Anti-Müllerian Hormone (AMH) and Fertility Assessment

Anti-Müllerian hormone (AMH), also known as Müllerian Inhibiting Substance (MIS), is a glycoprotein that belongs to the transforming growth factor beta family. First discovered in 1947 by Alfred Jost, it was later understood that AMH regulates sex differentiation in embryos/fetuses. In females, AMH is produced in small amounts by ovarian granulosa cells after birth, until menopause, and then becomes undetectable.

Clinicians have been using AMH in treatments related to reproductive health for over 20 years. High-quality diagnostic assays have come on in leaps and bounds over that time, continuing to provide precise insights to support clinical decisions made in the areas of reproductive aging, fertility and pregnancy monitoring.

Fertility overview

Women are born with their maximum number of eggs, which decline over time at varying rates until the menopause, when their eggs are fully depleted. Ovarian reserve refers to the supply of eggs at any given time and is closely associated with reproductive potential. Not all women have the same number of follicles, and their decline can be influenced by lifestyle and other factors. Both the decline in the number of eggs and the rate at which they decline are good predictors of ovarian reserve and, therefore, a woman's potential fertility.

The development of effective, readily available contraception has given women more control over their reproductive lives, making it possible to delay having children. However, this factor makes them more likely to run the risk of age-related infertility, as a marked drop in fertility is experienced 10-15 years before the menopause. As a result, women aged over 30 are increasingly seeking assisted reproductive technologies to help them conceive.¹

This is evident in statistical data. The mean age of women in the European Union giving birth to their first child, for example, has gradually increased from 28.8 years in 2013 to 29.4 years in 2019. A clear trend of mothers having children later in life in the UK was registered between 1991 and 2019, with the average age of mothers increasing from  27.7 in 1991 to 30.7 by 2019. 

Controlled ovarian stimulation

Traditionally, ovarian reserve was predicted by measuring the antral follicle count (AFC) via ultrasound. AFC and AMH are well correlated because AMH concentrations in adult women reflect the number of small follicles entering the growth phase of their life cycle, which reflects the number of primordial follicles that remain in the ovary. Both are effective in predicting pregnancy rates and the number of oocytes collected following controlled ovarian stimulation (COS). The main advantage of AMH is its very low cycle variability and that it is a simple blood test without the need for subjective interpretation.²

Women with normal AMH values tend to respond well to ovarian stimulation, which leads to more eggs being retrieved. In general, having more eggs improves success rates because clinicians are more likely to have at least one high-quality embryo, which can then be transferred back to the uterus. Women with a high level of AMH risk ovarian hyperstimulation syndrome (OHSS), a potentially life-threatening condition.³   Women with low AMH, however, are unlikely to respond well to in vitro fertilization (IVF) and should therefore be offered counselling or alternative treatment options.

Knowing a woman's AMH values can reveal whether she will respond to IVF, or not, and can be used for controlled ovarian stimulation (COS). Access AMH Advanced has determined that a cutoff of 6.64 pmol/L may predict poor ovarian response as defined by retrieval of ≤ 4 oocytes retrieved from women undergoing controlled ovarian stimulation. Should women have AMH values higher than the cutoff, it is likely that more than 4 oocytes will be retrieved during controlled ovarian stimulation.

Access AMH Advanced may also help physicians identify women at risk of hyperstimulation when undergoing COS by providing a cutoff AMH value of > 12.64 pmol/L which corresponds to an antral follicle count (AFC) value > 15 oocytes retrieved, indicating high ovarian reserve. This helps physicians make better decisions earlier on.

Access AMH Advanced brings additional benefits

Beckman Coulter is the market innovator of AMH assays, having introduced the first ELISA AMH assay and later automated AMH tests. The introduction of the first commercially available AMH assay facilitated valuable AMH research, while the evolution to automation of the assay has allowed adoption of AMH testing into routine clinical use. Beckman Coulter’s AMH assays have played an important role in supporting, participating and devising many of the studies that led to establishing the acceptance of AMH testing in the field of fertility.

The Beckman Coulter Access AMH Advanced assay features the antibody pair originally developed by Professor Nigel Groome,⁴ with the company retaining exclusive patent rights to these antibodies. Beckman Coulter also holds the sole patent license for use of AMH in the assessment of ovarian reserve.

The Access AMH Advanced assay will guide IVF treatment to avoid dangerous hyperstimulation with a cutoff value for ovarian reserve, empower physicians to make better diagnostic decisions early in the process with the help of a cutoff value for poor ovarian response and enable more personalized, accurate dosing of Ferring’s human rFSH (follitropin delta) with companion diagnostic claim.

As women seek more informed lifestyle decisions in the future, AMH may have a role to play in assessing reproductive status in the longer term. As new services such as egg freezing and egg donation become more readily available and women continue to delay conception, AMH will be a vital tool in assessing their next steps on their fertility journey.

References: 

1. Balasch J. Investigation of the infertile couple: Investigation of the infertile couple in the era of assisted reproductive technology: a time for reappraisal. Hum Reprod. 2000;15(11):2251-2257. doi: 10.1093/humrep/15.11.2251
2. Kovacs G ed. How to improve your ART success: an evidence-based review of adjuncts to IVF. Cambridge: Cambridge University Press, 2011.
3. Baker VL, Gracia C, Glassner MJ, et al. Multicenter evaluation of the Access AMH antimüllerian hormone assay for the prediction of antral follicle count and poor ovarian response to controlled ovarian stimulation. Fertil Steri. 2018;110(3):506-513.e3. doi: 10.1016/j.fertnstert.2018.03.031
4. Weenen C. Anti-Mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod. 2004;10(2):77-83. doi: 10.1093/molehr/gah015