There is ample evidence that antimüllerian hormone (AMH) is a poor predictor of unassisted conception in the general population and among women with infertility (1Steiner A.Z. Pritchard D. Stanczyk F.Z. Kesner J.S. Meadows J.W. Herring A.H. et al.Association between biomarkers of ovarian reserve and infertility among older reproductive age women.). In addition, data suggest that AMH is a relatively poor predictor of pregnancy and live birth following a single in vitro fertilization (IVF) cycle. However, there is debate regarding the value of AMH in the prediction of cumulative probability of pregnancy following IVF. Leijdekkers et al. (2Leijdekkers J.A. Eijkemans M.J.C. van Tilborg T.C. Oudshoorn S.C. McLernon D.J. Bhattacharya S. et al.Predicting the cumulative chance of live birth over multiple complete cycles of in vitro fertilization: an external validation study.) found that inclusion of AMH along with other markers of ovarian reserve slightly improved prediction models for cumulative probability of pregnancy following IVF.In this retrospective cohort analysis, Vagios et al. (3

Vagios S, Hsu JY, Sacha CR, Dimitriadis I, Christou G, James KE, et al. Pretreatment antimüllerian hormone levels and outcomes of ovarian stimulation with gonadotropins/intrauterine insemination cycles. Fertil Steril. In press.

) sought to determine the association between pretreatment serum AMH levels and cumulative incidence of pregnancy and miscarriage following gonadotropin stimulation followed by intrauterine insemination (IUI). They analyzed outcomes from 1,861 gonadotropin IUI cycles in 821 women. Women with low AMH (

In putting this article into context with the other literature on AMH and fertility, one must consider the study population and design. Women with diminished ovarian reserve were overly represented in this cohort with 25% of women having diminished ovarian reserve. This is a retrospective analysis of clinical data spanning many years (2007–2019). During this time period, practice patterns have changed, including the use of gonadotropins, measurement of AMH, and even the AMH assay itself. Of the 5,639 cycles that were eligible for inclusion in the study, only 1,861 cycles had an associated AMH level. Most likely, these were women who received care more recently. The AMH assay would have varied during the study period.

One can assume that the indication for gonadotropin therapy differed with AMH level. Women with high AMH levels were likely anovulatory, receiving gonadotropins for ovulation induction. This is evidenced by lower cumulative gonadotropin dosages and fewer follicles on the day of trigger. One can postulate that this was a better prognosis group (their only issue being anovulation). Another indicator that management or prognosis inherently differed between the groups was the higher dropout rate among the women with high AMH values. Women, with high AMH values, who did not conceive, participated in fewer gonadotropin cycles. One can postulate that they proceeded with IVF. Women with low AMH levels were more likely to continue with gonadotropin/IUI cycles. The success rate of any treatment is known to decrease over time. Given this informative dropout, the hazard ratios and cumulative pregnancy rates at six cycles should be interpreted with caution.

The data on low AMH and risk of miscarriage are interesting. Although most of their analyses did not find a significant association between AMH and miscarriage after adjusting for age, women with AMH values 4Schumacher B.M.L. Jukic A.M.Z. Steiner A.Z. Antimüllerian hormone as a risk factor for miscarriage in naturally conceived pregnancies.).What do we take home from this study? How do we use this information? Given the lower success rate, higher multiple pregnancy rate, and higher doses and associated costs with gonadotropins, women with low AMH should be prescribed oral agents for ovarian stimulation with IUI. This study provides further evidence that the American Society for Reproductive Medicine Practice Committee opinion recommending ovarian stimulation with oral agents in women with unexplained infertility should also apply to women with diminished ovarian reserve (5Practice Committee of the American Society for Reproductive Medicine
Evidence-based treatments for couples with unexplained infertility: a guideline.). Further research is needed to determine the etiology of the increased risk of miscarriage among women with very low AMH.ReferencesSteiner A.Z. Pritchard D. Stanczyk F.Z. Kesner J.S. Meadows J.W. Herring A.H. et al.

Association between biomarkers of ovarian reserve and infertility among older reproductive age women.

J Am Med Assoc. 318: 1358-1366Leijdekkers J.A. Eijkemans M.J.C. van Tilborg T.C. Oudshoorn S.C. McLernon D.J. Bhattacharya S. et al.

Predicting the cumulative chance of live birth over multiple complete cycles of in vitro fertilization: an external validation study.

Hum Reprod. 33: 1684-1695

Vagios S, Hsu JY, Sacha CR, Dimitriadis I, Christou G, James KE, et al. Pretreatment antimüllerian hormone levels and outcomes of ovarian stimulation with gonadotropins/intrauterine insemination cycles. Fertil Steril. In press.

Schumacher B.M.L. Jukic A.M.Z. Steiner A.Z.

Antimüllerian hormone as a risk factor for miscarriage in naturally conceived pregnancies.

Fertil Steril. 109: 1065-1071Practice Committee of the American Society for Reproductive Medicine

Evidence-based treatments for couples with unexplained infertility: a guideline.

Fertil Steril. 113: 305-322Article InfoPublication History

Published online: July 05, 2021

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DOI: https://doi.org/10.1016/j.fertnstert.2021.06.008

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©2021 American Society for Reproductive Medicine, Published by Elsevier Inc.

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