ObGyn | Clinical Briefings™: Clinical Reports from Penn Medicine

Surgical Correction of Uterus Didelphys with Obstructed Hemivagina

2011-10-14T09:01:00.002-04:00

Surgeons with the Department of Obstetrics and Gynecology at Penn Medicine are performing minimally invasive laparoscopic surgery to correct rare congenital anomalies in adolescents and young women, including uterus didelphys with obstructed hemivagina, a condition characterized by the duplication of the uterus, cervix and vagina and congenital absence of the ipsilateral kidney (see Figure 1).

Uterus didelphys is the result of a developmental anomaly of the urogenital septum and is linked etiologically with fetal renal development. In between 15 percent to 30 percent of females with uterus didelphys, one of the vaginal openings is obstructed by the transverse position of the septa (often the right side), resulting in a “blind,” hemivagina. This anomaly is often present in women with ipsilateral renal agenesis and other renal abnormalities.

The rarity and complexity of uterus didelphys with blind hemivagina make its diagnosis uniquely dependent upon the experience of the provider. Diagnosis rarely occurs prior to menarche, when acute symptoms resulting from menstrual fluids trapped in the obstructed vagina occur. Symptoms and findings may include dysmenorrhea, acute lower abdominal or pelvic pain, recurrent pain and/or a paravaginal mass. Endometriosis is not uncommon in these patients.

Specialists with the Penn Center for Advanced Gynecologic Surgery at Penn Fertility Care have extensive experience in the treatment of congenital anomalies, including uterus didelphys. At Penn, ultrasound and/or pelvic MRI confirms the diagnosis of uterus didelphys with blind hemivagina. The standard of care for this condition involves minimally invasive surgical techniques that optimize preservation of reproductive potential and evacuate the trapped contents of the obstructed vagina.

Typically, this procedure is done vaginally by removing a portion of the vaginal septum to allow the accumulated menstrual blood to be released and to connect the two sides to make a single vagina. Sometimes laparoscopy is performed at the same time to evaluate and treat co-existing endometriosis and adhesions caused by the flow of menstrual blood backwards through the fallopian tubes due to the vaginal obstruction.

Case Study

CJ, a 14-year-old female, was referred to Penn Medicine by her primary care provider with acute lower abdominal pain. At Penn, CJ was noted to be very uncomfortable and had difficulty walking. She reported that she had first menstruated at age 12 and that she had experienced cyclic pelvic pain of increasing severity for the last year. CJ’s mother, who was present, reported that she was born with a single left kidney.

Abdominal exam revealed a tender large mass in the lower abdomen extending half way up to the umbilicus. A pelvic ultrasound was ordered; this revealed a duplex uterus and a substantial right-sided mass in the lower abdomen. An MRI of CJ’s pelvis was then performed to permit further evaluation. These images revealed a dilated, fluid filled mass in the lower pelvis within a right-sided hemivagina, and confirmed the uterus didelphys (Figure 1).

In the operating room at Penn CJ had drainage of the right hemivagina and removal of the vaginal septum on the right. Laparoscopy revealed a uterus didelphys with the right side slightly larger than the left due to the distended hemivagina, and normal ovaries and fallopian tubes. There was extensive endometriosis throughout the abdomen but no adhesions.

She was discharged to home the same day. At her postoperative visit she looked happy, and reported that she had no pain or abdominal distention for the first time in many months and was able to participate in her school activities again.

Faculty Team

Specialists in adolescent gynecology at Penn Fertility Care offer evaluation and medical and surgical treatment for a wide variety of disorders that affect menstrual and reproductive function in young women. In addition to amenorrhea and delayed puberty, these disorders include ovarian cysts, polycystic ovary syndrome (PCOS) and congenital reproductive tract disorders (müllerian anomalies) or uterine anomalies.

For adolescents undergoing cancer therapy and cancer survivors, Penn physicians offer counseling regarding fertility preservation and treatment of the long-term reproductive and endocrine complications associated with cancer treatments. Our team collaborates with oncologists at the Children’s Hospital of Philadelphia and the Abramson Cancer Center and a consortium of researchers developing improved and effective fertility preservation options.

Performing Surgery for Uterus Didelphys at Penn Medicine

Hospital of the University of Pennsylvania

Clarisa R. Gracia, MD, MSCE
Assistant Professor of Obstetrics and Gynecology
Director, Fertility Preservation Program

Pennsylvania Hospital

Scott E. Edwards, MD
Assistant Professor of Clinical Obstetrics and Gynecology

Adolescent Reproductive Health

Clarisa R. Gracia, MD, MSCE
Assistant Professor of Obstetrics and Gynecology

Scott E. Edwards, MD
Assistant Professor of Clinical Obstetrics and Gynecology

Suleena Kansal Kalra, MD, MSCE
Assistant Professor of Obstetrics and Gynecology

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Penn Fertility Care
3701 Market Street
5th Floor
Philadelphia, PA 19014

Penn Fertility Care
Spruce Building, 7th Floor
801 Spruce Street
Philadelphia, PA 19107

Penn Medicine Radnor
Penn Health for Women
250 King of Prussia Road
Radnor, PA 19087

Reproductive Surgery at the Penn Center for Advanced Gynecologic Surgery

The Penn Center for Advanced Gynecologic Surgery at Penn Fertility Care is comprised of reproductive surgeons with expertise in the conservation of fertility and the correction of anatomical disorders that affect reproductive function. These specialists are experienced in the care of adolescents with müllerian anomalies and other conditions requiring surgical invervention, and often work in collaboration with pediatric urologists at the Children’s Hospital of Philadelphia.

To refer a patient to Penn Medicine, please contact Penn PhysicianLink^TM here or at 877-937-7366.

Download a pdf of this Clinical Briefing.

Clinical Research in Ovarian Cancer Immunotherapy

2011-07-13T10:07:00.002-04:00

Researchers at the Penn Ovarian Cancer Research Center (OCRC) are expanding their immunotherapy program to offer state-of-the-art personalized therapy to patients with recurrent ovarian, primary peritoneal and fallopian tube cancers.

Patients with these malignancies may be eligible to enter advanced clinical trials in immunotherapy to investigate the use of vaccines manufactured from the patient’s own tumor followed by T cells expanded in culture from peripheral blood.

Despite intense efforts to improve chemotherapy for ovarian cancer, no significant progress has been made over the past 30 years;survival rates have not changed in the past decade. Novel therapeutic approaches are direly needed.

Stimulating the immune system to attack tumors is not a new concept. What is new, however, is combining personalized vaccines based on autologous tumor with potent immune stimulators and post vaccine lymphocyte reinfusion. The underlying notion is that tumors are different enough from the normal body, such that they can be recognized and attacked as “foreign” or “non-self ” by the host’s immune system, once the latter is properly educated and activated.

Researchers at the Penn OCRC are currently conducting three phase I/II clinical trials for patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer using autologous vaccines developed from patients’ autologous tumor.

One vaccine protocol administers intranodally autologous dendritic cells loaded with autologous tumor lysate, in combination with bevacizumab (UPCC-19809). Patients must have a tumor lesion of >2 cm.

Another protocol administers tumor lysate intradermally in combination with an immunomodulatory drug, Toll-like receptor 3 (Ampligen) (UPCC-29810). Patients must be HLA-A2+ with a largest tumor lesion of <2 cm. Patients with recurrent disease are eligible, although tumor from primary debulkings can be banked for future use.

The third clinical trial works on the hypothesis that antitumor immune response generated by a vaccine can be significantly augmented by infusion of autologous activated lymphocytes. Accelerated recovery of CD4+ and CD8+Tcell counts would occur in the setting of lymphopenia in the wake of the adoptive transfer of in vivo vaccine-primed T cells in combination with bevacizumab (UPCC 26810). This trial is a sequential trial following the above vaccine studies. Eligible patients are those vaccinated with autologous vaccine.

In a pilot study that was completed in 2010, patients with recurrent progressive stage III and IV ovarian cancer with available tumor lysate from secondary debulking surgery underwent priming with intravenous bevacizumab and oral metronomic cyclophosphamide (bev/cy x 2 doses), followed by vaccination with an autologous DC preparation pulsed with autologous tumor lysate (5-10x10e6 DC per dose, 3 doses) plus bevacizumab (two doses).

This was followed by lymphodepletion using high-dose outpatient cyclophosphamide and fludarabine (cy/flu, 300 and 30 mg/m2/day, respectively, x 3 days) and transfer of 5x10 e9 autologous vaccineprimed, ex vivo CD3/CD28-costimulated peripheral blood T cells, in combination with vaccination.

Feasibility, safety, and biological and clinical efficacy were evaluated. Three subjects have completed vaccination and T cell transfer, while three additional subjects completed vaccination only. Therapy was feasible and well tolerated as an outpatient regimen. Vaccination following bevacizumab and metronomic cyclophosphamide preconditioning elicited vaccine-specific T cell response in four patients. Clinical benefit was seen in four out of six patients after vaccination where two subjects had partial response, two had stable diseases.

Following outpatient cy/flu lymphodepletion, adoptive transfer of vaccine-primed, CD3/CD28-costimulated autologous T cells resulted in clinical response in two of three patients, with one patient achieving CR. No toxicities were seen.

Case Study

Mrs. T, a 46-year-old woman, was diagnosed with stage 2C ovarian cancer and had her first debulking surgery in October 2007. She was then placed on carboplatinum/taxol standard of care chemotherapy. In December 2008, she recurred and underwent a secondary debulking surgery. She then received radiation followed by bevacizumab and cyclophosphamide.

Mrs. T recurred again in June 2009 and was debulked for the third time a month later. At this time, her tumor tissue (which would normally have been discarded) was used to create a personalized autologous vaccine. Mrs. T enrolled in a pilot vaccine study at Penn in November 2009.

She underwent priming with intravenous bevacizumab and oral metronomic cyclophosphamide (bev/cy x 2 doses), followed by vaccination with an autologous DC preparation pulsed with autologous tumor lysate plus bevacizumab. After completing this trial, she went on to receive additional maintenance vaccines, then reenrolled in the current vaccine trial (UPCC19809) in September 2010 and completed this trial in January 2011.

Mrs. T continued to receive maintenance vaccine until May 2011. She is currently disease-free, and has had no evidence of disease since entering the immunotherapy program at Penn in November 2009.

Penn Ovarian Cancer Research Center Now Storing Tumor Tissue
for Non-Penn Medicine Patients

Originally, the Penn Ovarian Cancer Research Center (OCRC) had restricted its immunotherapy program to patients who completed surgery at Penn Medicine. Now, Penn is accepting tumor tissue even when the surgery is performed at outside institutions. A patient who has surgery at her local hospital can have her tumor tissue shipped to the OCRC, where it is processed and stored live for future immunotherapy.

For more information, please contact us at 215-615-6727 or via email at lknd@mail.med.upenn.edu.

Faculty Team

The Penn Ovarian Cancer Research Center (OCRC) is a joint effort of the research and clinical facilities of the Perelman School of Medicine at the University of Pennsylvania, the Abramson
Cancer Center and the Department of Obstetrics and Gynecology.

The goal of the OCRC is to identify new methods to detect, prevent and treat ovarian cancer and to improve the quality of life for women with the disease. The Faculty of the Penn Ovarian Cancer Research Center includes world-renowned clinicians and researchers with a commitment to the investigation of novel, advanced approaches to the diagnosis and treatment of ovarian cancer.

Performing Research in Ovarian Cancer at the Penn Ovarian Cancer Research Center

Janos L. Tanyi, MD
Assistant Professor of Obstetrics and Gynecology

Lana E. Kandalaft, PharmD, PhD
Director of Translational Research and Clinical Development

Daniel J. Powell, Jr., PhD
Research Assistant Professor of Pathology and Laboratory Medicine

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Jordan Center for Gynecologic Cancer
Abramson Cancer Center
Perelman Center for Advanced Medicine,
West Pavilion, 3rd Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104

To find more information about clinical trials at the
Penn Ovarian Cancer Research Center, visit:
http://www.uphs.upenn.edu/obgyn/research/ovarian.htm

Download a pdf of this Clinical Briefing.

In Vitro Fertilization and Preimplantation Genetic Diagnosis

2010-11-12T08:58:00.002-05:00

Physicians at Penn Fertility Care are using preimplantation genetic diagnosis (PGD) to determine whether embryos produced by in vitro fertilization (IVF) carry the genes for a specific genetic diseases (such as cystic fibrosis, muscular dystrophy, etc).

PGD permits diagnosis to be made before embryos are transferred to the uterus for the establishment of a pregnancy, thus greatly reducing the risk that a couple will pass the disease on to their child. PGD can also be used to determine if embryos produced by IVF have chromosomal disorders that would otherwise lead to pregnancy loss or result in the birth of a child with impairment, deformity and/or mental retardation.

PGD is offered at Penn primarily to couples when one or both partners are carriers for a known genetic disease or have chromosomal abnormalities, such as translocations. In all these situations, PGD reduces the risk of achieving a pregnancy that will have the chromosomal abnormality or be affected by the genetic disease.

At Penn Fertility Care, the process of PGD is initiated following the in vitro fertilization of multiple ova (oocytes/eggs). Typically, one or two cells are safely removed from each embryo at an early stage of development (Figure 1). Next, the cells are analyzed using a powerful genetic amplification technique called fluorescence polymerase chain reaction (F-PCR) that has the capacity to make millions of copies of the piece of DNA of interest for a reliable diagnosis.

The product from the F-PCR reaction is then tested for the presence or absence of the known parental mutation(s) using a range of genetic techniques. To detect abnormalities in chromosomal number or structure, a technique called fluorescent in situ hybridization (FISH) uses fluorescent dye probes to identify specific regions in a chromosome. The chromosomes are then analyzed under a microscope that can distinguish normal chromosomes from cells with an unbalanced translocation or an abnormal number of chromosomes.

The results of the tests are reported by the morning of the day of embryo transfer (five days after oocyte retrieval). The best quality embryo(s) from those that are not affected by genetic disease are selected for transfer to the uterus. If additional good quality, unaffected embryos are available, they may be cryopreserved for a future embryo transfer.

Case Study
Mrs. R, a 39-year-old woman was referred to Penn Fertility Care for PGD to improve the likelihood that she would have a healthy child after genetic testing revealed that she and her partner were carriers of SMA (spinal muscular atrophy 1).

An inherited disease that causes severe, progressive muscle weakness, SMA is untreatable; affected infants generally live for two years or less. Together, Mrs. R and her partner had one healthy child. The couple then conceived a second child who had SMA and died a few months after birth. In a subsequent pregnancy, Ms. R underwent early chorionic villus sampling (CVS) at 11 weeks gestation and found that the fetus was affected with SMA.

The couple chose not to continue this pregnancy. Wanting to avoid having another child with SMA, they then consulted specialists at Penn Fertility Care for conception options, including preimplantation genetic diagnosis. The couple elected to proceed with IVF with PGD. They conceived after two cycles of IVF and had a baby girl who did not have SMA.

Additional Options at Penn Fertility Care for Couples with Heritable Disorders

Through the Division of Reproductive Genetics, Penn Fertility Care offers an array of prenatal genetic testing options for couples with a personal or family history of genetic disease. In addition to PGD, these tests include:

Amniocentesis
Chorionic villus sampling
Serum Screening for down syndrome and neural tube defects
First trimester and sequential screening for Down syndrome
Carrier screening for inherited conditions such as cystic fibrosis
Ultrasonography to detect fetal anomalies

The Division of Reproductive Genetics also provides comprehensive diagnostic services, medical management, counseling and follow-up care for individuals and families who are affected by or concerned about genetic disorders.

Team of Faculty
Penn Fertility Care physicians provide compassionate intervention, goal-oriented reproductive care and experience in male and female fertility diagnosis and treatment. Services include:

In vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and other assisted reproductive technologies
Egg Donation Program for egg recipients and donors*
Reproductive surgery
Penn Polycystic Ovary Syndrome (PCOS) Center
Reproductive options for cancer patients
Pre-implantation genetic diagnosis (PGD)
Adolescent reproductive health
Management of endometriosis and fibroids

With a certified, on-site laboratory, Penn Fertility Care is at the forefront of research to develop new infertility treatments and to improve patient care. The staff is renowned for their research contributions to the field.
*The egg donation program at Penn Fertility Care is under the direction of Christos Coutifaris, MD, PhD, the Nancy and Richard Wolfson Professor of Obstetrics and Gynecology and Chief of the Division of Reproductive Endocrinology and Infertility.

Performing Preimplantation Genetic Diagnosis at Penn Fertility Care
Anuja Dokras, MD, PhD Medical Director, In Vitro Fertilization Program Associate Professor of Obstetrics and Gynecology Susan Troncelleti, MSN, CRNP PGD Clinical Nurse Coordinator

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Penn Fertility Care
8th Florr
3701 Market Street
Philadelphia, PA 19104

Penn Fertility Care at Pennsylvania Hospital
7th Floor
801 Spruce Street Spruce
Philadelphia, PA 19107

Penn Fertility Care at Penn Health for Women
Penn Medicine Radnor
250 King of Prussia Road
Radnor, PA 19087

To refer a patient and/or consult with a physician: Call 800-789-PENN (7366) or visit: PennMedicine.org/referral

Fertility Research at Penn
Fertility research at Penn Medicine is devoted to increasing the understanding of human reproduction as it relates to fertility regulation, female and male infertility and women’s health issues with the goal of improving the health and well-being of women and their families and improving outcomes. To this end, the research conducted by the Reproductive Research Unit at Penn Fertility Care and Penn’s Women’s Health Clinical Research Center includes NIH-funded clinical trials and research on fertility, polycystic ovary syndrome, fertility preservation after cancer, and contraception.

For a complete list of active clinical trials in women’s health and reproduction, please visit pennmedicine.org/fertility/research.

Download a pdf of this Clinical Briefing.

Robotic-Assisted Laparoscopic Abdominal Sacrocolpopexy for Pelvic Organ Prolapse

2010-09-22T09:29:00.002-04:00

Surgeons with the Division of Urogynecology and Pelvic Reconstructive Surgery at Penn Medicine are performing robotic-assisted abdominal sacrocolpopexy to treat advanced pelvic organ prolapse, including cystocele, rectocele, enterocele and uterine prolapse.

Among a variety of complex urogynecologic surgeries available at Penn to treat pelvic organ prolapse, robotic-assisted laparoscopic abdominal sacrocolpopexy employs a sophisticated array of robotic instruments controlled by the surgeon from a console in the operating room. Abdominal sacrocolpopexy is the gold standard surgery for the treatment of pelvic organ prolapse, and among the most durable procedures for pelvic organ prolapse.

The long-term effectiveness of sacrocolpopexy derives from the use of a synthetic mesh to suspend the vagina from the sacrum, which addresses the pelvic floor muscle atrophy and endopelvic fascia detachment that cause pelvic prolapse.

The procedure can be performed as open, laparoscopic or robotic-assisted laparoscopic surgery. All of these approaches have advantages and drawbacks. Open sacrocolpopexy can be associated with morbidity for patients as a result of the laparotomy incision, blood loss and recovery time. The robotic and laparoscopic approaches seek to eliminate this concern, but surgeons can be hampered by steep learning curves and technical difficulties, sometimes resulting in increases in operating room time.

For surgeons, the comparative benefits of robotic-assisted laparoscopic sacrocolpopexy include enhanced visualization with three-dimensional magnified vision, wristed motions, direct hand-eye coordination, ergonomic comfort in the OR, improved degrees of freedom compared to standard laparoscopy and improved maneuverability. Compared to women having open surgery, patients who have robotic surgery typically have less blood loss, better cosmesis, decreased pain, shorter hospital stays and an earlier return to ambulation.

Robotic sacrocolpopexy can also be performed in combination with other procedures such as a hysterectomy, rectocele repair and anti-incontinence procedures such as a Burch urethropexy or midurethral sling.

Case Study
Mrs. S, a 55-year-old woman, was referred to Penn Medicine by her ob/gyn with a two-year history of urinary leakage, pelvic pressure and a vaginal bulge. At presentation, she was five years postmenopausal; her medical history included three vaginal deliveries and no major health problems. She had previously tried a pessary for her prolapse, which Mrs. S found unacceptable as a long-term solution.

Following a consultation with a surgeon at Penn, Mrs. S chose to have a robotic-assisted laparoscopic hysterectomy and abdominal sacrocolpopexy along with placement of a transobturator sling to address her prolapse and urinary incontinence. Urodynamics and a thorough pelvic exam were done as part of her evaluation. During surgery, Mrs. S was placed in the dorsal lithotomy position. Her umbilicus was everted and a 12-mm incision was made. A Veress needle was inserted and CO2 was infused to establish a pneumoperitoneum.

A 12mm trocar was advanced into the abdomen. A 12mm assistant port and three 8mm robotic ports were then inserted under visualization. Cautery was using to dissect away the adnexal structures from the uterus, as well as to obliterate the uterine arteries. The uterus was amputated away from the cervical stump. The bladder was then dissected away from the cervix and vagina, carefully creating a plane in that space. The rectum was dissected away from the posterior vaginal wall down to a level a few centimeters above the perineum.

Using polypropylene mesh fashioned into a Y-shape, the surgeons attached the mesh to the anterior and posterior walls of the vagina with a series of interrupted permanent stitches (Fig. 1). This basically covered the entire inside surface of the vagina and cervical stump. The bifurcation of the major vessels was then identified, and coming inferiorly, the peritoneum overlying the sacral promontory was elevated.

The surgeon dissected through the loose areolar tissue to identify a clear space on the anterior longitudinal ligament, avoiding the middle sacral vasculature and several veins. The last portion of the Y-shaped mesh was then attached to the sacrum using several interrupted stitches.

At this point, the mesh was reperitonealized to protect from bowel obstruction. Following the removal of the instruments and camera, the skin incisions were closed and placement of the transobturator sling initiated. An incision was made at the vaginal mucosa underlying the midurethra, and sharp dissection was used to create tunnels bilaterally out to the obturator membrane.

Trocars were then rotated from the medial thigh at the level of the clitoris in through these tunnels. The transobturator sling was attached to the trocars, which were then rotated back out through the same path. Cystoscopy confirmed that there had been no damage to the bladder during the procedure, including visualization of bilateral ureteral efflux. The sling was then tensioned appropriately and all incisions closed. Mrs. S tolerated the surgery well.
Following an uneventful recovery, she was discharged home the next day.

Team of Faculty
The goal of the Division of Urogynecology and Pelvic Reconstructive Surgery at Penn is to provide the highest quality of surgical care to women with benign urinary, bladder and pelvic floor conditions. The physicians here are committed to providing women with a wide range of medical, office-based procedures and surgical options, helping the patient decide what treatment option is in her best interest. Surgeons are using new techniques in minimally invasive and robotic-assisted surgery, and, in turn, shortening recovery times, reducing pain and blood loss and letting women get back to their lives in record time.

Performing Robotic Abdominal Sacrocolpopexy at Pennsylvania Hospital

Ariana L. Smith, MD
Assistant Professor of Urology in Surgery
Director of Pelvic Medicine and Reconstructive Surgery Division of Urology

Performing Robotic Abdominal Sacrocolpopexy at the Hospital of the University of Pennsylvania
Lily Arya, MD, MS
Associate Professor of Obstetrics and Gynecology
Chief, Division of Urogynecology and Pelvic Reconstructive Surgery

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PENN UROGYNECOLOGY
Hospital of the University of Pennsylvania
1000 Courtyard Building
3400 Spruce Street
Philadelphia, PA 19104

Pennsylvania Hospital
Spruce Building, 7th floor
801 Spruce Street
Philadelphia, PA 19107

Penn Medicine Radnor
Penn Health for Women
250 King of Prussia Road
Radnor, PA 19087

Penn Medicine Woodbury Heights
1006 Mantua Pike
Woodbury Heights, NJ 08097
DIVISION OF UROLOGY
Perelman Center for Advanced Medicine
3 West Pavilion
3400 Civic Center Boulevard
Philadelphia, PA 19104

Pennsylvania Hospital
299 South 8th Street
Philadelphia, PA 19106

To refer a patient and/or consult with a physician: Call 800-789-PENN (7366) or visit: PennMedicine.org/referral