Endocrine markers of ovarian function: Clinical and biological aspects with focus on Anti Müllerian hormone

Abstract: Declining birthrates and infertility are now a common problem in the Western World. Due to the tendency to postpone childbearing an increasing age of women who consider motherhood is generally seen. A factor closely related to female fertility is the ovarian reserve, a term used to designate both quantitative as well as qualitative aspects of the remaining gametes in the female gonads. Despite a natural age-dependent decline in terms of the amount of gametes, a substantial variability exists between individuals as to the age at which the actual decrease starts. In this setting biomarkers to assess the individual fertility potential are often requested. Currently the antral follicle count and the Anti Müllerian Hormone (AMH) level are considered to be the most predictive markers. The two markers roughly describe the same issue as they are both related to certain developmental stages of the folliculogenisis. Furthermore, the number of growing follicles is closely related to the activity of the hypothalamic-pituitary axis which controls the secretion of Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH). The aim of the present thesis was firstly to explore the age-related circadian variation of AMH in normally ovulating women and patients with Polycystic Ovarian syndrome (PCOS) and its relation to gonadotropin secretion; secondly to explore the inter- and intra-cyclic variation of AMH related to the number of antral follicles measured by ultrasound; thirdly to explore AMH as a marker of time to pregnancy in fertile women, and finally, to examine the significance of mid-follicular phase LH levels in patients undergoing IVF. The results show that, in contrast to women with PCOS, normally ovulating women reveal a significant circadian variation in AMH. The co-variation with androgens and LH, may indicate that LH masters the secretion of AMH. Moreover, in normally ovulating women, AMH shows a significant intra-and inter-cyclic variation which may question the current use of one measurement of the hormone as sufficient to evaluate the ovarian reserve. A significant positive correlation was found between AMH and the number of small antral follicles. Moreover, in a cohort of spontaneously pregnant women, AMH was found to be related to the number of menstrual cycles required to obtain a pregnancy. In women undergoing a long pituitary down-regulation with GnRHa and hormonal stimulation with gonadotropins to obtain multi-follicuar development prior to In Vitro Fertilization, the clinical pregnancy rate as well as the consumption of exogenous gonadotropins was inversely correlated to the mid-follicular LH levels. In conclusion, the present results demonstrate that normally ovulating women have circadian as well as intra- and inter-cyclic variations in AMH. Moreover, the AMH level seems to be related to time to pregnancy and closely linked to LH as a key player during folliculogenesis