Human ovarian reserve from conception to the menopause

Abstract

Current understanding is that the human ovary contains a fixed number of several million non-growing follicles (NGF), established by five months of gestational age, that declines with increasing age to the menopause when approximately 1,000 NGF remain at an average age of 50-51 years. With approximately 450 ovulatory monthly cycles in the normal human reproductive lifespan, this progressive decline in NGF numbers is attributed to follicle death by apoptosis. Individual histological studies have quantified NGF numbers over limited age ranges. However, no model describing the rate of establishment and decline of the NGF population from conception to menopause has been previously reported. Here we describe the best fitting model of the age-related NGF population in the human ovary from conception to menopause. Our model matches the log-adjusted NGF population to a five-parameter asymmetric double Gaussian cumulative (ADC) curve (r2 = 0.81). Furthermore we found that the rate of NGF recruitment into growing follicles for all women increases from birth until approximately age 14 years (coinciding with puberty) then decreases towards the menopause. The explanation for this new finding remains unclear but is likely to involve both paracrine and endocrine factors. We describe and analyse the best fitting model for the establishment and decline of human NGF; our model extends our current understanding of human ovarian reserve.