappears after birth, is overactive in intrauterine life. This zone secretes large amounts of adrenal steroids and synthesizes aldosterone.

• In the fetal pancreas, glucagon can be detected at week 8 and insulin at week 12. However, the fetus is unresponsive to hypoglycemia. By week 16, most of the pancreatic enzymes are present. Insulin is a growth hormone in all tissues of the fetus.

Ectopic Pregnancies

noreply@blogger.com (Unknown) — Wed, 1 Mar 2023 17:36:00 +0300

• Implantation of the fertilized ovum outside the endometrial cavity is called ectopic pregnancy. The incidence of ectopic pregnancy is about 1-2%. It constitutes 6% of all maternal deaths.

• The most common cause of maternal deaths in the first trimester is ectopic pregnancy.

Ectopic pregnancy localizations

Tubal pregnancies ----- It is the most common ectopic pregnancy localization

Ampulla (70%) ------The most common site of tubal ectopic pregnancy

Istmus (12%) ------The earliest ruptured tubal ectopic pregnancy

Fimbria ---------------(11%)

Interstitial (cornual) (2-3%) ------- It is the latest ruptured tubal ectopic pregnancy.

Ovarian pregnancies

· Abdominal pregnancies------The most mortal ectopic pregnancy

· Intraligamentary pregnancy ------ All occur secondary

Heterotopic pregnancies ------- It is the ectopic pregnancy with the highest incidence with assisted reproductive techniques.

Cervical pregnancies

Ectopic pregnancy in cesarean scar

· Posthysterectomy; rarest ectopic pregnancy

TUBAL ECTOPIC PREGNANCY

• It is the most common type of ectopic pregnancy. Tubal ectopic pregnancies are seen as ampullary, isthmic, fimbrial and interstitial (cornual) in order of frequency.

etiology

• Disruption of tubal anatomy is the main cause of ectopic pregnancies. There has been an increase in the number of ectopic pregnancies in recent years, the most important reason for this is the increase in the rate of salpingitis, ovulation inductions, IVF applications, increased use of contraceptives, tubal surgery and sterilizations, and earlier and more accurate diagnosis of ectopic pregnancies.

• Most ectopic pregnancies occur in multigravid women.

The risk of ectopic pregnancy increases in salpingitis isthmica nodosa, which is an acquired diverticulum of the tubule.

It increases the risk of ectopic pregnancy in peritubal adhesions that occur after appendicitis or endometriosis.

Congenital tubal anomalies, especially intrauterine DES exposure, also increase the risk of ectopic pregnancy.

All contraceptive methods reduce the incidence of ectopic pregnancy. However, the use of tubal sterilization, intrauterine devices with copper and LNG release, and pills containing pure progesterone increase the risk of ectopic pregnancy when pregnant. Barrier methods and combined oral contraceptives do not have an increased risk and are the contraceptive methods with the lowest risk of ectopic pregnancy. No increased risk has also been demonstrated with depot MPA, emergency contraceptive pills, or implants containing etonorgestrel.

There is no increase in the incidence of chromosomal anomalies in ectopic pregnancies.

Clinic

• Classical triad; pain, vaginal bleeding and delayed menstruation. However, these three may not always be seen together.

• Tubal ectopic pregnancies; They may result in tubal rupture, tubal abortion, or resolution of the product of conception..

• While ectopic pregnancies located in the isthmic region rupture in the early period, ectopic pregnancies located in the ampullary region tend to rupture later. Interstitial ectopic pregnancies rupture at the latest.

The earliest rupture occurs in the isthmic region (6-8 weeks), followed by the ampullary region (8-12 weeks), and the latest in the interstitial region (12-16 weeks).

Diagnostic Methods

Quantitative B-hCG measurement

► In a normal intrauterine pregnancy, while beta-hCG doubles in 48 hours in the first 6th week of pregnancy, this doubling rate slows down and does not become constant after the 6th week. This early doubling time may distinguish ectopic pregnancies from intrauterine pregnancies. If this folding is less than 35% in 48 hours in the early period, it indicates that the pregnancy is not normal (abortion, ex fetus, ectopic pregnancy).

Serum progesterone level

► Its level is lower than normal pregnancies. While progesterone level higher than 25 ng/ml excludes 92.5% ectopic pregnancy; Values below 5 ng/ml are found in only 0.3% of normal pregnancies.

Ultrasonography

► There is double decidual ring appearance in 64-95% of normal intrauterine pregnancies on ultrasonography. In ectopic pregnancies, there is usually a single-layered decidual ring appearance. Rarely, a double decidual ring may appear in ectopic pregnancies.

► The presence of vitelline sac (yolk sac) in the gestational sac is superior to the double decidual ring in excluding ectopic pregnancy.

► However, the most valuable finding in excluding an ectopic pregnancy is fetal cardiac activity in the gestational sac on ultrasonography. In addition, intrauterine centrally located false gestational sac, fluid in Douglas, mass in the adnexal region and adnexal rings (eg tubal ring) are also important ultrasonographic findings in terms of suggesting ectopic pregnancy.

► In the differential diagnosis of a mass in the adnexal area, corpus luteum, endometrioma, hydrosalpinx, ovarian masses (dermoid cyst) or pedunculated myoma should be considered.

► The presence of fetal pole and cardiac activity with adnexal located gestational sac is the most specific finding, but it is the least sensitive finding (10-17%).

► In order to obtain pregnancy findings in ultrasonography, the beta-hCG level must rise above a certain determinant level. They can be seen by transvaginal ultrasonography when the beta-hCG level reaches 1,500-2,000 mIU/mL. If an intrauterine pregnancy cannot be seen at these levels, a lost intrauterine pregnancy or ectopic pregnancy should be considered and serial beta-hCG monitoring should be performed. Descriptive in ectopic pregnancies (3-hCG level is 3510 mIU/mL. If an intrauterine pregnancy cannot be seen above this level, ectopic pregnancy should be accepted and treated.

If the beta-hCG level is below the determining levels and the intrauterine cavity is empty, the following differential diagnoses should be considered:

1. Normal intrauterine pregnancy (but too early to be seen)

2. Abnormal intrauterine pregnancy

3. A complete abortion that has just occurred: beta-hCG drops rapidly and within 48 hours

50% decrease

4. Ectopic pregnancy: beta-hCG level increases or plateaus

5. A woman who is not pregnant

laparoscopy

► In many cases, direct imaging with laparoscopy is a reliable diagnostic method and also provides treatment in the case.

Treatment

Medical Treatment (Methotrexate)

► Methotrexate is a folic acid antagonist that inhibits dihydrofolate reductase and inhibits DNA synthesis. A single dose is used. The success of the treatment is around 90% and a second dose may be needed in 15-20% of cases.

► Factors that increase the success of the treatment; (Low level of 3-hCG, small gestational sac, and absence of fetal cardiac activity. However, the most important factor in failure of treatment (high level of 3-hCG. If beta-hCG > 5000 mIU/mL, failure rate)

It is 15%.

► The most common side effects belong to the gastrointestinal tract; nausea, vomiting, stomatitis and abdominal pain. Other side effects; bone marrow suppression, hemorrhagic enteritis, alopecia, dermatitis, elevated liver enzymes, conjunctivitis, anaphylactic reaction and pneumonitis. However, these side effects are rarely seen in low doses and single applications used in ectopic pregnancies. If the treatment is prolonged, Leucovorin can be used to prevent side effects.

contraindications for methotrexate

1. Ruptured ectopic pregnancy (hemodynamically unstable patients)

2. Breastfeeding

3. Immunodeficient

4. Liver diseases (enzyme elevation)

5. Renal diseases (high serum creatinine)

6. Hematological diseases

7. Methotrexate sensitivity

8. Active pulmonary disease

9. Active peptic ulcer

10. Pregnancy

11. Alcoholism

12. Moderate to severe anemia, leukopenia and thrombocytopenia

Surgical treatment

► Laparoscopy is the first preferred method in the surgical treatment of ectopic pregnancies.

0 Salpingostomy

- If there is a desire to reproduce in the future in a hemodynamically stable and non-ruptured case, it should be preferred (it is the least invasive procedure).

- Factors that increase the risk of persistent trophoblastic tissue (5-20%) after linear salpingostomy:

• Very small pregnancies (duration of amenorrhea < 42 days)

• Serum beta-hCG level higher than 3000 mIU/mL

• Small gestational sac ( < 2 cm)

0 Salpingectomy

- Tubal resection can be used in the treatment of ruptured or non-ruptured ectopic pregnancies.

- To prevent recurrence of ectopic pregnancy, the entire tube should be removed.

If the patient is Rh (-) in all ectopic pregnancies, absolute Rh (D) immunoglobulin should be administered.

ovarian pregnancies

• It is the most common of non-tubal ectopic pregnancies . However, another reference book states that abdominal pregnancy is the most common non-tubal ectopic pregnancy.

• Risk factors are like tubal ectopics. However, in vitro fertilization and IUD use, increases the risk. The cases are often confused with ruptured corpus luteum cyst.

• Ovarian cystectomy and/or ovarian wedge resection is the most commonly preferred surgical method in these cases. Systemic or local (into the sac) methotrexate treatment can also be used.

CERVICAL PREGNANCY

• Although it is a very rare type of ectopic pregnancy, it is important because of the high risk of bleeding. The incidence rises with IVF procedures. Other risk factors are previous cesarean deliveries and previous curettage.

• Clinical findings:

► Painless bleeding (90%) (1/3 massive bleeding)

► The external os may be open; but the internal os is turned off.

► The cervix is enlarged and thinned.

• Treatment:

► First of all, medical treatment is tried. Methotrexate can be administered systemically or locally (into the sac).

In ultrasonography, when pressure is applied to the cervix with the transvaginal probe, the gestational sac does not move in cervical pregnancies (sliding sign is negative}, while the sliding sign is positive in incomplete abortion.

ABDOMINAL PREGNANCY

• They can be primary or secondary (following tubal abortion). Ectopic pregnancies have the highest maternal morbidity and mortality. Pregnancy can reach term. However, fetal mortality is also around 95%. The incidence of congenital anomalies is 20%, and the absence of extremities and CNS anomalies are the most common. The most common deformations are facial and/or cranial asymmetry and joint abnormalities.

• Abdominal pregnancy risk factors; pelvic inflammatory disease, multiparity, endometriosis, assisted reproductive techniques and tubal damage.

• Abdominal pregnancies should be terminated as soon as they are detected. If the fetus dies in the abdomen, calcifies and mummifies after a while, lithopedian; If it turns into a yellowish, oily mass, it is called an adiposen.

• If delivery has taken place in abdominal pregnancies, if the nutrition of the placenta can be determined, it is tied and removed. However, if vascular support cannot be determined, the umbilical cord is tied from the area close to the placenta and left in place to prevent bleeding. In cases where the placenta is left, it is followed by serial beta-hCG and ultrasonography. In these cases, methotrexate treatment is still controversial, as it causes sepsis with precipitated tissue necrosis.

INTERSTITIAL PREGNANCY

• Pregnancies located in the proximal segment of the tubule within the uterine muscular tissue. The risk factors are the same as for tubal pregnancies; however, ipsilateral salpingectomy due to ectopic pregnancy is a specific risk factor.

It constitutes a large percentage of deaths due to ectopic pregnancy (2.5%) due to its difficult diagnosis and high vascular support. Depending on the general condition of the patient, methotrexate can be given or laparoscopic cornuostomy or cornual excision can be performed.

INTRALIGAMENTARY PREGNANCY

• It is rare and is the secondary form of ectopic pregnancies, all of which occur as a result of secondary implantation. They abort from the tuba between the leaves of the ligamentum latum. They have clinical findings as in abdominal pregnancy and are treated like it.

heterotopic pregnancy

• It is the coexistence of extrauterine and intrauterine pregnancies.

• It is the ectopic pregnancy form with the highest incidence as a result of the use of assisted reproductive techniques (increases from 1:30000 pregnancies to 1:100-200 pregnancies).

• Since the hCG increase continues due to intrauterine pregnancy, serial beta-hCG is used in the diagnosis.

measurement is not helpful.

• If the continuation of intrauterine pregnancy is desired, systemic treatments should be avoided and ectopic pregnancy should be treated surgically or with KCI injection into the ectopic gestational sac.

cesarean section scar pregnancy

• It is the implantation of the embryo in the cesarean scar in the uterus. It occurs in 1/2000 of all pregnancies.

• Defined ultrasonographic criteria for cesarean scar pregnancy;

► Empty intrauterine cavity

► Empty cervical canal

► Presence of gestational sac located in the anterior part of the uterine isthmus

► Absence of normal myometrium between bladder and gestational sac

► Negative sliding sign

• Treatment; Curettage, methotrexate (local or systemic) or hysteroscopic intervention can be performed under the guidance of ultrasonography.

abortions

noreply@blogger.com (Unknown) — Tue, 28 Feb 2023 17:16:00 +0300

• Pregnancy loss before the twentieth gestational week is defined as abortion. Abortions can be spontaneous or induced.

Spontaneous Abortions

• Spontaneous pregnancy loss occurs before the 20th week of pregnancy and the most common complication of pregnancies is spontaneous pregnancy loss. Up to 30% of pregnancies are lost after implantation. About 2/3 of them are clinically silent (preclinical abortion, biochemical pregnancy).

• More than 80% of spontaneous abortions occur in the first 12 weeks. The risk of spontaneous abortions doubles as the age of the mother and father progresses.

etiology

Fetal Causes

About half of pregnancy losses are anembryonic. Therefore, there are no embryonic elements. The remaining miscarriages (50%) are embryonic losses, and usually anomalies of the zygote, embryo, fetus or placenta are observed. Half of the embryonic losses (25% of all miscarriages) have chromosomal abnormalities (aneuploid abortions). The rest of the cases are euploid abortions (normal chromosome structure).

Aneuploid Abortions: Both the abortion rate and the chromosomal abnormality rate decrease as the gestational age progresses. Most common first trimester abortion

The most common cause of first trimester abortions is fetal aneuploidy. 55% of 1st trimester losses, 35% of 2nd trimester losses and 5% of 3rd trimester losses are chromosomally abnormal. Aneuploid miscarriages tend to happen in the early weeks of pregnancy. 75% of aneuploid abortions occur in the first 8 weeks of pregnancy and while 95% of them have errors in maternal gametogenesis; Errors in paternal gametogenesis are observed in only 5% of them.

Euploid Miscarriages: They mostly occur after the 13th week of pregnancy and their incidence increases rapidly when the maternal age passes 35.

Chromosomal distribution in embryonic abortion materials

Medicine -------------------------------------------------------------- Incidence (%)

Euploid (46,XY or 46,XX) -----------------------------------------45-55

Aneuploidy:

- Autosomal trisomy -------------------------------------------------22-32

Trisomy 16 (most common trisomy) ----------------------------- 7-8

trisomy 22

trisomy 21

trisomy 18

trisomy 13

- Monosomy X (45,X) (most common alone) ---------5-20

- Triploidy-------------------------- 6-8

- Tetraploidy ----------------2-4

- Structural anomalies --------------2

Double or triple trisomy-----------------0.7-2

The only autosomal trisomy not identified in abortions is Trisomy 1.

Maternal Causes

Personal factors

0 History of spontaneous abortion

0 Advanced maternal age

0 increased gravida

0 Use of cigarettes, alcohol, and amphetamines

0 Uterine anomalies

0 Excessive maternal weight

0 Serious maternal trauma

0 Placental anomalies

Infections

0 Brucella abortus, Campylobacter fetus and Toxoplasma gondii

Its effects on pregnancy are not fully known.

0 It is thought that Listeria monocytogenes, Parvovirus, CMV and HSV do not have abortion-producing effects.

0 Detection of Chlamydia trachomatis in 4% of abortions (normally it should be below 1%) suggests that it has a low-preventing effect.

0 Periodontal polymicrobial infections have also been shown to increase the risk of miscarriage 2-4 times.

0 Bacterial vaginosis has been shown to cause miscarriages, especially in the second trimester.

0 Mycoplasma genitalium infections are associated with spontaneous abortions.

Medical diseases

0 diabetes mellitus

0 Thyroid diseases

0 Celiac disease

0 Cyanotic heart diseases

0 Inflammatory bowel diseases

0 SLE

Abortion Types

abortion imminens

► Low threat. Bleeding before the 20th week of pregnancy, but the cervix is closed. There is fetal cardiac activity.

► Bleeding is the most important predictive factor of pregnancy loss. 50% of cases usually end in miscarriage. However, if there is fetal cardiac activity, the risk is significantly reduced.

► Although there is no pregnancy loss in most cases of abortion imminens, poor obstetric outcomes may occur in the later stages of pregnancy. Increased complications in pregnant women with bleeding in the 1st trimester; The risk of preterm birth, IUGR, preterm premature rupture of membranes, abruptio placentae, placenta previa, fetal neonatal deaths, increased cesarean rates, low birth weight and manual removal of the placenta increases.

► There is no definitive treatment. Bed rest may be recommended.

Ectopic pregnancy should be investigated in the differential diagnosis of the threat of miscarriage.

incipient abortion

► Inevitable (unstoppable) low. Before the 20th week, these pregnant women have cramp-like pain in the groin, abundant vaginal bleeding, and an opening-wiping of the cervix.

► In these cases, miscarriage cannot be prevented and curettage is performed.

Missed abortion

► These are the cases where there is a pregnancy without intrauterine fetal cardiac activity before the 20th gestational week and the dead tissue is not excreted. The cervix is closed, with little or no cramping or bleeding.

► In this case, tissue thromboplastins may mix into the circulation and cause disseminated intravascular coagulation (DIC). Its treatment is rapid evacuation of pregnancy. The DIC panel must be checked before evacuation.

Incomplete abortion

► It is the situation where some of the embryo-fetus and its appendages are thrown out of the uterus cavity and some of them remain in the cavity.

► On ultrasonographic examination, the endometrium appears irregular and thick. On vaginal examination, the cervix is dilated and feto-placental fragments from the cervix can be seen protruding into the vagina (Ş-19).

► The only approach is rest curettage.

Complete abortion

► Embryo-fetus and its appendages are completely thrown out of the uterine cavity. No intervention is required.

anembryonic pregnancy

► · Although it is over the seventh and eighth weeks of pregnancy, the embryo has not developed and the structures of the embryo cannot be seen in the ultrasonography. Diagnosis is made if the gestational sac diameter is > 25 mm and the embryo cannot be observed in transvaginal ultrasonography. It is especially common in monosomy-X..

► Curettage is done.

Septic abortion

► Endomyometritis is the most common clinical picture. Clinically, there is fever, foul-smelling discharge, severe tenderness in the abdomen and cervical examination, and DIC may develop in neglected cases.

► In case of septic abortion, the cavity is cleaned by curettage and broad-spectrum antibiotics are given. If there are signs of sepsis and the desire to reproduce is completed, hysterectomy can be applied. Even if there is a desire to reproduce, hysterectomy may be required if clinical improvement cannot be achieved by curettage.

Anti-D immunoglobulin should be administered in Rh (-) cases following abortions.

REPEAT PREGNANCY LOSSES (RPL)

• RSO; Two or more clinically defined pregnancy losses occurring before the 20th week of pregnancy. Its incidence is 1/100 pairs.

etiology

• In more than half of the cases (50-60%), the cause cannot be found (idiopathic). Apart from this, genetic, anatomical, immunological, endocrinological, thrombophilic and infectious causes are held responsible.

Situations where the cause can be determined

1. Embryonic genetic anomalies ------------------------------------------------ 60-80%

2. Endocrine Causes -------------------------------------------------------------- 17-20%

3. Anatomical Causes ------------------------------------------------------------- 12-16%

4. Antiphospholipid antibody syndrome---------------------------------------- 12-15%

5. Infectious Causes ---------------------------------------------------------------- % 7 -56

6. Parental Genetic Causes--------------------------------------------------------- 2-5%

7. Immunological (other than AFAS) and thrombotic (thrombophilia) causes-► Undetected

• Gives clues about the cause in the week of pregnancy loss. Losses due to genetics are usually in the early stages of pregnancy (5-8th weeks); Losses due to autoimmune and uterine anomalies usually occur later in pregnancy (12-20 weeks).

Immunological Causes and Thrombophilia r

antiphospholipid antibody syndrome AFAS

It is a disease characterized by the development of antibodies against phospholipids. The incidence in women with recurrent pregnancy loss is 3-5%.

0 The main risk factor for poor pregnancy outcomes is the positivity of anticardiolipin antibodies, lupus anticoagulant and anti 132-glycoprotein-1 antibodies. Pregnancy loss is seen in 20% of patients with SLE. Antiphospholipid antibodies are the cause of almost all lost pregnancies in these patients.

0 The main pathology of AFAS leading to pregnancy loss is placental thrombosis. The fetus is lost due to the disruption of uteroplacental circulation that develops as a result of intervillous thrombi, intravillous infarcts and decidual vasculopathy, and fetal hypoxia resulting from this.

0 In the early weeks of pregnancy, anti-FL antibodies directly target FL in trophoblastic cells, inhibiting trophoblastic cell division or trophoblastic invasion and trophoblastic fusion as well, leading to early pregnancy loss. In the later weeks of pregnancy, anti-FL antibodies target the trophoblastic cells of the placenta and activate complement there. Depending on the extent of the damage in the placenta, either intrauterine fetal death occurs or IUGR occurs.

Conditions caused by anti-FL antibodies in pregnancy

1. Spontaneous abortion

2. Recurrent pregnancy losses (early and late)

3.Preterm birth (<34 weeks)

4. Gestational hypertension

5. Preeclampsia

6. Intrauterine growth retardation

7. stillbirth

AFAS Diagnostic Criteria

clinical diagnostic criteria

1. Presence of one or more vascular thrombosis of any type (arterial, venous, small vessels)

2. Pregnancy complications

- 3 or more spontaneous abortions occurring before the 10th gestational week (maternal anatomical, hormonal and parental chromosomal anomalies should be excluded)

- One or more unexplained fetal deaths in the presence of a morphologically normal fetus after 10 weeks of gestation

- Preterm birth caused by severe preeclampsia and placental insufficiency before 34 weeks

Laboratory diagnostic criteria: Two or more measurements at 12-week intervals should be positive.

1. High level of IgG and/or IgM type anti-cardiolipin antibodies

2. Positive lupus anticoagulant (prolongation in phospholipid dependent coagulation tests - aPTT etc.)

3. Anti-bita 2-glycoprotein-1 antibodies (IgG and/or M) titer > 99th percentile

Treatment: Preconceptional low-dose salicylic acid (aspirin) is started in all cases that cause thrombosis in placental vessels. After conception, in addition to daily aspirin intake, heparin or low molecular weight heparin is continued until delivery. With this treatment, 70-80% of live births are obtained.

Thrombophilias

As in AFAS, which can also be considered as an acquired thrombophilia, loss of pregnancy occurs with the same mechanism, namely placental thrombosis and infarction, in genetic thrombophilias.

0 As a result of some genetic mutations, predisposition to thrombosis increases. The most common among these are factor V Leiden mutation and prothrombin gene mutation. Mutation of methylene tetrahydrofolate reductase (MTHFR) enzyme is seen in the third frequency. A homozygous mutation of this enzyme results in hyperhomocystinemia, which is a factor that increases the risk of thrombosis. Other genetic thrombophilias include antithrombin, protein-C, protein-S and factor XIII deficiencies.

Thrombophilias; They can cause spontaneous or recurrent pregnancy loss, preeclampsia, ablatio placenta, IUGR and intrauterine dead fetus. Almost all of the pregnancy losses are in the II. and III. trimester occur.

0 There is no evidence-based method for the treatment of recurrent abortion in thrombophilias.

Anatomical Causes

► Abortions due to anatomical reasons are mostly in II. They occur at the beginning of the third trimester and the cause of abortion is usually insufficient intrauterine cavity and blood supply.

Congenital malformations

0 The most common uterine anomaly in women with the highest abortion rate and recurrent pregnancy loss is the uterine septum.

0 Along with the uterine septum, the anomaly that worst affects the course of pregnancy is the unicorn uterus.

Acquired lesions

0 Myoma uteri: Among uterine fibroids, especially submucous ones cause abortion, there is no such risk in intramural and subserous fibroids with dimensions less than 5-7 cm. Locations of fibroids are more important than their size. It is unnecessary to intervene in fibroids that do not disrupt the cavity.

0 Asherman syndrome (intrauterine adhesions): It causes 40-80% abortion and 25% preterm birth. As a result of hysteroscopic adhesiolysis, 50-90% term pregnancy can be achieved.

Cervical insufficiency: It can be congenital (with bicornuate uterus) or acquired (delivery, curettage, conization, exposure to DES). II. The immature fetus is exaggerated as a result of painless cervical dilation in the third trimester. Treatment in the weeks 12-16 . Cervical cerclage (Shirodkar or Mc Donald suture) is applied and tocolytic treatment (indomethacin) is given to the case for 48 hours following the intervention. Cerclage is contraindicated in cases of uterine bleeding, premature rupture of membranes, infection, fetus with anomalies, active labor.

0 Adenomyosis

0 Endometrial polyp

Endocrine Causes

hypothyroidism

0 Pregnancy may occur in mild-moderate hypothyroidism; however, RSC is frequently encountered due to ovulatory dysfunction and luteal phase defect. The risk of miscarriage is directly proportional to the TSH level. The limit for TSH is <2.5 mIU/ml.

Diabetes

Recurrent pregnancy loss in cases has increased 2-3 times compared to the normal population and the risk of miscarriage is directly proportional to the HbA1C level..

PCOS

0 There is an increased risk of abortion in PCOS cases. Hyperinsulinemia and insulin resistance are mainly responsible for the increase in this risk.

Luteal phase defect (LFD) and Hyperprolactinemia

0 It is the insufficient secretion of progesterone by the corpus luteum.

0 It accounts for less than 10% of recurrent pregnancy losses. The orpus luteum-placenta exchange occurs between the 7th and 9th weeks of pregnancy. In this case, hyperprolactinemia should be ruled out first.

0 The treatment is progesterone and it is the 7th-9th day of pregnancy. continues until next week.

Genetic Causes

► Recurrent pregnancy losses due to aneuploidy increase especially over 35 years of age and in women over 35 years of age with a history of recurrent pregnancy loss, the majority of the losses are due to spontaneous fetal chromosomal anomalies.

► Most of the preclinical and early clinical pregnancy losses are due to fetal aneuploidies. Pregnancy losses due to genetic reasons are usually in the first 4-6th week.

► Structural anomalies are seen in most of the cases, unlike spontaneous abortions, and the most common parental chromosomal anomaly accompanying recurrent pregnancy loss is balanced reciprocal translocation (50%). This is followed by Robertsonian translocations (25%). X chromosome mosaicism (47,XXY Kleinfelter syndrome) is in the third place (12%).

► Diagnosis of chromosomal anomalies is made by parental karyotyping. Preimplantation genetic diagnosis (PGD) is used in its treatment.

Infectious Causes

► The relationship of infections with recurrent pregnancies is controversial. It is thought that the detection of chronic endometritis in endometrial biopsy (histological demonstration of plasma cells) may be associated with recurrent pregnancy losses.

► In case of suspected infection in recurrent pregnancy loss, empirical antibiotic therapy is a more appropriate approach (azithromycin, erythromycin or doxycycline) instead of culture.

Other Reasons(10%)

► Impairment of uterine receptivity

► Environmental factors:

0 Toxin

0 Cigarettes: 10 pcs/day; Increases it by 2 times

0 Caffeine: 5 cups/day (500 mg/day); Increases it by 2 times

0 Drugs

► Placental anomalies: Circumvallate placenta and placenta with marginal insertion

► Medical diseases (cardiac, renal, hematological)

► Anesthesia gases, radiation, organic solvents, heavy metals

► Exercise: There is no relationship with moderate exercise.

► Male factor: Y chromosome microdeletions, sex chromosome abnormalities, MTHFR mutation and hyperhomocysteinemia may be associated with recurrent pregnancy loss.

There is no relationship between coitus and abortion in patients without cervical insufficiency.

Approach in Recurrent Pregnancy Loss

Tests with proven diagnostic value

► Chromosomal analysis of the product of conception

► Parental peripheral karyotype analysis

► Imaging of the intrauterine cavity (hysterosalpingography, hysteroscopy, sonohysterography, 3D transvaginal ultrasonography)

► Thyroid function tests

► Anticardiolipin antibodies, lupus anticoagulant and anti beta 2-glycoprotein-1 antibodies

► HbAlc

► Prolactin

Tests with UNPROVED diagnostic value

► Thrombophilia tests (Factor V Leiden mutation, prothrombin gene defect, protein S/C activity, homocysteine level, antithrombin defect)

► Ovarian reserve tests (3rd day FSH value, clomiphene citrate loading test, antimullerian hormone)

► Screening for PCOS (LH, androgen levels)

► Testing for THJTH2 cytokine dysregulation

► Preconceptional investigation of peripheral NK cells

► Antithyroid antibody measurements

► Measurement of other autoantibodies (rheumatoid factor, etc.)

► Obtaining cervical cultures for Mycoplasma, Ureaplasma and chlamydia

► Taking endometrial biopsy for the diagnosis of luteal phase defect (Noyes criteria)

Tests with NO diagnostic value

► Antinuclear antibodies

► Antipaternal cytotoxic antibodies

► Parental HLA profile

► Lymphocyte culture

► Measurement of cytokines, oncogenes, growth factors

PROGNOSIS

• Successful pregnancy is achieved in most of those with recurrent pregnancy loss. The prognosis for obtaining a live birth in subsequent pregnancies depends on the underlying cause and the number of previous miscarriages. Observation of fetal cardiac activity may be prognostic; but the underlying cause is very important. The probability of live birth is 77% in those with fetal cardiac activity.

Causes -------------------------- Possibility of Live Birth

Endocrine reasons---------------------------------------------► > 90 %

AFAS----------------------------------------------------------- ► 70-90%

Anatomical causes-------------------------------------------- ► 60% -90

Genetic causes------------------------------------------------- ► 20-80%

The risk of ectopic pregnancy and complete mole increases in those with recurrent pregnancy loss.

induced abortions

• Therapeutic abortion can also be applied in maternal situations where the mother cannot maintain the pregnancy (cardiac decompensated heart diseases, severe hypertensive vascular diseases, serious diabetes, invasive cancer of the cervix, post-rape pregnancies) or in severe anomalies of the fetus.

Surgical Methods

• Menstrual regulation (MR): It is the aspiration of the endometrium through a cannula connected to a vacuum device.

• Dilatation and curettage (D&C)

► Vacuum curettage: It is the safest and most effective method for terminating pregnancies younger than 14 weeks.

surgical curettage (definite curettage): 14-15 if there is no vacuum curette. It is used for termination of pregnancy less than 14-15 week. There is a high risk of blood loss, procedure time, and damage to the cervix or uterus. In addition, the risk of Asherman syndrome is high.

• Dilution and vacuation (D&E) is applied in pregnancies older than 16 weeks. It is the form of sharp curettage applied to large pregnancies. The complication rate is quite high.

• Hysterotomy or Hysterectomy. Both should never be used as a first method.

MEDICAL METHODS

• Medical abortion· The 3 most commonly used agents for this purpose are mifepristone, an antiprogesterone, misoprostol, a prostaglandin E, and methotrexate, an antimetabolite. The abortion effect of all three agents is to increase the contractility of the uterus. Since these agents are teratogenic, pregnancy must be terminated surgically unless medically terminated. It can be used in oxytocin in second trimester abortions.

• Intra-amniotic fluid: It is an old method used in second trimester abortions.

MATERNAL - PLACENTAL - FETAL UNIT

noreply@blogger.com (Unknown) — Wed, 22 Feb 2023 20:27:00 +0300

Definitions used in pregnancy and pregnancy diagnosis

Definitions Used in Pregnancy

• Gestational Age (Menstrual Age): The time from the start of the last menstrual period to the expected due date (approximately 10 months, 40 weeks or 280 days).

• Age at Ovulation (Postconceptional Age): Time from fertilization to expected due date (approximately 9.5 months or 38 weeks or 265 days).

• Embryonic Period: It starts 2 weeks after conception and ends at the end of 8 weeks. During this period, organogenesis is completed.

• Fetal Period: It is the period starting 8 weeks after conception.

• Antenatal Period: It is the period from conception to birth.

• Perinatal Period: It is the period from the end of the 20th week of pregnancy until the completion of the 28th day after delivery.

• Gravida: A woman who is currently pregnant or has had a previous pregnancy (it doesn't matter how their pregnancy ended).

► Nulligravida: A woman who is not currently pregnant and has never been pregnant before.

► Primigravida: A woman who has had her first pregnancy.

► Multigravida: A woman who has had multiple pregnancies.

• Parity: These are still or live births after the 20th gestational week.

► Nullipar: Women who have not given birth above the 20th gestational week (women who have not completed a pregnancy other than abortion or ectopic pregnancy).

► Primiparous: A woman who has given birth at 20 weeks of gestation or above (live or dead, one or more babies).

► Multiparous: Two or more women who have given birth above the 20th week of pregnancy.

The number of pregnancies reaching the 20th week determines the parity, not the number of babies born. Women who have given birth to twins once after 20 weeks of gestation are primiparous women.

• Term Birth: births between weeks 37-42.

• Preterm Birth: It is the birth that takes place before 37th gestational week.

► Early pretem; Those born before the 34th week of pregnancy is completed.

► Late Preterm; Those born before the 34th to 36th week is completed.

• Postterm Birth: It is the birth that takes place after the 42nd gestational week.

• trimester; Pregnancy consists of three parts called trimesters.

► I.Trimester: 0-14. between weeks

► II.Trimester: 15-28. between weeks

► III. Trimester: 29-42. between weeks

• Perinatal Mortality: Neonatal deaths occurring between the 20th week of pregnancy and the first 28th day after birth.

• Maternal Mortality Rate: Includes maternal deaths due to reproductive process per 100,000 live births.

Cardiovascular diseases, obstetric hemorrhages and infections are among the most common causes of maternal mortality.

Diagnosing Pregnancy

Suspicious symptoms and signs suggesting pregnancy

► Nausea and vomiting

► Frequent urination

► Fatigue and weakness

► Menstrual delay

► Changes in the breasts (mastodynia, colostrum secretion)

► Skin changes (chloasma, linea nigra, striae, telangiectasia)

► Purplish discoloration of the vaginal mucosa and cervix (Chadwick sign)

► Detection of fetal movements (18-20 weeks in primigravids, 16-18 weeks in multigravids)

► Excessive softening of the isthmus (Hegar sign)

► Uterine souffle (murmur parallel to maternal heartbeat)

► Positive hCG test in blood or urine

Positive Findings Confirming Pregnancy

► Hearing the fetal heartbeat (8 weeks with Doppler, 18 weeks with auscultation)

► Determination of active fetal movements by the examiner (20th week)

► Seeing the fetus sonographically or radiographically

MATERNAL PLACENTAL FETAL UNIT

Fertilization and Implantation

• After the mature oocyte fertilizes in the tube, it turns into a zygote (diploid cell with 46 chromosomes). Each cell formed by the mitotic division of the zygote is called a blastomere, and as the division continues, a morula consisting of 16 blastomeres is formed. Morula approximately 3-4 days after fertilization. days later it descends into the uterine cavity. With the accumulation of fluid between the blastomeres in the morula, the cell turns into a blastocyst (with 58-256 blastomeres).

• On the fourth day, 5 cells located in the inner part of the 58-cell blastula will provide embryo development (embryoblast), and 53 cells located outside will develop trophoblast.

• By the fifth day, 8 cells of the 107-cell blastocyst are responsible for embryo formation (embryoblast), while the outer 99 cells form trophoblasts. During this period, the blastocyst gets rid of the surrounding zona pellucida, and as a result, it secretes cytokines (IL la and IL-113) and hCG that will enable it to be accepted by the endometrium. The response of the endometrium to these signals from the blastocyst is the release of leukemia inhibitory factor, colony stimulating factor and follistatin. Maternal recognition of pregnancy occurs by signals emitted by the blastocyst.

Against antigenic incompatibility between mother and fetus (semiallogeneic fetal graft), its immunological recognition allows HLA-G (HLA-G2 isoform) found in extravillous cytotrophoblasts.

• 6-7 days after fertilization. The blastocyst implants into the endometrium. Implantation takes place in 3 phases;

► Apposition - attachment of the blastocyst to the uterine wall; often in the posterior upper part of the uterus

► Adhesion - Increase in endometrial integrins

► Invasion

The most suitable period for endometrial receptivity for implantation is the 20-24th of the cycle. between days.

Loss of microvilli and cilia in epithelial surface cells is required for endometrial receptivity. In addition, protrusions towards the lumen on the apical cell surfaces begin to become prominent and these are called pinopods.

decidua

• Decidua is the special and highly modified endometrial tissue of pregnancy. The decidual reaction (decidualization) is the transformation of the secretory endometrium into decidual and occurs with estrogen, progesterone, androgen and factors secreted from the implanted blastocyst. Decidua secretes large amounts of prolactin.

• Decidua anatomically consists of three parts.

► Decidua basalis to the section just below the blastocyst implantation,

► Decidua capsullaris, which surrounds the developing blastocyst and separates it from the uterine cavity,

► The part that covers the entire remaining endometrium is called the decidua parietalis.

• In the first weeks of pregnancy, there is a space between the decidua capsullaris and the decidua parietalis because the gestational sac cannot fill the entire uterine cavity. 14-16 days of pregnancy. The growing sac fills the uterine cavity and the uterine cavity is completely obliterated as a result of the fusion of the decidua capsullaris and the decidua parietalis. The structure formed by two combined decidua is called decidua vera.

• Where the invading trophoblasts meet the decidua, there is a zone of fibrinoid degeneration, called the Nitabuch layer. In cases where the decidua is detective, such as placenta accreta, this layer is not observed.

trophoblasts

• The formation of the placenta begins with the trophectoderm that differentiates for the first time at the morula stage. As a result of this differentiation, the trophoblastic layer surrounding the blastocyst is formed. On the 8th day after fertilization, trophoblasts differentiate into outer multinuclear syncytiotrophoblasts and inner mononuclear cytotrophoblasts.

• Upon completion of implantation, these trophoblasts differentiate into villous and extravillous trophoblasts.

► Villous trophoblasts form the chorionic villi in the placenta and their primary function is the transport of oxygen and nutrients between the mother and the fetus.

► Extravillous trophoblasts penetrate the spiral arterioles by invading the maternal decidua and myometrium. Extravillous trophoblasts are also divided into two groups.

0 Interstitial trophoblasts invade the decidua, penetrate the myometrium, and form giant cells in the placental bed and surround the spiral arterioles.

0 Endovascular trophoblasts penetrate the lumen of spiral arterioles.

• After erosion of the endometrial epithelium, the blastocyst invades deeply and is completely covered by the endometrium on the 10th day after fertilization.

• As the blastocyst and trophoblasts grow, one end of this mass moves into the uterine cavity and the other end is buried deep into the endometrium. Chorionic villi invading the decidua basalis form the chorion frondosum (the fetal component of the placenta). As the embryo grows, blood circulation is restricted on the side of the chorionic layer facing the endometrial cavity. Therefore, the growth of the villi on the decidua capsullaris side stops and they begin to degenerate. As a result, this part of the chorion (chorion laeve) begins to form the avascular fetal membranes.

• The chorion is primarily a protective tissue layer and provides immunological acceptance. It also contains enzymes that deactivate uteotonins (prostaglandin dehydrogenase, oxytocinase and enkephalinase).

Invasion of trophoblasts is mediated by the proteolytic enzymes they secrete and the proteinases they activate in the endometrium. There are many adhesive molecules that keep invading trophoblasts attached to the maternal decidua, the most important of which is fetal fibronectin, also known as trophoblast adhesive.

Placenta

• About 12 days after implantation, primary chorionic villi begin to appear in the placenta. Secondary villi are formed when solid trophoblasts are surrounded by mesenchymal cords originating from the extraembryonic mesoderm. The villi that emerge after angiogenesis begins in the mesenchymal nucleus are called tertiary villi.

• Approximately 15 days after implantation, maternal blood begins to fill the intervillous space, and on the 7th day, fetal blood vessels become functional and true placental circulation begins.

• The inner surface of the villi is covered with cytotrophoblasts (Langhans cells), and the outer surface is covered with syncytium (syncytiotrophoblasts) and are syncytiotrophoblasts that are in direct contact with the maternal blood in the placenta.

• Placental cotyledons: Each cotyledon is a functional unit fed by chorionic villi. It is seen in the form of lobes on the maternal face, and their number varies between 10 and 38. The number of cotyledons remains the same throughout pregnancy.

• Term placenta weighs approximately 500 g and is 20 cm in diameter and 2 cm in thickness. As the placenta ages, there is a decrease in cytotrophoblasts and stroma, structural changes (thinning) in syncytiotrophoblasts, and an increase in Hoffbauer cells (fetal macrophages).

• If a section is taken from the fetal side of the placenta to the maternal side, it includes the amnion, chorion (frondosum), chorionic villi, decidua (basalis), and myometrium, respectively.

• The maternal face contains the cotyledons and the fetal face contains the amnion. Fetal chorionic vessels pass under the amnion. Fetal deoxygenated blood travels to the placenta via bilateral umbilical arteries, which are branches of the hypogastric artery. Oxygenated blood returns to the fetus via a single umbilical vein. There are chorionic arteries and veins on the fetal face.

In the placenta, maternal blood directly washes the villous trophoblasts, but does not mix with fetal blood in the fetal capillaries in the villi (haemochorial).

• In the placenta, maternal and fetal blood are separated from each other by the fetomaternal barrier. Until the third month of pregnancy, this barrier contains syncytiotrophoblasts, cytotrophoblasts, embryonic mesoderm and fetal capillary endothelium (hemodicorial),

After 3 months, cytotrophoblasts lose their continuity and disappear (hemomonochorial). Maternal blood is poured into the intervillous space. Fetal blood is in chorionic villi.

amnion

• Amnion in the 7th-8th days of embryonic life. It appears as a small vesicle between the embryonic cell mass and adjacent trophoblastic cells. There are no smooth muscle cells, nerves, lymphatics and blood vessels in the structure of the amnion. The amnion internally surrounds the fetal surface of the placenta, the umbilical cord, and remains in a sac around the fetus.

Synthesis and Secretions of the Amnion

a) From Epithelial Cells:

1. Metalloproteinase-1 tissue inhibitor

2. IL-8

3. PGE2

4. Fetal fibronectin

5. Endothelin

6. Parathyroid hormone-like protein

7. Natriuretic peptide

8.CRH

b) From Mesenchymal Cells:

1. Type I, III interstitial collagens

2. IL-6, IL-8

3. PGE2

4. Monocyte chemoattractant protein-1

Umbilical Cord (Funis)

• The umbilical cord consists of two arteries (carrying deoxygenated blood) and a vein (carrying oxygenated blood). During its formation, the right umbilical vein usually disappears and the left umbilical vein remains open. It contains Wharton gel, which is an extracellular matrix. The most common anomaly is single umbilical artery.

Placental Hormones

Human Chorionic Gonadotropin (hCG)

► hCG is a glycoprotein hormone with a weight of 36,000-40,000 Da. It has a heterodimer structure and consists of beta and alpha subunits. A single gene on the 6th chromosome encodes the a subunits of hCG, TSH, FSH and LH hormones. The beta subunit is encoded by 6 different regions on chromosome 19.

► hCG is largely synthesized from trophoblasts in the placenta by stimulation of placental GnRH.

► The hCG level in maternal blood is increased in multiple pregnancies, erythroblastosis fetalis accompanied by fetal hemolytic anemia, presence of fetus with Down syndrome and gestational trophoblastic diseases. On the other hand, its level decreases in pregnancy losses and ectopic pregnancies.

► It can be detected in maternal serum or urine 8-9 days after ovulation with a sensitive test. 60-70 from the last menstrual period. It reaches its maximum level of 100,000 mIU/mL by day 10 (week 10). The doubling time is approximately 48 hours in the first 10 weeks of pregnancy. It then declines to the lowest level by week 16 and remains at these levels throughout the pregnancy. On day 14, it drops below 5 mIU/mL in maternal serum.

► Its half-life is 36 hours. 30% of hCG is metabolized by the kidneys and the remainder is metabolized by the liver.

► Functions of hCG:

0 The most important effect is to ensure that the corpus luteum continues to function.

0 It directly stimulates the release of testosterone from the fetal testicles.

0 Stimulates the maternal thyroid gland.

0 Provides the release of relaxin from the corpus luteum.

0 Increases vasodilation in the uterine vascular bed.

It provides relaxation of myometrial smooth muscle cells.

human placental lactogen (hPL)

► It has been named as hPL (chorionic somatomammotropin) due to its patent lactogenic effects and its growth hormone-like structure (96% common).

► It is in the structure of non-glycosylated polypeptide.

► hPL; It is synthesized in trophoblasts in the placenta. It can be detected in maternal serum from the 3rd week of pregnancy and gradually increases to reach its peak level at 34th week. is the hormone secreted in the highest amount in pregnant women and its release is directly proportional to the placental mass.

► The half-life is 10-30 minutes.

► functions of hPL:

0 Providing free fatty acids for nutritional purposes to the fetus through maternal lipolysis.

0 More glucose to the fetus by inhibition of peripheral glucose uptake

0 Increase in maternal insulin levels with the effect of insulin resistance, resulting in increased protein synthesis and supply of amine acid to the fetus.

0 Patent is an angiogenic hormone that increases fetal vascularization.

0 Leptin inhibition

Chorionic Adrenocorticotropin (Acth) and Corticotropin Releasing Hormone (CRH)

► Placenta! The physiological effect of ACTH is not fully known. Placental ACTH is not under feedback regulation of corticosteroids. Placenta! Placenta from ACTH release! CRH is responsible.

While cortisol suppresses CRH with (-) feedback in the hypothalamus; It increases CRH release with (+) feedback in the placenta.

► While the CRH level is 5-10 pmol/L in the serum of a non-pregnant woman, this level rises to 100 pmol/L in pregnant women and to 500 pmol/L at the beginning of the third trimester. With the onset of labor, a 2-3-fold increase in CRH level is detected.

CRH is thought to be the factor that initiates labor.

relaxin

► It is a peptide hormone that is structurally similar to insulin and IGF. It is produced by the corpus luteum, decidua and placenta . 4-5. It appears in the maternal serum in the 10th weeks, peaks at the 10th week and decreases until the term.

► Relaxin is effective in providing myometrial relaxation in early pregnancy. Relaxin has important effects on renal hemodynamics, increasing glomerular filtration rate and decreasing osmolarity. In addition, it has a role in preparing the connective tissue in the genital area for birth and in reducing the vascular resistance in the uterine artery. However, it is not associated with peripheral joint elasticity.

leptin

► Since it is secreted in both cytotrophoblasts and syncytiotrophoblasts in the placenta, in addition to adipose tissue, its amounts in pregnancy are quite high.

progesterone

► Progesterone, which is produced from the corpus luteum with hCG stimulation for the first 7 weeks, is produced from syncytiotrophoblasts in the placenta after this week.

estrogens

► The placenta can synthesize very high amounts of estrogen. Neither cholesterol nor progesterone act as precursors for estrogen biosynthesis in trophoblasts. The placenta cannot synthesize cholesterol from acetate and does not contain 17a-hydroxylase and 17,20-lyase (CYP17) enzymes that are absolutely necessary for the production of sex steroids. Therefore, in the placenta, 21-carbon steroids cannot be reduced to 19-carbon steroids.

► DHEA-S acts as the major precursor of estrogens during pregnancy, the major source of which in pregnancy is the fetal adrenal gland. Therefore, the main source of estrogen produced by the placenta in pregnant women is the fetal adrenal gland.

► In the placenta, DHEA-S is converted to estradiol (E2) by 4 critical enzymes found in syncytiotrophoblasts.

0 First, the steroid sulfatase enzyme converts DHEA-S to DHEA,

0 Subsequently, the 3(3-OHSD enzyme converts DHEA to androstenedione,

0 The generated androstenedione is converted to estrone (EI) by the cytochrome P450 aromatase (CYP19) enzyme.

0 This is converted to the end product estradiol (E2) by the 17(3-OHSD enzyme).

► Some of the DHEA-S is hydroxylated with the 16a-hydroxylase enzyme in the fetal liver and comes to the placenta in the form of 160H-DHEA-S. As a result of the reaction of this androgen with 4 enzymes, estriol (E3) is formed.

► All these steps show that the placenta and fetus (adrenal gland and liver) play a role together in the biosynthesis of estrogens. Estrogens delivered to the fetus are inactivated by hydroxylation in the fetal liver and the fetus is protected from excessive feminization. In this process, estriol is reduced to oesterol (E4).

There is no 3 beta-OHSD (Delta5-4 isomerase) enzyme activity in the fetal zone of the fetal adrenal gland. Therefore, progesterone and androstenedione synthesis in the fetal adrenal gland is limited. Steroid sulfotransferase activity in the fetal adrenal gland is very high.

Since placenta and fetus coexist in E3 synthesis, E3 is an indicator of normal functioning of the fetoplacental unit.

Situations where E3 increases

1. Fetal erythroblastosis (placental hypertrophy i)

2. Multiple pregnancies

Cases where E3 is down

1. Fetal death

2. Fetal anencephaly

3. Fetal adrenal hypoplasia

4. Fetal-placental sulfatase deficiency

5. Fetal-placental aromatase deficiency

6. Trisomy 21 (Down syndrome)

7. Maternal use of glucocorticoids

8. Mother's Addison's disease

9. Gestational trophoblastic neoplasms

Very low maternal serum estriol level (<0.25 MOM}, Smith Lemli-Opitz Syndrome (7-dehydrocholesterol reductase gene mutation), X-linked ichthyosis (steroid sulfatase deficiency}, congenital adrenal hypoplasia, adrenocorticotropin deficiency, hypothalamic corticotropin deficiency, and anencephaly associated with.

Hormones during pregnancy
fetal compartment	placental compartment	maternal compartment
Alpha-fetoprotein	hypothalamic hormones	Decidual proteins prolactin relaxin Progesterone-related endometrial protein IGFBP-1 interleukin-1 Colony stimulating factor-1 corpus luteum proteins relaxin pronenin
	GnRH
	CRH
	TRH
	Somatostatin
	GHRH
	Pituitary hormones
	hCG
	hPL
	GH variant
	PTH-like protein
	ACTH
	Oxytocin
	Other proteins
	Opiates
	Prorenin
	beta 1 pregnancy-specific glycoproteins
	PAPP-A
	Activin
	inhibin
	Follistatin
	Relaxin
	Calcitonin
	Leptin
	Atrial natriuretic peptide
	Neuropeptide Y
	growth factors
	IGF-1
	IGF-2
	Epidermal growth factor
	Fibroblast growth factor
	Platelet-derived growth factor
	Transforming growth factor a, B
	cytokines
	interleukin
	Interferon
	Tissue necrosis factor-alpha
	Colony stimulating factor-1

Gestational trophoblastic diseases

noreply@blogger.com (Unknown) — Tue, 21 Feb 2023 13:48:00 +0300

GENERAL INFORMATION

• Gestational trophoblastic diseases; It is a term used to describe a spectrum of histologically diverse diseases characterized by abnormal proliferation of placental trophoblasts.

histopathological types

Modified WHO (World Health Organization) Classification of Gestational Trophoblastic Disease

A. Molar pregnancies

Mole hydatiform (partial or complete hydatiform mole)

Invasive hydatiform mole

B. Trophoblastic Tumors Choriocarcinoma

Trophoblastic tumor arising from the placental region

Epithelioid trophoblastic tumor

• Gestational trophoblastic diseases can be histologically benign or malignant. While complete and partial mal is benign, invasive mal, choriocarcinoma, placenta! trophoblastic tumor and epithelioid trophoblastic tumors arising from the region are malignant.

• Malignant lesions can be locally invasive or metastatic and are called gestational trophoblastic neoplasia. Gestational trophoblastic neoplasms are the most treatable gynecological malignancies and are highly responsive to chemotherapy.

• Gestational trophoblastic diseases; It develops from three different cell types: cytotrophoblasts, syncytiotrophoblasts and intermediate (intermediate) trophoblasts. Except for placental site trophoblastic tumors and epithelioid trophoblastic tumors, diseases originating from villous syncytiotrophoblast and cytotrophoblast produce excessive amounts of hCG. Placental site trophoblastic tumors and epithelioid trophoblastic tumors are diseases of extravillous intermediate trophoblast origin and hCG production is low.

Characteristic markers of gestational trophoblastic diseases are Beta-HCG

Mole hydatiform

• It is the most common gestational trophoblastic disease. Molar pregnancies have a markedly different incidence in different geographic regions. The incidence of complete and partial hydatidiform moles is approximately 1:1945 and 1:695 pregnancies, respectively.

Risk factors

• advanced maternal age; The risk of complete mole increases 5-10 times over the age of 40.

• Very young maternal age

• Advanced paternal age

• History of previous molar pregnancy

• Low dietary carotene intake (a precursor of vitamin A) and a diet low in animal fat increase the risk of complete moles.

• Long-term use of oral contraceptives and a history of irregular menstruation are associated with partial mole.

• History of previous unsuccessful pregnancy; The probability of complete mole increases in patients with a history of recurrent pregnancy loss. The risk increases 2 times in those with a history of spontaneous abortion.

• Cigarette; It increases the risk of partial mole hydatiform.

• High level of education; It increases the risk of partial mole hydatiform.

Maternal age and nutritional factors are not associated with partial mole.

Complete Mole Hydatiform

• The genetic structure is only of paternal origin and is diploid. {Most often 46 XX). This genetic structure occurs in two ways:

• The haploid genome of paternal origin from a single sperm is 23X and its duplication

As a result, 46,XX structure is formed.

• The empty ovum is fertilized by two separate sperm (dyspermia) and forms a 46,XX or 46,XY karyotype.

In 90% of cases, the karyotype is 46,XX, and more rarely (10%) is 46,XY due to dyspermia.

Clinic

► Abnormal vaginal bleeding is the most common symptom (84%). Following bleeding, the molar tissue begins to be expelled as vesicles with painful contractions. Anemia due to bleeding (5%) can also be observed.

► Larger uterus for gestational age (28%).

► Preeclampsia (before 20 weeks of gestation) (27%)

► Hyperemesis gravidarum(8%)

► Hyperthyroidism (7%) occurs more in cases with high hCG levels.

► Theca lutein cysts are significantly enlarged (> 6 cm) in 50% of the cases. It is usually bilateral. Cysts develop due to the stimulus created by hCG and in parallel with the decrease in hCG level 2-4. It shows involution within a month.

► Trophoblastic embolism (2%): Typically, there is a picture of pulmonary embolism that develops within 4-6 hours following the evacuation of the mole and respiratory failure associated with it.

Diagnosis

► According to the gestational week, a significant increase in B-hCG level is observed.

► Macroscopically, it looks like a bunch of grapes.

► Ultrasound: A vesicular sonographic image (snowfall scene) is typical in a complete mole.

► Definitive diagnosis is made by histopathological examination of curettage material.

0 Diffuse trophoblastic hyperplasiaproliferation

0 Diffuse hydropic (hydatiform) swelling of chorionic villi

0 Hydropic villi are avascular

0 Embryonic or fetal tissues are not observed (due to avascularization).

0 Immunohistochemically p57 negative (as it is expressed by the maternal chromosome)

► Initially, a chest X-ray should be taken for lung metastases.

Treatment

► The uterus is evacuated by vacuum curettage. Because of the high risk of perforation, sharp curettage can be used for control purposes after vacuuming, not for emptying the uterus.

► Hysterectomy: If another pregnancy is not considered, it can be applied in elderly patients at risk of malignant development or in cases where bleeding cannot be stopped. Although the risk of metastatic disease decreases after hysterectomy, postoperative B-hCG follow-up should be continued, since it does not completely disappear.

► Theca lutein cysts are usually not treated.

Since trophoblastic cells secrete RhD, if the mother is Rh {-), anti-D Rh immunoglobulin should be administered.

Follow-up

► The same in those treated with curettage and hysterectomy:

► Absolute contraception should be provided during hCG follow-up after molar pregnancy treatment. COC or barrier method is used in patients who do not want surgical sterilization. IUD should not be used because of the risk of perforation. COCs do not increase the risk of postmolar trophoblastic disease.

► B-hCG level is monitored weekly until 3 times in a row and monthly for the following 6 months. In 70% of cases, B-hCG levels return to normal within an average of 9 weeks following uterine evacuation.

► Follow-up should be done with pelvic examination and chest X-ray.

► Risk of local uterine invasion after complete mole evacuation

While the risk of metastasis is 15%, it is 4%. This is particularly evident in high-risk groups.

High-risk criteria for invasion in malar pregnancies

Beta-HCG > 100,000 mIU/mL

overgrown uterus

Presence of bilateral theca lutein cysts larger than 6 cm

Age over 40

chemotherapy should be started in the presence of the following conditions during the follow-up period:

0 If B-hCG rises in 2 consecutive measurements or plateaus in 3 measurements

0 If B-hCG is high 15 weeks after uterine evacuation

0 If β-hCG rises again after falling to normal levels

0 If uterine size grows back to normal after

0 If bleeding occurs following uterine evacuation (suggests choriocarcinoma and invasive mole)

Partial Mole Hydatiform

• The genetic structure is of both maternal and paternal origin and is triploid. {most often 69 XXY). A diploid number of chromosomes comes from one parent, while haploid (n=23) chromosomes from the other parent: 69.XXY (58%), 69.XXX (40%), 69.XYY (2%),

Clinic

► Most of the cases present with a clinic similar to incomplete abortus or missed abortus. In these cases, the first finding is vaginal bleeding (73%). Larger-than-expected uterus (4%) and preeclampsia (3%) are rare findings. Theca lutein cyst, hyperemesis and hyperthyroidism are not observed.

► There is a fetus and it is usually lost in the first trimester and various anomalies can be seen in the fetus (syndactyly, hydrocephalus, growth retardation, etc.).

Diagnosis

► According to the gestational week, a significant increase in B-hCG level is observed. However, beta-hCG levels at the time of diagnosis are typically lower than the complete mole and usually do not exceed 100,000 mIU/ml.

► Ultrasound: Focal cystic areas in the placenta and an increase in the transverse diameter of the gestational sac are important in partial moles.

► Definitive diagnosis is made by histopathological examination of curettage material.

0 Focal trophoblastic hyperplasia/proliferation (with or without atypia)

0 Focal hydropic (hydatiform) swelling and cavitation in chorionic villi.

0 Hydropic villi are vascular.

0 Embryonic or fetal tissues are present (due to vascularization) .

0 Trophoblastic stromal inclusion and prominent villous aggregation.

0 Immunohistochemically p57 positive (as it is expressed by the maternal chromosome).

- Initially, a chest X-ray should be taken for lung metastases.

Treatment

► Same as complete mole.

Follow-up

► Absolute contraception is recommended after the procedure. Follow-up is just like a complete mole. The development of persistent non-metastatic tumors after partial mole is around 2-4%.

Comparison of molar pregnancies
	complete mole	Partial mole
karyotype	Diploid (46, XX)	Triploid (69, XXY)
clinical presentation
Diagnosis	molar pregnancy	Missed abortion
Larger-than-expected uterus	28%	4%
vaginal bleeding	84%	73%
hCG	>100,000 mlU/ml	<100,000 mlU/ml
hCG persistence	20%	0.5%
Medical complications
preeclampsia	27%	3%
hyperthyroidism	7%	no
Theca lutein cyst	50%	no
hyperemesis	8%	no
trophoblastic embolism	15%	no
Postmolar trophoblastic neoplasia	diffuse hydropic	4.6%
Pathology
Hydatiform swelling in chorionic villi	diffuse hydropic	focal hydropic
Fetal or embryonic tissue	no	There is
trophoblastic hyperplasia	diffuse	focal
Trophoblastic stromal inclusion	no	There is
Notching of chorionic villi	no	There is
p57 immunostaining	Negative	Positive
Genetic	parental	biparental

Gestational Trophoblastic Neoplasms

• This group includes invasive moles, choriocarcinoma, placental site trophoblastic tumors, and epithelioid trophoblastic tumors.

• Gestational trophoblastic neoplasms typically develop following any form of pregnancy, but are most common following molar pregnancies.

• They can be nonmetastatic (locally invasive) or metastatic. While invasive mole and placental site trophoblastic tumors are usually nonmetastatic; Most of the metastatic diseases are seen due to choriocarcinoma.

Most metastatic gestational trophoblastic neoplasms develop following non-molar pregnancies.

Histopathological Types

invasive mole (chorioadenoma destruens)

• It is a disease in which hydropic chorionic villi penetrate the myometrium or vascular areas of the myometrium and sometimes the peritoneum, adjacent parametrium or vaginal wall.

• Almost all invasive hydatiform moles originate from a complete or partial mole.

• Bleeding is the most important finding. It may cause intraperitoneal bleeding by perforating the uterus and excessive vaginal bleeding as a result of invasion of uterine vessels. They are generally locally invasive and most of the invasive moles seen after a complete mole are nonmetastatic.

• Since the invasive mole is clinically hidden, the diagnosis is usually made from the hysterectomy specimen performed due to the complication of hemorrhage.

• Pathological diagnosis is made by demonstrating molar villi that invade the myometrium or have reached the extrauterine areas.

• Treatment indications are arranged according to hemorrhagic complications.

Trophoblastic Tumor from the Placental Region

• It is a cellular mass involving the endometrium and myometrium. The predominant cell type is intermediate trophoblasts. Although it can occur following any pregnancy, it is most commonly seen following term pregnancy.

• Abnormal vaginal bleeding is the most common symptom. Continuation of bleeding, especially following a term pregnancy, provides suspicion for a tumor developing from the placental region. Uterine enlargement often accompanies it. They tend to be limited to the uterus and metastasize in the future.

• Masses have low beta-hCG production compared to their size (usually between normal and 1000 mIU/L). High hPL levels are an important indicator.

• Tumors that are partially resistant to chemotherapy compared to others, and hysterectomy is the primary treatment for non-metastatic disease. However, systemic chemotherapy and uterine curettage can be recommended for those who want a child. Metastatic placental site trophoblastic tumors have a worse prognosis than postmolar gestational trophoblastic neoplasms, and aggressive combined chemotherapy should be given.

Epitheloid Trophoblastic Tumor

• These tumors originate from chorionic type intermediate trophoblasts. It can occur long after the previous pregnancy, and in some cases the previous pregnancy cannot even be confirmed.

• Microscopically, the placental site resembles trophoblastic tumors, but the cells are smaller and show less nuclear pleomorphism. Macroscopically, the placental site shows a nodular growth pattern rather than an infiltrative pattern of trophoblastic tumor.

• The primary treatment method is hysterectomy because they are resistant to chemotherapy. More than 1/3 of the cases present as metastatic disease and their prognosis is poor since they are resistant to multiple chemotherapy.

Gestational Choriocarcinoma

• Although most of the cases are seen after evacuation of molar pregnancy, it can also be seen after non-molar pregnancies. 2/3 of the cases seen after non-molar pregnancies are term pregnancies, and 1/3 of the cases are seen after spontaneous abortion or pregnancy termination. Elevated B-hCG values after non-molar pregnancy should be considered as choriocarcinoma until proven otherwise.

• The most common symptom is vaginal bleeding, but it can mimic many pathologies, so diagnosis delay is common. The main reason for mimicking other pathologies is metastases involving various organ systems. These foci are fragile and may cause spontaneous bleeding. Its natural course is rapid progression and death occurs within a few weeks to a few months. The cause of death is often bleeding.

Metastases in gestational trophoblastic neoplasia
1. Lungs	80%
2. Vagina (Fornix or suburethral)	30%
3. Pelvis	20%
4. Liver	10%
5. Brain	10%
6. Kidney, intestine, spleen	5%
7. Other	<%5
8. Uncertain (persistence of BhCG after hysterectomy)	<%5

• It is a malignant tumor consisting of anaplastic cytotrophoblast, syncytiotrophoblasts and intermediate trophoblasts, characterized by hemorrhage and necrosis, with microscopically significant vascular invasion. However, chorionic villi are absent..

Staging

FIGO (2000) clinical staging of gestational trophoblastic neoplasms
stage 1	Patients with persistent hCG elevation with tumor limited to the uterine corpus
stage 2	Tumor outside the uterus but limited to the genital organs (adnexa, vagina, lig. latum)
stage 3	Lung metastases (with or without genital involvement)
stage 4	All other metastases such as brain, liver, kidney, gastrointestinal tract

Prognostic Risk Scoring

• World Health Organization (WHO) criteria: The World Health Organization (WHO) developed a personal risk scoring system for GTN to reliably demonstrate the potential for resistance to LT, and patients were classified as low and high risk.

• Single-agent chemotherapy is applied to the low-risk group, and combined chemotherapy (together with surgery and radiotherapy) is applied to the high-risk group.

Diagnosis

• The diagnosis of gestational trophoblastic neoplasia is made clinically by using Beta-hCG, which is an indicator of persistent trophoblastic tissue in most cases, rather than tissue diagnosis.

FIGO of Postmolar Gestational Trophoblastic Neoplasia (2000) diagnostic criteria

• A plateau (±10%) of 8-hCG level in four consecutive measurements for three weeks or longer (days 1, 7, 14, and 21)

• B-hCG in three consecutive measurements for two weeks or longer

An increase of 10% or more in the level (days 1, 7, and 14; >10% increase from day 1 to day 14)

• Elevated 8-hCG for 6 months or longer after mole evacuation

• Histological proof of choriocarcinoma

Presence of metastatic disease

Treatment

Treatment of non-metastatic (Stage 1) disease;

► If there is a desire to preserve fertility, single-agent KT is applied (methotrexate, actinomycin-D). In case of resistance to treatment, multi-agent (combined) chemotherapy is started.

► Hysterectomy can be performed and adjuvant single-agent CT is given in patients who do not have fertility problems and CT is ineffective.

► Hysterectomy is indicated in all cases of stage I placental site trophoblastic and epithelioid trophoblastic tumors that are relatively resistant to chemotherapy and the only curative treatment is hysterectomy.

Stage II and III disease treatment

► Single-agent chemotherapy in the low-risk group and combined chemotherapy in the high-risk group should be preferred as the initial regimen.

► Hysterectomy can be performed to control uterine bleeding or sepsis.

Stage IV disease treatment

► As the initial treatment, an appropriate combination of combined chemotherapy, selective radiotherapy and surgical treatment should be preferred.

► EMA-CO {Etoposide, methotrexate, actinomycind-D, cyclophosphamide, vincristine); In metastatic disease with high prognostic scores and low-risk disease resistant to single-agent chemotherapy, the EMA-CO regimen is the primary treatment of choice and is generally well tolerated.

Follow-up

Follow-up in stage I and low-risk stage 11-111 disease

► Beta-hCG level should be followed weekly until it is normal in 3 consecutive measurements, and monthly for the following 12 months. Contraception should be provided throughout the follow-up.

Follow-up in stage IV and high-risk stage 11-111 disease

► Beta-hCG level should be followed weekly until it is normal in 3 consecutive measurements, and monthly for the following 24 months. Contraception should be provided throughout the follow-up.

Prognosis

• Mol hydatiform is a completely cured disease. Cure is close to 100% in non-metastatic malignant GTD and reproductive functions continue in >90% of cases.

• There is no increased risk of any obstetric complications in subsequent pregnancies in cases with complete hydatid mole or gestational trophoblastic neoplasia treated with chemotherapy. Pregnancy outcomes are optimal for women who conceive 12 months after chemotherapy. After chemotherapy for persistent gestational trophoblastic disease, the risk of congenital anomaly did not increase, although she received chemotherapy.

The risk of hydatiform mole increases in subsequent pregnancies (1%).

In the patient who has remission after molar pregnancy, the next pregnancy most often ends with term live birth.

Ovarian and tubal cancers

noreply@blogger.com (Unknown) — Sat, 18 Feb 2023 18:07:00 +0300

TUBA CANCER

• It is a rare tumor (0.3%) that behaves like ovarian cancer. It usually occurs between the ages of 50-60. They are often metastatic rather than primary tumors. The presence of tubal epithelial dysplasia is required to call tubal carcinoma primary. In order of frequency, the most frequently metastasized tumors are ovarian, endometrial, gastrointestinal system and breast cancer.

• However, it is thought that primary tubal cancers are more common than previously thought. Today, it is accepted that the most common high-grade serous carcinoma is mostly caused by fimbria and tuba uterina, and its etiological origin is tuba uterine and peritoneal cancer.

• Almost all primary tubal cancers are cancers of epithelial origin and serous cancers are the most common. The presence of BRCA1 and BRCA 2 gene mutations is a high risk factor for the development of tubal cancer.

Clinic

• Although it is known with the classic triad of profuse watery vaginal discharge, pelvic pain, and pelvic mass, this triad is seen only in 15% of cases. On the other hand, vaginal discharge and bleeding are the most common symptoms (50%).

• 60% of the patients have a pelvic mass, and if this mass is pressed during the examination, this mass is felt to be getting smaller and smaller with an excessive watery vaginal discharge. This is called hydrops tuba profluens and is pathognomonic.

• Elevated Ca 125 levels are frequently observed in advanced cancers.

Spread

• Spread is most commonly in the form of peritoneal implantations by the transcoemic route. Lymphatic spread is also common, paraaortic lymph nodes are involved in 33% of cases.

Prognosis

• The prognosis depends on the stage of the disease.

Staging

• Staging is surgical and the same as for ovarian cancer.

Treatment

• TAH+BSO+ pelvic-paraaortic lymph node dissection+infracolic omentectomy is performed surgically. The most effective postoperative chemotherapy agents are alkylating agents and cisplatin (paclitaxel+carboplatin).

ovarian tumours

Gynecological malignancies with the highest mortality

Histopathological Classification

Epithelial Tumors (Occurring from Coelomic / Germinal Epithelium) (65-90%)

► Serous tumors; Benign, borderline, malignant (46%)

► Mucinous tumors; Benign, borderline, malignant (36%)

► Endometrioid tumors; Benign, borderline, malignant (8%)

► Clear cell (mesonephroid) tumors; Benign, borderline, malignant (3%)

► Brenner tumor (Transitional); Benign, borderline, malignant (2%)

► Undifferentiated tumors (2%)

► Mixed epithelial tumors; Benign, borderline, malignant (3%)

Germ Cell Tumors (5-15%)

► Primitive germ cell tumors

0 Dysgerminoma (30-40%) (most common malignant germ cell tumor)

0 Yolk sac tumor (endodermal sinus tumor) (10%)

0 Embryonal carcinoma (4%)

0 Polyembryoma

0 Choriocarcinoma (nongestational)

0 Mixed germ cell tumors

► Biphasic / Triphasic teratomas

0 Immature teratoma (10-20%)

0 Mature teratoma (most common germ cell tumor)

- Solid teratoma

- Cystic teratoma (dermoid cyst, fetiform teratoma-homunculus)

► Monodermal teratomas and somatic tumors associated with dermoid cyst

0 Struma ovarii (thyroid tissue)

0 Carcinoid (neurosecretory tissue)

0 Neuroectodermal tumor

0 Other; Melanocytic, carcinoma, sarcoma, sebaceous tumors, pituitary type tumor

Sex cord stromal (mesenchymal) tumors (5-8%)

► Granulosa-stromal cell tumors

0 Granulosa cell tumor; Adult and juvenile type

0 thecoma- fibroma group

- thecoma

- Fibroma

- Other; Cellular fibroma, Fibrosarcoma, Sclerosing stromal tumors, Signet ring cell stromal tumors, fibrothecoma

► Sertoli-stromal cell tumors

0 Sertoli-Leydig cell tumor group (Androblastoma)

0 Sertoli cell tumor

0 Stromal-Leydig cell tumors

► Mixed or unclassified sex cord stromal tumors

0 Sex cord stromal tumor containing annular tubules (may be associated with Peutz-Jeghers Syndrome)

0 Gynandroblastoma (components must be specified)

0 Unclassified sex cord stromal tumors

► Steroid cell tumors

0 Leydig cell tumor group

- Hilar cell tumors

- Nonhilar type Leydig cell tumors

- Leydig cell tumors not otherwise named

0 Steroid cell tumor not otherwise named

Metastatic Tumors (5-6%)

Bilaterality rate in ovarian tumors

Epithelial Tumors

- Serous cystadenocarcinoma ----------------------------------------------- --- ► 33-66%

- Endometrioid carcinoma ----------------------------------------------- ------ ► 13-30%

- Mucinous cystadenocarcinoma -----------------------------------------------► 10-20%

- Serous cystadenoma ----------------------------------------------- ----------------► 10%

- Benign Brenner tumor ---------------------------------------------- ---------► 6%

- Mucinous cystadenoma ----------------------------------------------- -----------► 5%

Germ Cell Tumors

- Benign cystic teratoma ---------------------------------------------- --------► 12%

- dysgerminoma ------------------------------------------------ -------------------►5-10%

- immature teratoma------------------------------------------------ ---------------►2-5%

- Other malignant germ cell tumors -------------------------------------------------rare

sex cord stromal tumors

- Tekoma ------------------------------------------------ --------------------------- ► Rare

- Sertoli-Leydig cell tumor ------------------------------------------ - ► Rare

- Granulosa-theca cell tumor------------------------------------------ ► Rare

Staging

Staging of ovarian tumors is surgical.

FIGO staging
1	Tumor limited to the ovary or ovaries
1A	Tumor limited to one ovary; Capsule intact, no tumor on the ovarian surface, no acid and/or washing liquid containing malignant cells
1B	Limited tumor in both ovaries; Capsule intact, no tumor on the ovarian surface, no acid and/or flushing cyst containing malignant cells
1C	Limited tumor in one or both ovaries accompanied by any of the following 1C1: Intraoperative surgical spread 1C2: Capsular rupture or tumor on the ovarian surface before surgery 1C3: Presence of malignant cells in ascitic fluid or peritoneal washes
2	Tumor involving one or both ovaries with pelvic extension
2A	Tumor that has spread and/or implanted to the uterus and/or tuba
2B	Tumor spreading to other pelvic intraperitoneal tissues
3	Tumor involving one or both ovaries outside the pelvis with cytological or histologically demonstrated peritoneal spread and/or metastasis to retroperitoenal lymph nodes
3A	Retroperitoneal lymph node metastasis and/or microscopic extrapelvic peritoneal involvement
3A1	Positive retroperitoneal lymph nodes only (cytologically or histologically proven) 3A1 (1): Metastasis size s 10 mm 3A1 (2): Metastasis size > 10 mm
3A2	Microscopic extrapelvic peritoneal involvement with or without retroperitoneal lymph node metastasis
3B	Macroscopic extrapelvic peritoneal metastasis s 2 cm in size with or without retroperitoneal lymph node metastasis
3C	Macroscopic extrapelvic peritoneal metastasis > 2 cm with or without retroperitoneal lymph node metastasis (includes liver/spleen capsule involvement)
4	Distant metastases other than peritoneal metastases
4A	Pleural effusion with cytology positive
4B	Extra-abdominal organ metastases, including involvement of lymph nodes outside the abdominal cavity and inguinal lymph nodes. (Includes liver/spleen parenchymal metastasis)

Depth of invasion has no role in staging ovarian cancer.

Capsular spread of the tumor to the omentum, spleen or liver is Stage IIIC, while isolated spleen or liver parenchymal metastasis is Stage IVB.

In the presence of transmural intestinal infiltration or umbilical tumoral deposits, it is stage IVB.

Epithelial Ovarian Tumors

• The most common ovarian tumors are epithelial ovarian tumors.

90% originate from the coelomic (germinal) epithelium or mesothelium. Each histologic type of epithelial ovarian tumor is further categorized as benign, borderline (tumor of low malignant potential), or malignant.

• The most common malignant epithelial ovarian tumors are serous cancers (75-80%), less frequently endometrioid (10%), mucinous (5%), clear cell (5%), Brenner (transitional) (<1%) and undifferentiated carcinoma (<1%) is observed.

• Each subtype of epithelial ovarian tumors is histologically similar to the lower genital system epithelium.

characteristics of epithelial ovarian tumors

histological type

• serous

• Endometrioid

• mucinous

• Clear cell

• Brenner

cellular type

• Endosalpingeal

• Proliferative endometrium

• Endocervical, Intestinal

• Müllerian, secretory or gestational endometrium

• Transitional

Risk factors

Risk factors of Epithelial Ovarian Cancers	Relative risk
Family history (especially mother, daughter or sister) and hereditary genetic predisposition - BRCA1 and BRCA 2 gene mutation, Lynch Syndrome - Having a family history of breast cancer also increases the risk.	3--4
early menarche	1,5
late menopause	1,5--2
nulliparity	2--3
infertility	2--5
old age	3
The white race	1,5
History of chronic perineal talcum powder use	1,5--2
Pelvic inflammatory disease
Postmenopausal hormone replacement therapy (long-term estrogen therapy alone)	3--5
Living in industrialized western countries; North America and Northern Europe	2--5
High socioeconomic or cultural level	1,5--2
BMI height and height; In particular, there is an increase in endometrioid type ovarian cancer.

Genetic Risk and Hereditary Ovarian Cancers in Epithelial Ovarian Cancers

► 10% of all epithelial ovarian cancers are hereditary. Hereditary ovarian cancers occur an average of 10 years earlier than non-hereditary ones. Because these mutations are inherited in an autosomal dominant manner, a complete pedigree analysis of the patient should be performed. The risk of ovarian epithelial cancer doubles in women who have had breast cancer.

► More than 90% of hereditary ovarian cancers are associated with BRCA1 and BRCA 2 mutations. About 2/3 of all hereditary ovarian cancers are located on chromosome 17. While the (17q21) BRCA-1 tumor develops as a result of a mutation in the suppression gene, approximately 1/3 of hereditary ovarian cancers are located on the 13th chromosome.

(13q12) It develops as a result of mutation in the BRCA-2 tumor suppression gene. Mutations in these two genes increase the predisposition to both ovarian and breast cancer. Patients with ovarian cancer with BRCA1 and BRCA 2 gene mutations are more likely to survive than those without mutations.

► MSH2, MLH1, MSH6 in Hereditary Nonpolyposis Colorectal Cancer Syndrome {Lynch Syndrome) which is another hereditary disease and progresses with Multiple adenocarcinomas (colon, endometrium, ovary, gastrointestinal (stomach), genitourinary system (ureter) tumors and skin tumors) There are mutations in genes responsible for repairing mutations such as PMS1 and PMS2. The gynecological malignancy with the highest increased risk in women with Lynch syndrome is endometrial cancer (40-60%), and there is an increased risk of ovarian cancer (2-5%). The mean age of ovarian cancer in women with Lynch syndrome is 40 years and the clinical features are better than sporadic cases.

Approach to women at high risk of ovarian cancer

1. BRCA1 and BRCA2 gene mutations should be investigated in high-risk patients.

2. Patients who want to preserve their fertility capacity or delay prophylactic surgery should be screened with TVUSG every 6 months.

3. Oral contraceptives should be offered to young women when they are not planning pregnancy.

4. Women who do not want to preserve their fertility or who have completed their family should be offered prophylactic bilateral salpingooopherectomy after the age of 35 (The risk is reduced by 96%)

5. In women with a strong family history of breast or ovarian cancer, annual breast screening should be started by combining MRI, mammography and ultrasonography from the age of 30.

6. In patients diagnosed with Lynch Syndrome, prophylactic hysterectomy and bilateral salipingooopherectomy should be recommended after completion of fertility desire. Endometrial biopsy and TVUSG evaluation of the ovaries can be considered between the ages of 30-35 in those with fertility problems. Colonoscopy should be started between the ages of 20-25 or 10 years before the age of diagnosis of the youngest patient in the family and should be repeated every 1-2 years.

Conditions that reduce the risk of ovarian cancer

1. Multiparity (having at least 1 child reduces the risk by 30-40%)

2. Use of combined oral contraceptives (5 years reduces the risk by 60%)

3. History of tubal ligation or hysterectomy

4. Breastfeeding

5. Prolonged amenorrhea

Scanning

► There is no effective screening method for ovarian cancers. The combined use of pelvic examination, tumor markers, and color Doppler ultrasound is beneficial.

Ca-125

► Since the CA-125 value increases due to many gynecological reasons, its specificity is very low, especially in women of reproductive age. Since it has been shown that CA-125 and transvaginal USG do not reduce mortality due to ovarian cancer, they should not be routinely used in ovarian cancer screening, especially in reproductive age.

► In the postmenopausal period, a CA-125 level of >200 IU/ml has a 96% positive predictive value.

► The upper limit of the normal value of CA-125 is 35 IU/ml.

► Malignant causes of Ca-125 elevation

0 Non-mucinous epithelial ovarian cancers

0 Tubal cancer

0 Endometrial cancer

0 Cervical cancer

0 Pleural, pericardial and peritoneal cancers

0 Pancreatic cancer

0 Breast cancer

0 Colon cancer

0 Lung cancer

0 Liver

0 stomach

ROMA index (risk of ovarian malignancy algorithm)

► Another tumor marker that can be used is human epididymal protein-4.

{HE4) and is used to determine the ROMA (risk of ovarian malignancy algorithm) index together with Ca-125. In most benign conditions that increase Ca125 level (especially in endometriosis), HE4 level is lower. Therefore, false positivity in screening for ovarian cancer is lower.

Color Doppler Ultrasonography

► Neovascularization and low resistance index in color Doppler USG

(<0.4) is in favor of malignancy.

Clinic

► Invasive epithelial cancers are most common between the ages of 56 and 60, and 80% of them are observed in the postmenopausal period.

► It can remain silent for a long time. The most common symptoms are swelling, tension and pain in the abdomen. Constipation or incontinence symptoms may occur as a result of compression.

► The most important finding is the detection of a pelvic mass. Solid, irregular and fixed pelvic mass is highly suspicious for ovarian cancer. In addition, if there is an upper abdominal mass and ascites, the diagnosis of ovarian cancer is almost certain.

Spread

► Transcoelomic: It occurs by the implantation of exfoliated cells on the peritoneal cavity surfaces. It is the most common and earliest way of spread.

► Lymphatic: Spread to the pelvic and paraaortic lymph nodes is common, especially in the advanced stages of the disease.

► Hematogenous: Rare.

Prognosis

Prognostic Factors

1. The stage of the disease; It is the most important prognostic factor in advanced cancers.

2. Histological grade; It is an important prognostic factor in early stage cancers and is a strong predictor for occult metastases.

3. Acid volume

4. Malignant peritoneal cytology

6. Extent of residual tumor after primary surgery

7. Age

8. Performance status; Survival was significantly reduced in patients with low Karnofsky index.

9. Histological type; The prognosis is worse in advanced clear cell and mucinous cancers.

10. biomarkers

• Aneuploidy (50-80%); It is the most important determinant of survival.

• S phase / proliferative phase

• Abnormal oncogene expression and tumor suppressor gene mutation

- HER-2/neu; Associated with poor prognosis

- p53; It is the most common mutation in ovarian cancers (50%).

- K-ras; Common in borderline serous tumors and mucinous tumors

- BRAF; Berderline serous tumors are observed in 20%.

- PTEN

- Cyclin E amplification; Associated with poor prognosis

- Myc amplification

Prognostic Factors in Early Stage Epithelial Ovarian Cancers

High risk

• High grade

• Tumor beyond the capsule

• There is surface involvement

• There is acid

• Peritoneal cytology (+)

• Preoperative rupture

• Aneuploid tumor

• Presence of dense adhesion

low risk

• Low grade

• Intact capsule

• No surface involvement

• No acid

• Peritoneal cytology (-)

• Absence of rupture or intraoperative rupture

• Diploid tumor

• Absence of dense adhesion

In early stage ovarian tumors, intraoperative iatrogenic rupture of the tumor does not have a poor prognostic effect.

Histological Types of Epithelial Ovarian Cancers

Serous Cystadenocarcinoma (75-80%)

It is the most common tumor among epithelial ovarian tumors. Papillary formations are seen in 80% of these tumors.

0 Psammoma bodies seen in areas of intussusception are associated with a good prognosis and are found in the primary tumor focus while being in the metastasis focus.

0 Composed of tubal epithelium (endosalpingeal}-like columnar ciliated epithelium

0 Most common bilateral epithelial ovarian tumor (50%)

0 Although it is believed that epithelial ovarian cancers arise from the surface epithelium of the ovary, increasing evidence indicates that some high-grade serous ovarian cancers arise from the fimbrial end of the Fallopian tube rather than the ovary. Therefore, serous epithelial ovarian tumors are divided into two different groups as type I (low grade) and type II (high grade) according to their cell origin, molecular pathogenesis and biological behavior.

Types of Serous Ovarian Cancer

TYPE I Serous Ovarian Cancer

• Has a slower developmental stage.

• Includes serous borderline tumors and low grade serous carcinomas.

• They are genetically stable tumors.

- • It is characterized by K-ras and B-raf mutations.

TIP 2 serous Ovarian Cancer (More Common)

• They are highly aggressive and mostly advanced stage tumors that grow rapidly, lack well-defined precursor lesions.

• They start from the fimbrial end of the fallopian tube.

• They are not genetically stable.

• They contain p53 and BRCA mutations.

Primary peritoneal tumors are histologically indistinguishable from serous tumors of the ovary.

Endometrioid Cystadenocarcinoma (10%)

0 Endometriosis can be observed in the pelvis or ovary in most of the cases (up to 40%).

0 These are tumors that are similar to grade I or 2 endometrioid adenocarcinomas in the uterine corpus. It is the most common ovarian tumor associated with endometrial cancer and is accompanied by endometrial adenocarcinoma in 15-20% of cases (synchronous multifocal disease).

Mucinous Cystadenocarcinoma (5%)

0 These tumors are the largest of the ovarian tumors (16-17 cm).

0 Well-differentiated tumors resemble mucin-secreting intestinal or endocervical epithelium. Therefore, it may be difficult to distinguish it from gastrointestinal carcinoma metastasis only histologically without clinical correlation. High-grade primary ovarian mucinous cancers are rare and metastasis must be excluded.

Pseudomyxoma peritonei can be seen in mucinous tumors, but the most common cause of this condition is appendiceal mucinous neoplasm or other primary gastrointestinal tumors. Therefore, appendix or other intestinal foci should be investigated and appendectomy should be performed in all cases.

Transitional Cell Carcinoma (Brenner tumor) ( < 1%)

0 99% of cases are benign and malignant Brenner tumor is extremely rare. It is transitional cell (similar to bladder epithelium). Coffee bean cells and Walthard islets are seen.

Clear Cell Carcinoma (Mesonephroid carcinoma) ( < % 1)

0 They are usually seen between the 5th and 7th decades and 2/3 of the cases are nulliparous women. Most are unilateral. It is often grade 3 and no grading is required.

0 There is a risk of developing hypercalcemia, hyperpyrexia or pelvic venous thrombosis paraneoplastically.

0 More than 50% of the cases are associated with ovarian or pelvic endometriosis. Focal endometriosis foci are common within the tumor, and mixed clear cell and endometrioid carcinomas may be seen.

Histologically, it is identical to clear cell carcinomas of the vagina and uterus that occur in young women as a result of inutero exposure to DES. Tumors lined with cells resembling mullerian epithelium histologically. Clear cells and hobnail cells are typical in tumors.

Typically, the tumor is limited to the ovary, but 20% of cases are advanced-stage tumors that are resistant to platinum-based chemotherapy and have a worse prognosis than serous carcinomas.

Borderline Epithelial Ovarian Cancers (Low Malignant Potential Tumors)

0 It is the most common type of epithelial ovarian cancer in the reproductive age. It is commonly seen in premenopausal women and younger age. The average age of onset is 46. The prognosis is usually very good.

Diagnosis of borderline epithelial ovarian tumors criteria

1. Mild nuclear atypia

2. Slightly increased mitotic activity

3. Microscopic papillary projection (micropapillary and cribriform structure)

4. Epithelial stratification; Epithelial hyperplasia with pseudostratification

5. Cellular pleomorphism and discrete cell clusters

6. Absence of destructive stromal invasion (no tissue destruction)

0 At diagnosis, the tumor is usually confined to the ovary and more than 80% of all cases have stage I disease. Rarely, peritoneal implants can be seen and these implants can be invasive or noninvasive.

0 Resection of the primary tumor is sufficient for treatment.

Treatment in Epithelial Ovarian Cancers

► In general, primary treatment in early stage cancers is total abdominal hysterectomy + bilateral salpingooopherectomy and staging surgery. In advanced disease, cytoreductive surgery should be performed if the patient is medically stable. In other words, it is aimed to remove all of the tumor and metastatic masses as much as possible (Debulking). Residual tumor diameter It should be < 1 cm.

► Platinum-based adjuvant chemotherapy is used after optimal surgery in epithelial ovarian cancers. All cases are given adjuvant chemotherapy, except for stage 1A or IB, grade 1 or 2 cancer. Commonly used chemotherapy regimen Paclitaxel + Carboplatin.

► PARP inhibitors (Niraparib, olaparib) can be used in platinum-sensitive epithelial ovarian cancers, especially in patients with BRCA mutations.

Germ Cell Ovarian Tumors

• 1/3 of all ovarian neoplasms are germ cell tumors. The most common germ cell ovarian tumor is mature cystic teratoma (dermoid cyst), and 95% of all germ cell tumors are benign. Germ cell tumors only

3% of them are malignant and they constitute 5% to 1% of all ovarian cancers. The most common malignant germ cell ovarian tumors are dysgerminoma, yolk sac tumor and immature teratoma.

• They originate from the primordial germ cells of the ovary. Due to the peculiarity of the migration pathway of germ cells in the embryological period, malignant germ cell tumors can also be seen in the mediastinum and retroperitoneum extragonadally.

• These tumors are tumors of the first 2 decades, but they can rarely be seen in the third decade. Most patients are diagnosed in stage I. Due to their sensitivity to chemotherapy, their prognosis is excellent even in advanced disease.

• Most of the signs and symptoms of germ cell tumors are related to tumor growth and hormone production. Germ cell tumors grow quite rapidly in contrast to epithelial ovarian tumors. They are usually manifested by subacute pelvic pain due to stretching of the capsule, hemorrhage or necrosis of the tumor. Hormonal changes are frequently observed in these tumors. They can cause irregular and excessive menstrual bleeding.

• 2 cm in the premenarchal age group. and above adnexal masses usually require surgical exploration. Preoperative hCG, AFP, LDH and Ca 125 levels should also be checked in young patients. Since germ cell tumors can develop from a dysgenetic gonad background, preoperative karyotype analysis should be performed in young patients with suspected germ cell tumors and in all premenarchal patients to determine whether both gonads should be removed.

• Classification of germ cell tumors is made according to histological features and the presence of tumor markers immunohistochemically.

Tumor Markers in Germ Cell Ovarian Tumors
dysgerminoma	AFP (-), hCG (±), LDH (+) Plasental ALP(+)
Endodermal Sinus Tumor	AFP(+), hCG (-)
immature teratoma	AFP(±), hCG (-)
choriocarcinoma	AFP(-), hCG (+)
Embryonal Carcinoma	AFP(+), hCG (+)
polyembryoma	AFP(±), hCG (±)
Mixed germ cell tumor	AFP(±), hCG (±)

Dysgerminoma (30-40%)

► It is the most common malignant germ cell ovarian tumor. 75% of the cases are between the ages of 10-30. It is the most common malignant ovarian tumor in pregnancy (20-30%)

► It is the most common malignant germ cell ovarian tumor with bilaterality. (10-15%)

► It develops from benign gonadoblastoma. Homologous to seminoma in males.

► Histologically, fibrous septa, granuloma and diffuse necrosis are found within the lobules. Therefore, it is confused with tuberculosis. Sometimes they may contain syncytiotrophoblastic giant cells, in which case precocious puberty or virilization is seen.

► The most common symptom is rapid enlargement of the abdomen.

► LDH and placental alkaline phosphatase (PLAP) levels increase in 95% of cases. AFP never rises in dysgerniomas. hCG is usually negative, but hCG levels may be elevated, typically < 100 IU, due to syncytiotrophoblasts in approximately 5% of cases.

► The most common form of spread is lymphatic spread and the most common lymphatic spread is ovarian tumor.

► Treatment is conservative surgery and the minimum surgery for dysgerminoma is unilateral salpingooopherectomy. In metastatic disease, adjuvant chemotherapy is applied. The most commonly used chemotherapeutic regimen is the BEP (bleomycin, etoposide, cisplatin) protocol.

► It is the only ovarian tumor sensitive to radiotherapy, but the superiority of chemotherapy over radiotherapy has been clearly demonstrated.

► Dysgerminoma is the tumor with the best prognosis among all malignant germ cell ovarian tumors.

Gonadoblastomas contain germ cells and sex cord stroma. They are defined as germ cell/sex cord stromal tumors according to the WHO classification.

Teratomas

Immature Teratoma (10-20%)

0 They arise from embryonic cells and contain immature embryonal structures and typically contain immature neuroepithelials. 50% of immature teratomas are seen between the ages of 10-20.

0 Tumor markers are often negative. In some pure teratomas, AFP may be elevated, but hCG will not. In some cases, there may also be elevated CA125, CA19-9 and CEA. The most common site of spread is peritoneal spread.

0 The most important prognostic factor is the grade of the tumor. The amount of immature neuroepithelial tissue is used to determine the grade and is associated with survival time.

0 Treatment consists of unilateral oophorectomy and marginal surgical staging for tumors confined to a single ovary in premenopausal patients. Routine contralateral wedge resection is not necessary, as they are rarely bilateral. Total abdominal hysterectomy + bilateral salpingooopherectomy and surgical staging should be performed in postmenopausal patients.

Mature Cystic Teratoma (Dermoid cyst)

It is the most common teratoma (95%). It also accounts for 10-25% of all ovarian neoplasms and 60% of all benign ovarian neoplasms. It is the most common non-functional ovarian tumor in the 2-3 decade. However, unlike other germ cell ovarian tumors, there is a wide age distribution.

10% shows bilaterality.

They contain endo, ecto and mesodermal components. The most common are the components of ectodermal origin (hair follicle, sebaceous and sweat glands). The karyotype is observed as 46 XX in all mature cystic teratomas. There is a risk of malignancy over the age of 40, but the incidence is low (1%).

0 The most common cancer of teratoma, which is completely benign at the beginning, is squamous cell carcinoma.

0 The most common complication is torsion and the most common torsion is ovarian tumor (15%).

0 Mature cystic teratomas are the most common benign ovarian tumors in pregnancy.

0 Cystectomy is sufficient for treatment, rarely oophorectomy.

Monodermal Tratoma

0 Struma ovarii is a benign teratoma. Its main component is the parenchymal tissue of the thyroid and gives clinical signs of hyperthyroidism. Treatment is simple surgical excision.

0 Carcinoid tumors arise from the gastrointestinal and respiratory epithelium within the teratoma. Most of the cases are postmenopausal. There is 5-HIAA excretion in the urine. The treatment is surgical excision.

Endodermal Sinus Tumor (EST) (Path Sac Tumor) (10%)

► It develops from the primitive vitelline sac and originates from the extraembryonic tissues. The mean age at diagnosis is 18 years and 1:3 of cases are in the premenarchal period.

► Very rapid growth is the characteristic finding. Abdominal or pelvic pain is the most common symptom (75%).

► Most tumors secrete AFP. The prevalence of the disease is also correlated with the level of AFP. The hCG level is normal. In a small proportion, detectable levels of alpha-I antitrypsin are secreted.

► Microscopically characteristic structures are Schiller-Duval bodies.

► Treatment is unilateral salpingooopherectomy. Surgical staging is not necessary for every patient, as every patient must receive absolute chemotherapy (BEP). There is no bilaterality and biopsy from the other ovary is strictly contraindicated as they are always unilateral.

► The most deadly malignant germ cell tumor is endodermal sinus tumor.

Embryonal Carcinoma

► They are primitive tumors consisting of undifferentiated epithelial cells, which are the precursors of many germ cell tumors and resemble cells in the embryonic disc structure. It is distinguished from choriocarcinoma by the absence of cyto and syncytiotrophoblast.

► Patients are characteristically younger than other germ cell ovarian tumors and the mean age at diagnosis is 14 years.

► They can sequester estrogen and accordingly, pseudopuberty precox and irregular bleeding can be observed.

► They secrete AFP and hCG

► Its treatment is unilateral salpingooopherectomy followed by combined chemotherapy (BEP).

polyembryoma

► It is a tumor in which embryoid bodies are observed and mimics early embryonic differentiation (endoderm, mesoderm, ectoderm).

► It has high AFP, and hCG levels.

► It tends to occur in very young, premenarchal girls and in premenarchal patients

may cause symptoms of pseudopuberty.

► It is very sensitive to chemotherapy.

Choriocarcinoma

► It originates from extraembryonic tissues.

► The vast majority are patients younger than 20 years of age. Rarely, it can be bilateral.

► There are high hCG levels. Premenarchal patients with high hCG levels have isosexual precocious puberty at 50%. In women of reproductive age, it can cause irregular and heavy menstrual bleeding.

► Since most of the patients have organ parenchymal metastases at the time of diagnosis,

The prognosis is very poor.

Mixed Germ Cell Tumors

► The most common coexisting structures are dysgerminoma (80%) and endodermal sinus tumor (70%). In addition, immature teratoma (53%), choriocarcinoma (20%) and embryonal carcinoma (16%) may accompany dysgerminoma.

► Depending on the type of their components, AFP and hCG may be secreted or none of them may be secreted.

► The most important prognostic factor is tumor size and the rate of presence of the most malignant component.

► Treatment should be determined according to the component other than dysgerminoma. BEP chemotherapy should be preferred after surgery in treatment.

There is no indication for adjuvant chemotherapy in stage IA dysgerminoma and stage IA, grade I immature teratomas. Adjuvant chemotherapy (BEP) should be given in all other and more advanced germ cell ovarian tumors.

Sex Cord-stromal Tumors

• This group of tumors originates from the sex cords of the gonad and the ovarian stroma (or mesenchyme). At the time of diagnosis, they are usually limited to one ovary and most of them have low malignant potential, and the primary treatment is surgical resection. Relapses are infrequent and recurrences are usually seen late and in the abdomen or pelvis.

• Almost all (90%) of these tumors produce hormones, and affected patients typically have symptoms and signs related to estrogen or androgen release.

• Unlike epithelial ovarian cancers and malignant germ cell ovarian tumors, they can be seen in all age groups.

Tumor Markers in Sex Cord Stromal Ovarian Tumors
Granulosa cell tumor (adult or juvenile)	Inhibin A and Inhibin B estradiol; Unreliable
Sertoli-Leydig cell tumor	Inhibin A and Inhibin B Alphafetoprotein (sometimes)
Sex cord stromal tumor with annular tubules	inhibin A and inhibin B
Steroid cell, not otherwise named	steroid hormones

Immunohistochemical staining with inhibin is used to differentiate ovarian sex cord stromal tumors from epithelial, germ cell and other spindle cell neoplasms.

Modified WHO Classification of Sex Cord Stromal Ovarian Tumors

A) Pure Stromal Tumors

Fibroma/fibrosarcoma

thecoma

sclerosing stromal tumor

Leydig cell tumor

steroid cell tumor

B) Pure Sex Cord Tumors

Granulosa cell tumor; Adult and juvenile type

Sertoli cell tumor

Sex cord stromal tumor containing annular tubules

C) Mixed Sex cord-stromal tumors

Sertoli-Leydig cell tumor

sex cord stromal tumors, NOS; Tumors not otherwise named

Granulosa Cell Tumor

► It is the most common malignant sex cord stromal tumor. There are adult (95%) and juvenile (5%) types.

► 20 cm to millimeter dimensions. Only 2% of cases are bilateral.

► DNA ploidy of the tumor is associated with survival and is an independent prognostic factor.

Adult type

0 It is most common in the 45-55 age group (immediately after menopause). 20 cm from millimeter dimensions. as much as they can.

0 Somatic point mutations are observed in the gene encoding FOXL2 (forkheaf box protein L2) in all adult type tumors. However, it is not available in juvenile form.

0 They usually secrete estrogen. Most patients in the reproductive period have menstrual irregularities or amenorrhea. Abnormal uterine bleeding is a common symptom in postmenopausal women. The most common causes of endometrial hyperplasia (25-50%) and endometrial cancer (5%) are ovarian tumors. For this reason, endometrial biopsy should be performed first for a premenopausal patient with a granulosa cell tumor in the ovary.

0 Granulosa cell tumors tend to be hemorrhagic and often rupture, causing hemoperitoneum.

0 Characteristic Call-Exner bodies are found

0 Inhibin is released from granulosa cell tumors and is a very useful marker in diagnosis and follow-up.

0 The adult type has a long natural course and is prone to late relapse.

0 If there is a desire to have children in early stage tumors, conservative surgery (unilateral salpingooopherectomy) is sufficient. Hysterectomy and bilateral salpingooopherectomy should be performed in perimenopausal and postmenopausal women.

juvenile type

0 They are the most common functional tumors in childhood. Affected patients often have menstrual irregularity or amenorrhea. In prepubertal patients, they typically cause isosexual pseudopuberty precox (75%) due to estrogen secretions.

0 Acute abdomen due to hemoperitoneum resulting from preoperative rupture is seen in 5-10% of the cases.

0 Concomitantly, Olier's Disease or Maffuci Syndrome may be seen.

0 Call-Exner bodies are rarely observed.

0 Less aggressive than the adult type. However, in advanced stage tumors, they are more aggressive than the adult type, and the relapse time and time of death are shorter.

0 Conservative surgery (unilateral salpingooopherectomy) is sufficient for early stage tumors.

thecoma

0 They are rarely malignant and typically occur in postmenopausal women (mid 60s). Bilateral ovarian involvement is rare (2-3%).

0 Among the sex cord stromal tumors, they are the most hormonally active tumors and generally secrete estrogen. Therefore, abnormal vaginal bleeding may occur. 78% of the cases are associated with endometrial hyperplasia and 21% with endometrial cancer.

0 They are clinically benign tumors and surgical excision is curative.

Endometrial biopsy should be taken in cases of granulosa cell ovarian tumor and thecoma, especially if fertility-sparing surgery is planned.

Fibroma

► They can be seen in all age groups, but are often seen in perimenopausal and menopausal women. They are hormonally inactive

► It is of mesothelial origin. They are rarely bilateral. They are solid and usually benign tumors.

► The presence of pleural effusion (hydrothorax) and ascites in the abdomen is called Meigs Syndrome. Fibromas are benign and in case of paracentesis, no malignant cells are seen in the ascitic fluid.

► Gorlin Syndrome, on the other hand, is a syndrome characterized by the presence of basal cell nevi and some hereditary anomalies in the early stages of life, usually characterized by bilateral ovarian fibromas.

► Treatment is unilateral salpingooopherectomy in benign fibroma

Sertoli Cell Tumor

► They are known as well-differentiated androblastoma. They are usually unilateral and the average age of onset is 30.

► Most of these tumors are clinically nonfunctional, but 25% of the cases may cause estrogenic or androgenic findings. Menstrual irregularity, postmenopausal bleeding, isosexual precocious puberty or increased libido may be observed due to estrogenic activity, as well as virilization due to androgenic activity.

► Rarely, the picture accompanies hyperaldosteronism, hypokalemia and hypertension.

► Conservative surgery is used in the treatment.

Sertoli Leydig Cell Tumor

► More than 90% of the cases occur in the reproductive age (usually in the 3rd and 4th decades), and 75% of the cases are under the age of 40. Their malignancy potential is low.

► They typically secrete androgens and virilization is seen in 70%-SS of patients. They are the most common virilizing tumors in women of reproductive age. Virilization findings; amenorrhea, breast atrophy, acne, hirsutism, clitoromegaly, deepening of the voice, and thinning of hair following oligomenorrhea. Plasma testosterone and androstenedione levels are increased, DHEA-S level is within normal limits or slightly elevated. Rarely, estrogenic activity can be seen.

► In women of reproductive age, unilateral salpingooopherectomy and evaluation of the contralateral ovary are usually sufficient. In older women, hysterectomy and bilateral salpingooopherectomy are appropriate approaches.

gynandroblastoma

► It is the rarest sex cord stromal ovarian tumor.

► Contains granulosa-theca and Sertoli-Leydig cell components. They are generally unilateral, small and benign.

► It can be estrogenic and/or androgenic as well as hormonally neutral.

► Contains intracytoplasmic Reinke crystals from Leydig cell components. It contains Call Exner bodies from granulosa cell components.

► Treatment is conservative surgery (unilateral salpingooopherectomy).

Steroid cell Tumor

Leydig Cell Tumor (hilar or nonhilar)

► It is a clinically benign tumor and typically occurs in postmenopausal women.

► Inclusions called intracytoplasmic Reinke crystalloids are characteristic

► They secrete testosterone and are often (3/4) associated with androgenic effects.

Steroid cell tumor (NOS) not otherwise classified

► It is characteristically seen in young women of reproductive age.

► Typically associated with androgen production (50% of cases) but overproduction of estrogen or cortisol (Cushing's Syndrome) has also been reported.

► 1/3 of the cases are clinically malignant and their prognosis is poor.

Sex Cord Tumors with Annular Tubules

► These tumors are divided into two subgroups according to whether they are accompanied by gastrointestinal polyposis and oral-cutaneous melanin pigmentation (Peutz-Jeghers Syndrome).

Those associated with Peutz-Jeghers Syndrome;

► 1/3 of cases. They are typically small, bilateral, and clinically benign tumors. The average age of onset is 27. In 15% of cases, adenoma malignum (a rare and well-differentiated adenocarcinoma) develops in the cervix. Treatment is conservative.

Those unrelated to Peutz-Jeghers Syndrome;

► It is 2/3 of the cases. Typically, this group is large, unilateral, and has a 15-20% rate of carrying a clinical malignancy. The average age of onset is 34. Surgical staging and TAH + BSO must be performed in the treatment.

Sclerosing stromal tumor

► They are rarely seen and the average age of occurrence is 20 years. They are clinically benign tumors and are typically unilateral. To the hormonal are inactive tumors.

► Contains histologically prominent areas of sclerosis.

Staging in Sex Cord Stromal Ovarian Tumors

Surgical

A) Staging Surgery IS REQUIRED

Granulosa cell tumor; Adult or juvenile type Fibrosarcoma

Sertoli-Leydig cell tumor (moderate or poorly differentiated type) Sex cord stromal tumor with annular tubules (type unrelated to Peutz-Jeghers Syndrome)

steroid cell tumor

B) Staging Surgery is NOT Necessary

• Tekoma

• Fibroma

• Sclerosing stromal tumor

• Gynandroblastoma

• Sertolileydig cell tumor (well-differentiated type),

• Sex cord stromal tumor with annular tubules (type associated with Peutz-Jeghers Syndrome)

Lipoid cell ovarian tumor; It is a tumor originating from adrenal cortex remnants at the edge of the ovary. It is often associated with virilization. Rarely, corticosteroid secretion is observed and may be accompanied by obesity, hypertension and glucose intolerance.

Small cell ovarian cancer; There are hypercalcemic and pulmonary types. Hypercalcemia is observed in 2/3 of hypercalcemic type tumors and is associated with SMARCA4 gene mutation.

Metastatic Ovarian Tumors (5-6%)

• Approximately 5-6% of ovarian tumors develop as a result of metastasis from other organs. These metastases often originate from the genital tract, breast, or gastrointestinal tract. Metastases to the ovary occur by direct adjacency, hematogenous lymphatic or transcoelomic routes.

Gynecological Metastases

► The most common cancer that metastasizes to the ovary is endometrial cancer. Although 5% of endometrial cancers spread directly to the ovary, the probability of synchronous coexistence of the two cancers is much higher than this figure (often endometrial adenocarcinoma + ovarian endometrioid adenocarcinoma).

► Tubal cancers can spread through the direct neighborhood and can also involve the ovary secondary in 13% of cases.

► Secondary spread of cervical cancers to the ovary is extremely rare (<1%). Most of these cases are adenocarcinoma or advanced stage cases.

Non-gynecological Metastases

The most common source of nongynecological metastatic carcinoma is the tubular gastrointestinal tract, especially colon cancer, followed by the breast and pancreatobiliary tract.

► Metastases of breast cancers to the ovary are very common and 80% of these cases were found to be bilateral.

► 30-40% of ovarian metastatic cancers are Krukenberg tumors

These tumors arise from the stroma of the ovary and classically contain signet ring cells filled with mucin. The primary tumor is most often in the stomach, less often in the colon, appendix, breast, or biliary tract. Very rarely, the primary tumor may also be in the cervix or bladder. Krukenberg tumors are also mostly bilateral.

► Colon cancer and, less frequently, pancreatic-biliary tract, appendix and small intestine cancers are among the other GIS-derived metastases that are not included in the Krukenberg group.

► Metastases of malignant melanoma and carcinoid tumors to the ovary are very rare. In lymphoma and leukemia, the ovaries can also be involved, which is usually bilateral. The most common lymphoma that metastasizes to the ovary is Burkitt lymphoma.

Pathognomonic microscopic markers in ovarian tumors
Histological Type	Pathognomonic Microscopic Marker
serous	psammoma body
mucinous	goblet cell
Clear cell (mesonephroid tumor)	Clear cells and hobnail cells
Brenner	Walthard islets
Endodermal sinus tumor	Schiller-Duval bodies
Granulosa cell tumor	Call Exner body
Leydig cell tumor	intracytoplasmic Reinke crystals
Krukenberg tumor	stone body cell
carcinoid tumor	respiratory epithelium

Pregnancy and Ovarian Tumors

• Pregnancy does not affect the prognosis of many ovarian tumors; however, complications such as torsion or rupture are common and lead to spontaneous abortion and preterm labor frequently.

• Torsion is the most common complication of ovarian tumors during pregnancy. More than half of the torsions are either in the 8-16th week, when the uterus enlarges rapidly. It happens during the puerperal involution of the uterus.

Pregnancy and Ovarian Tumors

Bening ovarian tumors (95%)

• Mature cystic teratoma (dermoid) (most common)

• Serous cystadenoma

• mucinous cystadenoma

Malignant ovarian tumors (5%)

• Malignant epithelial tumors (most common)

• Dysgerminoma (most common alone)

• Malignant sex-cord stromal tumors

Malignant and pre-malignant diseases affecting the uterus

noreply@blogger.com (Unknown) — Sat, 18 Feb 2023 12:33:00 +0300

Endometrial hyperplasia

• They are lesions that progress with proliferation in the glandular epithelium and stroma of the endometrium lining the uterine cavity and may undergo malignant degeneration. The pathological process can cover the entire endometrial cavity diffusely, or it can be seen focally in one or more areas.

• Severe hyperplasia often develops on the background of the proliferative endometrium, which occurs as a result of prolonged estrogen stimulation in the absence of progestin effect.

Risk factors

1. Anovulatory cycles in teenage girls and perimenopausal women (most common cause)

2. Endogenous estrogen-producing tumors (granulosa cell tumor, thecoma)

3. Early menarche (menarche before 12 years old)

4. Use of exogenous estrogen without progesterone

5. Liver failure (decreased estrogen breakdown and increased serum estrogen level)

6. Tamoxifen use

7. Obesity

Clinic

• The most common symptom is abnormal uterine bleeding. However, they can also be asymptomatic.

Diagnosis

• In order to predict endometrial hyperplasia in individuals with abnormal uterine bleeding, first of all, endometrial thickness should be measured by ultrasonography. Endometrial biopsy is required for definitive diagnosis.

Classification

• Hyperplasia without Atypia

► Simple (cystic) hyperplasia

► Complex (adenomatous) hyperplasia

• Hyperplasia with Atypia

► Simple (cystic) hyperplasia

► Complex (adenomatous) hyperplasia

Prognosis of endometrial hyperplasia
Type of Hyperplasia	Regression	Progression to cancer
Simple atypia (cystic) hyperplasia	80%	1%
Complex atypia (adenomatous) hyperplasia	% 70 - 75	3%
Simple atypia (cystic) hyperplasia	% 70 - 75	8%
Hyperplasia with complex atypia (adenomatous)	50%	29%

• The vast majority (74%) of hyperplasia regresses or remains constant (18%). The risk of hyperplasia progressing to cancer depends on the presence and severity of cytological atypia.

• When hysterectomy was performed in 25-43% of cases diagnosed with atypical hyperplasia as a result of endometrial biopsy, it was found to be associated with well-differentiated endometrial cancer.

Treatment

• Progesterone (oral, intramuscular or intrauterine LNG-IUD) is used in treatment

. Periodic endometrial biopsy or transvaginal ultrasonography should be performed, especially in patients treated for hyperplasia with atypia, since 25-43% have an undiagnosed endometrial cancer and a high recurrence rate (25%) after treatment.

• In premenopausal cases with complex hyperplasia with atypia, hysterectomy is recommended if there is no expectation of fertility. Hysterectomy should be performed in postmenopausal hyperplasia with atypia.

Oral progesterones are ineffective in the prevention and treatment of endometrial hyperplasia that may develop as a result of tamoxifen use.

ENDOMETRIUM CANCER

• It is the most common gynecological cancer in developed countries.

• It is a disease of especially old, postmenopausal women. The average age at diagnosis is 60 years. It is the cancer with the best prognosis among gynecological cancers. 80% of endometrial cancer patients are diagnosed in stage I.

pathogenetic classification

• There are 2 different types pathogenetically.

Types of endometrial cancer

Type 1 endometrial cancer; Estrogen-related, endometrioid

• More often (80-90%)

• Young age, perimenopausal period, obese, Caucasian patients

• Estrogen dependent (unopposed estrogen exposure; chronic anovulation, PCOS or estrogen replacement)

• Estrogen and progesterone receptors are generally positive.

• It develops on the background of endometrial hyperplasia

• Good histological type (endometrioid adenocarcinoma)

• Well and moderately differentiated (low grade)

• Minimal myometrial invasion

• Good prognosis and stable tumor

• Diploid

• PTEN gene mutation (most common mutation in Type 1 tumor), CTNNB1 (Beta-catenin), PIK3CA, K-ras and gene mutation and microsatellite instability

Type 2 endometrial cancer; estrogen unrelated, non-endometrioid

• Less (10-20%)

• Elderly, postmenopausal, thin, non-white, multiparous and smoking women

• Estrogen independent (sporadic)

• Estrogen and progesterone receptors are generally negative.

• There is no endometrial hyperplasia (it develops even on the background of atrophy), some of it may develop from the background of serous in situ cancer (endometrial intraepithelial carcinoma).

• Poor histological type (clear cell carcinoma, papillary serous carcinoma)

• Poorly differentiated (high grade)

• Deep myometrial invasion

• Poor prognosis and aggressive tumor

• Aneuploid

• P53 tm suppressor gene mutation, high Ki-67 index, chromosomal instability, loss of HER/2neu, p16, e-caderin and heterozygosity

Risk factors

• The most common risk factor is prolonged unopposed estrogen stimulation and most cases are due to unopposed estrogen.

Endometrial cancer risk factors	relative risk
1. Complex endometrial hyperplasia with atypia	29
2. Hereditary nonpolyposis colorectal cancer Syndrome (Lynch syndrome)	20
3. Simple endometrial hyperplasia with atypia	8
4. Obesity(It increases 3 times in those who are 10-23 kg overweight, 1O times in those who are >23 kg overweight)	3--20	2--3
5. Unopposed estrogen therapy; The risk increases with duration and dose.	4--8	10--20
6. Tamoxifen treatment	2--3
7. Nulliparity	2--3	3
8. Diabetes mellitus and insulin resistance	2,8	1,3-3
9. Late menopause (> 52 years)	2,4	2--3
10. Early menarche		1,5-2
11. History of menstrual irregularity,		1,5
12. Anovulatory cycles and polycystic ovary syndrome		>5
13. Infertility		2--3
14. Estrogen-secreting ovarian tumors (granulosa cell ovarian tumor, thecoma)		>5
15. Hypertension (concurrent pathology)		1,3-3
16. Hypothyroidism (concurrent pathology)		1,3-3
17. Gallbladder diseases		1,3-3
18. Advanced age		2--3
19. Residing in North America or Northern Europe		3--18
20. High socioeconomic or cultural level		1,5-2
21. White race		2
22. History of Pelvic Radiotherapy

Multiparity, combined oral contraceptives, progesterone therapy (eg, progesterone-containing intrauterine devices), smoking, and menopause before age 49 reduce the risk of endometrial cancer.

Histopathological Classification

Endometrioid adenocarcinoma (80%)

► It is the most common endometrial adenocarcinoma.

► Variants of endometrioid adenocarcinoma:

- Endometrial carcinoma with squamous differentiation: In the past, benign ones were called adenoacanthoma, and malignant ones were called adenosquamous carcinomas.

- Villoglandular (papillary) carcinoma

- Secretory carcinoma: These are the tumors with the best prognosis and are usually in the early stage and do not metastasize

Mucinous carcinoma 45%

► More than half of the tumor cells contain intracytoplasmic mucin. The prognosis of these tumors is good. Cervical, ovarian and intestinal tumor metastases should be investigated.

Tumors that are estrogen receptor positive, progesterone receptor positive, vimentin positive and p16 negative are almost always of endometrial origin.

Serous carcinoma (3-4%)

► It is the most aggressive histological type among endometrial cancers. These tumors are considered high-grade lesions and show deep myometrial invasion, mostly with lymphovascular space involvement. It tends to mimic epithelial ovarian carcinoma and spread into the abdomen.

► Serous carcinomas usually occur in elderly, hypoestrogenic women with advanced disease. Psammoma bodies are present in most cases. Severe p53 immune reactivity is observed in serous cancers.

Serous Adenocarcinoma in situ; It is called endometrial intraepithelial carcinoma because of its intraepithelial spread pattern and is considered as a precursor of serous carcinoma.

Clear cell carcinoma ( < 5%)

It is frequently seen in elderly women and has a very poor prognosis.

squamous carcinoma

It is very rare. Cervical stenosis, chronic inflammation often occurs at the time of diagnosis.

and together with the pyometra. It is one of the tumors with a poor prognosis.

Endometrial and ovarian cancers are the most frequently associated tumors among genital malignancies.

Serous and clear cell tumors can always be considered high grade and may not be graded.

Screening and Diagnosis

• There is no suitable method to screen populations for endometrial cancer. Since only 50% of the cases can be detected with scans, screening should be done in certain cases. These:

► Those with Lynch Syndrome (familial hereditary non-polyposis colorectal cancer) syndrome

► Those who use hormone replacement therapy without progesterone, especially in the postmenopausal period

► Premenopausal women with a history of anovulatory cycles such as Polycystic Ovary Syndrome

Contrary to these situations, routine screening with transvaginal ultrasonography or endometrial biopsy is not beneficial in patients using tamoxifen for breast cancer.

• Pap smear: In endometrial cancer, the probability of seeing malignant cells in smear is 30-50%, and therefore it is not a reliable screening method.

• Transvaginal ultrasonography; Ultrasonographic findings requiring further evaluation in postmenopausal women; endometrial double wall thickness >= 5 mm, presence of polypoid endometrial mass and presence of fluid in the uterus.

• Endometrial biopsy: Pipelle endometrial aspiration biopsy is the most appropriate method and is the first-line method in research.

Patients whose diagnosis of endometrial cancer should be excluded

1. All patients with postmenopausal bleeding

2. Postmenopausal women with pyometra

3. Perimenopausal women with intermenstrual bleeding or increased heavy menstrual bleeding

4. Premenopausal women with abnormal uterine bleeding (especially those with a history of anovulation)

5. Asymptomatic postmenopausal women with benign endometrial cells in PAP smear

6. Women aged 35 years and older with atypical glandular cells (AGC) in the PAP smear; Patients under 35 years of age with risk factors for endometrial disease (history suggestive of abnormal uterine bleeding or chronic anovulation).

• Abdomino-pelvic tomography; It is useful in cases where metastasis is suspected such as elevated LFT, hepatomegaly, ascites in the abdomen, abdominal mass, and extrauterine disease. Cystoscopy should be performed for suspected bladder involvement, rectosigmoidoscopy for suspected rectal involvement, colonoscopy if stool occult blood (+) should be performed. Magnetic resonance imaging gives information about myometrial invasion.

Spread

Direct spread to neighboring organs (most common form of spread)

► It is the most common form of spread. Cervix, tuba, and finally the vagina and parametrium can be invaded.

Transtubal spread of exfoliated cells into the peritoneal cavity

► Responsible for peritoneal relapses.

lymphatic spread

► Lymphatic spread is more common especially in those with lymph node involvement or cervical stromal invasion.

Hematogenous spread

► It is the least common form of spread (most commonly lung, liver, brain and bone). The strongest predictor of hematogenous recurrences is the presence of deep myometrial invasion.

Clinic

• There is vaginal bleeding in 90% of cases. Sometimes bleeding may not be observed due to cervical stenosis in very elderly patients, in such cases hematometra or pyometra may also be added to the picture, and this is usually associated with a poor prognosis.

Staging

• Surgical staging should be performed in all eligible patients.

FIGO Staging (Surgical)
1	The tumor is confined to the corpus
1A	No myometrial invasion or myometrial invasion < 1/2
1B	Myometrial invasion >=1/2
2	There is cervical stromal invasion but no extension beyond the uterus
3	Tumor outside the uterus, with pelvic extension
3A	Invasion of serosa and/or adnexa
3B	Vaginal metastases and/or parametrial involvement are present
3C	Pelvic and/or paraaortic lymph node metastasis
3C1	Pelvic lymph node metastasis
3C2	Paraaortic lymph node metastasis (with or without pelvic lymph node)
4	Bladder mucosal invasion and/or bowel mucosal invasion and/or distant metastases
4A	Invasion of the bladder and/or intestinal mucosa
4B	Metastases, including intra-abdominal metastases and/or inguinal lymph node metastases

It is a gynecological malignancy in which inguinal lymph node involvement is distant metastasis (Stage 4B). Endocervical glandular involvement is in Stage I. Positive abdominal cytology, size of the uterus and grade of the tumor do not change the stage.

Prognosis

Prognosis Factors

1. Stage of the disease (the most important prognostic factor)

2. Lymph node metastasis (clinically the most important prognostic factor in early stage cancers)

3. Age; Advanced age is a poor prognostic criterion

4. Histological type (recurrence and distant metastasis increased in nonendometrioid types)

5. Histological grade

6. Nuclear grade

7. Myometrial invasion (involvement of the outer 1/2 leads to passage into the lymphatic system and is a strong predictor of hematogenous recurrences)

8. Lymphovascular space invasion

9. Isthmus-cervix extension

10. Adnexal involvement

11.Intraperitoneal tumor

12. Tumor size (> 2 cm, the prognosis worsens)

13. Peritoneal cytology

14. Hormone receptor status (P and E receptor (+) cases have a better prognosis)

15. DNA ploidy (prognosis worsens as aneuploidy increases)

16. Type of treatment (surgery versus radiotherapy)

17. Genetic/molecular tumor markers:

K-ras mutation

Decreased expression of E-cadherin

Increased expression of the HER-2/neu oncogene

c-erb-B2 expression

Mutation in the p53 suppression gene (present in 90% of serous tumors and accompanying advanced stage)

PTEN gene mutations (accompanies endometrioid tumor and good differentiation)

MIB-1 (Ki 67) expression: It is a poor prognostic criterion

Microsatellite instability: It is a good prognostic criterion.

MLHL inactivation: It is a common evidence of type I cancer.

p16 inactivation

Treatment

• The standard approach is hysterectomy + bilateral salpingooopherectomy + peritoneal cytology and surgical staging. During surgical staging, lymphadenectomy should also be performed if the following conditions are accompanied;

► Grade III tumors

► Patients with Grade II and >2 cm tumors

► Patients with clear cell or serous carcinoma

► Myometrial invasion >50%

► Patients with cervical involvement;

► Extrauterine disease (abdominal metastasis)

• Adjuvant radiotherapy is used to prevent recurrence in cases such as grade 3 tumors, tumors with deep myometrial invasion, and tumors with lymph node metastases. Adjuvant radiotherapy is not required in stage IA, grade 1 or 2 tumors without lymphovascular invasion.

• Fertility-preserving treatment is generally preferred only in grade I (type 1 tumor) adenocarcinomas without myometrial invasion in imaging methods, and high-dose progesterone is used.

recurrence

• More than 10% of recurrences occur within the first 2 years, and nearly half of asymptomatic recurrences are detected by chest radiographs. CA-125 level is usually high in relapses.

• Local recurrences are most common (most common in the vaginal cuff). The places where extrapelvic metastases are seen are; most commonly lung, followed by abdomen, lymph nodes (paraaortic, supraclavicular, inguinal), liver, brain and bone.

uterine sarcomas

0 They are malignancies arising from tissues of embryonic mesodermal origin. They constitute 3-7% of malignant tumors of the uterus. Their biological behavior is aggressive and their prognosis is poor.

• Risk factors include chronic excessive estrogen exposure (eg, use of combined hormone replacement therapy for 5 years or more), tamoxifen use, race (African-American), and history of pelvic radiotherapy.

Histopathological Classification

Pure Sarcomas

► Homologous Sarcomas

0 Endometrial stromal sarcoma

- low grade

- High grade or undifferentiated stromal sarcoma

0 Smooth muscle tumors

- Leimyosarcoma

- Leiomyoblastoma

- Metastatic tumors with benign histological appearance

• Intravenous leiomyomatosis

• Metastatic uterine leiomyoma

• Leiomyomatosis peritonealis disseminata

► Heterologous Sarcomas

rhabdomyosarcoma

chondrosarcoma

osteosarcoma

liposarcoma

mixed epithelial-nonepithelial tumors

► Malignant mixed mullerian tumor

0 Homologous (carcinosarcoma) Carcinoma + homologous sarcoma

0 Heterologous (mixed mesodermal sarcoma); Carcinoma + heterologous sarcoma

► Adenosarcoma Benign epithelial component + sarcomatous stroma

The most common uterine sarcomas are leiomyosarcoma (60%) and endometrial stromal sarcoma (20%), respectively.

Carcinosarcomas were classified by FIGO in 2009 as a metaplastic form of high-grade endometrial carcinoma, but the term carcinosarcoma still remains in the 2014 WHO classification.

Clinic

• The most common symptom is abnormal vaginal bleeding. Pelvic or abdominal pain is also common. 1/3 of the cases complain of rapid abdominal enlargement, prolapse of the sarcomatous polyp from the cervix, or bleeding with clots.

Endometrial Stromal Tumors

• Most of the patients are in the perimenopausal 45-50 age group. It has nothing to do with radiotherapy and parity. The most common symptom is abnormal uterine bleeding. Diagnosis can be made by endometrial biopsy, but usually the preliminary diagnosis is leiomyoma.

► Endometrial stromal sarcoma

► Low grade endometrial stromal sarcoma

► High grade endometrial stromal sarcoma (Undifferentiated Sarcoma)

leiomyosarcoma

• Malignant tumors arising from smooth muscle cells in the myometrium or smooth muscle in the uterine blood vessels. It may be associated with a history of pelvic radiotherapy, but not with parity. The mean age at diagnosis is 54 years, and it is seen at a younger age compared to other uterine sarcomas, and survival is higher in the premenopausal group. Especially in a postmenopausal case, if the uterus is growing rapidly, it should be considered.

• Symptoms include abnormal uterine bleeding, a feeling of pressure or pain in the pelvis, and a pelvic mass. It is less likely to be diagnosed with endometrial biopsy. Dynamic MRI together with LDH-3 measurement can diagnose preoperative leiomyosarcoma with high accuracy.

• The histological diagnostic criteria of leiomyosarcomas include the mitotic index, the degree of nuclear atypia, and the presence of coagulation necrosis.

• Total abbominal hysterectomy + bilateral salpingooopherectomy + debulking surgery of tumors outside the uterus + removal of enlarged lymph nodes is applied in the treatment. Adjuvant chemotherapy is given. RT has no relapse-reducing effect in leiomyosarcomas.

Malignant Mixed Müllerian Tumor (MMMT)

• Homologous (Carcinosarcoma): Microscopically, they are in the form of a mixture of malignant epithelial and malignant mesenchymal components (homologous sarcoma). It may be associated with a history of pelvic radiotherapy. Almost all are seen in the postmenopausal age (62 years). The tumor protrudes out of the cervical canal like a polyp in almost half of the patients. The diagnosis is usually made by endometrial biopsy taken from the polypoid mass filling the cavity or from its protruding part. Total hysterectomy, bilateral salpingooopherectomy, pelvic-paraaortic lymph node dissection in treatment

+ adjuvant KT is applied.

• Heterologous: Microscopically, they are a mixture of malignant epithelial and malignant mesenchymal components (heterologous sarcoma).

adenosarcoma

• They are low-grade tumors, typically characterized by a benign epithelial component and a malignant mesenchymal component. It is mostly seen in postmenopausal women. It is typically in the form of a polypoid lesion that protrudes out of the cervical canal. The basis of treatment is hysterectomy and bilateral salpingooopherectomy and adjuvant RT.