Oral gonadotropin‐releasing hormone antagonists versus injectable cetrorelix for luteinizing hormone surge prevention in donor in vitro fertilization cycles: A retrospective cohort study of efficacy, embryology, and stimulation dynamics

OBJECTIVE: This study evaluates the effectiveness of oral gonadotropin-releasing hormone (GnRH) antagonists (elagolix and relugolix) compared to injectable cetrorelix in preventing premature luteinizing hormone (LH) surge and luteinization during controlled ovarian stimulation in donor in vitro fertilization (IVF) cycles and assesses their impact on oocyte maturity, embryo development, and stimulation efficiency. METHODS: A retrospective cohort study was conducted at a tertiary fertility center including 173 donor cycles allocated into three groups: cetrorelix (n = 60), relugolix (n = 55), and elagolix (n = 58). All donors met standardized inclusion criteria and underwent stimulation with recombinant gonadotropins. GnRH antagonist regimens were initiated when follicles reached ≥14 mm. Primary outcome was the composite rate of premature LH surge and/or luteinization. Secondary outcomes included mature oocyte yield (MII), fertilization and blastocyst development, gonadotropin usage, stimulation duration, and drug-related adverse events. Multivariable regression models adjusted for donor age, body mass index, antral follicle count, antral follicle count, and calendar time. RESULTS: Observed composite endocrine escape rates were low and numerically similar across groups (3.3-3.6%), although the study was substantially underpowered for this rare endpoint. However, suspected premature ovulation/empty follicle syndrome was observed only in the elagolix group (6.9% vs. 0%, P = 0.017); this finding is based on four events and should be interpreted as exploratory. MII yield and MII rate were significantly lower in both oral antagonist groups compared to cetrorelix (P < 0.001). Oral groups required higher gonadotropin doses and longer stimulation. No cases of ovarian hyperstimulation syndrome occurred. Adherence was high across groups; adverse events were more frequent with elagolix (12.1%). CONCLUSION: In this exploratory retrospective donor IVF cohort, observed endocrine escape rates were low across oral and injectable antagonist groups, but the study was underpowered to establish equivalence or non-inferiority. Oral antagonist use was associated with lower MII oocyte yield, greater stimulation burden, and fewer usable blastocysts. These findings are hypothesis-generating and require confirmation in adequately powered prospective trials.