The biological aspects of risks of infertility due to age: the female side.

When women reach their forties, and despite strong inter-individual variations, their fecundity, either spontaneous or assisted, is impaired then falls down from the age of 45 onwards. In humans the size of the ovarian reserve is definitely fixed at birth and decreases drastically with age. Follicles leave the stock of resting follicles in a continuous stream, either disappearing by apoptosis or entering the growth phase. From the age of about 38 years onwards, the rate of follicular depletion accelerates leading to a decreasing number of selectable follicles. As these follicles produce inhibin B, its circulating levels drop, resulting in an increase in circulating FSH concentration. The higher rate of growth of large follicles in women over the age of 40 than in younger women, likely due to high FSH levels, and/or an early selection of the preovulatory follicle seem responsible for the shortening of the follicular phase in women in their late thirties and early forties. An impaired endometrial receptivity and/or a decrease in oocyte quality, or both may be responsible for the increase of the frequency of spontaneous abortion when women reach their forties. In conclusion, it can be predicted that, although apparently inescapable, the fertility impairment due to ageing could be, at least partly, counteracted by the use of molecules preventing attrition of the ovarian reserve.