| Autor: |
Yano Maher JC; Eunice Kennedy Shriver National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA., Kumnick A; Eunice Kennedy Shriver National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.; Department of Obstetrics and Gynecology, Medstar Washington Hospital Center, Washington, District of Columbia, USA., Sinaii N; Biostatistics and Clinical Epidemiology Service, National Institutes of Health Clinical Center, Bethesda, Maryland, USA., Su HI; Department of Obstetrics, Gynecology and Reproductive Sciences and Moores Cancer Center, University of California, San Diego, La Jolla, California, USA., Cameron KE; Division of Reproductive Endocrinology and Infertility, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.; Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, USA., George SA; Division of Endocrinology, Department of Pediatrics, Emory University, Atlanta, Georgia, USA., Gracia C; Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Meacham LR; Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta and Division of Pediatric Hematology/Oncology, Emory University, Atlanta, Georgia, USA., Gomez-Lobo V; Eunice Kennedy Shriver National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA. |
| Abstrakt: |
Purpose: Female childhood cancer survivors (CCSs) risk infertility due to gonadotoxic chemotherapy/radiation. Anti-Müllerian hormone (AMH) helps evaluate ovarian reserve, and the 2020 Oncofertility Pediatric Initiative Network (O-PIN) risk stratification is utilized to counsel risk of gonadal dysfunction/infertility. This study analyzed how AMH levels after cancer treatment differ with age and correlate AMH with O-PIN risk level and clinical outcomes. Methods: A literature review and mega-analysis of individual patient data were performed. Females ages 0-20 years at the time of cancer diagnosis with AMH values post-treatment were included. AMH outcomes were compared by O-PIN risk stratification, age at diagnosis, cyclophosphamide equivalent dose (CED), and hematopoietic stem cell transplant (HSCT). Multivariable random effects mixed models correlated AMH with diminished ovarian reserve (DOR), premature ovarian insufficiency (POI), and pregnancy. Results: In 13 studies with 608 CCSs, the median age (years) at diagnosis was 12.0 (interquartile range [IQR] 5.2-16.2) and 21.1 (IQR 17.1-30.0) at AMH measurement. AMH values were higher with time since treatment and correlated with the O-PIN risk level. Patients with HSCT had very low/undetectable AMH levels regardless of CED; when stratified by CED, AMH levels were lower if treated peripubertally or older. AMH was detectable in 54% (34/63) of patients with POI on hormone replacement. Pregnancy did not correspond to the gonadotoxicity risk level ( p = 0.70). Conclusion: This study supports utilizing the O-PIN risk stratification system in estimating risk of DOR in CCSs and its categorization by pubertal status. AMH levels may return over time even after receiving the highest risk therapy. These findings may help counsel cancer patients pre- and post-therapy. |
