Limited Recommendations and Evidence for Timing and Frequency of Anti-Mullerian Hormone Screening in Female Pediatric Cancer Survivors: A Systematic Review from the Pediatric and Adolescent Committee of the Oncofertility Consortium

Abstract

Guidelines regarding the optimal use and timing of anti-Mullerian hormone (AMH) screening in childhood cancer survivors to evaluate for the risk of premature ovarian insufficiency or reduced fertility potential are lacking. We conducted a systematic review of the current evidence supporting AMH screening of female childhood cancer survivors with the overall objective to identify gaps in the literature needing further study, to allow for future data-driven recommendations. Search terms included "cancer, fertility, and anti-Mullerian hormone." We included original research articles that had ≥20 female childhood cancer survivors and excluded studies not including pediatric oncology survivors (≤18 years of age), did not include raw AMH values, were a mixed pediatric/young adult population which were minority pediatric, or did not separate pediatric from adult AMH data. In total, 17 studies (8 case-control, 5 cross-sectional, and 4 longitudinal prospective cohorts), encompassing 1106 total survivors met inclusion criteria and were further evaluated. Three studies evaluated the relationship of AMH to antral follicle count with generally good concordance. Four studies analyzed longitudinal changes in AMH with chemotherapy demonstrating that most patients will have an acute drop in AMH during therapy, and recovery of AMH over time is dependent on treatment intensity. No studies evaluated the optimal timing or interval of AMH testing. AMH correlates well with other markers of ovarian reserve, but there is insufficient data regarding the utility of AMH to predict the ability to conceive or timing of menopause. Optimal AMH screening initiation, duration, and intervals also require further study.

Keywords: AMH; anti-Mullerian hormone; antral follicle; childhood cancer; survivorship; systematic review.