L26/P-763 Clinical outcomes using an oral-antagonist of GnRH in IVF Cycles: A Retrospective Matched Case–Control Study

Abstract Study question Can Linzagolix 200 mg effectively replace injectable GnRH antagonists for ovulation suppression during IVF stimulation cycles without negatively affecting laboratory and clinical outcomes? Summary answer Oral Linzagolix 200 mg achieved effective ovulation suppression during IVF stimulation, embryological outcomes and pregnancy rates comparable to those observed with injectable GnRH antagonist protocols. What is known already GnRH antagonists are widely used during controlled ovarian stimulation in IVF to prevent premature LH surge and ovulation. Linzagolix is an oral, non-peptide GnRH receptor antagonist that induces rapid, dose-dependent suppression of gonadotropin secretion and ovulation and is currently approved for the treatment of leiomyomas and endometriosis-related symptoms. Its pharmacological profile suggests a potential role in assisted reproduction; however, evidence regarding its use as an ovulation suppressor during IVF cycles and its impact on reproductive outcomes remains limited. Study design, size, duration This retrospective, single-center, case–control study was conducted at the Fertility Center of IRCCS San Raffaele Hospital, Milan. A total of 108 IVF/ICSI cycles from 2019 to 2025 were included, comprising 27 cycles using Linzagolix 200 mg and 81 matched cycles using a standard injectable GnRH antagonist. A 1:3 matching was applied for gonadotropin active compound, starting dose, patient age, and body mass index. Participants/materials, setting, methods Twenty-seven IVF/ICSI cycles using Linzagolix 200 mg were matched to 81 control cycles treated with an injectable GnRH antagonist. All participants provided written informed consent for the off-label use of Linzagolix. Baseline characteristics, ovarian response, embryological outcomes and clinical pregnancy outcomes were evaluated. Continuous variables were compared using the Mann–Whitney U test, while categorical variables were analyzed using Fisher’s exact test. Statistical analyses were performed using R software. Main results and the role of chance No significant differences in ovarian response were observed between the oral and injectable GnRH antagonist groups. The median number of oocytes retrieved was comparable between the Linzagolix and control groups (9.0 [4.5–12.0] vs 8.0 [5.0–12.0], respectively; p=0.92). Similarly, the median number of mature (MII) oocytes did not differ between groups (6.0 [3.5–8.5] vs 5.0 [3.0–8.0]; p=0.41). The number of Day3 embryos available was comparable between groups (2.48±2.36 vs 2.44±2.58), with no significant difference observed (adjusted IRR 1.02, 95% CI 0.73–1.42; p = 0.918). The cumulative ongoing pregnancy rate per initiated cycle, defined by the presence of fetal cardiac activity at 7–8 weeks of gestation, was comparable between the injectable and oral GnRH antagonist groups (38.3% [31/81] vs 37.0% [10/27], respectively), with no significant difference observed (adjusted OR 1.02, 95% CI 0.39–2.63; p=0.97). Limitations, reasons for caution Limitations include the retrospective design, single-center setting and limited sample size, particularly in the Linzagolix group. The study was not designed as a non-inferiority trial, and residual confounding cannot be fully excluded despite matching. Wider implications of the findings These findings suggest that oral Linzagolix 200 mg may represent a feasible and patient-friendly alternative to injectable GnRH antagonists for ovulation suppression in IVF cycles. Confirmation in larger prospective studies is warranted before widespread clinical adoption. Trial registration number No