Role of Anti-Müllerian Hormone in pathophysiology, diagnosis and treatment of Polycystic Ovary Syndrome: a review

Abstract

Polycystic ovary syndrome (PCOS) is the most common cause of chronic anovulation and hyperandrogenism in young women. Excessive ovarian production of Anti-Müllerian Hormone, secreted by growing follicles in excess, is now considered as an important feature of PCOS. The aim of this review is first to update the current knowledge about the role of AMH in the pathophysiology of PCOS. Then, this review will discuss the improvement that serum AMH assay brings in the diagnosis of PCOS. Last, this review will explain the utility of serum AMH assay in the management of infertility in women with PCOS and its utility as a marker of treatment efficiency on PCOS symptoms. It must be emphasized however that the lack of an international standard for the serum AMH assay, mainly because of technical issues, makes it difficult to define consensual thresholds, and thus impairs the widespread use of this new ovarian marker. Hopefully, this should soon improve.

Fig. 1

Schematic model of AMH actions in the ovary. Dewailly, D., et al., Hum Reprod Update, 2014 [24]. AMH, produced by the granulosa cells of small growing follicles, inhibits initial follicle recruitment and FSH-dependent growth and selection of pre antral and small antral follicles. In addition, AMH remains highly expressed in cumulus cells of mature follicles. The inset shows in more detail the inhibitory effect of AMH on FSH-induced CYP19a1 expression leading to reduced estradiol (E2) levels, and the inhibitory effect of E2 itself on AMH expression. T, testosterone; Cyp19a1, aromatase. Figure modified from van Houten et al. (2010)

Fig. 2

Schematic diagram of AMH regulation by FSH and E2 in GC of small and large antral follicles. Adapted from Grynberg M et al. JCEM, 2012 [65]. Until the small antral stage, AMH secretion is stimulated by different factors like FSH. Estradiol (E2) production under the influence of FSH is impaired by the inhibiting effect of AMH on aromatase. When estradiol concentration reaches a certain threshold in large antral follicles, it is capable of completely inhibiting AMH expression through ERβ, which predominates in growing follicles, thus overcoming the stimulation by FSH. In large follicles from PCO, the lack of FSH-induced E2 production and the high level of AMH impair the shift form the AMH to the E2 tone, thus leading to the follicular arrest

Fig. 3

Rationale for the use of serum AMH assay as a probe for PCOM. Dewailly, D., et al., Hum Reprod Update, 2014 [24]. a All growing follicles secrete AMH but serum AMH reflects only the secretion from bigger follicles that are in contact with the vascular bed. As the numbers of follicles in all growth stages are strongly related to each other, serum AMH is considered to reflect the sum of growing follicles but not the number of primordial follicles that do not secrete AMH. b In PCO, the numbers of all growing follicles is increased, resulting in a marked increase in serum AMH level. AMH may be considered as a deeper and more sensitive probe to define follicle excess than the follicle count by ultrasound (U/S) since it appraises more follicle classes (blue arrows)