Declining fecundity and ovarian ageing in natural fertility populations.

Worldwide, human fertility declines with increasing maternal age, after contraceptive-use patterns and behavioral factors are taken into consideration. Here, we summarize some of our theoretical and empirical work examining the biological factors contributing to this age pattern of fertility. We undertook an 11 month prospective endocrinological study in a natural fertility (non-contracepting) population (rural Bangladesh) to estimate the contributions of fetal loss and fecundability (the probability of conception) to declining fecundity with age. Prospective interviews and urine samples for pregnancy tests were collected twice weekly from up to 700 women. These data were used to test mathematical models of the underlying biological processes contributing to changing fecundability and fetal loss risk with maternal age. The results indicate that much of the decline in fecundity can be attributed to an increasing risk of fetal loss with maternal age. Much of this fetal loss is due to chromosomal abnormalities--a result of ageing oocytes. Fecundability, on the other hand, does not begin to decline until the early 40s. We hypothesize that this is also a result of ageing at the ovarian level, namely follicular atresia, in the years just prior to menopause. The irregularity of menstrual cycles--longer cycles and increasingly variable hormonal patterns--at these ages may be a direct result of the small and rapidly dwindling remaining pool of follicles. We present a simple mathematical model of this process, and some preliminary laboratory results that support the model.