Reproductive health considerations for IDH-mutant glioma patients considering IDH inhibitor therapy: a retrospective cohort study

Introduction Reproductive health considerations are critical to patients with IDH-mutant (IDHm) glioma as they are mainly diagnosed during their reproductive years. Given the recent introduction of IDH inhibitors (IDHi) for the treatment of IDHm glioma, we sought to review the current understanding of reproductive implications of IDHi therapy, and report how frequently documented reproductive health conversations take place in clinic when considering IDHi initiation. Methods We searched the literature for studies evaluating the effects of IDHi therapy on reproductive health. We additionally retrospectively collected clinical data from reproductive-age patients with IDHm glioma treated at the Dana-Farber Cancer Institute and Mass General Brigham who received or were considered for IDHi therapy between 2018-2024. Medical records were reviewed for documentation of fertility and contraception discussions at the time of IDHi consideration. Results Other than limited preclinical studies described on FDA labels, no other data on the effects of IDHi on reproductive health were found. Of 119 patients considered for IDHi therapy, 54 (45%) had no documented fertility conversation in relation to IDHi and 92 (77%) had no documented contraception conversation. On univariable analysis, factors significantly associated with not having fertility conversations were older age (OR 0.94, CI 0.88-1.0), male sex (OR 0.50, CI 0.23-1.07), and prior fertility conversation (OR 0.41, CI 0.18-0.88). Conclusions According to our institutional data, conversations regarding IDHi reproductive risks are not generally documented, contrary to guideline recommendations. Future studies are required to better understand the impact of IDHi therapy on fertility and fetal development.