Female fertility is a multifaceted process that can't be assessed with just a few blood tests. Image by Anna Pritchard via Unsplash.
Something interesting is going on in cyberspace when it comes to female fertility: quite a number of new start-up companies offer all kind of services, claiming to be able to offer diagnostic services that in one way or the other, allow women to judge how fertile they are. Some are online fertility questionnaires, while others incorporate home blood tests for fertility. A word of caution from CHR: Be skeptical!
And here is why: Let’s start with the concept of “fertility.” The ability to conceive is, of course, highly complex. The better we understand the process, the more miraculous it seems that we all, indeed, exist as a species, considering how low our inherent fertility is: even at peak fertility, a young couple without fertility problems on either side will require 3-4 months on average to conceive. Moreover, assuming such couples do produce one embryo every month (women, with few exceptions, produce only one mature egg every month), only one in every 3-4 embryos, apparently, has pregnancy potential at even such young ages. As women age, that ratio increases, and by the time a woman reaches her 40s, the chance of an embryo to lead to a pregnancy is in the single digits.
Fertility, moreover, does not only depend on a properly functioning female set-up of circumstances but, to almost equal degrees, also on normally functioning male contributions: Roughly 60% of all infertility relates to female, and approximately 40% to male infertility causes (though recent data suggest that the proportion of male factor infertility is proportionally increasing), while in ca. 25% of cases one will find problems on both sides. A couple’s fertility, therefore, simply cannot be evaluated by only testing the woman.
What one can try to define is the ability of a woman to be impregnated, called “fecundity,” but even that is quite difficult to accomplish because a woman’s ability to conceive is so multifactorial. To protect maintenance of the species in evolutionary terms, nature has built into the process a large number of redundancies that can either reduce or completely eliminate the possibility of reproductive interruptions. Frankly speaking, even using very thorough diagnostic investigations (very different from what is being offered by companies on the Web), we are only able to diagnose the tip of the iceberg, i.e., the most obvious causes of infertility, like hormonal/ovulatory dysfunction, tubal occlusion or insufficient semen. In all other cases, we, still, are more or less guessing: We may suspect an immune problem causing infertility, but nobody can know for sure as of this point that such a problem really exists; or we may believe that an implantation problem exists, but we do not really have a tool or test to reach this diagnosis with any certainty.
Then, there is the other side of the coin: Every fertility specialist knows that, on rare occasions, “miracles happen” when women with absolute evidence of intractable infertility, suddenly, conceive. Those occurrences are, indeed, very uncommon but do point out the very obvious limitations of current diagnostic capabilities in the fertility field. To believe that a few basic blood tests would offer reliable information about a woman’s fertility status is, therefore, at best naïve and, certainly, misleading, and we strongly caution against making important decision in life based on such testing.
That, of course, raises the question: What kind of information can we reliably provide to the average woman who is not yet contemplating to conceive but is worried about her future fertility?
The answer to this question is again quite complex: In principle, there is only one way to reliably asses a woman’s fertility: to expose her to normal semen and see whether she will conceive. Everything else is simply hogwash, and only offers information on selected aspects of fertility. So, for example, blood testing and/or a vaginal ultrasound examination can tell us whether a woman ovulates, but just because she ovulates does not mean she is fertile. Or a hysterosalpingogram (HSG) can tell us whether fallopian tubes are patent and anatomically normal but, even if they are, this does not mean she can or will conceive.
While quite a number of these “fertility components” can be tested in a comprehensive infertility evaluation, even if all of those are found to be normal, couples may still be unable to conceive, a status often called unexplained infertility. But as was explained on prior occasions in these pages, as a diagnosis, CHR is not supportive of this term because how much will remain “unexplained,” of course depends on how deep one digs in any diagnostic work-up. A few blood tests, as currently offered by many of the previously noted start-up companies on the Internet, of course, do not suffice.
This is exactly the reason why CHR approximately two years ago, launched “What’s My Fertility,” a similar, yet at the same time very different concept, with what we believe is a much more logical and achievable purpose.
What's My Fertility
As we hope we here so-far have well explained, while a woman’s current and future fertility status is not determinable by just a few simple blood tests, whether a woman's ovaries are aging normally or will likely age normally going forward, is determinable with a high degree of accuracy. Premature ovarian aging is, therefore, predictable! In other words, whether a woman at any given age has a normal amount of eggs left in her ovaries for her age, can be deduced from a few simple blood tests. Moreover, a few questions in combination with a small number of routine blood tests, like anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH) in combination with determination of CGG repeat numbers on the FMR1 gene, provides a look into the future, which allows for the determination whether a young woman with, currently, still normal ovarian reserve (number of remaining eggs) either already suffers from premature ovarian aging (POA, also called occult primary ovarian insufficiency, oPOI), or is at increased risk to develop POA in the future.
A full 10% of women, independent of race, ethnic background or other characteristics, develop clinically significant POA/oPOI by approximately age 35. The condition is, however, usually already present, and diagnosable, long before egg numbers in ovaries drop below a certain threshold that leads to female infertility. Because, as the term oPOI so amply suggests, this condition develops quietly without symptoms (“occult”), women are usually unaware of their condition until they attempt pregnancy. By that point, this will, however, often mean that they, likely, will require costly medical help to conceive, in most cases in vitro fertilization (IVF). If POA/oPOI is by that point even more advanced and IVF can no longer help, they may even require third-party egg donation.
Though to a degree doing this as well, What’s My Fertility, in principle, does not aim to inform directly about the current or future fertility status of a woman but to allow the conclusion whether a young woman is at increased risk of developing POA/oPOI and, therefore likely will develop difficulties in conceiving once she gets older. Because 10% of all women will be affected by this condition, the idea of this screening program developed by CHR (and an awarded U.S. patent for the algorithm) is, to be able to facilitate the early diagnosis of POA/oPOI, at a time that gives affected women (and 10% of all women, of course, represent quite a significant portion of the female population) choices: They can change the timing of their reproductive plans, which in recent decades has led to ever-later first childbirths, or, if that is not a desirable option, women can freeze their eggs at young ages, when their ovaries have been affected by their POA/oPOI only minimally.
As these pages have repeatedly noted in the past, CHR does not support the excessive marketing drive toward egg freezing that has become another characteristic of recent years. At the same time, if there is a group of women who will clearly benefit from egg freezing, then it encompasses the young women who already suffer from POA/oPOI or are at increased risk of developing POA/oPOI.
If you are a woman under age 35 with future plans for children, or if you have a daughter, relative or friend in that age group, we, therefore, strongly urge you to visit What’s My Fertility at its informative website. There, CHR offers cost-free risk screening and individual advice. Arrangements have also been made with a national laboratory chain, accessible everywhere in the U.S., to offer discounted rates for the needed blood tests.
This is a part of the February 2020 issue of the CHR VOICE.
Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned specialist in reproductive endocrinology, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.
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