Can we test how fertile a woman is?

A recently published study in the prestigious medical journal JAMA received considerable medical attention, though in our opinion, for some of the wrong reasons (Steiner et al., Association between biomarkers of ovarian reserve and infertility among older women of reproductive age. 2017;318(14):1367-1376). The authors, a collaborative team from multiple U.S. medical schools, evaluated what they called biomarkers of ovarian reserve (follicle stimulating hormone, FSH; anti-Müllerian hormone (AMH), etc.), which they claim are being “promoted” as biomarkers of potential reproductive potential.

They concluded that in their study biomarkers indicating diminished ovarian reserve (what we at CHR call low functional ovarian reserve, LFOR) were, in comparison to levels of biomarkers indicating normal ovarian reserve, not associated with reduced fertility. Consequently, they further concluded that biomarkers, like FSH and AMH, should not be used to assess natural fertility.

That this manuscript was accepted by JAMA was somewhat of a surprise to us, here at CHR because this journal is usually very concerned about publishing “new” findings. And nothing this paper reported has not before already been reported, though, maybe not on such a large patient population. But what concerned us even more about this paper, was that the results of the study, so easily, may be misinterpreted and misused in the infertility arena.

Though the authors were very precise in their study description, we fear that their results, nevertheless, will be misinterpreted by colleagues who do not dig deep enough into the details of the study but, as is unfortunately common practice in medicine, only read the headlines.

For infertility patients, it is important to understand that this paper is not meant to speak to them! This study was not performed on infertile women. It was performed in a general fertile population, trying for the first time to conceive. This is a very important distinction because the same biomarkers, in this study demonstrated not to be predictive of pregnancy chances, in infertile women, are quite predictive of who will or may not conceive in established infertility patients. It, therefore, is of importance that colleagues and patients understand that all this study means is that, if a woman, who has never tried to conceive, asks to have her FSH and AMH levels tested in order to determine whether she is “fertile,” these tests will not provide an answer.

The reason is simple: We do not have a test to determine who is fertile or not; the only way to find out, is by trying to conceive. And if a woman (up to age 38) does not conceive within one year, she is presumed to have an infertility problem (the truth is, however, that most fertile couples will conceive within ca. 6 months).

One additional caveat applies, however, to our limited endorsement of this study, and that is the study’s claim to have investigated “older women.” Though investigated women had an age range of 30-44 years, their mean age was only 33.3 years, by no means what we or the rest of the literature considers “advanced age.” We, therefore, do not agree with the authors conclusion that biomarkers of LFOR, like FSH and AMH, do not predict fertility potential in “older” women. Their data, in principle, really only address younger and middle-aged women. In truly “older” women, which we define over 38-40 years of age, biomarkers such as AMH and FSH may, indeed, be “functional” like in infertile women, though that still needs to be proven. CHR’s Medical Director and Chief Scientist, Norbert Gleicher, MD, made this point in an interview he gave to Forbes Magazine (above).

This is a part of the November 2017 CHR VOICE.

Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned reproductive endocrinologist, 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.