Early Ovarian Reserve Depletion During Neoadjuvant Chemotherapy in Female Patients with Bone and Soft Tissue Sarcoma:...

Background/Objectives: Bone and soft tissue sarcomas frequently affect children, adolescents, and young adults, yet data on chemotherapy-related ovarian reserve decline in this population remain limited. We aimed to characterize anti-Müllerian hormone (AMH) dynamics during treatment and identify factors associated with post-neoadjuvant chemotherapy (post-NACT) ovarian reserve. Methods: We conducted a retrospective, single-center, longitudinal cohort study of 85 female patients with bone and soft tissue sarcoma who underwent serial serum AMH testing during treatment. In the paired cohort with complete baseline and post-NACT AMH measurements (n = 75), post-NACT AMH was defined as the value obtained at the surgery/post-neoadjuvant time point after completion of NACT. Log-transformed multivariable linear modeling and left-censored Tobit regression sensitivity analysis were performed. Results: Median AMH declined from 3.46 ng/mL at baseline to 0.39 ng/mL after the first NACT cycle and to 0.15 ng/mL after the second cycle, corresponding to reductions of 88.7% and 95.7%, respectively. In the paired cohort, median AMH declined from 3.81 ng/mL to 0.19 ng/mL post NACT, with a median absolute decline of 2.75 ng/mL and a median percent decline of 94.4%. In the log-transformed multivariable linear model, log(baseline AMH) was the sole independent predictor of log(post-NACT AMH) (β = 0.735, 95% CI 0.357-1.114, p < 0.001). In Tobit sensitivity analysis, 4 post-NACT AMH values were treated as left-censored at 0.05 ng/mL, and the pattern remained consistent. Conclusions: Ovarian reserve depletion in female sarcoma patients occurred predominantly within the first one to two cycles of NACT. These findings support early, individualized fertility preservation counseling in this population.