{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:05:33Z","timestamp":1784174733281,"version":"3.55.0"},"reference-count":71,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Early-onset colorectal cancer is increasing, making reproductive health an increasingly relevant survivorship issue. While immune checkpoint inhibitors have altered the management of deficient mismatch repair\/microsatellite instability-high (dMMR\/MSI-H) colorectal cancer, their implications for reproductive-age women remain insufficiently defined. We performed a focused narrative review, structured in line with the SANRA framework, to clarify this specific clinical domain. Immunotherapy may reshape female oncofertility counseling through two distinct mechanisms: direct reproductive uncertainty, including established endocrine toxicities and hypothesized, but currently unproven, direct gonadal effects; and indirect pathway-modifying effects, such as the potential avoidance of pelvic radiotherapy or radical surgery in selected patients with locally advanced dMMR\/MSI-H rectal cancer. Anatomical organ preservation should not be automatically equated with functional fertility preservation. The key clinical message is that reproductive counseling should not be restricted to historically gonadotoxic chemotherapy. Instead, early multidisciplinary guidance should explicitly distinguish CRC-specific evidence from extrapolated or theoretical concerns, integrate fertility preservation strategies when clinically feasible, and address pelvic and sexual health, contraception, washout, endocrine follow-up, and future pregnancy planning. Until prospective CRC-specific reproductive data become available, immunotherapy should not be presented as either reproductively neutral or fertility-preserving.<\/jats:p>","DOI":"10.3390\/jcm15145549","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T03:34:23Z","timestamp":1784172863000},"page":"5549","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Female Oncofertility in Colorectal Cancer: Reproductive Uncertainties and Potential Benefits of Immunotherapy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5001-8271","authenticated-orcid":false,"given":"Michele","family":"Miscia","sequence":"first","affiliation":[{"name":"Division of Gynaecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4843-5412","authenticated-orcid":false,"given":"Linda","family":"Cipriani","sequence":"additional","affiliation":[{"name":"Division of Gynaecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Conci","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy"},{"name":"Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4439-5254","authenticated-orcid":false,"given":"Tommaso","family":"Violante","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy"},{"name":"Surgery of the Alimentary Tract, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Notarangelo","sequence":"additional","affiliation":[{"name":"Division of Gynaecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Vicenti","sequence":"additional","affiliation":[{"name":"Division of Gynaecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Cortese","sequence":"additional","affiliation":[{"name":"Division of Gynaecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Maletta","sequence":"additional","affiliation":[{"name":"Division of Gynaecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8151-0947","authenticated-orcid":false,"given":"Marisol","family":"Doglioli","sequence":"additional","affiliation":[{"name":"Division of Gynaecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Raffone","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy"},{"name":"Department of Woman, Child, and General and Specialized Surgery, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Cobellis","sequence":"additional","affiliation":[{"name":"Department of Woman, Child, and General and Specialized Surgery, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Rottoli","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy"},{"name":"Surgery of the Alimentary Tract, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Seracchioli","sequence":"additional","affiliation":[{"name":"Division of Gynaecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3235-4378","authenticated-orcid":false,"given":"Diego","family":"Raimondo","sequence":"additional","affiliation":[{"name":"Division of Gynaecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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