Impact of cancer treatment on fertility in female childhood and adolescent cancer survivors: a systematic review and meta-analysis

BACKGROUND: With the improvement of the survival rate of children with caners, increasing attention is being paid to their long-term quality of life, especially the fertility concerns of female survivors. Here, we assess the impact of cancer treatment on the fertility in female childhood and adolescent cancer survivors. METHODS: To identify relevant studies, a systematic literature search was performed in PubMed, Medline, Embase, and other databases. The search focused on treatment-related fertility impairment in pediatric or adolescent cancer patients and included cohort, case–control, and cross-sectional studies. Only articles published in Chinese or English, spanning from database inception to July 29, 2024, were retrieved. Review Manager 5.4 software was employed for the meta-analysis. RESULTS: Following screening of 945 records, 20 studies met the inclusion criteria, yielding a final cohort of 7,217 patients.The synthesis results indicated that the impaired risk of fertility in female childhood and adolescent cancer survivors was significantly increased versus the population without cancer treatment (OR: 5.55, 95% CI: 2.38–12.89, P < 0.001). The survivors with hematologic malignancies had an elevated risk of impaired fertility (OR: 3.98, 95% CI: 1.18–13.45, P < 0.05). And, the risk in the survivors was significantly higher with alkylating agent doses greater than 8000 mg/m2 (OR: 8.29, 95% CI: 3.16–21.77, P < 0.001), Ovaries within the radiation field (OR: 43.40, 95% CI: 26.08–72.22, P < 0.001), and stem cell transplantation (SCT) (OR: 16.07, 95% CI: 8.00–32.29, P < 0.001). Furthermore, the survivors who received cancer treatment after puberty had the elevated risk (OR: 1.88, 95% CI: 1.23–2.88, P < 0.001). In contrast, treatment before puberty was not associated with a significantly increased risk in this cohort. CONCLUSIONS: For female childhood cancer patients undergoing cancer treatment, alkylating agents, ovarian exposure to radiation therapy, and SCT all elevated the impaired risk of fertility. Therefore, effective fertility preservation measures should be proactively provided to this population to mitigate the fertility damage associated with cancer treatments and protect the fertility function of female childhood cancer survivors. TRIAL REGISTRATION: PROSPERO registration number: CRD420250655189.