A Screening with Meaning – Measuring reproductive potential, by Shweta Nayak MD
While this may become an option in the future, it is important that, as with all screening tests, the results of a measure of ovarian reserve be carefully interpreted. Importantly, ovarian reserve is only a small piece of the larger puzzle of factors that can lead to infertility, and testing for ovarian reserve represents more often the functional capacity of young eggs, not the true count.
To Test or not to Test?
By definition, a good screening test is one that can correctly identify those at risk for disease as well as those who are not at risk, the test itself should be reasonably priced, noninvasive, and ultimately lead to early treatment and an overall improved prognosis for the patient. Ovarian reserve tests are screening tests used to identify patients with a history of infertility at risk for decreased ovarian reserve—those who are likely to have a poor response to fertility treatment and who may have a lower chance of achieving pregnancy with assisted reproductive technologies (like IVF). Since “normal” and “abnormal” values for ovarian reserve screening have mostly been defined in this patient population, interpreting the results in a patient population whose fertility status is unknown, i.e. the single woman deciding whether or not to freeze eggs, is tricky.
Technological advances in medicine have brought us the gift of many tests for screening and diagnostic purposes. However, as in any field, it is important to determine whether screening will yield information that needs to be acted upon, as opposed to data for its own sake. This is where the Art of ART (Advanced Reproductive Medicine) comes in. Prior to determining whether specific screening is warranted, a health care provider can gain understanding into a woman’s future risk for infertility through a detailed personal and family history. How old is she? Does she have a history of irregular or a lack of periods? A history of prior pelvic inflammatory disease, severely painful or heavy periods? A family history of premature menopause or infertility? These questions can provide some insight into basic risk factors for infertility, but the golden question—the one that most women will ask—is what their chances for future pregnancy are and whether they can wait to start a family. This becomes a critical question to both single women who are on the fence about freezing their eggs, as well as young women who have a partner but are just not yet ready to start a family.
AMH and the Biological Clock
AMH, a glycoprotein secreted by the support cells (granulosa cells) of small follicles, has quickly emerged as a quick (and easy) assessment of ovarian reserve in women with infertility. The blood test for AMH can be drawn at any time during a woman’s cycle and has good predictive value for how a woman will respond to ovarian stimulation. Even more importantly, there is some, although limited, normative data for AMH in a patient population with an unknown fertility status. That is, there have been prospective longitudinal studies which have described the trend of AMH (how it changes, and what average levels are at different ages) through a woman’s life.
But, is AMH a reliable marker for the number of remaining eggs? Theoretically, the larger the number of small follicles, the higher the AMH; but, as mentioned above, AMH is more a measure of the functional capacity of the follicles and not the actual count. Because of this, many now propose that we define ovarian reserve tests, like AMH, as measures of “functional, responsive, or dynamic” reserve (Monniaux 2014, Findlay 2015, Lambalk 2015). Additionally, studies exploring the normative trend in women with an unknown fertility status unfortunately capture all women—women with and without infertility, so the spread for age-expected values is large.
What we don’t know, at least not yet, is what the true value of AMH is in terms of future chance for pregnancy. This is, in large part, because there are many other factors that can contribute to infertility beyond ovarian reserve—like male or tubal factor infertility—that are not being taken into consideration. And here, again, having a detailed reproductive history becomes critical. Remembering that AMH is a measure of functional ovarian reserve, and not absolute count, practitioners should not rely solely on its value as a predictor for future reproductive potential or chance for future pregnancy.