Comparing the role of anti-Müllerian hormone as a marker of FSH action in male and female fertility

ABSTRACT

Introduction: Originally limited to the assessment of disorders of sex development, anti-Müllerian hormone (AMH) measurement has more recently been extended to several conditions affecting the reproductive axis in males and females. Follicle-stimulating hormone (FSH) regulation of gonadal function has been extensively studied, but its role on AMH production has been explored only recently.

Areas covered: We addressed the relationship between FSH action on the gonads and the usefulness of AMH as a marker in conditions affecting the reproductive axis.

Expert opinion: Sertoli cells are the most active cell population in the prepubertal testis. Serum AMH is an excellent marker of FSH action on Sertoli cell proliferation and function in patients with hypogonadotropic hypogonadism. Low serum AMH is expected to predict low sperm production and prompts initial FSH treatment followed by human chorionic gonadotropin (hCG) or luteinizing hormone (LH) addition. Gonadotropin treatment may be more effective if installed to mimic the postnatal activation stage of the hypothalamic-pituitary-testicular axis. In females, AMH secretion by small antral follicles is stimulated by FSH. Elevated AMH indicates increased follicle numbers and should be considered as a potential contraindication of gonadotropin treatment in infertile patients due to an increased risk of developing ovarian hyperstimulation syndrome.

KEYWORDS:

• Androgens
• azoospermia
• granulosa cells
• infertility
• oligozoospermia
• ovarian reserve
• polycystic ovary syndrome
• primary ovarian insufficiency

Article highlights

• In males, serum AMH is a specific biomarker of the existence and functional activity of prepubertal Sertoli cells. Basal AMH expression is independent of gonadotropins, yet FSH is capable of further increasing testicular AMH production.

• Males with congenital hypogonadotropic (central) hypogonadism have low serum AMH and small testicular volume, indicative of reduced Sertoli cell number and function. FSH treatment results in an increase in AMH levels. Low AMH is predictive of low sperm production in patients with primary hypogonadism and in those with hypogonadotropic hypogonadism.

• In females, serum AMH is indicative of the pool of primary, preantral and small antral follicles. It is used as a surrogate marker of the ovarian follicle reserve. Low serum AMH is indicative of a reduced mass of primary, preantral and small antral follicles, which can result from primary ovarian insufficiency or hypogonadotropic hypogonadism.

• The administration of FSH results in an early increase in serum AMH in females with congenital hypogonadotropic hypogonadism, but extended treatment is followed by a decrease in serum AMH, probably due to an increased recruitment of small antral follicles to large antral stages, which express less AMH. The reversal of impaired AMH production by FSH administration is indicative of a better fertility prognosis in females with congenital hypogonadotropic hypogonadism as compared to patients with primary hypogonadism.

• Elevated AMH is predictive of an increased response to FSH and a risk of developing ovarian hyperstimulation syndrome.

Declaration of interest

Romina P Grinspon and Rodolfo A Rey have received honoraria from CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), Argentina for technology services using the AMH ELISA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was partially supported by FONCYT (Fondo para la Investigación Científica y Tecnológica) [PICT grant number 2016-0993] of Argentina.