Menopause and Ovarian Reserve: Genetic and Clinical Aspects

Abstract

In the fourth month of fetal development, there is a maximum of about 6-7 million follicles present in the ovaries. Thereafter, follicle numbers decline slowly. The progressive loss of quality and quantity of oocytes is called ovarian ageing. During the process of ovarian ageing, different phases can be discerned with about 10 year intervals: optimal fecundity, infertility, sterility and menopause. Consequently, if menopause occurs early in life, a woman’s fecundity has been compromised decades before. Therefore, accurate prediction of the rate of ovarian ageing and the associated fecundity is desirable. Estimation of ovarian reserve is possible by a wide array of endocrine, ultrasound and genetic tests currently available. This thesis discusses the value of genetic, vascular and other factors in the prediction of menopause and the clinical applicability of ovarian reserve tests is evaluated. The results of the various studies in this thesis underline the complexity of ovarian ageing and the difficulties that prediction of menopause entails. Based on its relationship with age and the antral follicle count, its cycle stability and longitudinal decline with age, anti-Mllerian Hormone (AMH) seems currently the best ovarian reserve test to predict age at menopause. Future longitudinal studies should confirm its accuracy and clinical applicability. The plausibility of vascular factors determining age at menopause is based primarily on indirect evidence. Since there is no consensus about the definition and mode of measurement of vascular ageing, future research should be interpreted cautiously. Diverse ovarian reserve tests are integrated in fertility work-up worldwide, although their capacity to predict pregnancy is poor. Moreover, current research involving ovarian reserve tests often ignores female age and past treatment outcomes as predictive factors of pregnancy. Identification of women with an adequate prognosis seems possible based on strict test cut-offs. Future research should focus on improving the accuracy of prediction models, possibly by incorporating AMH, familial age at menopause and cycle regularity into these models. Currently, there is no single ovarian reserve test able to predict age at menopause with enough certainty in individual women. Future research should focus on combining various ovarian reserve tests to improve the predictive accuracy.