Ovarian aging: Is there a "norm"?

Ovarian aging: Is there a "norm"? Norbert Gleicher, MD

Female fertility declines with advancing age, principally because of changes in ovarian function. Ovarian aging always has been assumed to be the main culprit, but experience with human egg donation confirms that female fertility can basically be prolonged almost indefinitely, as long as "young" eggs are used in assisted reproduction.1

The decline in human fertility is predictable and can be quantified. Indeed, various authors have demonstrated that the downturn in women's fertility is the consequence of an age-dependent reduction in the number of remaining follicles, which starts during embryogenesis and continues. The initial pool of primordial follicles—at 16 to 20 weeks of fetal life—is believed to encompass approximately 6 to 7 million oocytes. At birth, the female's ovaries contain only 2 million oocytes, and by menarche, about 300,000 remain.2 That number is more than sufficient, as only about 450 monofollicular ovulations are required during a reproductive life of approximately 30 years.

Yet the number of remaining follicles does appear to matter, because when the follicular count falls to about 25,000—as it does in a physiologically normal ovary at approximately age 37.5—the decline in follicular numbers accelerates.3 Various authors, therefore, have suggested that what determines when a woman will experience menopause is not her age but how quickly her follicular count drops to approximately 1,000, the quantity at which menopause usually occurs.4 On average, that happens at age 51, or about 13 years after a woman reaches the 25,000-follicle milestone. In other words, at about age 37.5, a woman's fertility begins to accelerate, and about 13 years later, menopause sets in.