Could AMH Predict Fertility Treatment Success?

Antimüllerian Hormone as Predictor of Implantation and Clinical Pregnancy After Assisted Conception: A Systematic Review and Meta-Analysis

Tal R, Tal O, Seifer BJ, Seifer DB
Fertil Steril. 2015;103:119-130

Background

The assessment of ovarian reserve is an important part of infertility evaluation. Ovarian reserve testing can be performed by various tests.^[1] Age itself is an important marker as it is well known that as a woman progresses through her reproductive years, the number of eggs in her ovaries declines until it reaches such a low number that folliculogenesis can no longer be initiated, and she enters menopause.

In addition to age, ovarian reserve can be tested by multiple laboratory markers. Commonly, estradiol and follicle-stimulating hormone levels are measured at the beginning of the cycle, but early-cycle estradiol alone, inhibin B, and anti-Müllerian hormone (AMH) can also be used. There are dynamic tests that evaluate hormonal changes in response to clomiphene, gonadotropin-releasing hormone agonist, or gonadotropin. Ultrasound evaluation of the antral follicle count, ovarian volume, or Doppler indices can also be used. Finally, the combination of these tests may provide an even better estimate of the size of the follicle pool.

Why do we do such testing? The information obtained could be useful during counseling. The use of fertility treatment, the type of treatment, and its method can depend on these results.

It would be great, however, if we could predict treatment success based on these values. That way, we could guide patients to select the most appropriate treatment. AMH is considered one of the best markers of ovarian function. However, it has only been weakly associated with pregnancy or live-birth rates following in vitro fertilization (IVF) treatment. This meta-analysis tried to assess the capacity of AMH to predict implantation and clinical pregnancy rates.

Summary

The analysis is based on the results of 19 mostly prospective cohort studies. The authors separately analyzed the results of studies reporting implantation or clinical pregnancy rate as their primary outcome. Furthermore, they performed a separate analysis for women with polycystic ovary syndrome (PCOS), women with diminished ovarian reserve, and women with unspecified ovarian reserve.

Based on the results of 1591 women undergoing 1736 cycles, the authors found a modest association between AMH and implantation rate (odds ratio [OR]: 1.83; 95% confidence interval [CI], 1.49-2.25; sensitivity: 52.2%; specificity: 61.1%). The studies that used clinical pregnancy as outcome involved 5931 cycles altogether (poor ovarian reserve: 615; PCOS: 414; unspecified reserve: 4324). The predictive ability of AMH for clinical pregnancy was modest among women with unspecified ovarian reserve (OR: 2.1; 95% CI, 1.82-2.41; sensitivity: 44%; specificity: 66.5%). The association was somewhat stronger among women with poor ovarian reserve (OR: 3.96; 95% CI, 2.57-6.1; sensitivity: 69.9%; specificity: 64.7%). AMH was, however, not predictive of clinical outcome among women with PCOS (OR: 1.18; 95% CI, 0.53-2.62; sensitivity: 49.5%; specificity: 42.7%).

The authors concluded that AMH shows some association with clinical outcome, but the association is weak.

Viewpoint

AMH is a protein, a member of the transforming growth factor beta family. It is produced by the preantral and small antral follicles; therefore, its value correlates well with their number. Its secretion is independent of the day of the cycle and of hormonal influences; thus, it can be used easily in an everyday clinical setting. Various commercially available tests can be used to measure AMH.

Over the years, it has become the preferred test to assess ovarian reserve. It predicts poor response and hyperresponse with high accuracy, especially when combined with ultrasound assessment of the antral follicle count.^[1] Values under 1.1 ng/mL are consistent with an expected poor response, and values in excess of 3.5 ng/mL are associated with an increased risk for hyperresponse.^[2]

The measurement of AMH prior to treatment can be used to categorize the patient as a poor responder, normal responder, or hyperresponder. This categorization can then help the selection of the right stimulation protocol and gonadotropin dose. Several groups proposed nomograms, including AMH, for this purpose.^[3,4]

This kind of assessment, however, will only help us safely collect the "right" amount of eggs. Ideally, one aims for 10-15 eggs during IVF.^[5,6] There are multiple further steps that follow the retrieval and are required to achieve success. The eggs need to be fertilized, the embryos need to be cultured for 3-5 days, and one or two embryos that are supposed to have the highest implantation potential need to be identified and transferred. Finally, the endometrium has to be receptive to allow successful implantation. Can AMH predict these processes?

The answer, according to this meta-analysis, is that it cannot. AMH is, at best, only weakly associated with clinical outcome. One of the most important predictors for success is age. It is known that with age not just the quantity but the quality of the eggs declines. Poor-quality eggs will result in abnormal, poor-quality embryos that will be unable to attach to the endometrium and progress into a normally developing pregnancy.

Ovarian reserve testing will still remain an important part of infertility evaluation, and AMH is one of the best markers that can be used for this. AMH, however, should not be used to exclude patients from treatment unless there are multiple factors in addition to the low ovarian reserve that compromise the patient's chance of conceiving.

Abstract

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