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What We Know About Ovarian Reserve and Have Yet to Learn
March 28, 2013
At the 2012 National Institute of Child Health and Human Development and American Society for Reproductive Medicine (NICHD-ASRM) Conference, leading scientists in the field of reproductive medicine voiced their concerns about current measures of ovarian reserve, the need for better ovarian reserve prediction, and revealed new data that may drive us closer to these goals.
Ovarian reserve is currently one of the greatest predictors of a woman’s fertility, thus her ability to conceive with her own eggs. In addition, ovarian reserve provides insight into a woman’s age of menopausal onset. Existing measures of ovarian reserve include Follicle Stimulating Hormone (FSH), Anti Mullerian Hormone (AMH), Estradiol (E2), and Antral Follicle Count (AFC). Here are some of the findings presented at the conference which provide exciting new information on ovarian reserve prediction and suggestions for future research:
- For more than 60 years, we have believed ovarian reserve to be finite. That is, a woman is born with a set number of eggs in her ovaries. Ovarian reserve decreases over time and no new eggs are produced. New evidence suggests that stem cells found within the ovaries may contribute toward egg renewal at least once per lifetime, in early adulthood. However, follicular recruitment (being chosen as the egg to mature for ovulation) or the act of egg follicle degeneration sets the stage for ovarian lifespan (onset of menopause), so renewal of these eggs may not be significant unless more eggs can be recruited into the growth stage.
- There are no reliable indicators for measuring follicles in the pre-stimulation phase (before they are recruited for stimulation and ovulation). Antral follicles, as measured by AFC, are those that have already been recruited toward the stimulation phase. Because we do not have an accurate way of counting primordial follicles, AMH and AFC can only tell us about the eggs that are beginning the journey toward ovulation, not the pool of eggs that are not yet growing. About 99.9% of primordial follicles are not recruited toward growth and ovulation.
- Current methods of measuring ovarian reserve are unable to tell us about the speed at which a woman’s ovary will age. There are no indicators of fast aging or slow aging, though it seems there is a genetic link between a mother’s age of menopausal onset and her daughter’s age of onset. About 50% of the variation in age of menopausal onset is due to genetics.
- Studies have shown that women who have a deletion of the PTEN gene, which can cause growth activation, could be at an increased risk of premature ovarian failure (POF). Similarly, women with BRCA gene mutation are likely to experience onset of menopause at an earlier age than women without the gene mutation. Women with BRCA gene mutation also show lower ovarian stimulation response.
- No direct correlation has been found between lower AFC or AMH and increased risk of aneuploidy (chromosomally abnormal eggs or embryos).
- AMH indicates ovarian activity during childhood, puberty, and adulthood. There is a small decline at the onset of puberty, but a peak in ovarian reserve in a woman’s 20s. By the time she reaches 25, her ovarian reserve embarks on a steady decline until menopause (around the age of 51). AMH is currently the most accurate predictor of ovarian reserve.
- Age and menstrual cycle are most commonly used as biomarkers of fertility. This does not account for history of birth control use or irregular cycles in which ovulation does not occur, so it may not be the most accurate biomarker.
- Women with Polycystic Ovarian Syndrome (PCOS) have higher AMH readings that women without PCOS, even in later reproductive years. This may cause an inaccurate prediction of ovarian reserve.
- AMH levels may be helpful in predicting a woman’s fertility post-chemotherapy. Chemotherapy and other cancer treatments can be detrimental to a woman’s fertility. However, AMH does not speak to the quality of the remaining eggs, but provides an estimate on quantity.
While accurate at determining ovarian reserve for the individual at the present time, existing measures of ovarian reserve do not provide a window into the future of the woman’s fertility, how early or late her ovarian reserve will decline, and do not indicate any differences between race, body type, genetic factors, use of medications, or presence of infertility. Despite all we know about female fertility, there is much to be learned. Fertility doctors at the conference agreed that future research should aim to improve methods of measuring ovarian reserve.