Associations of anti-Müllerian hormone with primordial follicle density and in vitro maturation outcomes in girls with transfusion-dependent thalassemia undergoing fertility preservation.
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STUDY QUESTION: What is the association between serum anti-Müllerian hormone (AMH) levels, primordial follicle density (PFD), and ovarian tissue oocyte in vitro maturation (OTO -IVM) outcomes in pediatric and adolescent girls undergoing ovarian tissue cryopreservation (OTC) for fertility preservation (FP)? SUMMARY ANSWER: In pediatric and adolescent girls undergoing FP, serum AMH levels were not correlated with histological PFD, but were positively associated with oocyte yield and IVM outcomes, with each 1 ng/ml increase in AMH corresponding to a 14% increase in oocyte yield and a 3.50% increase in the maturation rate of IVM. WHAT IS KNOWN ALREADY: Serum AMH is an established biomarker of ovarian reserve in adults, reflecting the number of antral follicles. However, its value as a surrogate of the primordial follicle pool in pediatric and adolescent girls remains uncertain due to limited data. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study included 119 pediatric and adolescent girls with transfusion-dependent thalassemia (TDT) who underwent OTC between July 2021 and February 2025. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included 119 girls with TDT undergoing FP prior to hematopoietic stem cell transplantation. Preoperative serum AMH levels were measured. Ovarian cortical tissue was obtained for OTC, with a small fraction analyzed histologically for PFD. Immature oocytes retrieved from the tissue underwent IVM. Multivariate regression analyses evaluated associations between AMH, PFD, oocyte yield, and oocyte maturation rates. MAIN RESULTS AND THE ROLE OF CHANCE: Median preoperative AMH was 3.1 ng/ml (interquartile range: 1.9-4.4 ng/ml). AMH was not significantly associated with PFD (β = -0.04, 95% confidence interval [CI]: -0.12 to 0.03, P = 0.262). Higher AMH was positively correlated with increased oocyte yield (incidence rate ratio [IRR]: 1.14, 95% CI: 1.08-1.20; P < 0.001) and improved maturation rates of IVM (β = 3.50, 95% CI: 1.10-5.90; P = 0.005). Increasing age was associated with lower PFD (β = -0.07, 95% CI: -0.13 to -0.01, P = 0.032) and improved oocyte retrieval (IRR: 1.06, 95% CI: 1.02-1.11; P = 0.008) and maturation rates (β = 2.52, 95% CI: 0.54-4.51; P = 0.013). LIMITATIONS, REASONS FOR CAUTION: The study's limitations include the retrospective design and the disease-specific TDT cohort, limiting generalizability to other patient groups or healthy individuals. The dissociation between AMH and PFD indicates that AMH should be interpreted cautiously in FP counseling. As OTO-IVM remains experimental, AMH alone is insufficient to guide fertility preservation decisions, and OTC remains the most established option in pediatric patients. WIDER IMPLICATIONS OF THE FINDINGS: In children and adolescents with TDT, AMH is positively associated with IVM outcomes. It may be informative when counseling patients and families about the expected performance of OTO-IVM, particularly relevant in settings such as hematologic malignancies, where ovarian tissue transplantation may be contraindicated. However, AMH should neither be considered as a surrogate for the primordial follicle pool nor used to guide or alter clinical decision-making regarding fertility preservation strategies. Further prospective, multicenter studies are necessary to validate these findings. FUNDING: No external funding was received for this study. DISCLOSURES: The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.