Ovarian reserve is an expression of the number and quality of eggs available for conception. As a parameter for predicting pregnancy, ovarian reserve testing is often part of a fertility evaluation. Such testing requires specific measurement, and clinical judgment to interpret the results.

Egg numbers are at a maximum before birth, at around 20 weeks gestation. After birth, there is a progressive decline in the number of eggs from roughly one million at birth to 300,000 at puberty. Through the reproductive years the remaining eggs are lost, with the rate accelerating around the mid-30s, resulting in few eggs left at menopause, around age 50-52. The number of eggs available for reproduction at a certain age is the ovarian reserve, which is the target of the diagnostic tests described here.

Age is the most accurate predictor of egg health, but within age groups, there is considerable variation in the number of eggs remaining for reproduction. Age alone as a predictor of ovarian reserve is not sufficient, since, for individuals, fertility may be better or worse than the average for that age. Extreme examples of this variability include the teenager in menopause and the 59 year-old that delivered a natural pregnancy in 1997. This variability in pregnancy rates within an age group is present in all reproductive age groups.

To predict an individual woman’s fertility rate, in addition to her age, both clinical and laboratory methods are available to evaluate ovarian reserve. The best tests are direct measures of the ovary, such as the Antral Follicle Count (AFC) and Anti-mullerian Hormone (AMH) level; indirect measures, such as clinical history and levels of pituitary hormones, are common tools for prediction of ovarian reserve.

The simplest method of predicting fertility rates is clinical history, of both the individual and her closely related family. The number of months spent attempting to conceive predicts fertility. A couple that has been trying for some time will naturally have a lower fertility rate than a woman that has not had unprotected intercourse. Response to ovarian stimulation can also be used as a marker, as it is fairly consistent between cycles. Family history, i.e., the fertility of the woman’s mother or sisters reflected in age at menopause and age at conception are useful predictors. Such factors from clinical history can help define the risk of a problem with ovarian reserve.

Ultrasound is a useful tool for predicting ovarian reserve, as in measuring the Antral Follicle Count (AFC). Antral follicles are the smaller follicles, visible on ultrasound, between 2 and 10 mm, that are lost as a woman ages. In younger women, the AFC is 10-20, declining by 5% per year through age 37, and then accelerating to a loss of 10% per year thereafter. Women show a fairly consistent AFC loss rate of one follicle every two years.

AFC predicts the response to ovarian stimulation at least as well as blood tests, but its ability to predict pregnancy outcomes is limited, particularly when low. A woman with a higher AFC will show a better response to fertility drug treatments. A high AFC seems to predict pregnancy rates, but data remains limited, as there are no prospective studies published. A low AFC seems to be a less accurate predictor of ovarian reserve, particularly in older age groups. AFC may help predict outcomes, but should not be used to exclude patients from treatment.

Anti-mullerian hormone (AMH) is a blood test that directly measures ovarian reserve. Produced directly by early stage ovarian follicles, high levels (over 1.0) are favorable, while low levels (less than 1.0) indicate decreased ovarian reserve. AMH may be the best measure of the menopausal transition and ovarian age. It may also be useful in predicting ovarian hyperstimulation syndrome, the effects of chemotherapy, and in determining the treatment of PCOS.

AMH seems a superior predictor of ovarian response compared to other markers, including age, and day 3 FSH and estradiol. It offers similar predictive value compared to AFC. AMH can be drawn at any time in the menstrual cycle, and is not affected by hormonal therapy, including oral contraceptives.

AMH still requires further study. The range of normal variation is still being determined, and the true predictive value of the test requires a great deal more analysis. The specific range of reliability and predictive value by age is yet to be established.

Cycle day three FSH and estradiol, and, to a lesser extent, the clomiphene challenge test, remain viable tests for estimating ovarian reserve. These tests are established as predictors of response to ovarian stimulation. Prediction of pregnancy rates is more difficult. Recent studies concentrating on the predictive value of these tests have shown that they cannot be used to determine which patients cannot conceive, but are useful for screening and counseling.

All in all, these tests are only rough predictors of ovarian reserve. They are moderately good predictors of ovarian response to stimulation, and relatively poor predictors of pregnancy outcome. In a particular patient, the tests can be used to counsel about potential response to ovulation induction, but it remains difficult to predict pregnancy outcome based on the test results.

The ultimate test of ovarian reserve is response to treatment and whether a pregnancy results from that treatment. Stay tuned as we evaluate further research to establish the validity of ovarian reserve testing methods.

This past summer, I had the opportunity to travel to Amsterdam, Holland for the annual meeting of the European Society for Human Reproduction and Embryology (ESHRE). Though largely attended by Europeans, this scientific meeting draws physicians, embryologists and scientists from around the world to discuss their research, attend courses and lectures, and discuss the latest topics in our field. Although I don’t think this year’s meeting was as quite as good as last year’s ESHRE in Barcelona, there were still some good learning opportunities. Here are some of the highlights of the meeting:

“From Gamete to Heartbeat: The Missing Link”

This was a post-graduate course offered in conjunction with the meeting. The course covered sperm and egg evaluation,

expression of genes in the early embryo and in the endometrium (uterine lining) and some of the latest research into basic embryo implantation mechanisms.

One of the interesting talks was on gene expression in the early embryo. We have come to believe that the differences in pregnancy rates between younger and older women is mainly due to an increase in the number of abnormal chromosomes in embryos from women as they age (such as increased risk for Down Syndrome). However, this only explains part of the differences in successful pregnancy in younger compared to older mothers. New research into expression of proteins from embryonic genes is showing that in both chromosomally normal and abnormal embryos, there are differences in the number and types of genes encoding proteins in younger and older women. This suggests that it is not just changes in the number of chromosomes but subtler differences in the way individual genes are being expressed that affect the developmental competence of their embryos. Determining which genes and proteins are involved, and what the mechanisms are for regulating the expression of these genes in early embryos, will be an area of focused research in the coming years.

“Hyaluronic Acid (HA) favors selection of spermatozoa with intact DNA and normal nucleus, resulting in improvement of embryo quality” (Bologna, Italy)

This presentation (Parmegiani, et al.) looked at the percentage of sperm showing DNA fragmentation based on several methods of sperm preparation for IVF-ICSI (in vitro fertilization with intracellular sperm injection). They compared sperm in the fresh specimen 30 minutes after ejaculation, sperm that had been processed with a standard “swim-up” technique, and sperm that were placed in PVP (polyvinyl propylene), a substance used to slow sperm down so they can be picked up from a culture dish just prior to injection into the eggs. Lastly, they looked at sperm that had been placed into dishes that contain a ring of hyaluronic acid at the bottom of the dish, a substance to which some sperm will automatically bind. They looked at the percentage of sperm showing total or partial fragmentation of the DNA with each of these steps in the sperm preparation process. In the freshly ejaculated sperm, the DNA fragmentation was 16.5% of tested sperm. In the “swim-up” sperm prep, 11% were fragmented and in the PVP-exposed sperm, it was also 11%. Sperm that had bound to hyaluronic acid showed the least amount of fragmentation, at 5.3%.

These findings suggest that using HA binding to select sperm for sperm injection may result in fewer abnormalities in embryos, and possibly higher pregnancy rates. PFC is currently investigating HA binding on our own to see if it is something we would wish to routinely incorporate into IVF. The downside (like everything else!) is that HA plates are expensive.

Stress and Fertility – an enlightening symposium

Jacky Boivin, PhD., a researcher from Cardiff University in Wales, presented some very interesting data about the stresses of infertility treatment. She discussed a new study from Alice Domar’s group in Boston that surveyed why women/couples discontinued IVF treatment before achieving pregnancy (Fertility and Sterility, in press 2009). In this study, 132 women who had insurance coverage for IVF were surveyed. The two main reasons given for dropping out of treatment were the toll that infertility took on the couples’ relationship and being too anxious or depressed to continue. Among the less common reasons for dropping out were medication-related issues (such as difficulty with injections) and feeling the need for a female doctor. Dr. Boivin also discussed results from her own study that was published in the journal Human Reproduction in 2008. In that study, she developed a copingstratagem for women awaiting results of their treatment (i.e. the time between embryo transfer and first beta hCG). It is known that this is a most anxious time for women and the stress of waiting can become overwhelming. She utilized something called the “positive reappraisal coping intervention” card, or “PRCI” card. This is a small printed card that a patient can carry around in his or her pocket and it is meant to be read 2 times per day, every day during the 9-11 days between embryo transfer and first pregnancy test. The card has several little sayings such as: “During this experience I will try …to do something that makes me feel positive” and “During this experience I feel that….I’m energized or I’m creative.” This is a way of programming thoughts towards the positive and away from the negative. She and her colleagues were able to show that patient felt less stressed and felt that the PRCI was helpful during this period.

Currently, at PFC, we have begun a task force to look into ways to better incorporate counseling and tools for stress management for our patients. Please also see this recent Patient Odyssey. Support groups are a wonderful way to diffuse stress and feel more positive.

Corifollitropin: a modification of Follistim to allow a once-a-week injection.

As most people know, the medication we most commonly use for fertility treatment, Follistim, is pure human FSH, manufactured using recombinant DNA technology. The company that makes Follistim, Schering Plough, is working towards FDA approval of a modified version of Follistim, called Corifollitropin, that will make the drug very long-acting.

For those interested in the details; Corifollitropin is the recombinant FSH molecule + 22 C-terminal peptides from betahCG. It does not bind to the LH receptor. This modification lengthens the half-life of Follistim from 22-34 hours to 60-74 hours for Corifollitropin. The recommended regimen will be one dose per week, starting at baseline, then switch to daily recombinant FSH after that. After injection, peak levels are reached in 2 days then they slowly level. It may be possible to only take one injection per week!

A symposium at ESHRE presented information from the ENGAGE trial with data from 14 European and 5 Asian IVF centers, using women with body mass indices (BMIs) between 18 and 32 (generally less than 60 kg -132 lb). The patients were randomized to receive either Corifollitropin or conventional daily recombinant FSH for oocyte recruitment. The number of days of stimulation was the same in both groups (9). The number of eggs retrieved was significantly higher in the Corifollitropin group (13.3) vs. the FSH group (10.6). The rates of ovarian hyperstimulation syndrome were the same in both groups (about 3%). The pregnancy rates were 25% in the Corifollitropin group and 34% in the FSH group, a difference that did not quite reach statistical significance.

Data were also presented on a second study of Corifollitropin from the U.S. and Europe, comparing two doses of the drug. In the study, 100 mcg/dose was given to women less than or equal to 60 kg and women greater than 60 kg were dosed at 150 mcg. Over 1500 patients were included in this large trial. In this study, the average number of eggs recovered was 13.7 for the Corifollitropin group and 12.5 for the Follistim group. The mature egg and fertilization rates were the same. The percentage of good quality embryos was the same.

The clinical pregnancy rate in the Cori group was 38.9% and was 38.1% in the Follistim group. These rates were statistically the same. We expect that Corifollitropin will likely be available in the U.S. in 2010 or 2011.

We all know that fertility declines with female age, but what is not certain is how much in vitro fertilization (IVF) improves one’s chances of conception if a couple/woman is having problems conceiving on her own.

The table below is one I often use when counseling patients 40 and over about their chances of conception with in vitro fertilization.

This table represents pregnancy outcomes with PFC patients from January 2003 to March 2008, so most of the viable pregnancies tabulated here have been delivered.

One thing to note is that over half of the patients that get a positive beta-hCG result do not end up delivering a baby. This is consistent with the observation that most embryos from women 40 and over have abnormal numbers of chromosomes.

Another thing to be aware of is that pregnancies after age 43 are exceedingly rare, even with IVF. We encourage most women over age 43 to strongly consider ovum donation.
World-wide, over half the babies born from assisted reproduction to women over age 40 are born from ovum donation, not from their own eggs.

Every year, several Pacific Fertility Center professionals participate in ASRM’s national meeting. They evaluate the research and share their findings with PFC and Fertility Flash.

Among those attending the conference from PFC were Dr. Philip Chenette and Dr. Isabelle Ryan and Peggy Orlin, MFT. Their reviews cover the following topics: Update #1: Ovarian Stimulation Techniques, Update #2: PGD and Aneuploidy Screening Techniques, Update #3: Egg Freezing, Update #4: Acupuncture, and Update #5: Men and ART.

ASRM Update #3: Egg Freezing

Oocyte cryopreservation is the storage of the female gamete, the egg, prior to fertilization. Preservation of fertility for single women that must undergo cancer therapy or surgery, or that must delay or choose to delay childbearing, and donated oocyte banking are all applications of oocyte cryopreservation. The need for this technology is clear, but reports of success with oocyte cryopreservation have been limited.

Highly successful oocyte cryopreservation is now attainable. New studies are showing pregnancy rates with oocyte cryopreservation that are equal to traditional IVF techniques.

The key to this technology is oocyte vitrification – an ultrarapid cryopreservation technique. Researchers from Atlanta described their experience with vitrification. Out of 11 patients with transfers, nine conceived, with an implantation rate of 65%.

Pregnancies after oocyte cryopreservation have developed normally. An Italian study of 105 children born after oocyte cryopreservation showed no problems. A Chicago study of the genetics of oocytes, embryos, and children born after oocyte cryopreservation was reassuring. No increase rates of aneuploidy or malformations were reported, and normal development was found in post-natal follow-up.

These results are similar to those we have previously reported from our own research at Pacific Fertility Center (see December 2007 Fertility Flash). Oocytes are now cryopreserved with high success rates. Oocyte cryopreservation technology has matured, and we look forward to providing these techniques for our patients.

Philip Chenette, MD

Question: I am 35 years old and single, but am still hoping to find my life partner. I am getting a little concerned as my gynecologist has asked me about my plans for having children. She mentioned that I might want to consider freezing my eggs for future pregnancies. Is this something I should do?

Answer: Vitrification is a very new process for preserving unfertilized eggs. As noted in this month’s lead article, PFC has successfully been vitrifying oocytes from proven egg donors. Our first birth from this process occurred in October. Three additional pregnancies from this trial are ongoing. PFC undertook this vitrification trial in order to develop expertise with the technology of oocyte vitrification. For this reason, our study population was confined to donor eggs from healthy donors in their mid-twenties who had successfully completed conventional egg donation.

Why do we want to freeze eggs? For the many single young women diagnosed with cancer and facing fertility-threatening chemotherapy, egg vitrification will provide a fertility preservation option. This group of women has a compelling reason to consider undertaking the procedures and costs involved with in vitro fertilization. The potential threat to their ability to have their own biological children in the future may justify the unknowns that are involved with preserving their eggs in this manner. These unknowns include whether their eggs will survive the vitrification process and whether egg vitrification will ultimately prove to be as safe as conventional in vitro fertilization and embryo cryopreservation. The answers to these questions may not be answered until the patient’s eggs are warmed, fertilized and implanted, which may be years later.

We recognize that a much broader spectrum of the population will look upon oocyte vitrification as a way for women to preserve their fertility. Single women, such as you, who have not yet met their life partner, may be particularly interested in this option. In addition, it may also become an option for women in their 30’s who wish or need to delay their childbearing.

Many questions remain unanswered. Will eggs from women in their 30’s do as well as eggs from proven egg donors in their 20’s? Logic suggests older eggs will not do as well, but will the differences be significant? How many eggs would a woman need to preserve in order to have a reasonable chance for one or two children in the future? How many IVF cycles will that take? Is it safe to rely on these preserved eggs? Would having preserved eggs change a woman’s approach to reproductive planning in her life?

These are not trivial issues. They are important, life-changing concerns. For these reasons, we are not encouraging single women to prematurely jump on the egg vitrification bandwagon. Stay tuned. This area is changing rapidly.

Dr. Carolyn Givens

Question: I am 38 years old with age-related infertility (at least that is what my doctor, a Reproductive Endocrinology and Infertility Specialist (REI), thinks). It has been suggested that I undergo super-ovulation with injectable Follicle Stimulating Hormone (FSH) along with intrauterine insemination. I really don’t want to have twins, if possible, and certainly not triplets or more! But ideally, I would like to have more than one child. Even if I am successful in having one baby now, I am worried about trying to have a second child when I am 40 or more. What do you suggest?

Answer: We agree that having one baby at a time is the safest thing for you and your family. However, undergoing FSH super-ovulation is intended to create more eggs in one cycle in order to increase the odds that one or two will fertilize and implant. This helps to overcome the relative inefficiency of conception for women in their late 30’s. The risks are as you stated, twins or more. Luckily, the risks that a woman undergoing this treatment will get triplets or more is really fairly low – on the order of less than 10% of all pregnancies, with careful monitoring. The risk of twins is higher – on the order of 20% of such pregnancies.

If a woman at 38 years old has no identifiable cause for infertility, the goal is usually to get 3-6 follicles. Most of the time, if the treatment is successful, the pregnancy will be a singleton pregnancy (one baby). Your issue of wanting to have a second child and concern for difficulties beyond age 40 is a real one. You may want to discuss with your REI the option of in vitro fertilization. If your doctor thinks you may be a good responder to fertility medications, you could have extra embryos to freeze, which provides some back-up and allows you to preserve some embryos from 38 year old eggs for down the road.

Patients contemplating conception must consider lifespan expectations as part of their decision on whether to conceive. Such considerations are not, however, a reason to withhold treatment, and are ultimately the individual and family should decide.

– Dr. Carolyn Givens

So often I hear or read about what a mistake it is to postpone having children. As if for all of us this is a conscious choice. I wasn’t waiting until the perfect career moment, or until I achieved some lofty goal. I was waiting for a committed mate with whom to start a family. So at 39, my husband and I began what would become, in total, a six-year infertility odyssey.

I was not naïve going into this. I was, in fact, planning for a difficult time. I expected to chart my cycles, which would of course be unsuccessful, for six months, and, armed with all this useful data, insist on a referral to a fertility specialist. Imagine our surprise when I became pregnant on our first try. The pregnancy ended at around 10 weeks, when we went for our first ultrasound and was told there was no heartbeat. In a testament to denial and hope, and despite my initial pessimism and the dismal statistics for my age group, I never truly believed I would miscarry.

My emotional recovery from my first loss was complicated by a difficult physical recovery. Nonetheless, a few months later I was pregnant again, only to miscarry at six weeks. I was distressed and angry, resentful of every pregnant belly I’d pass on the street, feeling sabotaged by my own body. The wait just to get an appointment with the fertility specialist within my health plan was six months, so we anxiously turned to PFC, knowing that every cycle was a precious commodity.

We launched in with Dr. Ryan, taking every reasonable test, only to find that things looked pretty good and this was simply going to be luck of the draw. After several trying months of unexpected delays and barriers, we upped our odds with injectables and conceived our amazing daughter, Hannah. I remember that my first thought, after the nine days of shots, the trips to the City for ultrasounds, the anxious OPK readings, and the agonizing two-week wait, was that it had been ridiculously easy. That was five years ago. We have a son on the way now. I can feel him squirming around in there, poking at my bladder as I write this. We suffered many losses and deep disappointments to get to this point, and I have three sharps containers full of needles to prove it.

I can’t imagine what it must be like for women who breeze through conception and pregnancy, but I know I have benefited from the difficulty of my experience. I have gained a profound sense of wonderment about the entire miracle of pregnancy. I have an appreciation for the life I’ve brought into this world, and the one on its way, that I could never have found with any other path. I have developed a depth of sensitivity for those struggling to do what comes so easily to others that has enabled me to support them in a way I could never otherwise have done.

Maybe this isn’t the course I would have chosen, given the option, and there are some wounds that never heal, but after six long years, we are finally at a point where we can breathe. We can put the exhausting cycle of hope and grief behind us. Like us, anyone who has come out the other side of infertility gains a sense of their strength, endurance and resolve. And anyone who has found their way through infertility, whatever their path, knows the almost overwhelming sense of relief we feel down to our bones, every single day.

– Lauren

The public’s appetite for promising pills that purportedly slow down the aging process is stronger than ever. Sensationalized claims revolving around Dehydroepiandrosterone (DHEA), a natural steroid hormone produced from cholesterol by the adrenal glands, has followed this trend.

DHEA is a hormone secreted by the adrenal gland whose level in the body peak at early adulthood and then decline with age. As the most abundant steroid in the body, DHEA is chemically similar to testosterone and estrogen.

Because low DHEA levels brought on by aging also correlate with age-related diseases, DHEA supplements are openly marketed to prevent the effects of aging. Because a woman’s fertility declines with her age, it is no surprise that DHEA has been associated as a “promising” drug to offset age-related infertility. Yet there have been no scientific studies or evidence revealing that adjusting DHEA levels changes the development of age-related diseases. Nor has there been evidence that DHEA slows down the decline in fertility. Simply stated, there is no evidence that increasing DHEA slows down, stops, or reverses the aging process.

Some past rodent studies indicated DHEA was effective in controlling obesity, and prevented cancer, arteriosclerosis and diabetes. As a result, DHEA was quickly promoted as a miracle weight-loss drug. Yet no human studies have duplicated these results.

Nevertheless, DHEA has received considerable acclaim, with some authors touting it as a “superhormone” or “the youth and health hormone.” Articles on DHEA abound. In fact, DHEA received over 850 citations in a Medline search and 52 publications come up on an Amazon.com search.

A search of serious scientific research examining DHEA’s impact on fertility is scanty. There are less than a handful of scientific presentations or papers on the topic. Just last year a study (Fertil Steril. 2005; 84(3):756) conducted at the Albert Einstein College of Medicine announced: Increased oocyte production after treatment with dehydroepiandrosterone. This paper focused only on one 42 year old woman, whose number of oocytes retrieved increased after undergoing eight IVF cycles over the course of a year with DHEA supplementation. Not only did she take a DHEA dietary supplement, she also underwent acupuncture. Since she froze her embryos, it is not reported whether any of her eggs led to a successful pregnancy.

To date, no sound or controlled scientific studies have been designed to examine whether DHEA is able to reverse the results of aging on ovarian reserves.

A research paper was presented at the 2005 ASRM conference (O-101 by D. H. Barad and N. Gleicher). This retrospective cohort study examined 45 women previously diagnosed with decreased ovarian reserve who were treated with 25 mg DHEA for 4-48 weeks before undergoing ovulation induction for IVF. The study concludes that DHEA increased oocyte production and quality. Yet no pregnancy or live birth outcomes were reported. Both Drs. Barad and Gleicher are already offering “DHEA Therapy” in their practice.

Very little of the encouragement to self-administer DHEA is coming from the physician community, especially those who are initiating viable scientific research. Elizabeth Barrett-Connor, MD, professor and chair, department of family and preventive medicine at University of California, San Diego calls DHEA “a modern day snake oil”. Her initial research revealed that higher natural levels of DHEA in older men may help protect them against heart disease yet she recognizes the need for more studies.

Self-medicating by using DHEA supplements is a form of testosterone therapy. It is not likely to affect each individual in the same way due to variable existing androgen levels in the body and a lack of consensus on what are normal or benchmark levels. Increasing DHEA (and thus testosterone) may well lead to additional facial hair and possibly acne for women. Until more is known, taking DHEA is a risky gamble based on insubstantial evidence.

The hype about DHEA as a way to improve fertility will only continue as the public seeks information that they want to hear. An entire chapter is devoted to DHEA in an online book called “Mothers over 40”. If there were such an easy panacea to reverse the impacts of aging on infertility, the benefits would have been known much sooner.

– Eldon Schriock, MD

Question:
What is my fertility physician looking for in conducting an antral follicle count?

Answer:
Women are born with all of the eggs (oocytes) that they will ever have. This is a set number, which is determined before birth. This pool of eggs is never replenished. A female fetus will have the greatest number of eggs around 16-20 weeks of pregnancy (6-7 million); at birth this number decreases to about 2 million; and by puberty to about 300,000. This constant and dynamic process of decline continues until menopause and is not interrupted by birth control pills, pregnancy, or ovulation. From this reservoir of eggs, fewer than 500 eggs will ovulate during a woman’s reproductive life.

There is a continuous process occurring in the ovaries, where eggs are constantly being prepared for the maturation process. It takes 3-6 months for eggs to develop and mature. As the eggs are developing, they transition from a primordial, to preantral, to then antral follicle. Antral follicles are visible by vaginal ultrasound. Antral follicles therefore represent the reserve of eggs in our ovaries and those that are candidates for selection and growth by fertility stimulation medications (gonadotropins).

When assessing one’s ovarian reserve (potential for a successful pregnancy), a number of parameters are evaluated. One of these is called the “antral follicle count” (AFC). An antral follicle count is typically done during the 2nd-4th days of menstrual flow, though it can probably be as accurately done during other times of the menstrual cycle. Studies show that the AFC is predictive of the expected ovarian response to gonadotropins. An AFC less than 6 total (between both ovaries), predicts a poor stimulation response. For those undergoing IVF, a similarly low AFC will be associated with a higher cancellation rate. As women approach their 40s, and as day-3 FSH results rise above 10 mIU/ml, this typically correlates with fewer eggs overall in our ovaries, and therefore a low AFC. Indirectly, a low AFC can correlate with diminished ovarian reserve.

In the same way that there can be monthly variability in day-3 FSH test results, there can be monthly variability in the AFC. More variability is observed in the AFC of young infertile women than in older women. However, overall a single AFC is still quite predictive of ovarian response under gonadotropin stimulation, and there is fairly good agreement between repeated AFC over consecutive cycles. In conclusion, doing an AFC is an adjunct to the day 3-FSH test to predict ovarian reserve and ovarian response to fertility medications.

– Isabelle Ryan, MD

Q.
I’ve noticed that there are FSH urine test kits for sale over-the-counter to help women confirm the onset of menopause. Since FSH testing is involved in determining fertility reserve, can I use this over-the-counter FSH test to help realize my fertility potential?

A.
It appears as if a fair number of over-the-counter FSH test kits are indeed sold in drug stores and over the Internet. I am not going to comment on their efficacy for measuring hormonal changes that the pre menopausal body starts to undergo. But I can answer your question. These test kits are not useful tools to help you determine your fertility potential.

By way of background, human follicle stimulating hormone (FSH) produced by the pituitary gland stimulates primordial follicular growth and estrogen production by the emerging follicle that will mature into an egg.

The urine test kits provide a black or white – yes or no answer, not a glimpse of your FSH level in the context of a gray scale range of indicators. For accurate fertility potential diagnosis, we analyze FSH level in much more detail. On day two or day three of your cycle (following menses) we test your FSH level in conjunction with other tests including estradiol (E2) and an antral follicle count.

Most home urine tests, such as for pregnancy tests and ovulation predictor tests, use a threshold level of the hormone in the urine to detect a positive. With FSH test kits, only when the level reaches menopausal levels of FSH, equivalent to around 40-50 mIU/mL or higher in the bloodstream, will the test turn “positive.” For most women interested in testing for ovarian reserve, we would be looking for levels equivalent to 5-20 mIU/mL. So the sensitivity of the testing is set for menopausal and post-menopausal levels, not the levels seen in women with regular menstrual cycles. By the same token, they will not be able to discriminate normal from decreased ovarian reserve.

– Carolyn Givens, MD