Science Fiction or Science Fact

Nothing too helpful in today's blog...just some ruminations by DrG....

I don't have a very long commute to my office here in Arlington, VA on most days, but sometimes some idiot has crashed into a tree on Canal Road or has rear-ended the car in front of him while speaking on a cell phone and I end up in the car for quite some time.... A few years ago I joined Simply Audiobooks, which is like Netflix for books on CD. Over the years I have listened to a range of books from Jane Austen to Steven King and everything in between. I tend to gravitate to science fiction (much to my wife's chagrin) and recently I was listening to a novel by Isaac Asimov entitled "The Naked Sun" first published in 1957.

Much of Asimov's science fiction books involve sex, which would lead you to think of him as a "dirty, old man." In 1981, I actually met Isaac Asimov and had dinner with him. He was indeed a dirty, old man... but very charming and talented. In the "Naked Sun" there are several references to IVF, he called it something different, and the overall impression was that this approach to reproduction would be akin to a crime against nature.

Yet here we are in 2009 with IVF an accepted part of medical treatment and we have all become rather unimpressed with what is really an amazing process. The human egg, removed from the body, fertilized in the lab, sometimes even injected with a single sperm and then replaced into a uterus (usually that of the same woman, but not always in the case of gestational carrier IVF) with some embryos even stored in suspended animation in liquid nitrogen. It is sometimes just too fantastic to believe and yet most days I am too wrapped up in the details to step back and wonder in amazement that it ever works at all.

Today I spent a few minutes on the phone with a couple that were unsure about cryopreserving extra embryos. Ultimately, the biggest stumbling block was their feeling that this was just too weird to be safe. I tried to reassure them that the data is very reassuring and that in some countries like Finland, 40 % of the ART babies are from frozen embryos as there are strict limits enforcing single embryo transfer. But on some level I agree with them that it is incredibly weird to consider that a human embryo can stay in liquid nitrogen for a couple of years and then turn into a beautiful baby!

Asimov eat your heart out....my reality is weirder than your fiction. After all, who would have guessed back in 1981 that my daughter would tell her class at school "my Daddy puts babies in women's tummies."

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Avoiding "cookie-cutter" Medicine

Medicine has been called an art and to some extent this is clearly true. Although statistics, protocols and algorithms exist to guide therapy a thoughtful physician must always take into account the particular needs of his patient. I know that this sounds incredibly obvious but the reality is that with the advent of the internet additional voices have been added to the patient-doctor relationship. I stress to my patients that they are unique and although others may voice their opinions as to the best course of action, the final decision should rest between doctor and patient.

Recently I had a patient with a strong history of depression whose insurance required a series of 3 IUI cycles before covering IVF. She had only a single good fallopian tube and as a couple they had no previous pregnancies. The semen analysis was a bit borderline as well. So given the situation I was proposing moving directly into IVF. Looking at the whole picture this seemed an appropriate plan and the couple was motivated. The insurance company was resolute in their requirement of 3 IUI cycles. I spoke with several employees and was finally told by the Medical Director that the requirements were non-negotiable. This is "cookie-cutter" medicine. No personalized care, one size fits all, don't tell me the facts just follow the algorithm medicine. Bleh.

So I followed the rules. 3 stimulated IUI cycles failed. No surprise. However, IVF was successful on the first try and the patient appreciated the effort that we made to "fight City Hall."

As a physician I learned early in my career that if all else fails "Listen to the patient." I view fertility treatment as a joint effort between the couple and the physician. However, as the physician I have the benefit of having treated patients with similar problems and can take the long-view of a treatment plan. This creative approach was instrumental in Dr. DiMattina and myself launching the Natural Cycle IVF program. One size does not fit all. Some patients are best served by a very proactive approach, moving into stimulated IVF as fast as possible, whereas others take a more step-wise tact with increasing complexity of treatments if unsuccessful. Talk with your RE to develop the plan that meets your needs. If you are a Diplomat going on assignment in 8 weeks then your needs are different than the patient with a pathological fear of needles...or multiples....or OHSS....or being pregnant during August in Washington, DC!

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Fluid in the Endometrium

As usual I find myself apologizing for the long delay between blog posts and as usual I have no real excuse except that I am just a bit tapped out....sigh. The summer has flown past and soon we will be back in the grind of school and work with the playtime of summer a distant memory. This Fall will be memorable as my oldest child will be off to college. Hard to imagine. You know, when I started practice I used to get the "you look too young to be my doctor...." but now not so much! I was thinking about looking into microscopic hair transplantation but my wife assures me that she loves me even as my bald spot and waistline seem to growing inexorably larger. But enough about me....

Everyday I answer posts on the INCIID.org website. I have done this for over 10 years and hope that some of you have found the feedback helpful. Dr. DiMattina and I have launched an online community for our practice (Fertile Grounds) that also provides opportunities for both patients (and non-patients) to post questions to us. We try to answer to the best of our ability and rest assured that posting a question on Fertile Grounds will not result in you being hounded to switch clinics and become a patient of Dominion Fertility....although we would welcome you with open arms and provide all qualifying individuals with a 2 week vacation to the French Riviera.

Recently I had another post on the INCIID.org website concerning fluid in the endometrium. This problem crops up a couple of times a year and is often a great source of distress to the patient who is informed that the lining does not look normal.

So where does this fluid come from? Initially just after a period ends there may be some residual fluid in the endometrial cavity. This fluid is usually old blood and as the follicle(s) begin to develop the lining thickens in response to the rise in estrogen and the fluid vanishes. This type of fluid is not an issue.

More concerning is fluid that appears during stimulation for IVF or for an FET. In general, the etiology of this fluid can be divided into anatomic and hormonal causes. Anatomic problems that lead to fluid accumulation are usually the result of previous damage to the endometrium during surgery. The most common surgical procedures that could damage the lining are removal of fibroids (by laparotomy or hysteroscopy) or a D&C performed for a retained placenta following delivery. Scarring that is present within the cavity is usually called Asherman's Syndrome (especially if it results in the absence of menstrual flow). The risk of adhesions after fibroid removal can be reduced by taking care during the surgery to ensure the lining is not damaged or by treating with estrogen after surgery to induce the rapid regrowth of the endometrium to cover any raw areas within the cavity.

Hormonal causes of fluid accumulation may relate to the high estrogen levels that can be seen in some patients undergoing IVF or FET. If the problem occurs during an FET then the cycle could be aborted. If seen during stimulation then a cryo all could be contemplated. However, in my experience the fluid will often reabsorb once HCG is given or progesterone is started. If, by the day of ET, the fluid persists then the embryos could be frozen or the fluid aspirated and the transfer performed if the lining otherwise looks normal.

Evaluation of the uterine cavity in such cases usually includes hysteroscopy or water sonogram (hysterosconogram). I have also found in helpful to monitor the lining during a spontaneous cycle and see if the endometrium looks normal. If it does, then a Natural Cycle FET may be the best treatment option. In cases of severely abnormal lining the use of a gestational carrier may be the best choice but this option may not to acceptable to all couples.

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It only takes one!

Now some of you that read my last post are thinking - "Sure it's easy for him to say that you only need one embryo but I KNOW that I need more than that..." But I remain steadfast in my view that measurement of ovarian reserve can only get you so far.

For example, here is another clinical vignette right out of our practice here at Dominion Fertility:

TM is a 37 year old with a history of slightly irregular periods who had been treated previously at another fertility clinic. She was successful in 2004 conceiving after a cycle of CC/FSH/IUI. In 2006 she returned to that clinic and underwent another treatment of CC/FSH/IUI but had a biochemical pregnancy. Later that year she had another cycle using the same medications and ended up with a quintuplet pregnancy. She ultimately delivered healthy twins but clearly wished to avoid that situation at all costs in the future.

When I initially saw her back in Oct 2008 her ovaries looked rather small with a low antral follicle count. Her AMH was 0.3 (low) and her FSH and E2 were 13.9 and <20. Considering her relatively recent quintuplet pregnancy, it seemed pretty surprising that her ovarian reserve was now problematic but so it goes.

So my thought was that we were looking at a one egg/month situation in a patient who wished to avoid multiples but had previous IUI success, and thus we elected to go ahead with IUI for a couple of cycles.....no luck after 3 attempts. At this point we discussed Natural Cycle IVF as an option.

Now, the advantage of Natural Cycle IVF over IUI in this setting remains unproven in radomized double blind clinical trials but anecdotally we have had success in such cases. The patient agreed and underwent a cycle of Natural Cycle IVF in May 2009. Although her betas rose initially they soon fell to <5. She went immediately into a 2nd Natural Cycle IVF and again conceived but this time all went well and her sonogram this AM showed a singleton pregnancy with good cardiac activity. Needless to say she was very pleased and agreed to let me tell her story on the website.

So what is interesting here..... Well a couple of points jump to mind. First of all, ovarian reserve can diminish rapidly in some patients. Here we went from hyperstim (quintuplets) to hypostim (low AMH, AFC and high FSH) in just 2-3 years. Secondly, IVF may be more successful than IUI even in patients with normal tubes, normal sperm and previous success. In this case, we were 0/3 on IUIs and 2/2 on Natural Cycle IVF. Go Figure! Thirdly, after a biochemical pregnancy the body is ready to go when you start cycling..no waiting necessary. Finally, it is a case of good things happening to nice patients. It would be hard to imaging a more pleasant and upbeat couple than these two and just remember that "you catch more flies with sugar than with salt." Not that we play favorites but always nice to deal with easy-going individuals.

So for those who say that Natural Cycle IVF doesn't work, I restate my premise that it only takes one good embryo to make a baby!

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What is AMH?

Clearly the issue of ovarian reserve strikes many doctors and patients as "clear as mud!" Remember from our past discussions that ovarian reserve relates to the number of eggs that a patient has and the reproductive potential of those eggs. Ovarian reserve is not truly a test of egg quality as a woman's age is the final arbitrator of egg quality. As I am currently unable to make any patient younger, although I could retire if I could, we need to keep the difference between egg quantity (ovarian reserve) and egg quality (age) segregated in our mind.

So in trying to determine how a woman might respond to fertility drugs we use a variety of tests to predict her response. Day 3 FSH and estradiol, antral follicle count on sonogram and the clomid challenge test (CCCT) have been the methods used most recently. However, for the past 2 years we have also been measuring anti-mullerian hormone (AMH). This protein is made in the cells that line the follicles (the fluid filled cysts that contain a woman's eggs - 1 egg per follicle). The more follicles, the higher the AMH and the better the response to fertility drugs which resue the extra eggs that were doomed to run out of gas during the menstrual cycle.

Apparently AMH is getting some attention in periodicals outside of the medical literature as you can see in this link to the Wall Street Journal. We still rely on Day 3 FSH, estradiol and sonogram to get a complete sense of how a patient will respond to fertility drugs, BUT the AMH has proven helpful in many patients as we try to pick a stimulation protocol.

However, in doing Natural Cycle IVF, all tests of ovarian reserve may fail to predict success since by its very nature...natural cycle IVF is unstimulated. So if a patient is doing Natural Cycle IVF, whether or not they would respond to fertility shots is a moot point! What has been amazing to us is the ability of patients with high FSH, low antral follicle counts and low AMH to generate a beautiful embryo in Natural Cycle IVF. What matters is pregnancy and delivery but we have many patients whose ovarian reserve testing is poor and yet they have had success with Natural Cycle IVF. "It only takes one good embryo" as many patients are fond of saying!

So should you have an AMH level done. Yes, as long as you are working with a doctor who can interpret the results for you given the "big" picture and not lose sight of the forest for the trees.

Good luck

DrG

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Gestational Carrier IVF

Fertility doctors are pretty popular at cocktail parties (or so I hear since I really don’t get out much). Between OctoMom and the latest Hollywood star announcing that they are pregnant with twins using a surrogate, there is always some interesting aspect of reproductive gymnastics to be discussed.

In the past month I have discussed the use of a gestational carrier with a wide range of patients. Some have had previous uterine surgery that has made pregnancy problematic. Another has a history of severe medical problems that make her a risk for pregnancy and yet she and her husband do not want to consider adoption. Finally, another patient has experienced multiple unexplained pregnancy losses in the mid-trimester. All of these are valid reasons to consider this alternative pathway to family-building.

When a couple chooses to use a gestational carrier I ask them to arrange for me to interview her as one of the first steps. A few years ago, a couple found a gestational carrier through an agency and asked me to meet her. She lived in the Mid-West so I asked her to fax me a patient questionnaire. She never did (first red flag). One afternoon she appeared in person for an appointment. I asked her about her previous pregnancies. She looked away but said that everything ended up fine by the end (second red flag). Upon further discussion, it turned out that she was incredibly sick every pregnancy with hyperemesis (killer morning sickness) and required multiple hospital admissions and even intravenous feedings at home! Yikes! She didn’t (or wouldn’t) understand that the risk to her was real in terms of pregnancy complications and that the cost of any hospital admissions may be the responsibility of my patients. She called me several times that day on the way back to the airport but I remained steadfast that she should not be a gestational carrier.

So here is one of the few remaining questions from our book 100 Questions and Answers about Infertility…

85. What is a gestational carrier, and when should you consider using one?

Fertility doctors sometimes recommend the use of a third- party gestational carrier if the infertile couple wants to have their own biological child. Many medical conditions necessitate the use of a gestational carrier, including the absence of a uterus in the would-be mother, either because of a congenital (at birth) condition or when a disease necessitated its surgical removal. A gestational carrier may also be the best option when a woman has a systemic disease that may affect either her own or her baby’s health, such as advanced heart disease, severe diabetes, or multiple sclerosis. Likewise, a woman with a history of poor pregnancy outcome—including repetitive pregnancy losses, preterm labor, incompetent cervix, or severe preeclampsia—may be a good candidate for IVF using a gestational carrier.

Prior to the IVF treatment, thorough screening of the gestational carrier is routinely performed using ASRM guidelines. Gestational carriers are usually well known to the couple and may be relatives or friends. In addition, agencies exist that introduce gestational carriers to prospective patients. In such arrangements, the gestational carrier is usually compensated for her time and energy (especially if the pregnancy proves successful).

When using a gestational carrier, IVF is performed by combining the infertile couple’s sperm and eggs to produce their own genetic embryos. However, unlike in standard IVF, these embryos are then transferred into the uterus of the gestational carrier. This process resembles donor-egg IVF in that the process requires synchronization of two patients: the egg donor (genetic parent) and the recipient (gestational carrier). Pregnancy proceeds normally just as if the gestational carrier had become spontaneously pregnant. The major factor in determining the success rate is the age of the woman whose eggs are donated. The ideal gestational carrier is a woman who has had a previous uncomplicated pregnancy and delivery.

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Can my endometrium be too thick?

Wow, what a terrible blogger I have been these past few weeks. No new posts for a while and no insightful hints for the 3 regular readers of this blog (sorry Mom, I promise to call this week!). I could make up some incredible story about how I have been performing 80 hours of community service a week or that I have been traveling to South America with certain public officials from South Carolina or that I have been sick for weeks with the Swine Flu. Clearly, this last excuse may engender some sympathy....but the truth is that I have just been pulled in too many directions. Sorry.

So let's discuss the endometrium here since I recently received a slew of questions on the INCIID site about the thickness of the endometrium and what is ideal for fertility. Abraham Lincoln was once asked "How long should a man's legs be?" He astutely answered "Long enough to reach the ground." The same could be said for the endometrium in that it needs to be thick enough to allow for implantation of the embryo. Most studies suggest that "long enough" is anything over 7-8 mm.

So a few years ago I had a patient that was trying to get ready to do an FET cycle and had not had a period for 6 months and had PCOS. On sonogram the lining was pretty darn thick at 22mm (usual is 7-12mm). Patients with PCOS are clearly at risk for endometrial hyperplasia and even endometrial cancer. So I gave her a couple of weeks of Provera to get the lining to shed. No significant bleeding and the lining was still at 22 mm. So I did an endometrial biopsy which was read by pathology as possible cancer. Yikes! I immediately sent her to one of our local Gyn Oncologists who did an office D&C that yielded only scant tissue.

When I repeated the sonogram the damn lining was still 22 mm. I really was getting concered here but too a step backwards and decided to do a water sonogram in the office. Guess what. There was a large polyp sitting right there in the cavity and since polyps can have an unusual appearance on pathology that would explain the initial concern about cancer. The patient underwent hysteroscopy and I was able to easily remove the polyp. Case closed.

So when patient inquire about endometrial thickness I usually respond that as long as it is a normal lining without a polyp or a fibroid or cancer then thick is fine.

Thin endometrial linings can be another matter. Some patients have a thin lining becasue of previous surgery or simply because that is the lining that they have been giving and nothing can really improve upon it. I have tried all the usual voo-doo for thin linings....vaginal estrogen, Viagra, terbutaline, nitroglycerine, animal sacrifice...you name it. Some seem to help, some don't...I honestly have no recipe that works for everyone. The thinest lining that I ever had that resulted in a healthy baby was 5 mm!

So good luck growing those endometriums but try not to panic if you have an 8 mm and not a 15 mm lining. Anything >7mm should be fine and if waiting an extra week gains you a mm or two then all the better.

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