Developmental and endocrine aspects of normal ovarian aging.

Supplies of follicles are established during early fetal life and decrease exponentially thereafter by a process called atresia. Subfertility only starts at a mean age of about 30-31 years, when the remaining follicle reserve has become a fraction of its original number. Thereafter, a further decrease in both oocyte quantity and quality dictates the subsequent reproductive events including decrease of fertility, increased abortion rate, the end of fertility, the beginning of cycle irregularity and, when almost no follicles are left, the occurrence of menopause. The same remarkable variation of age at menopause almost certainly is also present for the preceding reproductive events. When quantity and quality of antral follicles drop below a critical threshold, there is a subsequent drop in inhibine B resulting in the selective FSH rise at a mean age of 37-38 years. This FSH rise explains the accelerated follicle depletion, the increased proportion of growing follicles reaching the selectable stage, the shortening of the follicular phase and the increased incidence of dizygotic twinning. The concurring decrease of oocyte quality is in line with the increased incidence of abortions and chromosomal aberrations after age 35.