How Immunotherapy Is Redefining Oncofertility in Colorectal Cancer

Early-onset colorectal cancer is increasing, making reproductive health an increasingly relevant survivorship issue. Immune checkpoint inhibitors have altered the management of deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) colorectal cancer, but their oncofertility implications remain insufficiently defined. We performed a focused narrative review, structured in line with the SANRA framework. PubMed/MEDLINE, international oncology and reproductive-medicine guidelines, colorectal cancer clinical practice guidelines and regulatory product information were searched up to 8 May 2026. Evidence was prioritized according to relevance to colorectal cancer treatment pathways, reproductive and sexual health, immune checkpoint inhibitor-related ovarian and endocrine effects, pregnancy and lactation safety, and fertility preservation counselling. Colorectal cancer should not be considered a single reproductive-risk scenario. Colon and rectal cancer differ anatomically, therapeutically and functionally; disease stage affects the window for fertility preservation; and dMMR/MSI-H status determines where immunotherapy is clinically relevant. Direct reproductive effects of immune checkpoint inhibitors remain uncertain and are supported mainly by biological plausibility, endocrine toxicity data, limited non-CRC ovarian-reserve data and pharmacovigilance. Conversely, indirect effects may be clinically important when immunotherapy reduces exposure to pelvic radiotherapy or radical surgery in selected dMMR/MSI-H rectal cancer patients. Counselling should be early, individualized and pathway-based.