Yano Maher Jacqueline C, Kumnick Allison, Sinaii Ninet, Su H Irene, Cameron Katherine E, George Sobenna A, Gracia Clarissa, Meacham Lillian R, Gomez-Lobo Veronica
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.
J Adolesc Young Adult Oncol. 2025 Apr;14(2):160-171. doi: 10.1089/jayao.2024.0093. Epub 2024 Sep 23.
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. 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. 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 ( = 0.70). 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.
女性儿童癌症幸存者（CCSs）因性腺毒性化疗/放疗而有不孕风险。抗苗勒管激素（AMH）有助于评估卵巢储备功能，2020年生育力保护儿科倡议网络（O-PIN）风险分层用于指导性腺功能障碍/不孕风险。本研究分析了癌症治疗后AMH水平如何随年龄变化，以及AMH与O-PIN风险水平和临床结局之间的相关性。进行了文献综述和个体患者数据的荟萃分析。纳入癌症诊断时年龄为0至20岁且有治疗后AMH值的女性。通过O-PIN风险分层、诊断时年龄、环磷酰胺等效剂量（CED）和造血干细胞移植（HSCT）比较AMH结果。多变量随机效应混合模型将AMH与卵巢储备功能减退（DOR）、卵巢早衰（POI）和妊娠相关联。在13项研究中的608例CCSs中，诊断时的中位年龄（岁）为12.0（四分位间距[IQR]5.2 - 16.2），测量AMH时为21.1（IQR 17.1 - 30.0）。AMH值随治疗后的时间增加而升高，且与O-PIN风险水平相关。接受HSCT的患者无论CED如何，AMH水平都非常低/检测不到；按CED分层时，青春期前后或年龄较大时接受治疗的患者AMH水平较低。54%（34/63）接受激素替代治疗的POI患者AMH可检测到。妊娠与性腺毒性风险水平不相关（P = 0.70）。本研究支持使用O-PIN风险分层系统来评估CCSs中DOR的风险及其按青春期状态分类。即使接受了最高风险的治疗，AMH水平可能会随时间恢复。这些发现可能有助于在癌症患者治疗前后提供咨询。
