The physiology and clinical utility of anti-Müllerian hormone in women

Abstract

BACKGROUND The measurement of circulating anti-Müllerian hormone (AMH) has been applied to a wide array of clinical applications, mainly based on its ability to reflect the number of antral and pre-antral follicles present in the ovaries. AMH has been suggested to predict the ovarian response to hyperstimulation of the ovaries for IVF and the timing of menopause, and to indicate iatrogenic damage to the ovarian follicle reserve. It has also been proposed as a surrogate for antral follicle count (AFC) in the diagnosis of polycystic ovary syndrome (PCOS). METHODS This paper is a summary of presentations at a European Society of Human Reproduction and Embryology campus workshop on AMH, with literature cited until September 2013. Published peer-reviewed medical literature about AMH was searched through MEDLINE and was subjected to systematic review and critical assessment by the panel of authors. RESULTS Physiologically, recent data confirm that AMH is a follicular gatekeeper limiting follicle growth initiation, and subsequently estradiol production from small antral follicles prior to selection. AMH assays continue to evolve and technical issues remain; the absence of an international standard is a key issue. The dynamics of circulating AMH levels throughout life can be split into several distinct phases, with a peak in the early 20s before a decline to the menopause, with a strong and positive correlation with non-growing follicle recruitment. There is a more complex rise during childhood and adolescence, which is likely to be more reflective of different stages of follicle development. AMH shows limited short-term variability, but the influence of states such as prolonged oral contraceptive use need to be considered in clinical assessment. There are only very limited data on relationships between AMH and natural fertility at different stages of reproductive life, and while it has a relationship to age at menopause the marked variability in this needs further exploration. AMH may be useful in assessing the need for fertility preservation strategies and detecting post-chemotherapy or surgical damage to the ovarian reserve. Long-term follow-up of patients to ascertain fully the value of post-cancer serum AMH in predicting long-term ovarian function is required. There is a linear relationship between AMH and oocyte yield after ovarian stimulation, which is of value in predicting ovarian hyperstimulation. AMH can also identify 'poor responders', but it seems inappropriate at present to withhold IVF purely on this basis. Women with PCOS show markedly raised AMH levels, due to both the increased number of small antral follicles and intrinsic characteristics of those granulosa cells, and this may contribute to anovulation. The value of AMH in the diagnosis of PCOS remains controversial, but it may replace AFC in the future. CONCLUSIONS For the first time in female reproductive biology, it is possible to measure the submerged part of the iceberg of follicle growth, i.e. the intrinsic, so-called 'acyclic' ovarian activity. ...

Anti-Müllerian hormone is produced heterogeneously in primate preantral follicles and is a potential biomarker for follicle growth and oocyte maturation in vitro

“…Physiologically, AMH may be a gatekeeper for follicular development as suggested by clinical studies [4]. AMH is also considered as a promising biomarker of ovarian function in a large array of clinical situations including assessing the need for fertility preservation for patients experiencing cancer therapies or surgeries that may cause ovarian damage [4]. As a member of the transforming growth factor beta (TGFβ) family, AMH signals by binding to a specific type II transmembrane serine/threonine kinase receptor, AMHR2 [5].…”

IVF results in patients with very low serum AMH are significantly affected by chronological age

“…Anti-müllerian hormone (AMH) is an established marker of OR and is considered the most reliable predictor of ovarian responsiveness to controlled ovarian stimulation (COS) [4]. A circulating AMH level of 0.7 ng/ml has been claimed to be the threshold value for poor ovarian responsiveness to COS [5,6], whereas levels below 0.1-0.35 ng/ml have been associated with a high risk of cycle cancellation due to extremely poor response [7,8].…”

AMH/MIS as a contraceptive that protects the ovarian reserve during chemotherapy

“…MIS | AMH | oncofertility | AAV9 | contraceptive M üllerian inhibiting substance (MIS), also known as antiMüllerian hormone (AMH), has long been appreciated for its role in sex differentiation and reproduction, and sensitive ELISAs measuring blood levels are used in fertility clinics around the world as a measure of ovarian reserve (1)(2)(3)(4)(5)(6). MIS plays important roles in the development of the gonad and the differentiation of the urogenital ridge.…”