Infertility Blog

Frequent Fertility Questions

2009-11-06T08:25:00.002-05:00

Hello to all,
Here is your latest entry.

What if I have had miscarriages but my HSG and clotting tests are normal? Make sure you get the karyotype test, the blood test to check your chromosomes.

What if your partner recently had a vasectomy reversal and the motility is only 20% with poor morphology. Will these numbers improve with time? Hard to say. If there is not much improvement in 6 months, there will probably not be much change after that.

Are there any tests to explain poor embryo quality? At this time there are none. We don’t know why within a batch of embryos, some look good and others do not. We don’t know why some women make nicer embryos than other women.

What about shared risk IVF programs? They have their pluses and minuses. The name is deceiving. It sounds like your doctor is somehow contributing to and sharing your financial burden, but this is not the case. Shared risk means the other patients in the program are all sharing the risk. The price of shared risk in many cases does not include all of your costs. It’s all figured out mathematically. Some patients will end up pay less, some pay more, but what the average a person pays in most shared risk programs is the same the average person would pay without the program.

Are there options other than IVF ICSI with 6% motility? Realistically; no. Miracles can happen. We don’t know why but to get pregnant on your own, your need millions of moving sperm. Even IVF without icsi requires millions, although not as many as you need for a natural pregnancy.

What if you are young and have had 4 unexplained miscarriages and your workup is normal? Facing another pregnancy and miscarriage sounds impossible to you, and your doctor says there are no other tests? The unemotional cold hard fact is that trying again is the only real option and the odds are that the next pregnancy will be successful. Your miscarriage risk is higher than others without your history. I’m not saying trying again is the best thing for you, I understand why you may not want to.

Mini IVF. It has its place. Things to watch out for are any hidden costs, which could be high. There is a higher chance that there will be no egg retrieved. You really need to know what the deliver rate is for people your age. The “pregnancy rate” is not the delivery rate. There are different versions of mini IVF. Most involve clomid, but sometimes low doses of injections are added. Also be careful about the freezing option. Many times the doctor will say the lining is not right and he wants to freeze the embryos, so they can be transferred when the lining is more favorable. This gets a mini Arghh. Mini IVF has a lower pregnancy rate and freezing embryos probably makes the rates lower still. Plus if the goal of mini IVF is to save money, it seems that the costs will add up between the cycle, the freeze and the frozen transfer.

What if you have been offered frozen donor eggs (not embryos). This could be a good option. Ask for details (not an estimate) about success at your clinic. If they do not have good results from at least 10-15 thaws, you may want to reconsider. People in the field feel all of donor egg will be using frozen eggs in the near future, although today the science is still new.

Should you consider a surrogate if you have had 2 failed fresh DE cycles, one with a proven donor? If you have no uterine issues i.e. a nice lining and no scaring/previous surgery, the added benefit from a carrier will be minimal. However, if you have access to a good carrier and are open to the idea it is not unreasonable to at least explore the option.

What if you only have access to insemination M-F? Not great. Most of the time there is room for getting inseminated a little early or late, but having weekend services available to you is much better.

Does natural cycle insemination increase your odds of twins? No. Twins come from 2 or more eggs and in the natural cycle, usually only one is produced.

What if you have pain and your doctor is not listening? Maybe your doctor does not feel that you have a pelvic problem that requires further evaluation because your exam and ultrasound are normal, and she does not feel a laparoscopy is right for you. If that’s the case your doctor needs to at least give you another complete exam and a repeat the ultrasound, and then needs to discuss your options. She needs to let you know what she is thinking and visa versa. If you can’t get this with her, try someone else.

What if you are 41, and have gotten pregnant easily twice. Is there an advantage to going to IVF? Theoretically yes because if you have more than one embryo to transfer you will increase your odds of success. The dilemma is that you are getting pregnant on your own easily, which does not necessarily mean you will get pregnant easily with IVF. If you decide to try on your own again, get help quickly if you don’t get pregnant soon.

What if you have stage 3 endometriosis and have not become pregnant with a few iuis? You should consider moving to IVF sooner than average. Pregnancy even without drugs is certainly possible, but the odds are lower because of potential tubal issues related to the endometriosis.

What about stress management programs to increase the odds of conception? I think these programs are extremely helpful. I started the NYU Fertility Center Wellness Program, which incorporates acupuncture, mind-body and yoga into our practice. I don’t like selling these things as ways to get you pregnant, because more research needs to be done. But they are very beneficial for stress management and treatment tolerance.

What’s better for low sperm counts, IVF/ICSI or donor sperm? Donor sperm is a lot easier and cheaper and may lead to a quicker pregnancy. That being said, most people prefer partner’s sperm, IVF and ICSI.

Could a hydrosalpinx prevent pregnancy? The answer is yes. A publication of the American Society of Reproductive Medicine states that a hydrosalpinx can lower pregnancy rates by as much as 50%. I think it’s closer to 30%. Many years ago I would remove a hydrosalpinx in any woman wishing to attempt IVF. More recently I let people know that a hydro will lower the odds in some women but not all, and with the hydro the odds are still good. So I let them decide if they want the surgery prior to IVF. Having a hydro will increase the chances of an ectopic pregnancy with IVF. Hydros can be a problem even if you are not yet a candidate for IVF. In other words if one tube is normal and the other a hydro, removing the hydro may help you get pregnant on your own.

What if you are 44 and were told the chances of IVF are 5%, but you make 14 eggs and have nice embryos? Are your odds higher? Yes they are. Most, but not all, women who get pregnant in their mid 40’s are lucky enough to make a high egg number. The more the better.

What if you were just diagnosed with terrible endometriosis and are offered Lupron? There are no good studies showing Lupron will take away any of the endometriosis or improve scarring. The story is different for pain; Lupron can help tremendously with that.

How to find the best IVF clinic? Start with SART.org and look up the pregnancy rates for your age group. The tables are a little hard to read, go to the line that says live births per retrieval. After that it’s about chatting it up in person and on line.

What if you are obese and the doctor is worried about doing IVF in the office safely? Different doctors will have different thresholds for maximum weight. Some are more relaxed when dealing with very obese patients. So get more opinions. Some IVF centers do their retrievals in the hospital, and they may be more eager to treat you. At 26 you do have time to lose weight before you start, which would be better for the baby. There is new data every day on the detrimental effects of obesity on the fetus. The old saying"you are what you eat" has been replaced by "you are what your mom eats."

What if you have a 2 cm endometrioma on your ovary? As long as they are sure that’s what it is, and it’s not another type of tumor, a 2 cm endometrioma will not hurt your chances of conceiving with IVF.

What next? You are young and have had a baby then 3 miscarriages, the workup doesn’t show much. Too many women have been hit with similar issues. It’s all about the tough decision to continue. If you get pregnant again, odds are that you will have the baby. However the thought of facing another loss sometimes overwhelms us. I try to encourage more attempts, but it’s your decision in the end.

Thanks for reading and read the disclaimer 5.17.06.

Dr. Licciardi

Please Vote for the InfertilityBlog

2009-10-17T08:35:00.003-04:00

Dear All,

Congratulations to all of you who read this blog, it has been nominated for the People's HealthBlogger Award. See the yellow blue and orange box to the right? Clicking it would be a great help. Winning would be very helpful because the blog would get more publicity, which will bring us more readers. This in turn could help us get the blog to even more health-related web sites. The voting ends December 15Th.

Thanks for everything through the years.

Dr. Licciardi
PS The company encourages you to ask your contacts to vote too. I guess they want some publicity too, which is fine with me.

Question and Answer Time

2009-10-16T19:43:00.002-04:00

Hello Again. I will spend the next few blogs catching up on questions. It’s been a while and I see that many were time sensitive, so I am sorry if missed your immediate problem. I’ll try to keep more up to date. One problem is that not all readers like the questions, but I like doing them, and if I make the answers relevant to a group of people, I think they work for a larger group of people. I got caught up in a bunch of topics that I wanted to cover, but for now, back to the questions.

What if you are young, make many eggs and embryos, have very nice quality, a normal uterus and are not getting pregnant? Could it be an implantation issue related to the uterus? Chances are this is not the case. Your doctor may be right, it could be bad luck. It could also be that you need to try another IVF clinic. It could also be there is some unknown genetic problem with your eggs or sperm, but the answer here is years away. Some would consider PGD in this case, but it is questionable if it would help.

If you do clomid, do you need to wait 2 weeks and provera to start? No. Your doctor wants 2 things. He wants you to bleed before the clomid, and he wants you not to be pregnant when you take the povera or clomid. There are ways around this. If you have not bled in many many months, it’s not a bad idea to get a period to start, so provera is not a bad idea. If you have had a period in the past few months, provera is probably not necessary. To be sure you are not pregnant; you can just do a progesterone blood test. You can’t be pregnant if you never ovulated, so if your progesterone is very low, it’s ok to start the clomid (if your doctor says it’s ok). If it’s high, you did ovulate, and you will need to wait less than 2 weeks for your period. If your period does not come, do a pregnancy test.

What if you were diagnosed with stage one enodmetriosis and were told to take Lupron for 3 months. Here is today’s ARGHHHHHHHHHH!!!!!
No one has ever shown that being on Lupron after surgery does anything to reduce endometriosis or improve pregnancy rates. It works like this. Endometriosis grows from estrogen; when Lupron takes away the estrogen the endometriosis stops growing. But Lupron does not kill the endo, it just suppresses it. So once the lupron is stopped, the endometriosis goes right back to where it was. Yes staying on the lupron will take away pain, but once the lupron is stopped, the pain comes right back. So the 3-6 moths of lupron will not help you become pregnant, it just makes you older and more frustrated. A new endometrioma should not appear on Lupron. If the cyst was not well removed at surgery, it can reappear, even if on lupron.

Is a large clot during the period a problem? Probably not. A very large clot is probably not coming from the uterus. It’s from fresh blood that flows from the uterus into the vagina, then sits there and clots. If you think overall the amount you are bleeding is excessive, there could be issues related to fibroids, polyps, etc.

Do we know more about Unexplained Infertility? The problem with writing about unexplained infertility (UI) is that patients are put in the category of UI only after the things we know about have been excluded. It is true that in the past many years, no new meaningful tests have been developed to get people out of the UI group and into one of the groups that are explained.

What if you have severe endometriosis and are not getting pregnant with IVF. Women with endometriosis do make few eggs than average, but 16 is plenty. Should you go to another IVF center? Look up their stats at SART.org. If the numbers look good, stay, if not, get another opinion. Genetic testing is always an option. With a mostly normal family history, the odds of a chromosomal problem are 1-3%.

What if you are 37-38 and your FSH is very normal buy you only make 4 eggs? Well FSH is not the whole story. It’s a good guide but if your number is low, it doesn’t mean you will definitely make many eggs. If you are starting on 2 Follistim and one Menopur, there is definitely room to increase your dose, which could make a difference.

What about a poor responder with normal FSH levels and antral follicle counts? Our pre cycle predictions don’t always match what we get during the cycle. Estrogen prime is probably as good as day 2 start. But if you have tried one, it makes sense to try the other next time.

What if you spot for 51 days straight? You need a pregnancy test and an ultrasound. Things may be just fine but there could be problems with ovulation (or non-ovulation) or uterine issues.

Are frozen embryos any worse because of ICSI? If they were frozen on day 3, is it ok to they and transfer day 5? Yes it is. ICSI will not negatively affect the embryo’s ability to grow from day 3 to day 5 after the thaw, depending on the labs experience with day 5 culture.

If you have regular cycles can you have mild PCO? No, because by definition, PCO women have irregular or lengthy cycles. Now this does not mean you can’t have ovaries that have a high number of eggs and follicles. So your ovaries can look like they are pco, but you don’t have a disease or syndrome. It also means that clomid could still be indicated, even if you do not have PCO.

Someone actually had a conversation with her doctor and he paid attention, and now she is pregnant. One of the most important things I learned in medical school was, “If all else fails, listen to the patient”. “When all else fails examine the patient” is another good one.

Should you have the laparoscopy or do the IVF? It would be easy to answer of either could get you pregnant right away. With a family history of endometriosis and severe cramps, and infertility, a laparoscopy is very reasonable. On the other hand, if you are a good candidate for IVF, the pregnancy will do a good job in suppressing your endometriosis, and some women have a permanent reduction in endometriosis pain after a pregnancy. If your tubes are open on HSG, and there are no endometromas of your ovary (ultrasound visible cysts of endometriosis), the odds of meaningful endometriosis (endometriosis severe enough to be preventing pregnancy) are low.

What about the third biochemical pregnancy in a row? The testing is normal so far. Here are just a couple of suggestions. If you and your husband did not have the blood karyotype test, that should be done. Even though you had a laparoscopy, consider a hysterogram.

After testicular surgery, will a sperm count of 18 million and 20% motility improve with time? It could go either way. At 31 you have few more months to see. Getting pregnant on your own with these numbers is not unheard of, but it may take longer.

I think I should have more frozen embryos. It is very disappointing to have 17 eggs, 12 embryos , 2 for transfer and none to freeze. There could be a few reasons related to the lab for this. If they transfer on day 3 and wait till day 5 or 6 to freeze, they may not have enough experience going to day 5, if they did they would do more fresh transfers on day 5. It’s also possible that the embryos look fair on day 5 and they just do not want to freeze them. There are 2 elements to this. One is a cycle using frozen embryos has a lower pregnancy rate than a cycle using fresh embryos, and that’s when using embryos that look very nice when they are frozen. So if you freeze embryos that are marginal looking, the pregnancy rates will be even lower, and many times not worth the freeze. The other element is that some programs are too restrictive on the quality of the embryos they freeze. I other words, they want their frozen rates to be high. One easy way to do this is to just freeze the really nice embryos and not the ones that look ok or worse. Lastly, it is possible you have some average or good embryos to transfer and all of the others are not really that nice. It may have nothing to do with the lab. Modifying your protocol may possible improve the quality of the lot.

We do not recommend amnio based on just ICSI. However, every case is different. For some, amnio may be indicated.

We have never dealt with a day 7 embryo.

Progesterone orally or vaginally? For IVF we use IM because we had some bad experiences with vaginal. However that was years ago, and maybe the preparations are better now (that’s what’s claimed). The oral is too unreliable to be used alone. If we use oral, it’s in combination with vaginal. Oral progesterone may make you very tired or dizzy.

What if you ovulate every month and on clomid, nothing, no ovulation? Yes indeed, this can happen. Why, we do not know, but it is pretty rare. If you are taking estrogen with the clomid, the estrogen may stop your cycle (like the birth control pill ) . But otherwise, we really don’t know why. If you take clomid another month, odds are you will ovulate. These types of problems usually do not recur.

Is it bad to switch doctors because the first doctor has your history? No not at all. We can all tell exactly what’s going on with you by listening to you in person and studying the paper work. IVF is about the stimulation and embryos, both of which should be clear in the documents.

It seems that there are doctors who tell patients that IVF is the way to go because in their case FSH iui is too risky. It is a little risky but it can be handled correctly. Start on a low dose, get monitored and stop the cycle you are on track to make too many eggs. If a low dose causes a big response, use even less drug next time. Yes, it’s easier to do IVF but if you chose to do FSH iui, talk to your doctor about trying.

If you hyperstimulated during an IVF cycle, and have frozens, generally it does not make sense to do another fresh. The point about saving young embryos for later is valid, although I do not push for that much. Saying you can get kids from a frozen cycle is not appropriate. You really don’t know if you will get pregnant from any embryos, fresh or frozen. If your plan is to have 3-4 kids, doing another fresh and saving the frozen is reasonable. Clearly you need a much lower dose of drug for the next fresh cycle.

OK that’s it for now, more to come.
Thanks and see disclaimer 5/17/06.
Dr. Licciardi

Dr. Licciardi on TV

2009-09-27T08:43:00.002-04:00

I was invited to the MSNBC show "Dr. Nancy". Here's what I had to say.

http://www.msnbc.msn.com/id/31388323/#33006217

When is the Right Time for hCG?

2009-09-27T08:09:00.003-04:00

The time between the hCG and retrieval
For an FSH injection cycle leading to insemination, it’s ok if the ovulation naturally occurs a little early (via a premature LH surge) because we can just do the insemination early. Rarely it’s too early, before the follicle is big enough, and we cancel the cycle. However, for an IVF cycle we have to cancel the cycle if there is an early natural LH surge, even if it’s only a little early, because the timing of the retrieval is very dependent on when the surge starts. The retrieval needs to be about 34-36 hours past the start of the surge (which would also be the time if the hCG shot).

Because we are not taking blood every hour, if the blood test shows a rise in the LH level, we don’t really know when the rise started so we don’t know the right time for retrieval. Lupron, Antagon and Cetrotide prevent the natural rise of the LH, so the premature surge usually cannot occur. However, these drugs do not interfere with the effects of an hCG injection. So there is no natural surge, but there is an artificial surge which starts the moment the hCG goes in.

Final Maturation
There is a second very important job of the LH Surge/hCG injection:
it causes the egg to mature. As the days of stimulation progress the eggs are slowly maturing, but more is needed for the final maturation. Necessary last minute changes occur inside the egg from the LH/ hCG.

Why is this important? An immature egg will not fertilize. If the retrieval is before about 33 hours after the hCG, the result will be immature eggs. Sometimes they are all immature, or just some.

If the retrieval is 38-39 hours after the hCG, the eggs will be mature but they will already have ovulated. We would retrieve none; they would be floating in the pelvis around the ovaries waiting to get picked up by the tubes. So we need to grab the eggs just after they mature but just before they ovulate, which is at about 34-37 hours after the hCG injection.

What day should you get your hCG?
hCG can only mature eggs that have been growing for enough time for the follicle to become large. The sizes of all of the follicles need to be taken into consideration before giving hCG in IVF cycle.

Not all of the follicles grow at the same rate. For example, if there are 10 follicles, and the biggest is 18mm, they will not all be 18 mm. Some will be mid-sized and some will be much smaller. Each follicle does not need to be 18 mm to produce an egg that is mature. As long as the biggest (the lead follicle) is 17-18mm, the mid-sized (13-16) should also have mature eggs. The small follicles (10-12) may or not be mature. But if the lead follicle is 14 mm, none of the eggs have yet reached maturity. Giving hCG would not be enough to achieve maturity.

How Important are Estrogen Levels?
Not very. When you are monitored for your IVF cycle, the follicle size is much more important that the estrogen (estradiol) levels. We need the estrogen to rise, but if midway through your cycle we see 10 follicles, with the biggest being 13 mm, we don’t really care if the estrogen level is 500 or 900. Estrogen is more important when we are monitoring someone who may be on track for hyperstimulation.

Therefore, we use mostly the size of the follicles, with not much emphasis on the estradiol levels, to determine when to give the hCG. At NYU we feel the best time to get the hCG is when the lead follicle reaches 18 mm. Now because there are many variations from cycle to cycle and from patient to patient, it’s not easy to say that 18 mm is the rule.

For example, let’s say there is one follicle 18 mm, three that are 15 mm and others that are smaller. Here we may worry that some of the small ones may be too immature, so we may wait another day before giving the hCG. Let’s say there are 20 follicles, with the biggest 17mm and an estrogen level of 2900. Here we are aware that the smaller follicles may be immature, but we also are concerned about the estradiol getting much higher because the woman would be increasing her risk of hyperstimulation. So we give the hCG at 17 mm, which may yield some immature eggs, but should give us enough mature eggs to work with.

And there are many more variations. Some women have gotten their hCG a little on the early side and have all mature eggs. Some women in their first cycle get the hCG at 18 mm with lots of good size follicles, and have ½ their eggs be immature. So next cycle we wait till the follicles are 20-22 mm before giving hCG. This sometimes gets more mature eggs but sometimes no matter what we do, that woman’s ovaries make more immature eggs than expected.

So why not wait and give hCG later? Because eggs can get over-mature. This over-maturity can lead to lower embryo quality and lower pregnancy rates.

When we see the records of women who have failed IVF elsewhere, many times we see that he hCG was given with large sized follicles. The first and easiest “fix” we can do is to give the hCG earlier in her next cycle, more inline with our standard procedures.

Why do some doctors wait longer to give the hCG?
Some may feel that the higher the estradiol level the better, so by waiting estrogen levels will go up. This is probably not important. Others may feel that it is necessary to wait so there will be no immature eggs. Well this sounds good, but it may not be worth sacrificing the quality of the eggs form larger follicles, which are probably the best eggs anyway.

And back to the original question.
What if instead of the average 11-12 days it takes to grow the follicles, they are of the right size after only 6 days or 8 days?
If the size is good, but it seems early, we usually go at least one more day that we normally would, maybe 2. If it’s day 9 and the follicles are 19-20 mm, it really sounds ok to give hCG. If it’s day 7 (so 5-6 days of FSH injections), and the follicles are 17-18 mm, more time would probably be a good idea.

Thanks for reading and don’t forget the disclaimer 5/17/06.

Dr. Licciardi

The Natural LH Surge vs. the HCG Injection

2009-09-13T10:10:00.003-04:00

We are still working towards the timing of the hCG shot, but we first need a little more background. We need to go over difference between the natural LH surge and the hCG injection.

After LH leaves the pituitary during the surge, it causes the ovulation by landing on specialized spots on the ovarian cells, the LH receptors. All hormones act by landing on (binding to) their specific receptor, and usually one hormone does nothing if it lands on the receptor of a different hormone. There has to be a match.

This is usually dictated by shape. It’s like a lock that recognizes the shape of the key. FSH and LH are similar hormones, but their shapes are a little different. So if LH comes across a FSH receptor, it would not bind.

There is a notable exception. Because hCG and LH are chemically very similar, with very similar shapes, hCG can bind to the LH receptor, and can do it well. Since hCG can land on the LH receptor, hCG can do the same job as LH.

This is actually very important to pregnancy. Pregnancy needs progesterone, which comes from ovarian cells with LH receptors. So LH causes the ovary to make progesterone after ovulation. Good: the progesterone allows the embryo to implant. Then the embryo makes hCG. Better: this causes the ovary to make even more and more progesterone which keeps the implantation going strong. Both occur via the LH receptor.

That hCG can behave like LH is good for treating fertility patients because we can cause ovulation with an injection of hCG instead of an injection of LH. This is good because hCG is easier to get than LH.

So why not just give LH? Up until very recently, LH was not available. Years ago the only way to get FSH for our fertility drugs was to extract it from the urine of menopausal women.

(This is a whole story by itself. Initially, starting in the 1970’s, the urine was obtained from menopausal Italian nuns who would leave jugs of pee for the drug company Serono to pick up in the mornings. Menopausal women have really high amounts of FSH in their blood, and most of it comes out in the urine. The pee would be taken to a factory with a swimming pool-sized pee vat, and they would somehow get the FSH from the pee. Serono went on to be the most profitable company in the world. The Catholic Church was rewarded for its cooperation. Even today, pee swimming pools exist for companies who make fertility drugs from urine.)

Because FSH and LH are similar molecules, the methods used to pull out the FSH grabbed LH too. Once we got the FSH/LH mix, we didn’t have the science to separate the two. So we could not get enough pure LH to cause ovulation. Today we can get pure LH made in a lab, but still in small amounts, not enough to get a good ovulation going.

How do we get the hCG? That is piece of cake, we get it from placentas. There are tons hCG in placentas and it’s easy to extract. Today hCG is also made in a lab, that’s the Ovidrel. It’s pure stuff, and that’s why it can be given in the skin. The placental hCG is given IM because it’s contaminated. hCG is also a protein, and the system for extracting the hCG protein from placentas is pretty crude, so tons of other placental proteins get caught in the net too. These extra proteins can cause a local allergic reaction when given in the skin, but not when given in the muscle.

When we used to get fertility drugs from urine, same thing, they had protein contaminants and needed to be given into the muscle. Recent exceptions are Menopur and Bravelle. These are from urine but using new systems that are better at cleaning out most of the unwanted contaminating proteins. Gonal-F and Follistim are both made in the lab and do not have the contaminants. They are given into the skin.

Today there are 2 products, placental hCG given in the muscle, and the lab-made hCG given in the skin. The placental is still cheaper and words great.

In a cycle stimulated with injected FSH (for IUI or IVF), most of the time the natural LH surge does not occur at all, so we need to give the hCG. In some cases the LH surge does occur, but it happens too soon, before the eggs are mature. This is probably due to the fact that estrogen levels are higher earlier in a medicated cycle, so the LH rises earlier. We don’t know why a premature LH surge only happens in about 20% of cases.

The bottom line is that we cannot count on the natural surge to occur at all, or at the right time, when we are using FSH injections. We need to use the hCG injection for proper timing of ovulation and proper timing of the egg retrieval.

That’s it for now. Next time we finish up by talking about the right time to give the hCG shot.

Thanks for reading,

Dr. Licciardi

A Little More About Normal Ovulation

2009-09-03T08:04:00.005-04:00

Here is a question someone asked about the timing of hCG. It’s a good starting point for this blog.

“I am 40 and just had a failed first IVF cycle that resulted in all immature eggs (7 retrieved) after only 5 days of stims (follistim/menopur + ganirelix days 4 & 5) before the hCG shot.
The doctors were very surprised that by day 5 I had 7 follies 12 - 19 (more <10) and they said I had to trigger, my final E2 was only around 700. I had a good hCG level after the trigger.

I have never heard of anyone only stimming for 5 days. I am curious what your experience has been with people who are fast responders and what you recommend in terms of changing protocols? Do you believe that follicle size alone determines egg maturity or can a short follicular phase be a problem even with larger follicles?”

Figuring out the right time is not that difficult, but there are a few important factors that must be taken into consideration. We need to first start with a brief review of what happens in the natural menstrual cycle, then it will be easier to understand how the IVF cycle works. There are 3 important elements: the growing follicle’s schedule, estrogen levels, and the size of the follicle at ovulation.

Just a reminder: the follicle is the fluid-filled cyst that houses the egg. Each follicle has one egg. We can't see the egg on ultrasound because it's microscopic. But we can see the follicle.

The Growing Follicle’s Schedule: By the 2-3rd day of bleeding, the previous month’s follicle has disappeared and the new one, which has already been chosen, has not started to grow much. On ultrasound you may see it, but you may also see other small ones that look the same. It’s the FSH coming from the pituitary gland (the pituitary will be a blog to come) which causes the little follicle to start and continue to grow.

As the next week goes by, the chosen (or dominant) follicle gets bigger and bigger, until it ovulates somewhere usually between days 11 and 20, most often close to day 14. It’s pretty rare to ovulate before day 11, but not so rare to ovulate later. The day of ovulation is related when the follicle starts to grow, and the cycle length gives us a hint as to when this was. It takes about 2 weeks for the follicle to grow from tiny to big. That means for a 28 day cycle, the follicle grows till ovulation, usually day 14.

What if the cycles are, say, 35 days? Well it still takes the 2 weeks to grow, it just starts later. So for a 35 day cycle the early follicle sleeps for about a week, then wakes up and starts growing day 7 and ovulates day 21. We don’t know what causes these differences.

What if the cycle is 24 days? In this case the follicle probably takes less than 2 weeks to grow, so 2 weeks is not mandatory. Again, the reason for these differences are unknown.

Estrogen Levels: As the follicle grows, it makes more and more estrogen, so the blood levels of estrogen rise each day. The estrogen is not coming from the egg, it comes from the tons of little ovarian cells (the granulosa cells) that surround the egg. The estrogen is probably not important for the egg, but one of estrogen’s very important jobs is to thicken up the lining of the uterus.

Estrogen’s second job is to cause the ovulation. The pituitary gland is constantly monitoring the estrogen levels, and when they get high enough, the pituitary dumps out LH (this is what your home ovulation kit reads) and this is what causes the egg to pop out.

There is not an exact estrogen level that causes the ovulation. Most of the time it’s anywhere from 150 to 350. Why there is a difference we do not know, it may be that there are other unknown hormones that work with the estrogen to get the job done.

Follicle Size: The size of the follicle is important too. Most ovulations occur with a follicle that is 20-25 mm(about one inch), but 16 mm is close to the bare minimum and 30 mm is close to the top size.

Next time we will talk about the timing of ovulation in an IVF cycle.

Thanks for reading,

Dr. Licciardi

This Time Even I Got a Little Mad

2009-08-14T08:00:00.000-04:00

It wasn’t supposed to end this way. We all knew going in that nothing was guarantied, but we felt good and optimistic about starting. Together, we believed that if we just obeyed the rules and had faith, that good things can happen to good people. We anticipated sacrificing time, emotion and money, for a process that was logically the most reliable way to go. We figured it was the best option, and we were “all in” to work towards success.

Shari was 41 when we first met and she was already at it for more than a year. She was very smart and informed. Shari understood the small details of each treatment, but didn’t dwell on the negativity. She was super practical. The plan, which she started at 39, was to start with iui, and move to IVF if nothing happened. She eagerly and compliantly stuck to the plan, and had 2 IVFs under her belt by the time she first saw me.

At our consultation I definitely saw hopeful signs from her previous cycles. She made 15 eggs the second time. Plus her embryo quality was very nice. I explained that 3 things really help when you are trying to get pregnant with IVF at 41; a high egg number, good looking embryos and chromosomally normal embryos. We knew off the bat that she at least had 2/3. More eggs means more selection. We all know that a large percentage of embryos have bad chromosomes, so if you have more embryos, you are increasing your odds of at least one of them being normal. And if they look nice, all the better.

Wow, she called to tell me she got pregnant on her own. Sweet. But there was no heartbeat at 7 weeks, and she needed a D and C. This caused her to pause, and logically concluded that maybe FSH iui could work. So she tried to no avail.

Doing more IVF cycles was not an easy decision. She had some infertility insurance coverage, but that was all gone, so she had to pay for anything else, including the medications. But she weighed the options and decided to proceed with more IVF based on her good response, recent pregnancy and advancing age.

So off she went into her 3rd and 4th IVF cycle with me. Each time producing eggs and very good embryos. We changed the protocol a bit, but in the end she had cycles that most other women could not achieve.

Except for the two negative pregnancy tests.

And that’s the end of the story.

When we last spoke she was again very practical. She just didn’t see the value in going into a 5th IVF cycle. She could not afford donor egg. She was very kind, expressing her gratitude for the treatment she received. But this was it; she was done. She had ended her quest for a baby. Stated differently, she was probably not going to have a baby.

So why am I bringing this story to you, as this is not the first tale of woe in the infertility world.

I think this one was tough for me because she had to stop, but I still had some hope in the chest. For many, stopping becomes the best option because multiple attempts have given me information saying that it really may not be worth continuing. Few eggs, very poor embryo quality, advanced age etc. When younger women have to throw it in, I can at least feel that with time their situation will change, and although it looks like the end now, they may get another shot later on. It’s also easier when the best option is donor egg, and donor egg is agreeable and affordable to the patient.

Now every doctor does get very disappointed every time a patient has a negative pregnancy test. But the story about Shari just left me hanging a little more than usual. Many eggs, nice embryos, and my sense that if she could just do more cycles her time would come. Maybe. The thing was, I couldn’t tell her it would happen, and that always makes it tough. And I couldn’t lay on the optimism thing, even though had some. After 4 cycles, the energy and drive to continue has to come from the patient.

But I will continue to have hope for her. Maybe she will fall into an insurance program that will get her at least one more cycle. She doesn’t have much time for that. May be her financial situation will change and she will get to donor egg. This she has a little time for. And maybe, she will get pregnant on her own, which is not out of the realm of possibilities.

Thanks for reading, and Shari is a substitute name.

Dr. Licciardi

Dr. Licciardi’s “Infertility Blog” named as one of the top 50 Pregnancy Blogs

2009-07-09T07:12:00.000-04:00

The list can be found at http://onlineultrasoundschool.com/2009/top-50-pregnancy-blogs-required-reading/.

Back to Frequently Asked Questions

2009-07-01T06:57:00.000-04:00

Before getting to FAQ’s here is a little vignette.

Last week I saw a woman who has been trying for 3 years. 3 years ago she told her doctor she had an extremely heavy period, and during her other periods she was losing more blood than she did in the past. No ultrasound was performed. Well 3 years later another doctor got a scan right away and she was found to have a huge fibroid in the middle of the uterine cavity. There is no way she could have become pregnant in the past few years with this fibroid in place. She lost 3 years. Take home message: abnormal uterine bleeding requires an ultrasound. In fact all infertility patients need an ultrasound right off the bat.

Can you travel by plane after IUI and IVF? There is no evidence that plane travel hurts anything. However, you need to have a very flexible schedule. There are a few things that could force you to stay home after a cycle. One is hyperstimulation. The other is an abnormal pregnancy. If you’re pregnant, the worse time to plan travel is about 2 weeks after your transfer. This is a bad time because often enough we don’t the location of the pregnancy. So if the day 35 blood test does not show a doubling every other day, your doctor may order you to stay put. No one wants you to rupture a tubal pregnancy, especially on a plane. The condition and location of the pregnany will mostly be determined as the next 1-2 weeks progress, so after that travel becomes more of a possibility.

Prolactin: Will get its own blog

MTHFR: Methlyenetetrahydrofolate reductase (yes, I had to cut and paste): This is an enzyme (a protein that is involved in a chemical reaction in the body) that is involved with the metabolism of folic acid. Folic acid can’t be properly utilized if there are problems with this enzyme. We have 2 copies of the DNA for this enzyme. It’s more common to have on abnormal copy, but 2 abnormal copies are more rare. If there are one or 2 bad copies, the next step is to measure the homocystine level. If the homocystine is normal, this indicates that even of the copies are abnormal; folic acid is still doing its job. If the homocystine is high, there is an interference of folic acid’s function. In this case, treatment may be necessary, with folic acid and other vitamins. Some doctors will recommend Lovenox (a heparin blood thinner). Some doctors recommend these therapies when the homcystine level is normal, but this is very controversial.

Late Onset Congenital Hyperplasia(CAH). Testing is via hormone levels, however there is a DNA test. If you have CAH, you shuold have the DNA test and your partner needs to be tested too. Just like above, you have one copy. He may have one copy too. The bigger problem is that your offspring may inherit one from you and one from him, and have 2, which is a much more serious disease. As far as treatment and pregnancy attempts, if you have a mild form of CAH, DEX may be overkill. Ask your doctor about other options such as just going to clomid.

Is IVF the only option for 1% sperm morphology? No, you also have the option trying on your own or iui.

What if you did 3 FSH iui cycles and can’t afford IVF? Practicality will dictate your path. You can get pregnant with FSH iui in the 4th 5th or 6th try. The odds become lower in the later cycles, but it’s still better than on your own or with clomid.

A 29 year old who made 10 eggs and had 2 average quality embryos is being told she needs donor egg. ARRGHHHHHHHH!!!. Give me a break. Can I guarantee you will get pregnant with your own eggs? No. Keep at it. Keep tweaking it, and get to the best program you can.

One tube and Clomid. If you have one tube clomid can work, but it does help to have the follicle on the same side as the tube. You may not need IVF right away. Usually with FSH iui you can make eggs on both sides at the same time giving you a better chance each month.

What IVF protocol is best? No one knows. I prefer the day 2 start with pure FSH. Why? Because no one has ever shown that one protocol is better than another. This is especially true when comparing pure FSH with FSH combined with LH. So if they are the same, why not make it simple. With the day 2 start there are no pre-cycle medications, and with FSH only there is just one drug to worry about. If that does not work, I can use all of the other protocols out there. I do feel that day 21 lupron is not the best for women we expect to be low responders.

How long after having a baby should you try before seeing your RE? It depends on your fertility problem. Obviously there is no waiting for severe tubal or sperm issues. If ovulation was the problem, you can wait a little to see if your cycles straighten out, but if even early on you see that things are as they were, get back to the RE.

What about a short luteal phase when taking clomid or FSH? Studies have shown that the luteal phase in a clomid or FSH cycle is better than a luteal phase from a natural cycle, probably because the progesterone levels are higher. I routinely do not prescribe progesterone for clomid or FSH. However, occasionally a patient will let me know that the luteal phase after a drug cycle was unusually short, maybe 8-11 days. I don’t know why it happened but I agree it sounds too short. Now maybe it’s ok, and if there were a conception, early bleeding would not have happened, but here I make sure we give progesterone in any subsequent cycles.

What should my progesterone level be? It needs to be over 8. No one has shown that 11 is worse than 40. When using clomid we sometimes get levels to be sure ovulation took place, but I don’t worry about the level.

Female anti-sperm antibodies. I would definitely believe in them if there were quality papers showing they play a role in infertility.

What if you have a short cycle but home ovulation testing shows a color change late? Well either the kit is off or there is a short luteal phase. In this case, office monitoring is the way to go. There are a few people who do well growing the follicle, but it just sits there a few days before deciding to ovulate.

Should you take progesterone with normal levels and a normal luteal phase? Data does not support its use.

Is DE the only option if the FSH level is 16. You have to ask your doctor what the odds of having a baby are using your eggs with an FSH of 16. I am sure the odds are very very low. So you have to decide if the numbers make it worth it to you.

Should husbands with male factor get genetic testing? It depends on the counts. The lower the counts, the greater the chances of a genetic abnormality, although even in cases where the sperm counts are less than 2 million, the genetic testing usually comes back normal. So I suppose it’s up to you and the urologist. There’s always a small chance that the genetics will be abnormal.

What about clomid in the case of severe endmetriosis and and at least one blocked tube. You can try clomid, but with the enod and only 1 tube, your odds with clomid are low. Remember, for women with normal tubes and sperm and FSH levels, the odds with clomid are only 8%. So with a problem pelvis, the odds will only be lower.

What if you became pregnant naturally with a sperm count of 3.8 million, and you want to now try again? Yes miracles do happen, but not often enough. Start with repeating the semen analysis. Maybe the counts are higher now. It’s also possible that they are lower, so you should check. If they are still 3.8, you can try for a little while, but I would get help if you are not pregnant quickly.

This is for relatively young women who don’t make many eggs. Get off the lupron. Many times, but not every time, more eggs are produced without lupron. If the egg number remains the same, then you are stuck and you will have do decide if its worth going through with the retrieval.

How often do you need to monitor progesterone levels after IVF? Usually progesterone levels are very high the first week after retrieval, but after the ovaries decrease their progesterone production in the second week. If the levels are high enough 1 week after, they will probably be fine as the second week progresses. The hcg produced by the early pregnancy will increase the ovaries output of progesterone. The point is is that if the progesterone levels are low on the day of the pregnancy test, it’s probably because there is no pregnancy, not because there is not enough progesterone being given to the woman. If a person is getting more than the usual amount of progesterone(IM plus vaginal and or oral), measuring levels will be less helpful.

If you have a family history of miscarriage, genetic counseling is indicated.

That's it for now, thanks again. Please see disclaimer 5/17/06.

Dr. Licciardi

Spotting and other Variations in Bleeding

2009-06-06T07:59:00.000-04:00

Spotting.

Really frustrating. Where does it come from? We first look for an anatomical reason (a problem due to some sort of growth that we can see usually with the ultrasound). The most common reason is that there is a polyp inside the uterus. A polyp is a benign growth inside the uterus, kind of like a skin tag on the inside. They are easily removed via hysteroscopy. If you have had polyps removed and still have spotting, you need to have a sono hysterogram to be sure that the polyps were completely removed. Or maybe they grew back. If the lining is pristine, you we have to look for other causes. Adenomyosis is another reason for spotting. Usually there is evidence of adenomyosis on ultrasound. If not, an MRI will make the diagnosis.

Women with endometriosis are more likely to have spotting, and this may be may be due to a few causes. With endometriosis, the glands of the uterus grow in areas they shouldn’t. The most common abnormal areas are around the ovary and tubes, but there can also be spots of endometriosis on the surface of the cervix. Because the glands don’t always behave as the normal endometrium, they can bleed anytime, causing spotting.

Another source of spotting in women with endometriosis is a hydrosalpinx. A hydroslapinx is a big scarred fallopian tube that is blocked on the part away from the uterus, near the ovary. If the hydro is caused by the chronic inflammation of endometriosis, blood can slowly built up inside the tube. This blood can sometimes back up from the tube into the uterus and then out the cervix, causing spotting. It’s usually not red, but more of a chocolate brown.

Occasionally no reason for the spotting is discovered. So we blame in on being “hormonal”, but we really don’t know what the specific hormonal abnormality is. Could spotting a few days before the period be due to a luteal phase defect and low progesterone levels? There may be one rare woman who has this issue, but for most women with pre-period spotting, their hormones are just fine. I have found that persistent spotting stops when moving to injectables, which do increase both of those hormones.

Post ovulation spotting can in many cases be controlled with progesterone and estradiol in the luteal phase. I remember one patient from years past who had the spotting mid cycle, had a negative hysteroscopy, and got pregnant on her own a few months later. So even though she had monthly spotting it had little effect on her ability to conceive. Maybe the spotting was normal for her and it stopped once she became pregnant.

If you are anovulatory due to PCO and you have frequent spotting, you may need to have a biopsy of the endometrium. PCO women who rarely get a period are at higher risk for endometrial hyperplasia or even cancer. This usually causes heavy irregular periods, but sometimes it’s just spotting. An office biopsy can usually make that diagnosis.

Other Variations in Bleeding

“I don’t bleed for a long as I used to”. I hear this a lot. Typically someone will say they used to bleed for 4-5 days and now they are finished after 3. There is no evidence that this means anything bad. Certainly after a delivery such changes are more common. But even without pregnancy, some women have changes that are hard to explain. I don’t think this means there is a change in fertility.

Heavier bleeding is more of a problem because it is more likely to signify a change that may be important. Remember that fibroid the doctor told you you had, but said it’s not a problem because it’s small? Unfortunately they can grow and become a problem with time. Increased estrogen levels associated with repeated drug cycles can accelerate their growth. Adenomyosis can also progress, leading to increased bleeding.

Consistent heavy bleeding in the setting of normal anatomy may require a consultation with a hematologist. Many of us are born with blood abnormalities that don’t’ allow for proper blood clotting. These issues are usually discovered in adolescence after the first periods are found to be abnormally heavy.

And of course, unexplained heavy bleeding may also require an office biopsy or hysteroscopy to rule out pre-cancerous or cancerous cells.

Thanks for reading and please see disclaimer 5/17/06.

Dr. Licciardi

2009-05-15T08:57:00.000-04:00

In February 2009, “The Infertility Blog” celebrated 3 years of production. I have been very pleased with the response. At least once per week someone tells me how valuable they find the information and how much they appreciate the effort.

Not only is it an effort to produce, I am finding it’s a lot of work for patients to read the 121 entries to date. Sometimes patients ask me to write on a certain topic, and I have to say, “I already did, go back and check.”

So to make it easier, here is the table of contents of Blogs so far. These are the “topic blogs”. They are not all of the blogs as there are many “Answers to Questions” sprinkled in between. Hopefully this will give you easier access to the information from earlier chapters. You can also print it to keep as a reference.

In addition, you can search the blog. In the upper left next to the orange e sign, is a box for you to type in your search words. If you type in a word such as FSH or SART, blogs containing those words will be listed.

Here you have it. Feel free to share it with others needing help.

2/05/06: A Woman Who Thought Her Hysterogram was normal. A classic story of a woman being surprised when I told her the radiologist read her hysterogram incorrectly.

2/07/06: From No Sperm, to a Few Sperm, to Twins. A classic story about a couple who was told by one doctor they had no sperm, but who saw another who said they had sperm.

2/15/06: No More Happy Birthdays. Birthdays and infertility can mix.

2/22/06: The Dreaded Biochemical Pregnancy. Explains the diagnosis and meaning of a biochemical pregnancy.

3/05/06: The First of a Few about FSH levels. Day 3 FSH levels explained.

3/09/06: FSH Levels: An Excuse to Send Patients Away. In some cases pregnancy is possible with elevated FSH levels.

3/12/06: FSH and Estradiol (Estrogen). Discusses day 2/3 estrogen levels and their relationship to FSH levels and pregnancy rates.

3/21/06: But Doc, What Went Wrong? Maybe Nothing. Your doctor can’t always explain why cycles are not successful.

3/27/06: Endometriosis: It’s Everywhere, but in Small Amounts. An introduction to endometriosis and its effect on fertility.

4/02/06: Endometriosis: What Are you Waiting For. Endometriosis is both over-diagnosed and under-diagnosed.

4/07/06: Why Do We Do IUI? Insemination can be more successful than intercourse.

4/12/06: Is There Enough Sperm for IUI? IUI can help with low, but not very low counts.

4/18/06: What are Your Odds? Don’t start treatments until you know your odds with each procedure.

4/22/06: This is Your Brain, This is Your Brain on Clomid. Clomid had some unique side effects.

4/27/06: The Clomid Death Sentence: Too many months on Clomid can kill your chances.

5/4/06: Sperm Morphology Mythology. Morphology may not be that important.

5/11/06: Abnormal Sperm Can Fertilize Eggs and Make Babies. More on morphology.

5/17/06The Disclaimer: Medical advice must come from your doctor.

5/19/06: Hysterograms: Let’s Not Forget the Uterus. Focusing on the tubes can miss important information about the uterus.

5/31/06: Who is Reading Your HSG? Reading the report without looking at the films doesn’t cut it.

6/04/06: Pregnancy Rates Matter. The pregnancy rates from each program are published by SART and the CDC. You should read the reports.

6/16/09: Your Doctor’s IVF Pregnancy Rates are Available to You. More of the same.

6/22/06: Ovarian Cysts Part One: Normal Ovulation. The term “Ovarian Cyst” can have many meanings.

7/01/06: The doctor said I can’t start because I have a cyst. What it means to have a cyst on day 2/3.

7/06/06: PCO: Pretty Cute Ovaries? What is PCO?

7/13/06: You Can't Have a Baby Unless you are Pregnant. The positive pregnancy test can be the start of a good thing.

7/20/06: How to subscribe to this blog. Get the blog sent to you.

7/21/06: Uterine Scar Tissue After a D&C. D &C, and the potential for scarring.

8/03/06: Abnormal Bleeding? Don’t have a D and C without a Hysteroscopy (and have an ultrasound first). “Blind” scraping doesn’t help much.

8/20/06: The Boxes of Pregnancy and Miscarriage. Especially when infertile, miscarriage really hits home.

8/28/06: Diagnostic Laparoscopy. Becoming a less-important infertility treatment.

9/11/06: Psychologists are Available: Consider Using Them. Why go it alone.

9/19/06: Hysteroscopy 101. An explanation of Hysteroscopy.

9/25/06: Is LH Important for IVF Success? There is little controversy; LH is not so magic.

10/05/06: Blocked Tubes: 2 Cases of Proximal Tubal Occlusion. Blocked tubes can mean different things.

10/17/06: I called and an embryo picked up the phone. Embryos do grow up.

10/27/06: What About Tubes that are Blocked at the Other End, Near the Ovary? More discussion about tubal blockage.

11/09/06: How Many Embryos are You Putting Back? Fewer is usually better.

11/20/06: How Can the Pregnancy be Bad But Still Growing? A few details about early pregnancy loss.

11/30/06 What’s a Hormone? Definition and examples of reproductive hormones.

12/09/06: What is Lupron and Why Are Only Some People Using It? Insight into different stimulation protocols.

12/12/06: More On Lupron and Why We Don’t use it as Much. More of the same.

1/08/07L Microdose or Microflare or Flare Lupron. More of the same.

1/20/07: Sperm Deficient Females Can Be Quite Fertile. Many donor sperm patients get pregnant quickly.

1/28/07: So Your Uterus is Bicornuate? Check Again, and Again. It may really be a septum, and it’s very important to know.

2/06/07: Bicornuate or Septate? What’s difference and why it matters.

2/26/07: Last One About Septums. How and why they are corrected.

3/10/07: When and How to time the IUI. Home and office monitoring.

3/16/07: A Little More about IUI. Inseminate one day or 2?

3/15/07: More on PCO. The basics workup, cysts and treatment.

4/02/07: Polycystic Ovaries and Insulin Resistance. What PCO can mean for your health.

4/04/07: Even More about Polycystic Ovaries. Is Metformin useful?

4/23/07: The Last Word on PCO, For Now. Modifying fertility the work-up for PCO patients.

5/06/07: The PGD Paradox: On paper, PGD for aneuploidy sounds great, but so far it has not lived up to expectations.

5/15/07: 3 Good Stories About 2 Opinions. Why wouldn’t you get a second opinion?

5/23/07: More About PGD. The pros and cons of PGD for aneupliody.

5/31/07: Ectopic Pregnancy. One woman’s story of a tubal pregnancy.

6/09/07: Ectopic Pregnancy FAQ’s. Some basics about ectopic pregnancies.

6/19/07: More questions About Ectopic Pregnancies. Treatment with Methotrexate.

6/29/07: Miscarriage and the Immune System (antibodies). Testing of the immune system.

7/12/07: Miscarriage, Infertility, Antibodies and the Immune System. More evidence would be helpful.

7/22/07: Meeting Your Doctor: What are You Thinking, What is the Doctor Thinking? Your doctor should make your first visit a positive experience.

7/30/07: A Bit More on Seeing Your New Doctor. Don’t let pre-conceived notions keep you from seeing a fertility doctor.

8/17/07: The Follicular Phase and the Luteal Phase. A basic understanding of the menstrual cycle.

8/25/07: Luteal Phase Defect. What are we looking for in the biopsy?

9/05/07: Luteal Phase Defect 3. More about how we make the diagnosis.

9/11/07: Four Simple Clicks Will Help You Have a Baby. You owe it to yourself to check the pregnancy rates of your clinic. It’s all at SART.org.

9/28/07: More About Pregnancy Rates: How to decipher the pregnancy statistics.

10/06/07: Why is Progesterone Used for IVF? The sources and actions of progesterone.

11/06/07: Are You Sure You Need Donor Eggs? Some women are pushed into Donor Egg.

11/19/07: What’s a Fibroid? What they are, how they start and the problems they cause.

12/01/07: Myomectomy. How it’s done.

12/06/07: Fertility and Diet. Mostly involves losing excess weight to improve ovulation.

12/17/07: Exercise. Please exercise.

1/03/08: Your Fibroid: Should it Stay or Should it Go? Which fibroids require removal.

1/12/08: More About Fibroid Surgery. Complications of the myomectomy procedure.

1/21/08: Minimal Stimulation. Less may not be more.

2/01/08: If You Live in the State of New York, the Government May Help Pay for Your IVF. It’s called the New York State Demonstration Project.

2/19/08: Fertility Questions: SCSA. Sperm DNA tests are unproven.

3/11/08: Fertility Preservation. Authoritative information about egg freezing.

4/13/08: Varicocele. A controversial operation.

6/10/08: The Endometrium. The essentials about the uterine lining.

6/22/08: The Endometrium Part II. The thin lining and scar tissue.

7/21/08: Improving Endometrial Thickness. Tricks of the trade to make the lining thicker; limited success.

8/02/08: The Endometrium Part III. Less conventional therapies.

9/01/08: Polyps. The significance of these benign growths inside the uterus.

11/26/08: Stories of Persistence. Women who succeeded by not listening to the doctor.

12/14/08: The Road to Blastocyst: Eggs and Embryos. Understanding the embryology part one.

1/12/09: More About Embryos. Developing embryos and embryo morphology.

1/27/09: Just Before Blastocyst: The Morlula. Day 4 embryos.

4/08/09: Meet the Blastocyst: Photos and descriptions of blastocysts.

4/27/09: What Can Blastocyst Do For You? A good blastocyst program can help you get pregnant with fewer embryos.

What Can Blastocyst Do For You?

2009-04-27T10:31:00.000-04:00

The advantage of a day 5 blastocyst transfer has to do with selection. These days most reputable programs are putting 2 embryos back in youngish women (I know what you’re thinking, but we’ll skip the octo discussion). Anyway, let’s say you’re lucky and have 5 nice embryos on day 3. Even though some may look a litter nicer than others, we really may not be able to tell which embryos are the best ones. So, we can wait 2 more days. In that time, some embryos may not grow well, but probably those embryos would not have survived in the uterus anyway.

The advantage here is that the embryos that do survive are probably stronger, and these can give you a better chance of pregnancy. It’s like a stress test, those that pass are probably better. One of my partners puts it nicely: just because a horse is leading ½ way around the track doesn’t mean it’s going to win the race.

But not all programs use the day 5 transfers, and some do it selectively i.e. only in some patients. Why is that? Some of it has to do with initial experience. At NYU, our initial experience was excellent, in fact better than expected, so we felt very comfortable continuing with it and this led to more and more cases and more expertise with time. Other programs had a bad experience initially. They were therefore less eager to increase their blast cases. Once something does not go well, especially in medicine, it’s really hard to go back to it.

Why would there be different experiences in different programs? Hard to say. I am prejudice in favor of the NYU lab, the people are all excellent, but there are other good labs around.

It may have something to do with the media. Media is the nutrient juice we grow your embryos in. We used to make it from scratch (what a pain), but now we buy it. An important factor making blast possible is the media. The old types of media could only support an embryo in culture for 3 days, and some very important changes in media composition were necessary to allow the embryos to grow 2 more days in the lab.

Initially, there was some variation in the new blastocyst media composition and quality, and there were batches that did not grow blastoctys well. So if you were an IVF lab who just happened to start out with an inadequate media batch, your outcomes would be lower, and you would be reluctant to explore blast culture further. Thanks to your lab directors and staff, we had a very careful process of testing media and analyzing which worked best. This allowed up to keep up the embryos quality in the face of variable conditions.

Among the programs that go to day 5, there is considerable variation in their criteria for going to blast. Some IVF centers need you to have 10 nice embryos on day 3 before they will consider growing the embryos longer. Others need you to have 6 day 3s, some 5, etc etc. Programs also put age in the mix; in other words less likely to go to day 5 the older you are. The more comfortable a program is with blastocyst, the softer their criteria will be.

Our criterion is that if you have more embryos than we want to transfer, you go to day 5. We transfer 2 embryos in most women which means if you only have 2 viable embryos on day 3 we do the day 3 transfer. If you have 3 or more, as is usually the case, you go to day 5.

Naturally, the obvious by-product of a good blast program is a lower multiple rate. Getting you better selected embryos, will help you become pregnant with fewer embryos. We started with blastocyst transfer in 1999. At the time we had a 20% of women under 38 had 3 embryos implant and now the rate is 1.9%. And many of those women had 2 embryos transferred, but had one of them split into identical s.

We went from putting in an average of 3 embryos per patient to two. Our pregnant rates would not be as high as they are if we put 2 embryos in on day 3. It’s just too hard to tell which are the best ones on day 3. Besides we have numbers to support our work. The implantation rate per embryo (this is a number that is used a lot. It’s the odds of each embryo sticking) was 34.5% in women under 35 and now its 43.4%.

So if your program is not doing a lot of blastocyst, does this hurt your chances? It really depends on the published pregnancy rates from your clinic. If they have great rates, but don’t do much blastocyst, that’s not so bad. Unless of course they are putting in more embryos per transfer to maintain the higher pregnancy rates. It’s not always easy to predict who will not get pregnant and who will get pregnant with triplets or quads. If you want to avoid 3s and 4s, your best bet is to not take the risk.

Sometimes there can be a diagnostic advantage to blastocyst transfer. If you are not getting pregnant with day 3 transfers, it may be time to try blastocyst. Occasionally, the embryos look much worse on day 5 than they did on day 3. This would not be not good news but at least you would know where you stand. It is also possible that they look just ok on day 3, but perk up very nicely by day 5, and this information might be of help to you.

Thanks for reading, and please see disclaimer 5/17/06.

Dr. Licciardi

Meet the Blastocyst

2009-04-08T17:54:00.000-04:00

Hello everyone, this blog will describe the blastocyst. I will show you some pictures and tell you what is good and what is less good. Next time I will tell you a little about our blastocyst experience at NYU.
Let’s start with an easy one, a nice one. This is a very nice blasotocyst.

This is the type of embryo you may see on doctor’s web sites.

So what are we looking for? In no particular order, one is the thickness of the zona. This is the thin membrane around the embryo; it looks like a clear plastic shell. The thinner the better. As the embryo grows, gets larger, and becomes ready to pop out of the zona. The zona gets thinner, and this is a good sign. We don’t measure the thickness; we just look at it and make a judgment. The bigger embryo in the picture below has a really thin zona, almost impossible to see, which is a good thing.

This embryo has a much thicker zona, not as good.

What else are we looking for? We look inside the embryo. You may not be able to tell by looking right away, but the inside is hollow. Thus the name blastocyst: the inside is like a fluid filled cyst. That’s a good thing. So the next embryos have a lot of space on the inside, the cavity (the space inside) is large, another good thing.

This familiar embryo has a smaller cavity, not as good, but not a terrible embryo overall.

What about the cells of the embryo? There are 2 types. There is the inner cell mass and the trophectoderm. The inner cell mass goes on to become the fetus/baby, the trophectoderm cells go on to become the placenta. Many more cells are designated for the placenta than are for the fetus. Ideally, the inner cell mass (ICM) is easy to see as a clump of tightly bound cells more towards the center of the embryo. Here is the nice embryo we saw before with a nub of cells at about 8 o’clock. This is a good-very good inner cell mass.

These embryos have ICMs that are smaller; in fact it’s hard to see the ICM in the bigger embryo.

Next we move on to the other cells of the blastocyst, the cells that make up the outer area. These are the trophectoderm cells, troph cells for short (really sorry about all the terminology, it just goes with the territory). Cells that are more plentiful and smaller make a better embryo. The larger embryo below has very nice troph cells (and the ICM is really nice too).

This embryo has troph cells that are not quite as good: they are larger and fewer in number.

The embryo on the left below has just a few troph cells and they are really spread out, not so good.

The next embryos are not very good looking. The top left does have a cavity, and the cells are not very good. The top right has a very small cavity. The bottom embryo looks like there is no cavity.

The next embryos have cavities, but not the nice ICM cells and troph cells we have previously seen.

These embryos have thick zonas, the lower left has no cavity, and the upper right has a small cavity and few large cells inside.

This poor embryo has a nice thin zona, but just a few cells inside. The troph cell at 4:00 o’clock is just spread so thin, across almost half the embryo. The ICM at 11 o’clock is tiny.

So now you know more about blastocysts than the average person undergoing infertility. I realize that some of you are not as interested in the details, and others really use the details to get through the infertility day.
Next time I will talk a little about the numbers we assign and a little about the NYU blastocyst experience.

Thanks and see you sooner next time,

Dr. Licciardi

Infertility FAQs

2009-03-07T15:19:00.000-05:00

Hello Everyone, catching up on the questions again. I know the topics are popular and I owe you one for next time.

I changed the format a bit for this time. I have the answers in more of a FAQ format with a little less verbage. I go through the question and try to distill out the major point. Hopefully this will be more efficient and informative, plus it allows for me to get to more issues more quickly. Let's see how it goes. Next entry will be a topic.

Do you need to remove Hydros? I am assuming your RE made the tubal surgery an option; some people can get pregnant with hydros in place. I make it an option with most of my patients. Of course you need to discuss this with your doctor, he knows your case better than I. It’s too early to tell about the Essure.

Is a high estrogen bad for implantation? I have not seen this to be the case. It is very true in mice, but mice are very different.

Why would someone who is 33 have 2 kids then 4 miscarriages in 15 months? If your workup is negative, we don’t know. It is important to have a hysterogram. I have had women with 4 miscarriages go on to have more than one child.

Is the estrogen prime good for low responders? It is no worse than anything else. If other stimulations have failed, give it a try.

If you make a lot of eggs does that mean you have PCO? It does not. It could mean you just make a lot of eggs. We see this all of the time.

If you are discouraged because you failed you fresh DE cycles, should you bother with your frozen? Believe it or not, we have some women who did not get pregnant with their fresh de embryos and have not returned for their frozen. Now there may be many reasons for this. If you would like to be pregnant, get up the nerve for the frozen cycle.

If you do not ovulate with clomid, should you add metformin? Consider the other option of very low dose injections. Metformin an option, but it may take months to get results, and in many cases ovulation dose not occur even with metformin.

Will acupuncture help? We don’t know, but I have many women doing it. In fact, in our office we provide acupuncture services, and the patients are very happy we do. We also provide Yoga and Mind body and psychological services. It’s all under the NYU Fertility Center Wellness Program.

FSH on day 2: should you wait for a lower number? Not sure. We prefer if our patients start with a number less than 13.4.

Can coasting have a negative effect on egg quality. Absolutely. Probably less so if the coasting is 1-2 days, but longer coasting is at times very bad for egg quality.

Can someone be prone to chromosomal miscarriages? Yes, there are some women who have a high proportion of chromosomally abnormal embryos.

Septum and PCO, which to fix first? Yes there are women with a septum who have had normal fertility and pregnancies, although I would be hesitant to leave a septum in because of the potential problems. It’s between you and your doctor. PCO is always fixable.

Is obesity a problem? No hard data, probably leads lower IVF rates. It’ more of a problem for pregnancy because of harm to the fetus. 11 eggs is ok, a few more may be better, ask your doctor about increasing your dose.

Should infertile women have a laparoscopy? Very few of my patients get a laparoscopy. If the only thing your insurance will cover is laparoscopy, then it’s a more reasonable approach. However, if there is no pain, no cysts and open tubes, the odds of a laparoscopy helping anything are low. Yes there are some women who everyone thought were fine who were found to have bad endo, but these cases are rare and usually there is a sign of the problem pre op.

Low sperm morphology: Usually not a factor. Some exceptions exist.

PCOS-like. I am happy that your doctor put it that way. Too many women are labeled with PCOS.

Temperature charting was good for the cave people. Please use a predictor kit.

What are the chances of conceiving with Clomid at age 40? Probably around 3-5 % per try.

Sperm clumping is probably not a problem. If anything, it should be solved with iui.

Stay with Clomid? Getting pregnant with clomid, but 2 miscarraiges. If you are getting pregnant, there is more of a reason to stick with it. I don’t think the clomid is causing the miscarriages, so getting pregnant with the injections amy be no different. See what your doctor thinks.

BPA leaching from cans an interfering with implantation? I wouldn’t worry about it.

Can a 34 yo with a poor response to the drugs become pregnant with IVF? Yes. At your age you only need a few eggs. Now more eggs would be better, but the odds are still very good with few eggs.

How to deal with antisperm antibodies? IUI or IVF.

Polar bodies are different than pronuclei. They both contain chromosomes. The polar bodies are the cells garbage. The pronuclei stay inside the egg and fuse the day after the fertilization. They come together to become the complete genetic material.

Is going for more than 9 eggs at 34 greedy. No , if your doctor thinks adding more drug will safely get you a few more eggs, that’s not so bad.

Is a lining of 16 mm too thick? It is if there is a reason it is thick. That is to say, if there are polyps making it thick, that’s not so good. If the lining is perfectly normal, and it’s thick, that’s ok.

Nuclear transfer and cytoplasmic transfer are not allowed in the USA. Just like many things in medicine, some preliminary results looked ok, but no one ever proved any benefit.

Does thyroid disease, like Hashimoto’s, cause miscarriages? This has been debated for the last 20 years, and there is no good evidence that it does. We are trying to do yet another study to look at the problem.

Does age matter for frozen embryos? No it’s the age you were when they were frozen, not the age you are now.

How come I became pregnant easily at age 23 and am having trouble now that I am 39? This is not uncommon, 16 years is a long time. A lot can happen.

Can you have regular cycle and not ovulate? I don’t think so. Ask what your progesterone levels are, even if they are over 3, you are probably ovulating. If you are not, well then it’s time for induction of ovulation.

Will DHEA help? It might, and if you are making a very low number of eggs, it may be worth a shot. I have had mixed results.

If you have frozen embryos, should you use them or jump into a fresh cycle? It is easier to use the frozens, but if you want the higher pregnancy rate, do the IVF again. If you only have 1-2 frozens, it may be better to do another fresh because not all embryos survive the thaw well.

Can a chromosomally abnormal embryo look beautiful? Absolutely, we see this every day.

What is the optimal TSH level? It depends who you talk to. The endocrinologists are going crazy trying to get everyone’s under 2. There is no real conclusive science showing this is important. Probably ½ the population has a TSH over 2, and ½ the population can’t be abnormal.

Can antidepressants interfere with FSH levels? Probably not.

Will assisted hatching reduce miscarriage? No it will not.

Can you have too much progesterone? No.

Does everyone with endometriosis need IVF? No. It depends on the status of your tubes. If the endo is causing scar tissue around the tubes and ovaries, than yes, IVF may be the best option.

Is a 12 cell embryo on day 3 a bad thing? The embryologists seem to think so. You cannot say you have a serious egg problem after 1 cycle.

Are fragments removed? They are typically removed f you are having hatching because the same little tool used to hatch can be used to suck out some fragments (unless you are having laser hatching). However, no one has ever showed that fragment removal makes a difference. Same goes for assisted hatching.

How do you define poor egg quality? I would say embryos that look less good than average. Embryos that are fragmented more than 20% are poor, even 20% is not great. Slow embryos are poor. However if you just did one cycle, you cannot be given the label until another cycle is performed.

What’s better, a frozen cycle with estrogen, or a natural frozen cycle? They are about the same. I find that sometimes the natural cycle gets a little confusing with the timing, and a small number of people ovulate earlier than expected, so if you do a medicated cycle, less is left to chance. However a natural cycle FET is a very acceptable practice.

See next time. Please read disclaimer 5/17/06. Dr. Licciardi

Back to More Fertility Questions

2009-02-16T18:29:00.000-05:00

There will be 1-2 more for the blastocyst, but I will answer a few questions first.

Sorry, some of these questions were asked a while ago and my responses may be a little late if immediate action was necessary. I will still answer many of them hoping the answers will help others. If I skip your question, it does not mean it’s a bad one, it just means I cannot comment, or I just don’t have anything additional that will help.

There are a number of women who have tough stories about failing many IVF cycles and being faced with the donor egg decision. I always feel I want to recognize the problem by commenting, but my responses have been similar. Usually, it’s just up to you. The boring answer is get tot the best clinic possible and weigh your options. If I see anyone who I think is getting pushed to donor egg too soon I’ll comment.

Jennifer was discouraged because on clomid she found it difficult to time her intercourse because the cervical mucus remained thicker.
You should use a different method of checking for ovulation, namely the ovulation predictor kits. Clomid does make the mucus thicker, but not in some and partially in others. You can get pregnant if the mucus is thicker, but it depends how thick. This is another reason to consider insemination in order to remove the mucus from the equation.

Muriah had septum surgery but the HSG post op showed some septum remained. Why?
This is more common when the septum is very large. With a large septum, there is quite a bit of cutting. Of course we don’t want to cut too much, so at the top it may look like a dramatic improvement, but in reality, a little more should have been cut away. It is also possible that the doctor saw that there was a little left, but felt he had cut enough, but did not. It is also possible that as the uterus healed, it scarred a little at the top, making it look like the septum remained, when in fact it was cut properly but did not heal well. In any event, when I have a patient with a large septum, I do say that a second procedure may be necessary, although it has not been necessary in years.
It is also possible that there is a little left, but it’s not clinically significant. This is very common. I sometimes see a bit left and I say it’s not enough to worry about.

Jamie has spotting being treated with progesterone.
Just make sure your uterus is normal. Make sure you have a thorough ultrasound and HSG, and maybe a sonohysterogram, to be sure there are no polyps or fibroids. Some women need a biopsy. Otherwise, some women spot for unknown reasons and progesterone, sometimes with estrogen, fixes the problem.

Ruby’s husband has anti-sperm antibodies. I do not think this means anything.

KSNYC makes a few follicles but only makes 2 eggs Why? We do not know. If you had only done 1 cycle, we could say it’s just one of those things, try again. But after 4 cycles with varying protocols, and consistent results, well, that’s how you behave. I would say that at age 34, you should not give up yet.

Ronni is 40, makes nice eggs and embryos, has severe male factor, and is being told to do DE after 3 failed cycles. She is being told it’s an “egg issue”.
It’s up to you. Of course your problem is an egg issue, but you eggs can still give you a chance. I am going to guess that your odds are 15-25% with your eggs. You may want to consider traveling farther for a better clinic.

Amanda was on clomid, and injections are being suggested but is worried about multiples/hyperstimulation. Yes minimal stimulation is the way to go. We use anywhere from 37.5 -75 units.

Katrina’s husband has zero morphology. There is not much that can improve morphology. Spotting may or may not be a problem. See the post above.

Flycat is Catholic and does not want IVF or IUI. My suggestion is for you to speak to your priest/pastor. You never know, they may be more permissive and sympathetic than you think.

Helen has a bleeding cervix. You are right, cautery or freezing may scar the cervix. Get another opinion.

Lazarus is 41 and has failed a few cycles. Her doctor does not want to use the estrogen pirme. I say why not? It may or may not help, you just need to see.

Mina is 33 and was told she is in premature ovarian failure. You need to repeat the FSH and estrogen levels every 6 months, and least for a while. Sometimes things get better. However odds are the numbers are accurate and your doctor is correct.

Tracylayne’s husband has a translocation and 6 sperm. It seems that your advice is accurate. We do not know with certainty about odds of pregnancy and miscarriage.

Rehab nurse is considering reversing her tubal ligation. You are right in that you need to get to the right doctor, but it is hard to know who that person is. Some states have insurance companies that cover the procedure so doctors there have more experience because they do more. It’s the balance between reversing the tubes and just doing IVF. Some women prefer the IVF because they can still have contraception after the baby is born. The operation may cost more than one IVF cycle, however it may take more than one IVF cycle to get pregnant.

Chris has severe endometriosis. She has done 2 retrievals , makes a good egg number and has nice embryos. She has also done frozens.
Make sure you don’t have a hydrosalpinx (blocked swollen tube). Assuming you do not, it may just be a matter of trying again. Your history does sound like there are many positives that can work in your favor.

Karen has triplets and the new fertility clinic is criticizing her for wanting another baby. Go elsewhere, their attitude is not appropriate.

Heather wants to know if she should do back to back iuis. It probably is not necessary, providing the timing of the one iui is proper. If there is a question about the timing, use the 2.

The Kinsleys had a nice fresh cycle that failed and are worried that their frozen cycle will fail too.
There is not much to worry about. If they thought the embryos were good enough to freeze, they are probably more than good enough. This is one of the main reasons we freeze, if the fresh fails, you have the backup. It can work.

Curley wants to know if poor sperm can cause embryo quality issues. This is tough one. Usually not. However, I have seen a few cases along the way. The big problem is how to find out. If you make 20 eggs, you can feel better about splitting the eggs and using 2 sperm sources. If you have make 4 mature eggs, the experiment may not give you the answers you need. Most of my patients will try a few IVF cycles first, and then be forced to make a decision. May do not opt for the husband/donor split.

Just Before Blastocyst: The Morlula

2009-01-27T17:40:00.000-05:00

So what happens after day 3? Two days later we would like it to be a blastocyst. The day before it becomes a blastocyst, it should be a morula. A morula forms when the 8 cell embryo divides further, and at the same time the cells become very close to each other. Here it’s difficult to see the borders of the cells, so the morula looks like one big blob. It ‘s solid in the middle. It’s still inside the shell. There are about 12-30 cells in a morula.
Here are some pictures:

Here is a nice looking morula.

Here are a few others . The top right looks nice, the others look OK, the bottom right looks the worst.

Most morulas (some write the pleural morulae, but most write it morulas) look about the same, so we don’t give them a number or a grade. We may say “nice” for a good one, but that’s about it.

Is it ok to transfer a morula? If your doctor wants to transfer your embryos on day 4, you will probably have morulas, but it will be hard for you to get a handle on quality. Most programs transfer day 3 or day 5. Day 4 transfer is ok, but most of us would say if you are waiting till day 4, just wait till day 5 so that the embryos have more time to grow, and quality can be better assessed.

What if on day 5 you are told the best embryos are morulas, not blastocysts? Not so good. I have had patients get back 2 morulas and become pregnant with twins. However the chances of pregnancy are much higher if you have blastocysts.

If there are morulas on day 5, isn’t it better to wait another day until they are blastocysts? No, because even if they become blasts on day 6 they are still a day behind. Rarely, we transfer on day 6. This may happen if , for example, there are 4 morulas and we want to give them, one more day to see which ones, if any, develop a little more.

Can we do anything to make the embryos grow faster? The same answer as last time. We try to change things up a bit next cycle, but there is no special drug protocol for slow embryos. Its just a matter of trying again and hoping for a better outcome.

Thanks again,

Dr. Licciardi

More About Embryos

2009-01-12T10:35:00.000-05:00

The questions: at the time of this writing there were 84 questions to answer. I will read through them and get to most, but probably not all. I am sure this is most difficult for those who write about the here and now, i.e. questions about a cycle in progress. Many of you have commented that the topics are more helpful than the questions, so I want to continue with the embryo blogs, and then go to more questions. I do like answering the questions.

The egg is one cell, the fertilized egg is one cell, and then the egg divides, becoming 2 cells. The 2 cells are smaller than the one big one, and with each division, the cells become smaller. After 2 they become 4. Actually many times they become 3. Both the 2 cells may not divide at the same time. That’s why an embryo can be a 3, 4, 5, 6, 7, 8 or other cell number. It does not need to be an even number.

So here are pictures of 2 cell, cell 4 cell and 8 cell embryos.

The overall size of the embryo does not change. The zonna pellucida stays the same size, so the cells need to fit inside. Just like a developing chick can’t be bigger than the egg, till the end.

These are pictures of perfect looking embryos. Most embryos do not look like these, and that’s ok. These are the typical embryos you see on web sites.

Most of the questions about embryo development we cannot answer. Why do some embryos look prettier than others? Why are some embryos slower than others? Why are some embryos fragmented? We are not close to understanding these questions. We prefer if an embryo looks “better”, meaning the cells are dividing at the right rate and there is minimal fragmentation.

How quickly should an embryo grow? 1 day after the retrieval, they are still one cell, but the next day division should take place. A 4 cell may be the best, but a 2 or 3 may be ok. And of course, they have to keep growing, so that the next day, day 3, they should be 5-8 cells. A 4 cell on day 3 is really slow. Certainly, as with many other slow embryos, a baby is possible with a 4 cell on day 3, but it’s better to have an embryo that is more advanced. The closer you get to 8 the better, 6 is the minimum “good” number”.

Most clinics have their own classification system for grading embryos. Some labs call their best embryos A’s. Some 1’s, some 5’s. There is a reason for this. IVF is a relatively new science and many of the lab directors who started 10-20 years ago had little human IVF experience. There just were not a large group of scientists who previously worked in IVF labs. They had backgrounds in brain science, animal science and all sorts of other areas. Some of them turned into great lab directors (hats off to our lab director, Dr. Krey), but there was not grading system that the whole country followed. Each program just made up its own system for grading day 3 embryos. We could all get on the same page, but now it’s too hard to go back.

It would be really difficult for each program to go back through 20 years of charts and change the numbers assigned to each embryo. Plus if we all change now to a new system, it’s hard have some embryos graded one way and some another, especially for research purposes. So things will stay as they are. It just makes it a little difficult when you talk to your friends to compare embryos. To jump ahead a little, there is a system most of us follow for day 5 embryos.

What is fragmentation? Fragments are little pieces of the cell that break off as the embryo divides. A little bit of fragmentation is normal. As the degree of fragmentation increase, the odds of implantation go down.

Let’s look at some day 3 embryos to see varying amounts of fragmentation.
This close up shows the normal larger cells, and some smaller round “fragments”.

Here is a group of embryos from the same woman. The embryo far right is the best. It has very few fragments. The top embryo looks good too. The bottom middle looks ok, but is a bit more fragmented.

This embryo has a high degree of fragmentation (compare to the nice embryos at the begining).

In this picture, the far right embryo is full of fragments.

We frequently assign a fragmentation score by estimating the percentage of the embryo volume that is replaced by fragments. 0% is actually rare, some fragments are expected. 0% is ok, but it does not happen much. We consider up to about 10% to still be very good. 10-20% is still OK, not quite as good. More than 20% is more abnormal, we consider the embryo to be of poorer quality. Pregnancy can occur with a fragmented embryo, but the odds are lower.

Sometimes fragments are removed from an embryo in the lab, by making a small hole in the shell and sucking out the fragments on day 3. This is done at the time of hatching since the hole is the same. The embryo can look much better, but we do not know if it means the embryo is really in better shape.

Can we reduce a woman’s chance of producing fragmented embryos? We try, but we never know if our efforts helped, or things improved as a result of chance. We add lupron, remove lupron, add LH, remove LH, lower doses, increase doses, give few days or more days of stimulation, etc etc.

So what’s worse, a slow embryo or a fragmented embryo? Of course it depends on how slow or how fragmented, but basically, it’s a tie

An important issue here is that if you have done 1-2 cycles of IVF, and you make eggs and embryos and have fragmented embryos, donor eggs may still not be necessary. Get a second opinion at the best program possible. Maybe DE is the best thing for you, but maybe another try under different conditions will do the trick.

Thanks for reading, and please read disclaimer 5/17/06.
Dr. Licciardi

The Road to Blastocyst: Eggs and Embryos

2008-12-14T08:54:00.000-05:00

This is the first installment of blastocyst blog; but it's a bit of a pre-requisite. To give you a feel of where we are going, I will start with pictures of eggs and embryos and then blastocysts.

This is an egg. I doesn't really look like an egg. Part of the reason for this is that in this picture there are hundreds of cells, but just one that is an egg. The dark circle in the center is the egg. You can see how big eggs are compared to the rest of our cells. The surrounding specs are granulosa cells. These are the ovarian cells that line the inside of the follicle. Prior to ovulation, the egg's position in the follicle is along the edge, so the granulosa cells that are growing along the inside of the follicle surround the egg. When the egg ovulates, it carries some of these cells along. When an egg is retrieved during IVF, it is also surrounded by granulosa cells.

The granulosa cells make the estrogen (estradiol). So as the follicle grows, more granulosa cells form, and estrogen rises. In an IVF cycle, the more eggs there are, usually the higher the estrogen levels.

This is a picture of an egg a few hours after retrieval, after the granulosa cells have been removed.
In the case of IVF using ICSI, the embryologist needs to remove the granulosa cells a few hours after retrieval. This is necessary so she can see the egg and to properly inject the sperm. If ICSI is not necessary, we can mix the eggs and sperm together, and the sperm will swim through the granulosa cells to get to the egg.

The little round object on the top is the first polar body, and this is an indication that the egg is mature. The first polar body contains chromosomes, as does the larger egg cell. For the egg to accept the DNA of the sperm, it needs to dump some of its own DNA, otherwise there will be too much. So the egg unloads some of the DNA into the polar body, which just withers away. Sometimes testing the DNA of the polar body can tell us about genetic diseases in the egg. For the most part, we can not use an egg that is not mature. There is some encouraging research looking at maturing eggs in the lab, but so far the process of maturing eggs in culture has not been widely accepted.

This is what we call a 2 pn zygote (or 2 pn embryo). The picture was taken one day after the retrieval. You can see a few granulosa cells still hanging around.
The halo around the embryo is the zona pellucida. It's the shell of the egg. It has the consistency of a thin vitamin E capsule. Inside is the egg (or oocyte). In the middle of the egg, you can see 2 little round objects, and these are the pronuclei (pn). One contains the genetic material from the egg, the other from the sperm. In some animals we can tell which came from where, but not in the human, although as our microscopes improve, I suspect we will very soon be able to tell. So if we expose eggs to sperm, and look the next day, and do not see 2 polar bodies, fertilization has not occurred. Sometimes we see one, and this means fertilization possibly occurred. In this case we may or may not see 2 later in the day. The 2 pn will combine to complete the fertilization process.

Dr. Licciardi

Stories of Persistence

2008-11-26T15:46:00.000-05:00

I know you are waiting for the blastocyst blog. I am just getting some photos together and will have it ready for next time.

Like it or not, the holidays are here. Maybe it’s a good time to spread a little message of hope. Now hope isn’t for everyone, but let’s face it, it’s probably the number one thing that keeps us going. It’s an emotion than can be applied rather universally, applicable to mostly all of our basic functioning.

Anything we need or want, we hope for.

As stories from the internet have shown, some women with low chances can become pregnant.
Here are a few of my own. And these are only a few out of many others, these just came to mind.

Ms. A was 38 when we met. Her FSH was 22. She was “dismissed” from another program. 2 years earlier she delivered, but this was after trying for 18 months. The sperm motility was a little low, but the sample was close enough to normal, ICSI was not needed.
She first tried a day 2 start, her FSH was 13,4, and was cancelled and converted to IUI because there were only 3 follicles. The plan: keep trying. Her second cycle never got off the ground because of a day 2 FSH of 17.7.
Her FSH was 11.9 on her 3rd attempt and she went on to make 4 eggs, 4 fertilized . On day 3 one looked good, the other fair. This ended in an early biochemical loss.
Her next cycle we changed up the protocol a bit. She had 4 eggs, and 2 embryos transferred, both looked good. This worked, and she just delivered.
So here we have a woman who most doctors would tell there is no chance, but she persisted.

Ms. B was 35 when we met. Her FSH was 14. Her resting follicle count was less than 5. She started a cycle with an FSH of 12, got 6 eggs, poor fert and a cancelled transfer for arrested embryo growth.
Her second cycle was cancelled for no response (not one follicle).
She got pregnant on her own. This theme is an internet favorite. Buy the way, she did not use DHEA.

Mrs C. was 36 and suffered from severe edometriosis. She did 2 IVF cycles before we met.
She did 3 more retrievals with me, always making a good egg number and having good embryo quality. She travelled long distance to get to NYU. On her 3rd cycle (5th total) she became pregnant.

The next one goes under the dumb doctor category (that would be me). Mrs D, a 38 year old from overseas, e-mailed me and told me about her FSH of 25. Realizing she was from far away, I tried to save her some travel time and money and told her IVF was out, but donor egg was in. The couple came to see me, heard the donor egg schpeal and as I finished the husband looked up and said that his wife was going to be day 2 in a few days, could they try IVF while they were still in the States? Without boring him with the low odds speech, I just said, “sure why not.”
Sure enough the FSH was 12, she made 9 eggs and delivered twins. I think they are happy with me, but I am sure they have their reservations.

How can we put these all together?
1) They about women under 40. I don’t mean to exclude the 40 and over crowd from the hope discussion, as there are plenty similar stories about women in their 40’s, but the facts support that it’s easier to beat the odds when you are younger.
2) FSH may not be as important as we once thought. Again, a bad FSH is better under 40. Every so often there is a paper or abstract reminding us that pregnancy rates shoot down with increasing age and FSH levels. Which leads us to the next point:
3) Some infertile women can at times become pregnant on their own. We do use this fact when recommending that some women cancel their cycle or give up on IVF. We say yes you can get pregnant with IVF, but your odds are low, about the same as getting pregnant on your own. Of course this is much more difficult concept to accept when there is a severe male factor.

So for Mrs. A, C, and D, their persistence is what lead to their success. They did not accept the advice of a doctor; they did what they felt they needed to do. Of course we have to keep in mind that it is also true that there are women who try and try unsuccessfully.

Sometimes the fertility establishment is criticized for giving a bit too much hope, while profiting nicely from tons of women who are needlessly spending tons of dough. And sometimes we are criticized for not giving an infertile woman the chance she deserves.

But it will always be true that for most women with low odds, there is a small chance, and sometimes their only chance, using IVF. So it all goes back to getting to the right clinic and getting informed about your odds. After that it’s between you and your doctor, sometimes with a little tug of war.

Dr. Licciardi

A Marathon of Infertility Questions

2008-11-06T16:16:00.000-05:00

As this Sunday was the New York City Marathon, I figured I would have my own little marathon and answer all of the outstanding questions. Here it is.
It took me a few days to cross the finish line, but I was able to eat and sleep along the way, possibly experience some weight loss, and I seem to be injury free.

From October 4th

Niki has had a very tough time trying to have a child. She has had a number of bio-chemicals and worse (see her post). Her basic questions are 1) is a thinish lining the reason, or is it an immune problem, or some other problem we just don’t know about?
I also do not buy into the immune issues. These have been studied now for many many years and never has anyone produced a quality study showing they mean anything. However, you have few choices, so it may be reasonable to consider getting tested and treated, if something shows up. I am not recommending one way or the other. You should give equal consideration to a carrier.

Esther had open tubes on hsg and a few weeks later had both tubes blocked at laparoscopy. She is being told she needs IVF.
I am not so sure. When I have open tubes on HSG, I don’t even check at laparoscopy. Why? Because it is common for tubes to be open on hsg and closed at laparoscopy. It’s a mechanical issue. Sometimes the doctor just has trouble getting dye out the tubes at laparoscopy. Now it depends on where the blockage is. If you have proximal occlusion (blocked at the uterus), this may be a false finding. If he says you have bilateral hydrosalpinx (blocked near the ovaries) that’s different and real. If there is any question, the answer is simple, just repeat your hsg. If the tubes are open on your next hsg, there were not blocked at your laparoscopy.

Mosche and his wife need IVF with ICSI due to male factor, however even with ICSI, there was no fertilization.
I have only had one young patient make many eggs and not fertilize with icsi. So it can happen, but it is rare. It’s a little more common when there are also issues with advanced maternal age and low egg number.

Ruby asked about sperm antibodies.
I do not believe in them because no good recent scientific paper written showing me that sperm antibodies are relevant.

Angie did a clomid IUI cycle, and the sperm count was 18 million with 56% motility.
The count sounds reasonable for iui. Although you should still ask for the total motile count, and look for that to at least be over 5 million, preferably over 10.

Tabi did 4 IVF cycles, 3 with lupron, one without. The non-lupron was her worst.
We don’t know if it was the no lupron, or was it just going to be a bad cycle for you that month, independent of your stimulation protocol. It may be that in your case lupron is better. For most women who make few eggs, this is not the case, but not all women are the same. I don’t think you are declining.

Ali did IUI. The sperm count was 143 million with 48% motility. However for the iui, only 3 million were recovered.
This is strange and does not make much sense; unless the initial volume was very low (2cc is normal). I am not worried about his morphology. “Abnormal” sperm are not removed when preparing for iui.

Manny and his wife are trying to conceive. He is asking if the lining could be an issue, especially because she takes anti-migraine medication that theoretically could restrict blood flow to the uterus.
The question is interesting, but unknown. One option is to measure the lining on and off the medications. Or, try to conceive off the medication. Another option is to look elsewhere for a potential problem. Do the basic workup i.e. semen analysis, HSG, day 3, to see if there are not bigger problems with more known quantities.

Anonymous has PCO and 2 weeks of bleeding after clomid.
This is not normal. Actually, the first cycle sometimes the bleeding can be unusual, but once you get into a pattern of periods, they should not be 2 weeks long. You need a good exam and ultrasound and maybe an endometrial biopsy.

Anonymous is 42 yo with 3 failed IVF cycles. Some borderline FSH levels and 1, 1 and 3 embryos available for transfer. Should she stop?
Your odds are what they are, low. It depends on your clinic, but your chances are probably about 5-10% per try. Many women, probably most, would stop here. But some persist, and a few get pregnant. As you know there are emotional, physical and financial issues to wade through. You can’t say you didn’t try. I hope it works out.

Mark is asking if he and his wife should consider natural cycle or minimal stimulation IVF vs. the standard IVF using more drugs.
You will need to decide. My only comment on your post is that it is not true that fertility drugs for regular IVF will ruin the eggs forever. But the opposite is also true. If you do a natural cycle, you can always do a regular cycle later. Regular IVF may not be for everyone, however, for most people, it has a higher pregnancy rate, which means a better chance of having a baby. The cost is less for natural, but with its lower pregnancy rate, it is common (not in every case) to spend at least as much money because the cost of multiple cycles really adds up fast. If you get pregnant early, great, you were the lucky one.

Erika has had 9 pregnancy losses and IVF is now recommended.
I understand the theory; if you put more than one embryo in, maybe if one fails another one will stick and you can have a normal pregnancy. Certainly, your odds of loss will be higher than the average person, even with IVF. I don’t think we can tell you that your odds of loss will be lower than from a natural pregnancy. However, your options are limited, so it may be worth a try.

Dizzy has totally unexplained infertility. All tests are very normal and she is 31. She has done 6 FSH iuis and is considering IVF, but insurance does not cover.
IVF is the next step. No one will be able to tell you why you are not getting pregnant, but IVF has an excellent pregnancy rate, even if you have failed FSH iui. You odds with FSH iui are now going down, because it has not worked. Of course you could do more FSH iui, and it may work, but it may be more of the same.

Purple Mocha has a 3 mm lining on clomid.
Sounds a little too thin. You can try again, or change to FSH. You could also check you lining in a no drug cycle to see what your baseline is. Of if you want to get going, just go to the FSH.

Mtroth has some endo and failed one IVF cycle, which was complicated by hyperstimulation. She has frozens. Did an undiagnosed biochemical pregnancy lead to her hyperstimulation?
You may have had a biochemical, but probably had plain old hyperstimulation. Your estradiol was high and you needed to be coasted. I do not think the endo was an issue. You can’t prepare for the FET. The good news is you seem to have nice embryos and should do well.

Athena has 8 months of infertility, short luteal phases of about 10-11 days, and serious pelvic pain. Her doctor will not see her until she has a year of infertility.
Maybe you have insurance that will not pay your doctor until there is a year of infertility, or maybe he is not a nice person. See which it is. If you think your timing has been good, it would be better if you saw him or another doctor soon. In general I do not believe in luteal phase problems, but you may be an exception because your luteal phase is so short. But do not only get that treated; work on other things at the same time. Get the hsg and ultrasound to look for cysts and endometriosis. Get the sperm checked.

Anonymous is an over-exerciser and because of this does not get her period on her own and does not bleed after provera. Because clomid starts after the period she does not know that do about starting the clomid.
You can start the clomid without a period, providing you get a pregnancy test. I am fine with you trying the clomid, but may women like you do not ovulate on clomid because, due to the exercise, your pituitary does not have much FSH or LH, and clomid works by releasing FSH and LH from the pituitary. Most of time, injected FSH is necessary to get you to ovulate. But you can try, sometimes it works.

Milka is 37 and her doctor told her her IVF failure was age related. He also wants to repeat her sonohyst and cultrures
I do not repeat those tests unless there is a good reason. Failing IVF is not a good reason. Your failure was not age related, you are young compared to many fertility patients.

From October 15th

Niki wrote back and did her IVF cycle, froze all due to lining issues. She is considering a carrier and does not want pgd.
It all sounds reasonable to me. It will have to be your choice.

Anonymous has pco and endometriosis. She did 8 clomid cycles and is in her last FSH iui cycle. Should she do IVF?
If you have done 2-3 FSH iui cycles, IVF is the next step. I like the way your doctor is doing the FSH iui. I am very optimistic. You are 28 and have eggs, that’s all it takes (in most cases). I expect you to do well and get pregnant quickly.

Anonymous is 33 and has had 3 miscarriages.
You odds are still excellent of having a baby in your nest pregnancy. Your doctor needs to do a miscarriage workup.

Anonymous has a normal pap with some cells missing and burning and numbness in her vagina.
As long as your doctor and the report say the pap is normal, it’s normal. I do not think the burning is related to antibodies, and it’s not due to the pap.

Diana was diagnosed with a septum and that was corrected. She then had to delay fertility treatment for treatment of thyroid cancer. New she is trying again without success. She is 35.
Give it the 3th month, but start making plans if things do not work. As far as your next steps, you know the drill. Get the options, get the pregnancy rates, and then decide which treatment sounds best for you. Be sure all of the septum is gone. I see many patients who have had septum surgery, only for me to tell them their doctor left a lot of septum still in place.

Anonymous does not get her period and is starting with a SIS.
I does not matter if you see her or a RE, but you need assistance ovulating ASAP. I don’t get the SIS, unless she sees something suspicious on ultrasound. You need to ovulate and this will probably require medication. Ask the doctor about getting the HSG before you try, or trying a little while (with ovulation) and then getting the HSG.

April did an IVF cycle with some immature eggs and late icsi. The embryos did not look good.
It sounds like there were a few issues with your cycle, but they seem correctable in the next try. It’s hard to tell if there was a problem with your IVF clinic, or things just want bad on their own. If you think you are at a very good place, give them another try. If you have reason to believe there is a better clinic near you, make the switch.

Shari in Chicago has endometriosis. She was treated with lupron and is waiting a long time for her period to return.
It works like this. The lupron is given every month (unless you have the 3 month version), and that lasts about 5-6 weeks in your system. Then you need to start your cycle again, and most women ovulate 2 weeks after that, and get a period 2 weeks later. That means you get your period about 8 to 10 weeks after you last shot.

Christine asked if IVF babies were born earlier and or smaller than non-IVF babies.
The answer is maybe. Some data suggests this is the case. However not all studies break out singletons from multiples, which usually deliver early. If there is an association, it may be due to the fact that some women with infertility may have uterine abnormalities that cause premature delivery. It is also possible that infertile people are more likely to have subtle genetic issues interfering with the length of pregnancy or the size of their babies. Or it may be that there is no difference at all and the right studies have not yet been done. Or maybe the IVF process is flawed and babies are smaller and deliver early. At this point, if there is a difference it does not seem to be great.

Alesha is trying to have her second IVF baby. Her first was at age 32, she will be 35 in January; her FSH is normal. Because she is a teacher, she wants to wait till summer to try. Her doctor says try now; her ovaries may change in the next 7 months.
It will be a little harder then, but if you are very fertile now, you will be very fertile then. Although there is a small chance he is right. Don’t forget you will be 3 years older than you were at your first try. I think it’s up to you, but consider this. Many women become very sad when they get pregnant on their first try, but not on their second, because it seemed so easy the first try. This could happen, and your following cycle will need to be during school, which is what you were trying to avoid. Therefore, why not just do one during school now. The logic is a bit of a stretch but I hope you get the point.

Leila has endometriosis and a fair response to meds. Her first 2 cycles yielded few eggs, and she did much better with a day 2 start than with lupron or microdose. If this fails, should she try again?
This cycle was very encouraging. You are only 36 and make 11 eggs, not bad at all. Question for your doctor: do you really need icsi? It sounds like you are on the right track. Consider the same protocol or estrogen priming.

Anonymous asked why go to FSH iui after 6 failed clomid cycles? Why not go to natural iui?
For younger patients, natural iui has a 5% pregnancy rate and FSH iui has a 20% rate. You can do whatever treatment you are comfortable with, just know the odds.

Anonymous is 42 years of age and has a FSH of 18. She failed a response using 14 days of lupron and 750 units of FSH. Should she stop?
It really does not sound encouraging. If you really wanted another try, ask your doctor about the estrogen priming protocol. Lupron is not the best for poor responders.

Anonymous has irregular cycles and is trying with clomid. She is using cervical mucus to time things.
Use an ovulation predictor kit instead. You can get pregnant with mucus that is thicker, but, if the clomid does not work after 3-6 times, ask your doctor about FSH. You may get pregnant before you get to the FSH.

Anonymous did 2 clomids, 3 FSH iuis and one IVF. She made 9 eggs but had slow embryos.
Get yourself to the best IVF clinic available. It may be where you are, or you may need to switch. Check rates at SART.ORG. Use a different protocol. I hope it works out.

Beth was diagnosed with endometriosis and is not ready to conceive. Should she go on Lupron for 9 months?
9 months sounds like a long time to me. The pill is definitely an alternative to lupron. Ask your doctor or get a second opinion.

Amila had an iui, had intercourse that evening and then had an iui the next day. The second iui had a lower count.
Probably too much. Stick to the iui’s.

Jesse b: Wife 30 he is 34. They just started the workup and were found to have one blocked tube and a low morphology. Their doctor is already talking about IVF.
Wow, they are going fast! First of all, if the tubal blockage is “proximal occlusion” a laparoscopy is aggressive. It is an option, so is repeating the hsg. It may have been spasm. If it shows distal occlusion, maybe surgery is more indicated. The morphology is probably not an issue. I don’t why they don’t just consider clomid first. Even if one tube is blocked and one is normal, it may be worth a shot with clomid. Of course, ask your doctor or get a second opinion.

Anonymous is 37, has a bicornuate uterus and a poor response. 4 failed ivf cycles, 0-6 eggs each. Her husband had a vasectomy.
Since your last protocol seemed to work best you could try one more cycle. You could also consider stopping. If you do another, consider the same protocol you just used. The reversal is not a bad idea, because at least you can try every month. But, they don’t always work, or they work but the counts are low.

Lisa tried many natural donor sperm cycles then used low dose FSH and got only 1 egg. She is worried that if she made only one on FSH, maybe she made none on her own or on clomid.
I believe you made one on your own and one or more on clomid. Your doctor did the right thing trying to control your dose, but now it seems you need a little more. It can work with the one. If not you may need a little more drug.

Anonymous has a doctor who wants to do an endometrial biopsy the month before the IVF cycle to promote a better lining.
Most of us do not do this. If your doctor can do a study, or maybe he has seen such a study proving it works, fine with me. But I am not aware that this method is of any value.

Kate is 31 yo and she did 2 IVF cycles. Her response is fair, 5-6 eggs, and after her first cycle her embryos did not look good. They got rid of the lupron and in her second cycle she had nice embryos. A pregnancy ended in a miscarriage at 6 weeks. She was told she has bad eggs.
I do not see that you have bad eggs. Your last cycle gave you nice embryos, and it almost worked. I think your chances are still very good. You could change to a microdose, or you can stick with your last stimulation, or you can consider an estrogen prime protocol. They will all be similar, it’s hard to say which one will be the best for you. Check pregnancy rates, if their results are good stick with them.

Murgdon’s husband has very low counts and her RE and urologist feel there is nothing practical that will raise counts, leaving them with IVF as their only option.
It’s hard for me to give specific advice about your husband’s condition, but in most cases, the advice you have received is correct.

Indigirl is 40 with a couple of cancelled ivf cycles for poor response. She switched to the estrogen prime and had 10 eggs. Her FSH is 10-12 and she has a bad AMH level. Is 10 a bad count?
10 is a very nice number, definitely enough to work with. We do not know enough about AMH to know if a bad level means pregnancy is not possible. Right know it’s a guide. The technology of PGD changes for the better every day, but ask your doctor what he thinks about not doing PGD. There is an element of embryo damage that can occur. PGD may be the best thing for you, but double check.

EAS is considering IVF with PGD because she has had a biochemical, 6 week misc at 6 weeks, and now a beta that does not look promising.
As long as you are informed about the pros and cons of PGD, then the choice to use PGD is reasonable. I just get upset when patients are led to believe that PGD is a perfect science.

Anonymous is 27 and does not ovulate or get her period, even with provera and clomid. What should she do? Her doctor is suggesting metformin.
Some women go great with metformin, but they are a mininority. The down side to metformin is that you need to wait another 3-6 months to see if it works. Certainly, it’s less expensive than getting FSH injections and monitoring, and you don’t need the doctor’s visits. It is a less aggressive way to go. Weigh your options.

Kahla’s husband has a low count. They got pregnant and had a baby on their first IVF try. The next 2 cycles failed and she had a 6 week miscarriage on her 4th try. She has had it and is considering iui.
It depends on the sperm counts, and you need to know your odds with iui and IVF. Most people find it really hard to go back to iui after doing IVF. But, if the counts are at least adequate for iui, you could do iui, and IVF later if necessary.

Jennifer’s mom has the BRCA gene discovered after being diagnosed with breast cancer twice. Should Jen take clomid?
Maybe you should get another opinion. Clomid is not that different than tamoxifen, a drug used to treat breast cancer. However, breast cancer is not my area, so I will defer. You could use letrazol to stimulate ovulation. This can cause ovulation, but is also used a breast cancer drug. Make sure you are not pregnant if you take it. Make sure you are fully screened for cancers before you try.

Elize has had enough history for 5 women. Check her entry for details. Now she is left with multiple major surgeries, miscarriages, and a uterine scar.
Much depends on how much scar there is. If it’s a little area, and most of your uterus looks good, and your normal endometrium looks thick enough, you may be ok, even if the scar comes back. If scarring returns after the first surgery, the odds of a second of third operation permanently removing the scar are much lower, especially if the scar takes up a large amount of the enodmetrium. We are not sure why you had the miscarriages, so I can’t say that you are at high risk for another miscarriage. Rupture is really rare, more common if you needed to have a large uterine incision for your myomectomy. A scar will incresase your odds of miscarriage and premature labor, but again it depends on the size of the scar. Scar will increase your odds of placental problems such as increta (where the placenta grows too deeply into the uterus)

Jesus my best friend has a unicornuate uterus with an open tube, and was encouraged to try on her own.
It sounds like a good plan to me.

OK, see you next time with a topic, probably blastocyst.
And please see disclaimer 5/17/06.
Dr. Licciardi

Infertility Questions and Answers: Almost Caught Up

2008-10-15T19:38:00.000-04:00

Anonymous asked about really trying to nail down the best progesterone for her IVF attempts. She failed one fresh cycle and 2 frozen cycles. She tried the injections and cream and Crinone. Her latest problem is she bled on Crinone, and had a thin lining in the luteal phase, and now is scheduled for a biopsy on Crinone.
Why? Crinone may be a good drug for some, but in your case it does not work. Why do a biopsy when you already know this drug gives you problems? I have never done an ultrasound in the luteal phase to check the lining. Maybe your doctor is on to something, but for most of us it’s all about the lining before your progesterone(ie we check in the follicular phase). Your problem highlights the reality that progesterone in oil, as difficult as it is, gives consistent results. If vaginal progesterone is your only option, and Crinone does not work out, you can consider old fashioned progesterone suppositories.

Anonymous asked about not getting her period after lupron.
This commonly happens. You odds of pregnancy will be based on your clinic’s success rates. Remember it’s the age you were when the embryos were frozen, not your age now.

Wannabmomma has PCO and has tried 5 clomid cycles with intercourse, no luck yet. She is 26 yo.
It is almost time to move to the injections. Most of us make your limit 6 cycles, fewer if you have regular cycles on your own. But, you are only 26, so you could consider a couple more with insemination. I really think this can be up to you.

Big Childwish has a significant miscarriage problem. She has had 4 consecutive miscarriages at about 7 weeks, all with a sac but no fetal pole. All of her testing is normal. She tried the blood thinner.
I am assuming you had a hysterogram, if not you need it. I am not sure if you have had a d and c with any of the pregnancies? This would tell you about the chromosomes of the fetus, possible giving you more information about the causes of your problems. Otherwise it may depend on your age. If you are younger, your chance of a baby in your next pregnany is still over 50%. If you are older, your odds are much lower.

Katie has PCO, did an IVF cycle with 7 eggs, 5 fertilized and 2 embryos for transfer on day 3, one 4 cell and one 5 cell.
OK, there are some positive things here. I like the way your doctor was cautious stimulation, and you do make eggs and embryos. You can use the information to improve your next try. First a little more drug will be OK. You don’t need to make 30 eggs, but 15 may be better than 7. If you are at a clinic with a 26% pregnancy rate, but can travel to a clinic with a 49% pregnancy rate, I say travel. If your clinic treats 100 patients, 74 will not get pregnant. If the other clinic treats 100 patients, 51 will not get pregnant. That’s a big difference.

Alibee has a complicated history. She has a unicornuate uterus with a normal tube and 2 ovaries. She has a fairly large fibroid. She has done 5 FSH iui cycles and 1 fresh IVF cycle and 3 FETs, and maybe more more fresh IVFs?
It sounds like your fresh IVF cycles were excellent because you had so many frozen embryos. It’s hard to prognosticate your future after failing frozen cycles. They just do not work as well as the fresh. They are worth doing, but if they don’t work, it’s hard to say things are bad. Your last fresh IVF cycle yielded very nice embryos. So why no pregnancy? Can it be your uterus? Possibly. Most women with a unicornuate uterus are not infertile, but there are a few who have trouble implanting, we don’t know why. Is it just bad luck with IVF? Possibly, but why are you not getting pregnant on your own? This is going to be a case of trying again, if you wish. Should you consider a carrier? It should be a consideration, but of course even that is not a guarantee.

Emily has unexplained infertility and has started clomid. Her first try did not work. She asked about some recent press concerning a terrible article about clomid not working for unexplained infertility.
That will be another blog, but they are wrong. There have been many many studies showing clomid does work. Just remember the odds, which are 8% per try in women with regular cycles. So you are on the right track, I hope it works out.

Jen seems to be hanging in there with her endometriosis progression and pain. Keep us posted.

Anonymous is concerned because her first IVF cycle worked and her second did not. She is worried about the 8% morphology.
This is not the issue. Morphology will not lower IVF pregnancy rates. It’s common that success in the first cycle causes fear when the second cycle does not work. Stick with it. Even in the best clinics, odds are 50% for young women, meaning it’s a 50% failure rate.

Amelia’s husband has an inversion in chromosome 1, causing low sperm counts. She asked about IVF with PGD.
This all depends on what your needs are, and the advice of a counselor. Of course you need to ask about the problems associated with this inversion. Is it just a low sperm count, or are you at risk for a miscarriage or even an abnormal child? You also need to be informed about the costs and success and failure rates of doing the IVF with PGD. In addition, you need to ask about the error rate of your PGD procedure.

Singh did 2 IVF cycles. The first resulted in 10 eggs, but 8 fertilized with more than 1 sperm (polyspermy). Her second cycle she did ICSI and did not have polyspermy. She is wondering if the polyspermy means her overall egg quality is bad, leading to a failure in her second IVF cycle.
We do not know if your problem is egg related, or related to a lab issue. Since you say you had nice embryos in your second cycle, your eggs are probably fine.

EMLU has severe endometriosis. Had Twins with her first IVF cycle, but has since had 2 fresh cycles, and then a frozen cycle revealed fluid in the uterus so the cycle was cancelled. She still has fluid in her uterus and a biopsy revealed endometritis.
Fluid in the uterus is a very difficult problem. I have a few patients with this and it’s tough. In your case you may want to a have a hysterogram (after the endometritis is cured) to be sure you do not have a hydrosalpinx, as this is the most common cause for fluid. You have another possible cause: endometriosis. Some women with advanced endometriosis also have adenomyosis (endometriosis of the uteris) and this can cause fluid. Definitely get treatment for your endometritis. However, most cases on biopsy are not really endometritis, it depends how quick your pathologists are to make the diagnosis. Some overdo it.

Anonymous has unexplained infertility and failed 6 months of clomid.
I would say that’s enough clomid, and you should consider FSH iui or IVF.

I agree with Christine

Beth asked about clomid for raising sperm counts.
It depends why the sperm counts are low. If his FSH is present but low, clomid may help, but that’s a really rare cause for low sperm counts. If his hormones are normal, clomid probably will not help. In fact some doctors think clomid lowers sperm counts by raising men’s estrogen levels. In any event, it’s ok to try some of these things, but don’t waste time waiting for results. Move on with your plan of action in the meantime.

Anonymous had a low progesterone and was put on clomid. So far so good. Then her luteal phase was only 10 days on clomid, and now she thinks she has not ovulated on clomid.
OK, see if you can get office monitoring on the clomid. Ask about getting an hCG shot once your follicle has reached 18-20 mm. This should straighten everything out. If monitoring shows that your cycle is not behaving properly, switch from clomid.

Anonymous is 27, but only got 3 eggs at her IVF cycle. Her doctor was overly cautious with the dose of drug.
OK, so now you know, you need more drug. It sounds like you had at least one nice embryo, so with more eggs you will get more nice embryos and have a much better chance of pregnant. I am optimistic.

Anonymous had infertility, tried clomid, and got pregnant with FSH iui. She miscarried twins at 6 weeks. She is a carrier for factor V.
It sounds like you are doing all of the right things. You just have to wait for the results of all of your tests. I hope it works out.

Mrs C was told she needed IVF because her husband had 1% morphology.
He was wrong, she was right. She got pregnant on her own.

Pam is 40, and failed 2 fresh donor cycles, with 2 good donors and nice embryos. She failed the frozen cycle and has 3 frozens left.
This could be bad luck or fair medical care. I can’t tell. You want to be sure you have had a hysterosalpingogram after your myomectomy. Make sure your doctor reads the films. After that it’s too hard to say form the blog what’s going on with you. Check the delivery rates form your clinic for DE. Most good centers are at least 50-60%.

I can’t comment on one article showing success with a strange therapy in a small number of patients. Let’s give it more time.

MiraclesdDHappen: 26 yo, trying for 7 years, 6 failed clomid.
We are all sorry to hear your still are not pregnant, but it’s time to move on. It’s either FSH iui or IVF. It can happen, it’s just going to take more work.

See you next time, and please read disclaimer 5/17/06/.

Dr. Licciardi

Answers to Infertility Questions

2008-10-04T09:12:00.000-04:00

Mas asked about Rogaine and low sperm motility. My urologists tell me Rogaine has no effect on sperm production or motility. However, just like everything else, maybe he is the one out of hundreds whose system is very sensitive. See if stopping the drug changes anything.

QVC has had elevated FSH levels but recently had a 1.9. Make sure there was an estrogen level done at the same time. Once the estrogen (or estradiol- same thing) goes over 50, it will artificially make your FSH lower. Once the estrogen is over 100, levels like 1.9 are common. You should still be on a protocol designed for women with high FSH levels.

Stephanie had a low egg number using a long lupron protocol. I suggest removing the lupron. I rarely use lupron anymore. I have also started using the estrogen priming protocol. So far I can’t say it’s better, but it seems to be at least as good.

The infertility acupuncturist asked about progesterone after IVF. There is a theory that you need more progesterone for IVF because the follicles, which become the progesterone producing corpus lutea(CL), become disrupted by the needle at retrieval. This may not be the case, but we are not sure. I would think that even in this is true, there are so many CL with IVF, progesterone production should be just fine. However there is more to the story. IVF drugs, especially lupron, but possibly antagon or cetrotide, may lower progesterone production. This is because lupron stops your pituitary from making LH, and LH drives progesterone production. Once you stop lupron, LH function returns, but it takes a few days and by then it may be too late. There are many studies showing if you use lupron, pregnancy rates are higher with progesterone. I don’t believe such studies have been done with antagon. Most studies show no improvement in pregnany rates with fertility drugs and iui. This may be because Lupron or antagon are usually not used for iui.

Melinda asked about ectopic pregnancy. She had one and is worried about another with IVF. Yes you are at increased risk, however the odds are still low, even lower if they took out the tube with the ectopic. I do not know the status of the remaining tube. Your odds could be anywhere from about 2-8% for having another ectopic. It’s good that they told you about potentially having an ectopic, but ask them to check their numbers.

Hopeful in Arkansas asked about clomid iui with male factor. It depends on the total motile count. This number is arrived at after the wash. It’s the total number of sperm you are getting back. The higher the better. Less than 5 is bad, 5-10 is ok, 10 or more is good. If you are getting low number back, consider IVF. If you are getting good numbers, then it’s up to you.

M asked about embryos that were frozen when her husband was drinking excessively. There is just not enough information out there to answer your question. Sorry, I wish I could help you with this one.

Helen asked about taking estrogen pills during her cycle. It is not a good idea to take estrogen pills as part of a natural cycle. It will interfere with ovulation, making it come early, late, or not at all.

Michelle asked about her iui cycle # 12. I am sorry you cannot afford IVF right now, I hope you can find a way. I hope this iui works.

Aimee asked about the necessity of an HSG. I skip it in only a few patients. I have to be really comfortable with their age, history and ultrasound to let it slide. If your doctor is even hinting at it, get it done. You will know soon if your first doctor was wrong. Odd are he was right, but you will see.

Nina asked about extra fertility testing before getting further treatment. I can’t really know what you specifically may need; however for most people the testing is pretty basic. It’s a HSG, SA and day 3 bloods. After that it’s all about your history and the philosophy of your doctor. You can waste a lot of time and money on tests that are not mainstream. Progesterone problems are rarely the cause of infertility. Remember, they go up and down throughout the day. Ask your doctor, taking some extra may not hurt, but don’t go on progesterone for 6 months without doing something else at the same time.

Della hit the jackpot! Very nice.

Julie has immature eggs. DO NOT GIVE UP!! Get a second opinion. I am not sure if you had the same problem both cycles. Taking more HCG may be the answer, but not if your levels were high enough. Let another doctor look at your records. Some women make a huge percentage of immature eggs no matter what we do, but even they can be successful with persistence.

Jen-Jen is 42, PCOS, considering IVF. Well, the good news is that you have PCOS. So many women think this is a bad thing for IVF, but it is a good thing, and as you get into your 40’s it’s a great thing. If the diagnosis is correct, you will make many eggs. IVF success in your 40’s is increased but getting high egg numbers. On the other hand, iui should make many eggs and your odds may be higher than expected. But, IVF rates are always 2-3 times higher than iui. So if you are considering IVF, do it soon, because you will never be younger.

Stacey came to see me and has 3 year old twins. Thanks for writing; let’s hope for good luck to all who need it.

Dove has a very high estrogen from IVF drugs. I am sure you had to make a decision before today. I hope it worked out.

So there it is. See you soon. Read the disclamer 5/17/06.

Dr. Licciardi