Serum Anti-Müllerian Hormone Levels and Risk of Premature Ovarian Insufficiency in Female Childhood Cancer Survivors: Systematic Review and Network Meta-Analysis.

Abstract

Simple SummaryOver the last twenty years, innovations in the treatment of childhood cancer have increased survival rates. However, female childhood cancer survivors (CCS) are prone to late reproductive aftereffects, including premature ovarian insufficiency (POI). Nonetheless, patients might experience different side effects on fertility according to the type of diagnosed cancer and subsequent treatment. Anti-Müllerian hormone (AMH) is currently used in reproductive medicine to screen for impaired ovarian reserves. However, it does not represent the gold standard in oncofertility. In this systematic review and network meta-analysis of age-matched case–control studies, we evaluate the role of AMH for ovarian reserve screening according to the type of childhood cancer and determined which group of survivors are more prone to POI by means of direct and indirect comparisons among the CCS cohorts.Background: Female childhood cancer survivors (CCS) might have impaired ovarian reserves, especially after alkylating agents or radiotherapy. The purpose of this systematic review and network meta-analysis is to evaluate the role of serum anti-Müllerian hormone (AMH) for ovarian reserve screening and the risk of premature ovarian insufficiency (POI) according to the subtype of childhood cancer. (2) Methods: PRISMA-NMA guidelines were followed. We carried out a network meta-analysis based on a random effects model for mixed multiple treatment comparisons to rank childhood cancers effects on fertility by surface under the cumulative ranking curve (SUCRA). Studies were selected only if they had an age-matched control group. Quality assessment was performed using Newcastle–Ottawa Scale. The co-primary outcomes were mean AMH levels and the incidence of POI. (3) Results: A total of 8 studies (1303 participants) were included. Women treated for a neuroblastoma during infancy were more likely to be ranked first for impaired AMH levels (SUCRA = 65.4%), followed by mixed CCS (SUCRA = 29.6%). The greatest rates of POI were found in neuroblastoma survivors (SUCRA = 42.5%), followed by acute lymphoid leukemia (SUCRA = 26.3%) or any other neoplasia (SUCR A = 20.5%). (4) Conclusions: AMH represents a trustworthy approach for ovarian reserve screening. Direct and indirect comparisons found no differences in mean AMH levels and POI risk between subtypes of CCS and healthy controls. SUCRA analysis showed that female neuroblastoma survivors were more at risk for reduced serum AMH levels and increased risk of POI.