Genetic Epidemiology of Ovarian Aging

The purpose of this study is to identify clinical and genetic markers of ovarian aging. In this process, we will evaluate environmental factors that may affect fertility and the age at which fertility declines, and may influence the age at which women enter menopause. Wide variability exists between women both in the age at which menopause occurs and the rate of decline in oocyte number and reproductive capability. As the loss of ovarian function has profound impact on women's hormonal milieu and their subsequent risk for the development of disease, improving our understanding of the factors that determine the timing and rate of reproductive aging is critical to improving quality of life for all women. In addition, improving our understanding of reproductive aging has profound economic, and social, implications given the complex choices women face regarding the timing of childbearing and the growing burden of infertility. While the inter-individual variability in age at menopause has a large genetic component and possible environmental influences, to date no studies have addressed the relationship between oocyte number as reflected by antral follicle count (AFC) and genetic inheritance. We hypothesize that ovarian aging, as reflected by antral follicle count, is largely determined by common genetic polymorphisms that impact the initial oocyte endowment and/or the rate of oocyte loss over time thus lowering antral follicle count for any given age. We further hypothesize that antral follicle count will be an improved marker of ovarian aging. Thus, we propose a study of the genetic and environmental factors that influence age-specific variability in antral follicle count.