Oncologic Safety of Assisted Reproductive Technologies: Implications for Breast, Ovarian, and Endometrial Cancer

Abstract Introduction The use of assisted reproductive technologies (ART), including in vitro fertilization and ovulation induction, has increased substantially over the past several decades in parallel with rising infertility rates and delayed childbearing. Given the supraphysiologic hormonal exposures associated with many ART protocols, concerns have been raised regarding potential long-term risks of hormone-sensitive malignancies, particularly breast, ovarian, and endometrial cancers. Purpose This narrative review aims to synthesize current epidemiologic and mechanistic evidence on the relationship between ART and the risk of breast, ovarian, and endometrial cancer, to contextualize findings within baseline infertility-related risk factors, and to identify key methodological challenges and knowledge gaps relevant to clinical counseling and future research. Materials and methods A narrative review of prospective cohort studies, population-based registries, systematic reviews, and meta-analyses was conducted, focusing on long-term cancer outcomes following ART exposure. Evidence was interpreted in light of underlying infertility diagnoses, reproductive history, specific fertility drugs and protocols, duration of follow-up, and guidance from professional societies such as the American Society for Reproductive Medicine. Results Across contemporary studies, ART exposure is not associated with a clinically meaningful increase in breast or endometrial cancer risk after adjustment for confounding factors. Breast cancer risk does not appear to vary by fertility drug type, number of cycles, or protocol intensity, including among BRCA mutation carriers, although data in high-risk subgroups remain limited. For ovarian cancer, a modestly increased risk—particularly for borderline ovarian tumors—has been observed, largely confined to women with preexisting risk factors such as endometriosis, nulliparity, or prolonged infertility. Evidence suggests that infertility itself, rather than ART exposure, accounts for much of the observed excess risk. Significant methodological challenges, including confounding by indication, exposure misclassification, and insufficient long-term follow-up, limit definitive causal inference. Keywords: Assisted reproductive technologies; in vitro fertilization; breast cancer; ovarian cancer; endometrial cancer; infertility; fertility drugs; long-term cancer risk; hormone-sensitive malignancies