Serum anti-Müllerian hormone as a marker of ovarian reserve after cancer treatment and/or hematopoietic stem cell transplantation in childhood: proposal for a systematic approach to gonadal assessment

Objective Female patients treated with alkylating agents in childhood are at risk for ovarian impairment. We aimed at describing the pattern of residual ovarian function in a cohort of survivors of hematological malignancies and/or hematopoietic stem cell transplantation (HSCT) and assessing the relationship between Cyclophosphamide Equivalent Dose (CED) and Anti-Müllerian Hormone (AMH). Design and methods Gonadal health was clinically and biochemically assessed in 124 post-menarchal survivors who underwent treatment for pediatric hematological malignancies and/or HSCT between 1992 and 2019. Results Overt "premature ovarian insufficiency" (POI) was detected in 72.1% and 3.7% of transplanted and non-transplanted patients, respectively; milder "diminished ovarian reserve" (DOR) in 16.3% and 22.2%. In non-transplanted patients, increasing CED values were associated with lower AMH-SDS (p 0.04), with the threshold of 7200 g/m2 being the best discriminator between DOR/POI and normal ovarian function (AUC: 0.75 on ROC analysis) and with an observed decrease of 0.14 AMH-SDS for each CED increase of 1 gr/m2. In addition, age at diagnosis ≥10 years played a detrimental role on ovarian reserve (p 0.003). In the HSCT group, irradiation was associated with a statistically significant reduction in AMH-SDS (p 0.04). Conclusions In non-transplanted patients, CED ≥ 7200 mg/m2 was associated with a DOR, while younger age at diagnosis played a protective role on ovarian reserve. As a result of the data collected, we propose a systematic algorithm to assess iatrogenic gonadal impairment in young female patients exposed to chemo-radiotherapy in childhood for hematological disorders.