If At First You Don't Succeed...

In the past 8 years that I have moderated the IVF and High Tech Pregnancy Bulletin Board on the INCIID website, the most frequently asked question has been: Should I try again? A simple question but one that is so difficult to answer. The costs of fertility treatment are financial, physical, emotional, psychological and social. Fertility treatments can consume people and wreck marriages and relationships as well as drain your bank balances quicker than the Nigerian Foreign Minister who only needs your bank account number and social security number to park $30 million dollars for a few days….

So how can we answer this question. I usually review the reasons for IVF, the outcome of the cycle and look at all options. At some point it is appropriate to consider other paths: adoption, donor egg, donor sperm, child-free living, etc. One of our most important jobs as physicians is to advise when to move on and stop being a professional fertility patient. Of course, if we make that recommendation and the patient goes to another clinic and delivers a baby then we get slammed all over the internet, but what can we say except that no one has all the answers…


Here is a joke that I may have already told:


Question: What is the difference between God and a Reproductive Endocrinologist?


Answer: At least God knows that He is not a Reproductive Endocrinologist!

Since I am not God and do not have all the answers all I can provide is today’s Question of the Day:


77. My last IVF failed. Should I try again?


To make the best decision about whether to do another IVF, your first step is usually to sit down with your doctor and re- view your history and the details of the failed cycle. This would include a discussion of the rationale behind attempting IVF in the first place and a careful examination of the results of the IVF cycle.

Clearly, if a woman can conceive only through the use of IVF (for example, because she has no fallopian tubes or because her male partner’s sperm is of such poor quality that no other alternative is available), then the decision becomes one of whether another attempted IVF is warranted. In reviewing the previous IVF cycle, the woman’s response to the stimulation protocol should be carefully examined as well as the findings at the time of egg collection. If the eggs appeared immature at the time of egg collection, then in the future the trigger shot should probably be withheld until the follicles reach a larger diameter. If the stimulation and number of eggs are appropriate but fertilization was unexpectedly poor, then the use of ICSI for a future IVF cycle could be considered. If stimulation, fertilization, and embryo development were good and yet the cycle still failed, then consideration should be given to either an FET cycle (if appropriate) or a repeat cycle of IVF. If the stimulation was poor and the number of eggs was suboptimal, then other stimulation protocols should be discussed. If maximum doses were used and a poor response was still seen, then IVF may not be an appropriate choice; in such a case, other options—ranging from IUI to donor egg or adoption—may warrant discussion.

In cases where patients have frozen embryos remaining from the fresh IVF, we usually encourage them to attempt pregnancy with a frozen embryo transfer. Many patients who fail to conceive on a fresh IVF will conceive on the FET. The post-IVF consultation is one of the most useful discussions that a couple can have with the physician. It allows the couple to review all aspects of their care and to determine whether IVF represents the best approach to their particular situation. We firmly believe that this feedback is crucial to develop an appropriate plan of treatment for each couple.

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You've got to Change Your Cheating Ways

It is so tempting to just snatch one of those Clear Blue Easy kits off the shelf and run home and cheat…but do you really want to do that? Using home pregnancy tests after IVF is not uncommon. I usually know who did it because they are bouncing around the office on the day of the blood test (having seen positive home tests every day for 5 days). However, I have seen positive blood tests in spite of a negative urine test and vice versa. So what can I say. If you do it and cheat you can always post anonymously on the INCIID board and I will give you my 2 cents worth…just use a good pseudonym.

With that sound advice here is the “Question of the Day” from the book that has broken the advanced sales records for all of the other patient-centered books that I have written.



78. When can I do a home pregnancy test after IVF?

Hormonal detection of pregnancy may be performed by testing for the presence of the hormone beta-HCG in either the urine or the blood. Both types of tests are reliable and highly accurate. Sometimes, however, a home urine pregnancy test can be misleading and give a spuriously negative or positive test result when performed too early (regardless whether the desired pregnancy is from an IVF treatment or a spontaneous conception). Performing a pregnancy within 7 days after the egg collection procedure can result in a false-positive result because of residual HCG after the shot is given to trigger the final maturation of the eggs. In addition, the urine pregnancy test may be spuriously negative if performed less than 14 days after the embryo transfer. In our practice, we have had patients with a serum beta-hCG level of more than 200 IU who nevertheless had a negative urine pregnancy test. We advise patients to obtain a blood pregnancy test 12 to 14 days after an IVF embryo transfer and to avoid home pregnancy testing. In-office blood pregnancy tests provide the most reliable and accurate result.

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Sex during Treatment

Several years ago I had a patient undergoing IVF who was at risk for developing ovarian hyperstimulation syndrome (OHSS) so we planned to retrieve and freeze all embryos. Following the retrieval and freezing the patient did well but failed to get her period. Finally she called and said she was confused as I had told her that her period would certainly come within 2 weeks of the egg collection. I asked her to come in for a sonogram and bloodwork.

When I did the sono I was shocked to see a normal intrauterine pregnancy! The couple had sex a single time during the IVF cycle, 5 days before egg collection and we got 23 eggs. So 5 day old sperm found the one egg that I missed and she ended up delivering a baby! Go figure. I am still not sure how this was reported in our CDC stats…cancelled IVF ET with a delivery…

Since that time I have instructed patients at risk for OHSS not to get too frisky just in case..

So here is the “Question of the Day” from 100 Questions and Answers about Infertility; the book that launched a thousand blogs (or at least one…):


46. Can we have sex during a treatment cycle?


In general, the answer is yes. Many experts, however, recommend no coitus for 2 to 3 days prior to an anticipated IUI to “build up” the male partner’s sperm count and volume. Also, some men may experience difficulty producing a specimen if they have recently had coitus. For men who have a low sperm count or motility, it is recommended that they abstain from sexual relations for 3 to 5 days prior to a planned IUI.

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Endo is a pain

There are few entities in reproductive medicine as puzzling and frustrating as endometriosis. It can grow silently for many years and then present as an emergency visit to the hospital when the chocolate looking fluid begins to leak out of an endometrioma. I have seen minimal endometriosis in patients with terrible pelvic pain and severe endometriosis in patients in whom I expected a laparoscopy to be completely normal.

So let's start with some basics about endometriosis and its diagnosis. Here is the "Question of the Day" from 100 Questions and Answers about Infertility...the book that will sell itself as long as Dr DiMattina and I get invited on Oprah!


36. What is endometriosis and how is it diagnosed?


Endometriosis is the presence of endometrial-like tissue located outside of the uterine cavity. Most commonly, it is located on the ovaries, but it can also be found on any of the organs inside the pelvic–abdominal cavities. Although its etiology is unknown, endometriosis may arise when menstruation is obstructed, resulting in retrograde menstrual flow into the tubes and pelvic cavity. Just as the endometrium bleeds every month during menstruation, so, too, does the ectopically located endometriosis. This phenomenon leads to inflammation of the pelvic reproductive organs, causing pelvic pain, painful periods (dysmenorrhea), and infertility. Pelvic adhesions or scar tissue may also develop. Endometriosis may be suspected when patients complain of increasingly severe dysmenorrhea, pelvic pain, or infertility, but it can be definitively diagnosed only via surgery. Most often, a diagnostic laparoscopy—a simple outpatient surgical procedure—is used to diagnose endometriosis. Other nonsurgical techniques such as ultrasonography, CT scan, or MRI can occasionally be helpful in their abilities to detect endometriosis.

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How Times Have Changed

I still remember the day that my Dad came home the hospital completely outraged over the actions of one of the other surgeons practicing at Quincy City Hospital (where my Dad had served as Chief of Surgery and President of the Medical Staff at various times over his 30 year career). Wow, I figured the guy must have done something really bad as even my Mom was shaking her head and lamenting how far the medical profession had fallen. The crime that the physician in question had committed? He had taken out a display ad for his practice in the Yellow Pages!

I have never really spoken to my Dad about advertising in IVF, but he has seen the ads in the Boston Globe (not mine, of course, as I am in Washington DC), noted them in the inflight magazine for American Airlines and heard them on the radio in Boston. This is a competitive field and since much of the treatments are out of pocket decisions can be driven by financial considerations. Hence the development of the “Financial Guarantee” or “Shared Risk” programs.

I have mixed feelings about these programs and I really don’t want to sound like the cashiers at Best Buy: “Are you ABSOLUTELY sure that you don’t want to buy the Extended Warrantee on that DVD palyer…Tsk, Tsk.” So what do I tell patients? I tell them 2 things:

1) No good IVF program is losing money on their Money Back Programs because the candidates are either the patients with the best prognosis for IVF success OR the patient must agree to use an egg donor if they fail to stim well or have poor quality embryos with repeated IVF attempts.

2) The only patients who have gotten mad at me are the ones who could have done a money back program but elected not too. They tell me “Dr. Gordon, if I knew that I wasn’t going to get pregnant the 1st time then I would have done the guarantee program.” Heck, if I knew who was and wasn’t going to get pregnant I wouldn’t have to work anymore and I could retire to my seaside mansion nextdoor to all the insurance company CEOs.

So go ahead and peruse the “Question of the Day” and if you leave a comment by midnight tonight we will throw in the Ginsu Knife set for FREE.

19. How expensive are infertility treatments?

Some insurance plans may cover the cost of fertility treatments. In those patients without insurance coverage, the cost of fertility treatments varies widely depending on the specific treatment utilized. For example, a cycle of ultrasound monitoring without the use of fertility medications, culminating with intrauterine insemination (IUI), may cost $1300 to $1500 in many clinics. Compare this with the cost of IVF with intracytoplasmic sperm injection, freezing of extra embryos, and assisted embryo hatching, for which the price tag can total $14,000 to $16,000, which must then be added to the cost of injectable fertility medications ($2000 to $4000). The use of donor-egg IVF, although extremely successful, is also very expensive, because the donor must be reimbursed for her time and effort as part of the treatment and also because of the extreme screening tests mandated by the FDA. The price for donor-egg IVF typically ranges between $25,000 and $30,000, depending on the clinic.

In most cases, the more expensive, more invasive fertility treatments usually result in the highest pregnancy rates. Couples are advised to carefully consider the proposed course of treatment and the costs that may be involved. Many IVF centers in the United States offer “money back” (refund) programs. A couple accepted into such a program pays a premium that covers several fresh IVF cycles as well as frozen embryo transfers (FET). If they fail to conceive or are deemed to no longer be appropriate candidates for treatment, then all or a percentage of their initial payment is refunded.

These programs have remained somewhat controversial but can allow couples to pursue other options if IVF proves unsuccessful. According to the ASRM Ethics Committee Statement of June 2006: The controversy surrounding such programs relates in part to the concern that such arrangements “appear to violate long-standing ethical prohibitions against paying contingency fees in medicine. This concern is based on Opinion 6.01 of the AMA Code of Medical Ethics, which states, “a physician’s fee should not be made contingent on the successful outcome of a medical treatment.” Furthermore, the Committee Statement (which can be found on the ASRM website at http://www.asrm.org/Media/Ethics/ethicsmain.html) concludes, “the risk-sharing form of payment for IVF is an option that might be ethically offered to patients without health insurance coverage for IVF if certain conditions that protect patient interests are met.

These conditions are that the criterion of success is clearly specified, that patients are fully informed of the financial costs and advantages and disadvantages of such programs, that informed consent materials clearly inform patients of their chances of success if found eligible for the risk-sharing program, and that the program is not guaranteeing pregnancy and delivery. It should also be clear to patients that they will be paying a higher cost for IVF if they in fact succeed on the first or second cycle than if they had not chosen the risk-sharing program, and that, in any event, the costs of screening and drugs are not included. “The Committee was especially concerned about the incentives that risk-sharing programs create for providers to take actions that might harm patients in order to achieve success and avoid a refund. For risk-sharing programs to be ethical, it is imperative that patients be aware of this potential conflict of interest, and that risk-sharing programs not overstimulate patients to obtain a large supply of eggs or transfer more embryos than is safe for the patient, fetus, and prospective offspring. Patients should be fully informed of the risks of multifetal gestation for mother and fetus, and have had ample time to discuss and consider them prior to egg retrieval.”

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How about an ICSI split?

Life would be much easier for me if I had a crystal ball at work. Then I could be sure who needed ICSI and who didn’t. I could always be 100% sure of when to trigger with HCG for IVF and no one would ever get OHSS (ovarian hyperstimulation syndrome). Clearly there are honest differences of opinion between physicians and this can be confusing to patients who sometimes believe that there is an absolute right answer to medical questions. Sometimes there is an obvious answer but not always. So what do you do when 2 well-trained, well-educated physicians suggest different plans? That is the topic of today’s “Question of the Day” that goes hand-in-hand with yesterdays topic.

59. My husband and I were told by one RE that we needed ICSI, but another RE says that we don’t. What should we do?


ICSI is accepted as a standard treatment option for infertile couples with severe male factor infertility. In most clinics, approximately 50% to 90% of the eggs that are injected with sperm using ICSI will fertilize normally. Some eggs do not survive after injection with the sperm and subsequently degenerate. The criteria regarding what constitutes severe male factor infertility, however, vary from clinic to clinic. Some clinics use ICSI for all (or nearly all) patients based on the theory that assisted fertilization is better than no fertilization at all.

In general, ICSI is employed in cases where the semen analysis reveals abnormalities related to sperm count (less than 20 million/mL), sperm motility (less than 50% are motile), or sperm morphology (less than 30% have a normal shape). ICSI should also be considered in couples with no previous evidence of fertilization or a history of failed fertilization with a prior IVF attempt. In our clinic, we often perform an IVF/ICSI split. That is, the eggs that are collected during the oocyte retrieval phase are divided between normal fertilization and ICSI. If some component of male factor infertility is present, splitting the eggs between ICSI and IVF may reveal whether the sperm can actually fertilize an egg. If the eggs fail to fertilize with IVF but fertilize normally with ICSI, then the logical conclusion would be that the sperm is incapable of fertilizing the egg with IVF alone.

Couples with unexplained fertilization failure with IVF may have a problem with the sperm, the egg, or both. In such cases a repeat cycle of IVF using ICSI will usually yield good fertilization results and, ideally, a pregnancy.

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To ICSI or not to ICSI, that is the Question

Several years ago I was having a beer with one of the Chief Embryologists at a well-known fertility clinic. The conversation turned to ICSI and I asked him what criteria he used to determine whether ICSI was indicated. He replied, “we only do ICSI on patients who really need it.” When I suggested that his >70% ICSI rate seemed a bit high, he walked off to chat with someone else…Oh well, so much for friendly professional banter which is why I am terrible at cocktail parties.

So can a physician be absolutely certain that ICSI is needed? The following “Question of the Day” looks at this question and tomorrow’s question will give some additional thoughts on this issue.

58. Who needs ICSI, and how can my reproductive endocrinologist be certain that I need it?

Most couples undergoing treatment with IVF do not require ICSI. The most common indication for ICSI is male factor infertility associated with an abnormal semen analysis. For example, men with unproven fertility whose sperm count, motility, or morphology is suboptimal may require IVF with ICSI to ensure fertilization of the ova. Another common indication for ICSI is unexplained infertility. In these couples, neither the man nor the woman has any apparent fertility-related problems. Their diagnostic evaluation is entirely normal, yet infertility exists. In such couples, traditional IVF may result in failure of the man’s sperm to fertilize the woman’s eggs. By using ICSI, the eggs are “forced” to fertilize, and the pregnancy rates are usually high.

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Video Games and ICSI

As a teenager growing up in the Boston suburbs I spent a lot of my Saturdays in Harvard Square playing video games at the arcade that was next to the Orson Wells Theatre. My kids can’t imagine why I would go into Boston to play video games. They can’t believe that there was no Nintendo, no Playstation, and no X-box at my home . They laugh at the screen shots from my Atari. I still remember spending a lot of money feeding quarters into the Defender game or Robotron or Galaga. My Dad thought this was a complete waste of time, but in fact it was some of the best medical training that I ever received. Laparoscopy is really similar to a video game. ICSI also requires video game skills. Watch the embryologist catch a sperm. Watch him crimp the sperm tail and load it into a micropipette. Watch him inject the sperm using a smooth motion and release the sperm into the middle of the egg. Score one for the good guys...

So for those who have no idea what I am talking about, the “Question of the Day “ is all about ICSI (pronounced ick-sea). Or you can skip this blog and just go to Amazon.com and preorder the book!



57. What is ICSI, and how does it differ from IVF?


In routine IVF, eggs are placed in a laboratory dish in culture media together with prepared sperm. The eggs and sperm are allowed to spontaneously fertilize and grow until the embryo transfer procedure, which is usually performed 3 to 5 days after the egg retrieval. Intracytoplasmic sperm injection (ICSI) differs from IVF in that each egg is individually injected with a single sperm using a tiny needle under microscopic guidance (Figure 4). The resulting embryo is then cultured similarly to an embryo produced in a non-ICSI IVF treatment. ICSI was initially introduced by the IVF team working at the Brussels Free University in Belgium. At that time, assisted fertilization was being attempted through the insertion of the sperm under the eggshell (zona pellucida). The Belgian group took the extra step of injecting the sperm not only under the eggshell but actually into the middle of the egg itself. The first ICSI pregnancies were reported in 1992. Since then, tens of thousands of children have been born as a result of this unique procedure. Both ICSI and non-ICSI IVF have similar pregnancy rates and outcomes. The embryos produced by either method should not be considered to be superior to those created with the other. ICSI is simply a method to ensure that the egg is fertilized. ICSI is a safe and proven IVF method that does not increase the likelihood that the child conceived in this way will have a birth defect.

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A Special Donation

Every year physicians who are training in Obsterics and Gynecology (interns and residents) have to take a yearly test called the CREOG (Council on Resident Education in Ob/Gyn) exam. Almost every year there is a question regarding severe male factor that asks which treatment option is the most cost-effective. Given their training by Reproductive Endocrinologists (like yours truly) most residents immediately choose the IVF/ICSI answer. But that is incorrect. Donor inseminations using high quality cryopreserved sperm actually work quite well. Success rates depend upon the age of the woman but it is hard to beat donor inseminations for simplicity.

The hardest part about using donor sperm is making the decision to use gametes other than one’s own. For some couples, this is not an acceptable option whereas for others it has been a wonderful and relatively affordable way to have a family.

So who needs to consider using donor sperm? Funny you should as because that is the “Question of the Day.”


35. Should I consider using a sperm donor to conceive?


Couples who desire a child but in whom the male partner has a very low sperm count (oligospermia) or no sperm at all (azoospermia) often consider using third-party sperm donation and artificial insemination. Donor sperm can also be used by single women or lesbian couples. Many high-quality, reputable commercial sperm banks exist. They recruit and thoroughly test the donors and provide a listing of their available donors and their characteristics from which the couple can then choose. The donated sperm is obtained from the donor, tested, and quarantined for at least 6 months at the sperm bank. The donors are then retested.

The specimen is released for use only after the tests results are confirmed as normal. The frozen sperm is then usually sent to the physician’s office, and artificial insemination is performed around the time of the woman’s ovulation. Placement of the sperm inside the uterus (IUI) results in better pregnancy rates than placement of the sperm in the vagina or cervix. Frozen donor sperm can also be used for more advanced fertility procedures such as gonadotropin/IUI or IVF with or without ICSI. If a woman wishes to use sperm from a known donor with whom she does not have a physical relationship, then the sperm must be quarantined for at least 6 months and the donor retested for infectious diseases before the specimen can be used for fertility treatments.

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Testicular Sperm = ICSI

In most cases of infertility the male role is important but certainly pales in comparison to what our female patients have to endure. Although I offer to provide the couple with syringes filled with saline so the male partner can experience the joy of taking fertility shots, not a single guy has taken me up on this offer so he can better commiserate with his significant other. However, in men who require a testicular biopsy there is a more equitable distribution of effort as the couple moves through fertility treatment. Just remember that testicular sperm cannot fertilize without IVF and ICSI. I know that this seems pretty obvious to most patients but last year I had a couple come in for fertility. The man had undergone a vasectomy. I explained the option of vas reversal vs. IVF/ICSI in a 40 minute consult. We again discussed the process in a follow-up visit. Once the sperm was obtained the woman came in to discuss IUI. I explained that IUI was not an option and that was why we had spent a lot of time discussing IVF in the first place. I know that I went over the whole IVF process in excruciating detail. But she claimed no knowledge of any of this in spite of all the paperwork that I had given her and my detailed diagrams etc. She is probably out there in cyberspace as we speak bashing me and my clinic but what can you do.???

So how can you go from no sperm to baby? Here is the roadmap as I present the “Question of the Day” from the book that my Mother calls “the best book he has written yet!”

34. Can men with azoospermia father children?


When the male partner has either obstructive or nonobstructive azoospermia, the use of IVF and ICSI may still enable the couple to successfully achieve pregnancy. Sperm from the testis or epididymis are essentially unable to fertilize an egg without ICSI. To obtain sperm for use in IVF, a needle aspiration of the testis or epididymis can be performed under local anesthesia. If the male partner has nonobstructive azoospermia, a urologist usually performs a testicular biopsy in the hospital while the patient is under general anesthesia. In either case, the testicular tissue or the sperm aspirate can be frozen in liquid nitrogen and maintained relatively indefinitely. If a testicular biopsy reveals no mature sperm, then the only option is to use donor sperm or to pursue adoption. Occasionally, the sperm retrieved in this fashion is of exceedingly poor quality. In such cases, a repeat testicular biopsy on the day of egg collection for IVF or even use of a cryopreserved specimen from an anonymous sperm donor may be considered as a backup plan.

Rarely, men with diabetes or those taking certain antihypertensive medications may suffer from retrograde ejaculation. In this condition, there is no emission of fluid with male orgasm because all of the fluids travel backward into the bladder instead of out through the urethra. Retrograde ejaculation can easily be diagnosed by checking the post-ejaculation voided urine for sperm. Sperm present in the man’s urine can be washed and used for either insemination or IVF. Pretreatment with bicarbonate the night before sperm collection may improve sperm quality by increasing the pH of the urine.

One final (and interesting) cause of azoospermia is anabolic steroid abuse. Some men with azoospermia may have used testosterone or other steroids as part of their strength and conditioning training. High doses of these steroids can suppress sperm production. In such patients, sperm production can be reinitiated by stopping the steroids and placing the men on gonadotropin therapy (analogous to ovulation induction in women). Although clomiphene citrate has been used to improve sperm quality in men, most studies reveal it to have little to no benefit.

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Azoospermia

Over the years I have seen many men with the absence of sperm in the ejaculate (azoospermia). Some went on to have children with IUI because they had retrograde ejaculation, some conceived with IVF/ICSI and others through donor sperm or adoption. The ability to conceive in spite of azoospermia is truly one of the medical miracles of the past 20 years. During medical school at Duke I took an elective in Reproductive Physiology. In that class we learned about the number of sequential steps required to ensure that normal fertilization took place. If I had ever raised my hand and said “Hey, why not take a single sperm, break its tail and ram it into the middle of the egg” I would have been laughed out of the classroom…and yet that is exactly what we do with ICSI. But before we launch into treatment, there should be some consideration given to why would a man’s sperm count be zero.

So with our investigative hats on, here is today’s “Question of the Day”:

33. What can cause my husband to have no sperm at all?


Assuming that there was not a problem in collecting the specimen, the absence of sperm on a semen analysis—a condition known as azoospermia—requires thorough evaluation. Azoospermia can be divided into two major categories: obstructive and nonobstructive. Obstructive azoospermia occurs when the duct carrying the sperm from the testicle to the urethra becomes blocked. This blockage may be the result of previous surgery on the scrotum or testicle, or even follow repair of an inguinal hernia. During such surgery, the vas deferens may have been inadvertently damaged or even cut. Scar tissue can also form either postoperatively or following an infection (most commonly gonorrhea, though other infectious diseases may also cause blockage of the sperm duct). Some men are born without a vas deferens on either side. This congenital bilateral absence of the vas deferens (CBAVD) is associated with the gene for cystic fibrosis. In other words, CBAVD is a rather unusual presentation of cystic fibrosis that occurs in the absence of any chronic lung disease. For this reason, any man with azoospermia associated with congenital absence of the vas deferens should undergo genetic testing to determine whether he carries the gene that causes cystic fibrosis. Nonobstructive azoospermia is the result of a dysfunction in sperm production and can represent a more problematic situation. The source of the production problem may be the result of either a testicular issue or a pituitary or hypothalamus issue causing a failure of sperm production in an otherwise normal testis. If a hormonal evaluation reveals normal levels of prolactin and thyroid hormone, then testicular sperm production may have failed. If this finding is associated with an elevated FSH level, then the chance of finding any sperm production in the testis is quite unlikely. A testicular biopsy can be performed to assess whether any sperm are present within the testis. Even very low levels of sperm production may allow for attempts at IVF using ICSI. Genetic testing to rule out a chromosomal problem is often suggested in cases of very low or absent sperm production.

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Boxers vs Briefs?

Several years ago my good friend Dr. Bruce Gilbert, a Urologist in Great Neck, NY specializing in male infertility, presented a paper at the annual meeting of the American Society for Reproductive Medicine (ASRM). Dr. Gilbert’s presentation was on the debate between briefs and boxers for male infertility. When Bruce told me about the paper he was going to present I told him that I was sure that he would be interviewed by the press regarding that research. As predicted, Bruce was indeed interviewed by the usual media outlets for that story (CNN, ABC etc etc). It seems that this question resonated with the general public and they all wanted to know. So what did Dr. Gilbert’s study show? I will leave it to you, dear reader, to find out for yourselves. Or Google Dr. Gilbert and check out his website.

So here is the “Question of the Day” from the book that has yet to catch Harry Potter in advance sales:


32. Is there anything my husband can do to improve his sperm count, such as wearing boxers and not briefs or taking vitamins?


Sperm parameters demonstrate considerable variation from sample to sample, so researchers have not been able to identify any specific diet or lifestyle change that might potentially improve sperm quality. Although the presence of a varicocele has been suggested to play a role in male infertility (see Question 30), the benefit of varicocelectomy remains controversial.

Some studies have suggested that wearing boxers instead of briefs can improve a man’s sperm count. The avoidance of extremely high temperature may also improve sperm counts, so care should be taken to avoid prolonged exposure to extremely high temperatures, such as within a sauna or a hot tub. The effects of a variety of nutritional supplements on semen have been studied. Some researchers have suggested that antioxidants may improve sperm quality, thereby leading to improved pregnancy rates (the desired outcome). Although the data on nutritional supplements with antioxidant properties are somewhat limited, a commercially available product based on this research is available (Proxeed, Sigma-Tau Pharmaceuticals). This nutritional supplement is available for purchase only over the Internet. Although it has been frequently pre- scribed by some urologists, additional studies are required to confirm its benefits.

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The Weaker Sex

One week from today will be Father’s Day. So in honor of that completely manufactured holiday I think that we should spend the next week focused on the weaker sex…men.

I honestly believe that if men had to be pregnant and go through labor & delivery that the human species would vanish in 1-2 generations. Men are chickens but hate to admit it in most cases. There are certain advantages to being a male gynecologist. If a patient tells me her periods are bad, she gets moody or she finds an exam uncomfortable I will always agree with her 100%. Since I don’t have the equipment, I cannot contradict any comments regarding said anatomy by my patients. If they tell me it hurts I believe them.

It is always tricky to deal with the emotions wrapped up in infertility treatments. In cases where there is severe male factor the woman may still have to be the one undergoing the majority of the procedures. This is not fair but it is the reality of the situation. The use of sperm donation is always an option but usually not the first choice of most couples.

So here is the first “Question of the Day” to start our week of exploring male factor infertility:

31. Can surgery improve sperm quality?


Surgical treatments for male factor infertility are very limited. Historically, varicocelectomy has been the surgical procedure most commonly used to improve sperm quality. In this procedure, dilated veins in the scrotum (varicocele) are cut or ligated. One theory is that these dilated veins may increase the scrotal-testicular temperature, thereby diminishing the sperm quality. By cutting the veins, the scrotal temperature is restored to normal and fecundity may be improved. Unfortunately, well-designed control studies have not shown any statistical increase in pregnancy rates following varicocelectomy. Furthermore, many fertile men have varicoceles. Today, this procedure is rarely, if ever, indicated. In most cases of male factor infertility, the best treatment involves intrauterine insemination or, more often, proceeding directly with in vitro fertilization (IVF) and possibly intracytoplasmic sperm injection (ICSI).

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I Want Answers

We all want explanations in life and it is human nature to seek out the answers to our questions. Unfortunately, life is not simple and sometimes there are questions that we cannot answer and outcomes that we cannot understand.

Although we can often determine the root cause of infertility, sometimes we are at a loss to explain why a couple is not conceiving. The problem is that in such cases we are forced into treating empirically and hoping for the best. IVF can offer some insight into these cases but sometimes it is a hard concept to get across to the patient:

DrG: I have good news…all of your tests are normal.

Couple: That is great news…we were so worried that you were going to tell us we needed IVF!

DrG: Uh….

Couple: So what are you going to recommend?

DrG: IVF.

Couple: Uh…..

IVF is not the only option in such cases but it is the only option that provides clinical information even in the face of a negative pregnancy test.

So here is the “Question of the Day” on this hot and humid Sat AM in Washington, DC.


14. Can infertility be unexplained?


Although the etiology (underlying source) of infertility in many couples can be elucidated by various forms of testing, including careful physical examination and history, there still remains a sizable percentage of couples in whom no obvious cause of infertility can be identified. Some studies estimate that approximately 10% to 20% of patients fall into this category. However, “unexplained infertility” is not necessarily equivalent to “untreatable infertility.” If a couple has prolonged, unexplained infertility with no previous pregnancies, then a number of etiologies are possible. If the woman is having normal, regular menstrual cycles, it is likely that an egg is growing and being released in an appropriate fashion. If pregnancy has never occurred, however, we cannot be sure that the woman’s fallopian tubes are able to catch the egg or that her male partner’s sperm are able to swim through the cervix and uterus and find the egg in the fallopian tube (where fertilization normally occurs). If the sperm is able to reach the egg, the absence of a previous pregnancy raises the question as to whether fertilization can, in fact, occur. The scope of this problem is made clear when we look at the fertilization results for patients who undergo IVF. Typically the rate of failed fertilization with IVF is approximately 2%, but this rate increases dramatically—to approximately 20%—in couples who have prolonged infertility with no previous pregnancies. Failed fertilization can be the result of a problem with either the sperm or the egg, or both. Since the introduction of intracytoplasmic sperm injection (ICSI; described later in this book), however, the specific causes of fertilization failure are not as important as the fact that we have a means to avoid this unfortunate outcome in most cases. One of the most significant developments in the treatment of infertile couples has been the move away from extensive diagnostic testing and toward a more rapid recommendation to undergo IVF. We often recommend that patients with prolonged unexplained infertility consider IVF with ICSI, as this combination has both diagnostic and therapeutic benefits.

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Urban Legends and the Postcoital Test

Here is a true RE urban legend. Many years ago a very trustworthy and honest infertility specialist (not yours truly although I would hope to be described in this fashion) arrived at the office for his usual consultations. He was informed that Mrs. Jones (not her real name) was waiting for Dr. James (not his real name) in the exam room. She was scheduled for a postcoital test.

Dr. James went into the room, said hello and then sat down to perform the postcoital. As he was placing the speculum he asked Mrs. Jones the usual questions: “What cycle day are you?” “Day 14 ,”she replied. “Did you have an LH surge?” “Yes, last night,” she promptly informed the doctor. “OK, so how many hours ago did you have sex?” No answer. Dr. James asked again. The patient hesitated and then blurted out, “But Dr. James I am here for a postcoital test!” “Yes, I know, so when did you and your husband have relations?” She hesitated and then clarified her misunderstanding. “Oh my gawd, Dr. Jones, I thought I was supposed to have sex with you!” Dr. James removed the speculum. Stood up. Walked out of the room with his face blazing in embarrassment.This story was related to me by Dr. James, at a conference one year, so I have no reason to doubt its veracity. Of course, this became a huge inside joke at Dr. James’ practice as Dr. James was routinely asked after that exactly how much time he needed to perform any scheduled postcoital test!

We all want to help our patients and in the process we form some very close relationships, but clearly there are some limits that should never be crossed…even as part of the diagnostic evaluation.

So given yesterday's post on the endometrium and today's on the postcoital here is the "Question of the Day" from the book that "Pregnancy Magazine" was not interested in as "our readers are already pregnant."


16. My friend keeps asking whether I had an endometrial biopsy or a postcoital test. Do I need these tests?

Many couples ask their physicians about performing an endometrial biopsy or a postcoital test. Unfortunately, both of these tests have limited benefit in assessing the infertile couple. An endometrial biopsy is performed just before the onset of a woman’s menses and represents an attempt to identify an abnormality of the lining of her uterus. The problem with the endometrial biopsy in terms of its usefulness as a fertility test is that abnormal biopsies are obtained in more than one-third of women with proven fertility. Therefore, the finding of an abnormal endometrial biopsy in fertility patients is of uncertain benefit. Most reproductive endocrinologists prefer to have their patients take extra progesterone, essentially obviating the need for the endometrial biopsy. At the present time, this test is most useful as a means to rule out endometrial cancer in those patients who are at increased risk of this disease. Patients at increased risk for endometrial cancer include those who have polycystic ovarian syndrome and infrequent, heavy periods but who do not receive the protective benefit of oral contraceptives or other progesterone-containing medications. The postcoital test was initially proposed as a means to evaluate the interaction of the male partner’s sperm and the female partner’s cervical mucus. This test is performed approximately 8 to 24 hours after intercourse at midcycle (around days 12–14 of the menstrual cycle). During a speculum exam, the physician collects a sample of cervical mucus. This sample is then placed on a slide and examined under a microscope for the presence of motile sperm. In addition to the presence or absence of sperm, the physician records the quality, quantity, and appearance of the mucus. Unfortunately, the postcoital test has very poor reproducibility and limited utility in the evaluation of infertile couples. Couples for whom no motile sperm were observed during the postcoital test have conceived, for example. Although the spontaneous pregnancy rates are higher in those patients with a normal postcoital test, the information gathered in this way seldom provides any useful insight when developing a therapeutic plan. Postcoital tests may prove more valuable in couples in whom, for social or religious reasons, the male partner is unable to provide a specimen for semen analysis. In these cases, a postcoital test reassures all parties that sperm are actually deposited in the vagina during the act of intercourse.

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Fun in the Sun...Dominion style

Sometimes it is hard to get away from the office. Several summers ago we were vacationing on the Outer Banks of North Carolina. The weather was outstanding..hot, sunny and no hurricanes. Meanwhile back in the office I had a patient undergoing a mock cycle in preparation for a frozen embryo transfer (FET). We had frozen all of the embryos from her fresh IVF because of the risk of hyperstimulation and just like the patient that posted to me today on my INCIID bulletin board, this patient also had hypothalamic amenorrhea (more about that in a later question) with a suboptimal endometrial lining.

As we tried to move forward with a FET we hit a roadblock as her uterine (endometrial) lining just would not cooperate. We had tried a bunch of different drugs to ready her lining but I could not get the thickness that I wanted (although I think that the pattern was OK). Our plan that summer was to try another recipe and then do an endometrial biopsy to check the lining. At least that was my plan...

While I was in Corolla one of my most trusted nurses, Mary Ann, called me on my cell. I just happened to be back at the house for lunch. Mary Ann was very apologetic. The patient was getting close to the point in the cycle to start progesterone and set up her endometrial biopsy, but suddenly her lining looked very good and she was hoping to just go for embryo transfer rather than the biopsy.

The only spot in the house where I could get a reliable cell was on the roof deck and it was about 110° in the sun. Mary Ann asked me to call the patient and for the next 30 minutes we went over all the options. While I was roasting at the picnic table on the deck we decided to go ahead with the ET when I returned to DC the following week.

The story has a happy ending...the transfer went well with both embryos implanting and she delivered healthy twins. I can still remember sitting in that boiling sun, talking on the cell phone and wondering if it was the correct decision.

So here is the "Question of the Day" from that beach book "100 Questions and Answers about Infertility" regarding endometrial lining issues:



71. My endometrium is only 6 to 7 millimeters thick. Can I do anything to improve its thickness?


The thickness of the endometrium normally changes throughout the menstrual cycle. During menstruation. the endometrium is shed. Under the influence of the hormone estradiol, the endometrium then regenerates and usually develops to a normal thickness of 8 or more millimeters (mm). When a woman is undergoing infertility treatment, the thickness of her endometrium is regularly measured using ultrasonography. When the endometrium fails to develop to at least 8 mm, the embryo may fail to implant because of endometrial immaturity or dyssynchrony. Although this problem is not very common, when it occurs, it can be difficult to correct. Typical treatments consist of providing additional estrogen early in the menstrual cycle or altering the timing of progesterone administration. Other therapeutic agents include small doses of aspirin (80 to 100 mg per day), and some physicians have prescribed Viagra vaginal suppositories for their female patients with variable success. Some women cannot achieve pregnancy in a fresh IVF embryo transfer cycle but readily become pregnant when the embryos are transferred in a frozen–thawed nonstimulated treatment cycle. On rare occasions, a couple may need to use a gestational carrier to successfully overcome abnormalities involving the endometrium and implantation. Of course, failure of the endometrium to achieve a minimum thickness of 8 mm does not necessarily translate into a problem with the endometrium. In our practice, we have seen many patients with maximal endometrial development of only 4 to 7 mm successfully achieve pregnancy, including delivery of twins. A variety of testing methods to assess endometrial maturity have been proposed, including endometrial biopsy testing for surface proteins called integrins, but such testing is currently considered experimental.

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Mistaken Identity

Writing a book is a very interesting proposition and there some ups and downs along the way. When Mike (Dr. DiMattina) and I started the project we were in contact with the nice folks at Jones and Bartlett Publishing and Chris Davis, the Publisher, came down to Arlington to meet with us. He is the only member of the team that we have met face-to-face. Everyone else has either been in contact with us by phone or by email. So this afternoon as I reviewed the near final proof of the inside back cover I knew that there was something a bit odd about the biographical information as presented.

As those who know us can see, the photos were reversed. When I spoke to Mike Boblitt on the phone we laughed about it and I told him it was just like working with the medical students or residents. When faced with a 50/50 choice they always seem to guess wrong! So not to fear, in the final edition Dr D and Dr G will have the appropriate photos next to their names...I hope.

So here is the Question of the Day. A pretty basic one but one that we talk about ALL the time with our patients.


9. Which tests are routinely performed on the infertile couple?

The basic infertility evaluation consists of a handful of tests: transvaginal ultrasound, blood tests, an assessment of the fallopian tubes (for the female partner), and semen analysis (for the male partner).

Transvaginal ultrasound allows the physician to assess the appearance of the uterus and the ovaries. During this examination, the physician may discover uterine abnormalities such as fibroids (benign growths of the muscle of the uterus) or uterine polyps (benign growths of the lining of the uterus). Ultrasonography can also identify the location of the ovaries and determine the number of follicles present (antral follicle count), which correlates with the woman’s response to fertility medications. In addition, examination of the ovaries may reveal the presence of abnormal ovarian cysts such as endometriomas, dermoid cysts, or—in rare cases—precancerous and cancerous lesions.

In addition to the routine vaginal ultrasound, an assessment of the fallopian tubes and the uterus cavity is appropriate when the woman is having trouble conceiving. This examination is usually accomplished through a hysterosalpingogram, an x-ray test that is performed under fluoroscopy by either the fertility physician or a radiologist. Although it may sometimes cause mild uterine cramping, the vast majority of patients tolerate this procedure without difficulty. Alternatives to the hysterosalpingogram include laparoscopy and hysteroscopy; these outpatient surgical procedures are described in Questions 10 and 11.

Laboratory tests on the female partner of an infertile couple usually include routine screening tests such as those for blood type, blood count, and rubella immunity. In addition, most physicians perform tests that check the woman’s prolactin and thyroid-stimulating hormone (TSH) levels. Additional reproductive hormone testing for ovarian reserve is usually part of the routine evaluation as well (see Question 9).

Routine testing of the male partner of an infertile couple includes a basic semen analysis evaluating the volume of semen, the concentration of sperm (sperm count), the percentage of moving sperm (sperm motility), and the percentage of normally shaped sperm (sperm morphology). Although some clinics perform additional sperm function tests, such as the acrosome reaction and hypo-osmotic swelling test, the overall benefit of these two tests remains somewhat controversial. Both of these tests attempt to predict the functional ability of the sperm in terms of its ability to fertilize an egg. Ultimately, however, the best evidence of normal sperm function is a recent pregnancy or normal fertilization during a cycle of IVF.

Tests to detect the presence of antisperm antibodies in the blood of the female partner or coating the individual sperm may sometimes be recommended. Female antisperm antibodies may cause infertility that is best treated by IVF. Antisperm antibodies present on the sperm themselves may inhibit normal fertilization. In such cases, collecting a semen sample in media for use in artificial insemination may be considered, but most of these patients pursue IVF with intracytoplasmic sperm injection (ICSI).

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It Takes 2 to Tango...

Although certainly some of our patients are single women or single-sex couples, the vast majority are married couples seeking to start (or add to) their family. As such, infertility is unique in that there are always 2 patients in every setting. Some of the men have been a bit shy of the spotlight to say the least...Why? I think that for many men the concept of being reduced down to a number is very anxiety provoking. It seems like keeping track of batting averages. Every man who has been told that his sperm count is great, suddenly puffs out his chest a bit more and acts like he has won the lottery. Women do not respond to FSH levels in this way...thank God.

Men with low sperm counts always want to know why and how they can make them better. Unfortunately, there is not a whole lot that we can do but work with what we have in most cases. However, sperm counts really do vary quite a bit. My beloved wife, Allison, is a REAL doctor with a PhD in engineering who laughs at how we make medical assessments based upon a single data point. She is right. If we want a line we take one additional data point and then stop... But reproductive medicine is not like engineering unfortunately. There are few straight lines and very few right angles. The best we can do is ride the ups and downs and try our best to guide our patients appropriately.

So here is the Question of the Day from that soon to be bestselling book "100 Questions and Answers about Infertility."

32. Is there anything my husband can do to improve his sperm count, such as wearing boxers and not briefs or taking vitamins?

Sperm parameters demonstrate considerable variation from sample to sample, so researchers have not been able to identify any specific diet or lifestyle change that might potentially improve sperm quality. Although the presence of a varicocele has been suggested to play a role in male infertility (see Question 30), the benefit of varicocelectomy remains controversial. Some studies have suggested that wearing boxers instead of briefs can improve a man’s sperm count. The avoidance of extremely high temperature may also improve sperm counts, so care should be taken to avoid prolonged exposure to extremely high temperatures, such as within a sauna or a hot tub. The effects of a variety of nutritional supplements on semen have been studied. Some researchers have suggested that antioxidants may improve sperm quality, thereby leading to im- proved pregnancy rates (the desired outcome). Although the data on nutritional supplements with antioxidant properties are somewhat limited, a commercially available product based on this research is available (Proxeed, Sigma-Tau Pharmaceuticals). This nutritional supplement is available for purchase only over the Internet. Although it has been frequently pre- scribed by some urologists, additional studies are required to confirm its benefits.

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Insurance Issues

Not a day goes by here when I am not faced with an insurance issue to address. It still amazes me that insurance companies can take your monthly payments and then go ahead and shut you out in terms of treatment. Clearly not all insurance companies are problematic but I will say that many of them are...

Last year we had very productive discussions with Aetna and they were very open to discussing what we do here and how we do it. Other companies were not at all interested in our views.

Here is a true story: Several years ago I had a patient whose husband was azoospermic - no sperm in the ejaculate. We had arranged for a testicular biopsy with a urologist and had frozen sperm that could be used for IVF. Everything was going great until the patient called in a panic. She said that her insurance company said that IVF could not be approved because she had not completed all the needed tests. I couldn't imagine what was going on so I called them and got a representative on the phone. Here is our conversation as I remember it:


DrG: Hello, I am calling about Mary Brown (not her real name) and I was wondering why her IVF was not approved.

Insurance agent: Hello, Dr Gordon. Well, she hasn't done all the needed infertility testing yet.


DrG: Really? What is she missing?


Insurance agent: We don't have the results of her post-coital test.


DrG: That's because I didn't do one.


Insurance agent: We can't approve IVF until we know the results.


DrG: I didn't do one because her husband is azoospermic...he has no sperm in his ejaculate.


Insurance agent: Still, I need to know the results of a post coital test.


DrG: Do you understand that the post coital test looks for sperm in the cervix and since he has no sperm the test will be pretty obviously abnormal....


Insurance agent: Still, I need to know the results of a post coital test.


DrG: Hold on a minute....(10 second pause) ...OK I just did the post coital test. It shows no sperm...


Insurance agent: Thanks Dr Gordon she is approved for IVF.


Funny but sad.... OK so here is today's Question of the Day from the upcoming book by yours truly.


20. Will my insurance pay for my fertility treatments?

Insurance coverage for infertility varies widely across the United States. Several states, including Massachusetts, Illinois, and Maryland, have passed legislative mandates for infertility coverage. In these states, access to fertility treatment is guaranteed through the patient’s employer. in the vast majority of states, however, fertility coverage is inconsistent. Some companies may offer extensive fertility benefits, while others offer no coverage at all to their employees. It is important that you understand your specific benefits before you seek out any kind of fertility treatment. Insurance plans may provide a specific dollar amount to spend on fertility treatments or cover a certain number of cycles of either IUI or IVF. You should work with your fertility provider’s billing staff to determine which benefits are available to you before launching into a treatment plan. Given that some insurance plans may cover infertility more extensively than others, it is always appropriate to examine your insurance options during periods of open enrollment for health benefits. Many insurance companies will not cover fertility treatments in patients who have been voluntarily sterilized (e.g., vasectomy, tubal ligation). Plans may also have specific requirements in terms of duration of fertility and exclusion criteria for IVF concerning ovarian reserve testing or age.

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Career Choices

Growing up in a medical family can somewhat limit your career choices. My grandfather was a GP in Quincy, MA and did a lot of obstetrics. He was beloved by his patients and his office was actually in his big, white house on School St. Every morning he would have breakfast then walk across the entry hall to the big sliding doors that led to his waiting room. What a great commute! His patients paid as they could, sometimes with goods or services if they were short on cash. His son is a famous endocrinologist, Lewis Braverman. In fact, Uncle Lew wrote the book on the thyroid gland...literally. It is a huge textbook dedicated to that little gland that sits in your neck. My father is a general surgeon. Still working several days a week at the VA Outpatient Center in Boston after having closed his successful private practice after 35 years. There is only so much golf that one can play and my mother would pay the VA to let him come to work if they ever ask him to retire. My older brother, Mike, is also a general surgeon in a medium sized NC town south of Chapel Hill. Brother Steve is the CEO of Children's Hospital in Boston (the suburban campus in Waltham).

So not a lot of career options when you like science and people and come from a family like that: 3 generations of doctors.

In medical school at Duke I loved my rotation in Ob/Gyn and especially my elective in RE with Dr. Charles Hammond and Dr. Arthur Haney. However, my Dad really couldn't understand why I would choose OB. "In his day," he stated, "only the guys at the bottom of the class chose Ob/Gyn." And since I was not at the bottom of the class why choose it? "Besides," he said, "those guys only have 7 operations that they do and 2 of those are cut the right ureter and cut the left ureter." When I said that I was actually interested in RE he rolled his eyes a bit. "Not like your Uncle Lew I hope. He spent his whole life on a small gland with only 2 little arteries that I can take out in 5 minutes in the O.R."

Well, my Dad now understands what I do and seems pretty proud of his non-surgeon son. One of his best friends has triplet grandkids from IVF so he gets the concept of treating infertility. Of course, given the fact that the leading NYC fertility expert of the day told my parents in 1948 that my Mom would never have children (obviously prior to having her 3 sons) certainly warped his view of fertility physicians but that story has to wait until we discuss uterine malformations.

So although both of the people reading this blog know what an RE is and how one becomes an RE, here is my Question of the Day from the forthcoming book (buy before midnight tonight and get the Ginsu knife set for free).

6. What is a reproductive endocrinologist?

A reproductive endocrinologist (RE) is a physician who specializes in the treatment of reproductive disorders and infertility. To specialize as a reproductive endocrinologist, a physician undergoes 4 years of training in general obstetrics and gynecology following his or her completion of medical school. At the end of these 4 years of training (internship and residency), which includes exposure to normal and high-risk obstetrics, gynecology, gynecologic oncology, and reproductive endocrinology and infertility, a physician must then apply for an additional 3-year fellowship in reproductive endocrinology and infertility. After completing these 7 years of training, the physician takes a series of written and oral examinations to become board certified in this specialty. Although not all practitioners of reproductive endocrinology and infertility have undergone formal fellowship-level training, the majority have, and this training includes both clinical and basic science experience. There are several professional organizations for physicians who are interested in the treatment of the infertile couple, including the American Society of Reproductive Medicine (ASRM) and the Society of Reproductive Endocrinology and Infertility (SREI). Any physician who is interested in infertility may join ASRM, but members of SREI must be board eligible or board certified in reproductive endocrinology and infertility. Both of these organizations maintain websites that allow patients to identify local specialists (www.ASRM. org; www.socrei.org).

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The OHSS woes

There is an adage in medicine that "problems come in 3s" and having now dealt with three recent potential cases of ovarian hyperstimulation syndrome (OHSS) this seems quite appropriate. OHSS is no fun. It is tough on the patient and tough on the doctor. It is hard to counsel a patient about a possible outcome whose prevention requires her to derail the chance of getting pregnant after working so hard to reach that point. However, I have NEVER regretted canceling a cycle or freezing all embryos to avoid OHSS, but I have been surprised to see OHSS arise in a patient in whom I was not anticipating it to develop (kinda tortured english there, but I was a biology major). So with OHSS on my mind here is the Question of the Day:


67. My doctor said that I might get ovarian hyperstimulation syndrome. What is ovarian hyperstimulation syndrome, and what can I do to prevent it?

Ovarian hyperstimulation syndrome (OHSS) is a complication associated with the use of fertility drugs. As the ovarian follicles grow, they secrete a wide range of substances, the most important of which is estrogen. Estrogen causes the lining of the uterus to thicken, enabling the embryo to implant there after ovulation and embryo transfer. After a woman receives an HCG injection, her follicles eventually collapse, releasing the eggs within; the follicles may also be aspirated with a needle to harvest the eggs for IVF.

Within a few days, the fluid within the follicles is restored. Each follicle is now called a corpus luteum (Latin for “yellow body”), referring to the fact that it contains large stores of cholesterol that are used to produce the steroid hormones estrogen and progesterone. In addition, the follicle begins to produce a host of other growth factors—including vascular endothelial growth factor (VEGF), a protein that is likely responsible for the emergence of OHSS.

Mild OHSS results in enlarged, tender ovaries but usually only minimal free fluid in the abdominal cavity. By contrast, moderate and severe forms of OHSS are associated with fluid accumulation in the abdominal cavity or sometimes even in the pleural cavity surrounding the lungs. In its severe form, OHSS can result in nausea, vomiting, shortness of breath, and dehydration. As the fluid builds up in the abdomen, the woman becomes increasingly uncomfortable, and diminished blood flow to the kidneys may lead to decreased urine production. This situation can spiral downward rapidly, and complications of blood clot formation and kidney damage can occur if OHSS is left untreated.

Patients with severe OHSS are best managed in the hospital, where they can receive intravenous resuscitation and the fluid can be removed via paracentesis. Occasionally, the fluid around the lungs may need to be removed if the woman is suffering from respiratory difficulties. However, most of the respiratory complaints associated with OHSS result from the inability of the diaphragm to move appropriately given the marked amount of fluid present within the abdomen.

Prevention of OHSS is always the best strategy. This syndrome can best be avoided by judicious use of fertility medications, which is why most physicians individualize gonadotropin doses based on the patient’s history, the appearance of her ovaries on ultrasound, and her previous response (if any) to fertility medications. Patients older than age 35 in whom fewer than 12 eggs are retrieved rarely develop significant hyperstimulation. In contrast, patients with polycystic ovarian syndrome are at the highest risk for developing OHSS. Other high-risk patients include women who have many small and medium-size follicles associated with estrogen levels of more 4000 pg/dL at the time of HCG administration.

However, not all patients who fall into this category will develop OHSS, and some women who might not otherwise seem to be at risk for it will, in fact, go on to develop the syndrome. This randomness of OHSS makes the decision-making process somewhat problematic when trying to prevent this complication. A woman who exhibits an excessive response to fertility medications associated with a large number of follicles and a high estrogen level should be counseled regarding OHSS prevention strategies.

The first option is to withhold the HCG trigger shot, cancel the cycle, and avoid any attempt at pregnancy. Alternatively, a reduced amount of HCG (5000 units) can be given, followed by follicle aspiration, egg fertilization, and freezing of the embryos with no fresh transfer in that cycle. In such cases, the severe form of hyperstimulation is rarely encountered. In our practice, we have experienced outstanding pregnancy rates during subsequent FET cycles in these patients. Even if no transfer is performed, the woman may still require a brief hospitalization or drainage of the abdominal fluid. Ultimately, it is the HCG trigger shot or the HCG produced by a successful pregnancy cycle that induces the ovarian production of VEGF and the other substances that are the cause of OHSS. In patients who are stimulated without GnRH agonists (Lupron), an alternative method to reduce the risk of hyperstimulation is to use Lupron itself as a trigger rather than HCG. Given that the majority of women undergoing IVF are already taking Lupron, however, this strategy would apply to only a small percentage of the patients pursuing infertility treatment. Furthermore, this strategy would simply eliminate the initial symptoms of OHSS associated with the HCG trigger shot; if pregnancy subsequently occurs, the patient would still be at risk for the OHSS associated with a successful cycle.

OHSS is an unpleasant experience for patients, but fortunately the incidence of severe OHSS is low (only 1% to 2%) and the vast majority of patients recover quickly with no long-term problems. In cases where OHSS is associated with pregnancy, this problem can last 2 to 3 weeks and may require several procedures to drain the excess fluid. In addition, because of the dehydration associated with OHSS, patients with this syndrome are at risk for the formation of blood clots in the leg or lung. To prevent this complication, most hospitalized patients receive prophylactic daily doses of a blood thinner such as heparin or Lovenox.

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More on Ovarian Reserve

As a Reproductive Endocrinologist one of the toughest parts of the job is explaining things to patients that simply do not make sense and fly in the face of logic. A case in point: Several years ago I saw a patient that had been to another local clinic where she had spent over $70,000 on 4 failed IVF/ICSI attempts. She was 35 years old and not interested in donor sperm or donor eggs. Her FSH was 12 and her response to stimulation had been poor with 2 cancelled cycles. She had been told that ICSI was the only way the sperm would fertilize the eggs because of poor morphology. So she arrived with all of her records and put me on the spot saying she wanted to hear my opinion. Well, I thought that the sperm didn't look too bad so I suggested that if she was unwilling to go with donor egg or donor sperm that we could just give unmedicated IUI a shot but the odds were pretty long that this would work...

She was very motivated so we jumped right into a natural cycle IUI and 14 days after the IUI she came in with a look of disbelief and a positive home pregnancy test. Her betas rose appropriately and her pregnancy was picture perfect. She delivered a healthy full-term baby.

When she had a toddler at home she came back for a consult. I told her that we could try it again but not to hold her breath because she really had a miracle baby there at home. But as the unstimulated IUI was only $2000 she was willing to roll the dice. The next cycle we did another IUI and amazingly enough she had another positive beta and delivered another healthy full-term baby!

Last Christmas I got a card from her letting me know that all was well and shockingly enough she was about to deliver baby #3 conceived without any help at all...at 40 years old!

So the lesson here is that I never tell patients that they have no chance to conceive unless there are no eggs, no sperm or no tubes....other than that all bets are off.

So here is today's question from the book:

41. How do I know if IUI is an option for me?
IUI is a good option for many infertile couples. It can be performed in conjunction with a woman’s natural cycle or can be combined with the use of fertility drugs. IUI can also be effectively used in couples who have sexual dysfunction or infrequent coitus for either medical or nonmedical reasons. For example, some couples may have busy work schedules such that one or the other partner is frequently out of town around the time of ovulation. If the male partner’s sperm is obtained and cryopreserved (frozen) in advance of ovulation, the physician (or nurse) can perform an IUI and, ideally, facilitate pregnancy without the woman missing a menstrual cycle. The best candidates for IUI are those couples without tubal disease (female partner) or severe male factor infertility (male partner). Women with severe endometriosis or a history of pelvic adhesions are not good candidates for IUI. Although couples with male factor infertility can attempt IUI, the success rates are fairly low in such cases, and prompt consideration should be given to IVF (and ICSI) if pregnancy fails to occur after three or four attempts.

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