The role of anti-Müllerian hormone in female fertility and infertility - an overview

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Abstract

Anti-Müllerian hormone (AMH) plasma levels reflect the continuous non-cyclic growth of small follicles, thereby mirroring the size of the resting primordial follicle pool and thus acting as a useful marker of ovarian reserve. Anti-Müllerian hormone seems to be the best endocrine marker for assessing the age-related decline of the ovarian pool in healthy women; thus, it has a potential ability to predict future reproductive lifespan. The most established role for AMH measurements is before in vitro fertilization is initiated, because AMH can be predictive of the ovarian response, namely poor and hyper-responses. However, recent research has also highlighted the use of AMH in a variety of ovarian pathological conditions, including polycystic ovary syndrome, granulosa cell tumors and premature ovarian failure. A new commercial enzyme-linked immunosorbent assay for measuring AMH levels has been developed, making results from different studies more comparable. Nevertheless, widespread clinical application awaits an international standard for AMH, so that results using future assays can be reliably compared.

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Anti-Müllerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment.

Christien Weenen, Joop Laven, Anne Von Bergh … (2004)

Anti-Müllerian hormone (AMH) is a member of the transforming growth factor-beta superfamily, which plays an important role in both ovarian primordial follicle recruitment and dominant follicle selection in mice. However, the role of AMH in folliculogenesis in humans has not been investigated in detail. In the present study, AMH expression was assessed using immunohistochemistry in ovarian sections, obtained from healthy regularly cycling women. To this end, a novel monoclonal antibody to human AMH was developed. AMH expression was not observed in primordial follicles, whereas 74% of the primary follicles showed at least a weak signal in the granulosa cells. The highest level of AMH expression was present in the granulosa cells of secondary, preantral and small antral follicles

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Antimüllerian hormone serum levels: a putative marker for ovarian aging.

E. de Beaumont, J. Laven, Axel P N Themmen … (2002)

To investigate whether serum concentrations of antimüllerian hormone may be used as a marker for ovarian aging. Longitudinal observational study. Academic research center. Forty-one normo-ovulatory premenopausal women and 13 healthy postmenopausal women. Concentrations of serum antimüllerian hormone (assessed on two occasions 2.6 +/- 1.7 years apart), FSH, inhibin B, and estradiol and number of ovarian follicles on ultrasonography. Concentrations of antimüllerian hormone decreased significantly over time (median value, 2.1 microg/L [range, 0.1-7.4 microg/L] at visit 1 vs. 1.3 microg/L [range, 0.0-5.0 microg/L] at visit 2), whereas the number of antral follicles and levels of FSH and inhibin B did not change. During visits 1 and 2, concentrations of antimüllerian hormone correlated with age (r = -.40, P=.01 and r = -.57, P<.001, respectively); number of antral follicles (r =.66, P<.001 and r =.71, P<.001); and, to a lesser extent, with FSH level (r = -.29, P=.07 and r = -.37, P<.05) but not with inhibin B levels. Serum concentrations of antimüllerian hormone decreased over time in young normo-ovulatory women, whereas other markers associated with ovarian aging did not change. Concentrations of antimüllerian hormone correlate with the number of antral follicles and age and less strongly with FSH level. Concentrations of antimüllerian hormone may be a novel marker for ovarian aging.

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Elevated serum level of anti-mullerian hormone in patients with polycystic ovary syndrome: relationship to the ovarian follicle excess and to the follicular arrest.

Yann Robert, Christine Cortet-Rudelli, Sophie Jonard … (2003)

The serum level of anti-Mullerian hormone (AMH), a product from granulosa cells involved in follicle growth, has been shown to correlate tightly with the small antral follicle number (FN) at ultrasonography (U/S) in women who do not have polycystic ovary syndrome (PCOS). Because PCOS is associated with a 2- to 3-fold increase in growing FN, we investigated whether an increased AMH serum level correlates to other hormonal and/or U/S features of PCOS. Serum AMH has been assayed in 104 women (59 symptomatic PCOS, 45 controls) between d 2 and 7 after the last either spontaneous or progestin-induced (in PCOS) menstrual period. Mean serum AMH level was markedly increased in the PCOS group (47.1 +/- 22.9 vs. 20.8 +/- 11.6 pmol/liter in controls; P < 0.0001), an increase in the same order of magnitude as the one of the FN in the 2- to 5-mm range at U/S (12.8 +/- 8.3 vs. 4.8 +/- 1.9; P < 0.0001, respectively). The ratio AMH/FN was similar between the two groups (4.8 +/- 3.4 vs. 4.8 +/- 2.9; P = 0.55). By simple regression, both in PCOS and controls, the AMH level was positively related to the 2- to 5-mm FN at U/S (P < 0.0001 and P < 0.03, respectively), but not to the 6- to 9-mm FN, and was negatively correlated to the serum FSH level (P < 0.02 and P < 0.04, respectively). AMH was also positively related to the serum testosterone and androstenedione levels, in PCOS exclusively (P < 0.0005 and <0.002, respectively). No relationship was found between AMH and age, serum estradiol, inhibin B, and LH levels in both groups. After multiple regression only the 2- to 5-mm FN remained significantly related to AMH in PCOS whereas testosterone, androstenedione, and FSH were no longer. In conclusion, the assay of the serum AMH may represent an important breakthrough in the diagnosis and in the understanding of PCOS. Our data suggest that the increase of AMH serum level in PCOS is the consequence of the androgen-induced excess in small antral FN and that each follicle produces a normal amount of AMH. We hypothesize that an increased AMH tone within the cohort could be involved in the follicular arrest of PCOS, by interacting negatively with FSH at the time of selection.