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

• Published in: European journal of endocrinology Vol. 185; no. 5; pp. 717 - 728
• Main Authors: Molinari, Silvia, Parissone, Francesca, Evasi, Veronica, De Lorenzo, Paola, Valsecchi, Maria Grazia, Cesaro, Simone, Fraschini, Donatella, Sangalli, Roberta, Cacace, Gianluca, Biondi, Andrea, Balduzzi, Adriana, Cattoni, Alessandro
• Format: Journal Article
• Language: English
• Published: England Bioscientifica Ltd 01.11.2021; Oxford University Press
• Subjects: Adolescent; Adult; Age Factors; Algorithms; Alkylating agents; Anti-Mullerian Hormone - blood; Antineoplastic Agents, Alkylating - administration & dosage; Antineoplastic Agents, Alkylating - therapeutic use; Biomarkers - blood; Cancer therapies; Child; Children; Clinical Study; Cohort Studies; Cyclophosphamide; Cyclophosphamide - administration & dosage; Cyclophosphamide - therapeutic use; Diagnosis; Female; Gonads - physiology; Health Status; Hematological diseases; Hematology; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Humans; Ovarian cancer; Ovarian Neoplasms - blood; Ovarian Neoplasms - physiopathology; Ovarian Neoplasms - radiotherapy; Ovarian Reserve; Ovaries; Patients; Pediatrics; Primary Ovarian Insufficiency - blood; Primary Ovarian Insufficiency - physiopathology; Radiation therapy; Radiotherapy - adverse effects; Reproductive status; Retrospective Studies; Statistical analysis; Stem cell transplantation; Young Adult
• ISSN: 0804-4643; 1479-683X
• DOI: 10.1530/EJE-21-0351

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 g/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.