Anti-Müllerian Hormone and Ovarian Reserve: Update on Assessing Ovarian Function

Abstract

Context: Anti-müllerian hormone (AMH) is produced by granulosa cells of small, growing follicles in the ovary. Serum AMH levels strongly correlate with the number of growing follicles, and therefore AMH has received increasing attention as a marker for ovarian reserve. This review summarizes recent findings and limitations in the application of serum AMH in ovarian reserve assessment.

Evidence acquisition: A PubMed search was conducted to find recent literature on the measurements and use of serum AMH as a marker for ovarian reserve.

Evidence synthesis: Serum AMH levels are measured to assess the "functional ovarian reserve," a term that is preferred over "ovarian reserve," since AMH levels reflect the pool of growing follicles that potentially can ovulate. Serum AMH levels are used in individualized follicle-stimulating hormone dosing protocols and may predict the risk of poor response or ovarian hyperstimulation syndrome but has limited value in predicting ongoing pregnancy. Serum AMH levels are studied to predict natural or disease-related age of menopause. Studies show that the age-dependent decline rates of AMH vary among women. The generalized implementation of serum AMH measurement has also led to an increase in diagnostic assays, including automated assays. However, direct comparison of results remains problematic.

Conclusion: Serum AMH remains the preferred ovarian reserve marker. However, the lack of an international standard for AMH limits comparison between AMH assays. Furthermore, little is known about endogenous and exogenous factors that influence serum AMH levels, which limits proper interpretation of AMH values in a clinical setting.

Keywords: AMH; AMH assays; fertility prediction; functional ovarian reserve; menopause; ovarian reserve.

Figure 1.

Anti-müllerian hormone expression and concentration in relation to folliculogenesis and ovarian reserve. (A) Anti-müllerian hormone (AMH) expression increases from the secondary stage onward until the small antral follicle stage. In preovulatory follicles, AMH is only expressed in cumulus granulosa cells surrounding the oocyte (dark pink layer). (B) With increasing age, the functional ovarian reserve decreases as a result of exhaustion of the primordial follicle pool. This leads to a decrease in the number of small antral follicles and consequently to a decrease in serum AMH levels, reaching undetectable levels at menopause. Figure created with Biorender.

Figure 2.

Potential anti-müllerian hormone (AMH) isoforms and AMH assay characteristics. (A) Illustration of the possible AMH isoforms present in the circulation. The black dotted lines represent the cleavage sites at amino acids 229 and 451, respectively. The N-terminal proregion is shown in green, and the C-terminal mature region is shown in red. (B) Depicts the characteristics of the different AMH assays. The capture antibody is shown in purple, and the detector antibody is shown in orange. The assay type, limit of detection, and the measurement range of the different AMH assays are shown in the table below. Figure created with Biorender.