RELUGOLIX, A NOVEL ORALLY ACTIVE GnRH ANTAGONIST IS EFFECTIVE IN IVF PROTOCOL.

The aim of this study was to clarify the effectiveness of relugolix, a novel orally active GnRH (GnRH) antagonist in in vitro fertilization (IVF) protocol. This study was prospective, without randomization study which was conducted at Kyono ART clinic Sendai, Morioka, and Takanawa in Japan from December 2019 to March 2020. This study was approved by the Ladies Clinic Kyono Ethics Committee. This study includes a total of 113 controlled ovarian hyperstimulation (COH) cycles with GnRH antagonist protocol in IVF. 63 cycles were in daily injection of ganirelix (0.25mg) or cetrorelix (0.25mg) group (Ga/Ce group), and 70 cycles were in every 36 hours oral administration of relugolix (40mg) group (Rel group). GnRH antagonist (ANT) was administrated by fixed day 6 protocol or flexible protocol. Hormonal profiling (LH, FSH, E2 and P4) was assessed in the previous or the day of GnRH antagonist administration (ANT start day), and the decision day of oocyte pick-up (Trigger day). Number of retrieved oocyte and MII oocyte, fertilization rate, Day3 good embryo rate and good blastocyst rate were compared between each group. The statistical analyses were done by Welch T test and Chi square test. P<0.05 was considered statistically significant. Patient characteristics including age, BMI and AMH level in each group were similarly. There were no significant differences in hormonal profiling in the ANT start day (Ga/Ce group vs. Rel group: LH; 4.2±5.6 vs. 4.2±5.6, E2; 720.8±544.4 vs. 795.8±443.8, P4; 0.3±0.3 vs. 0.3±0.3, respectively) and the Trigger day (Ga/Ce group vs. Rel group: LH; 3.0±3.9 vs. 2.8±1.7, E2; 1659.3±1044.4 vs. 1606.4±872.8, P4; 0.5±0.7 vs. 0.5±0.3, respectively) between each group. A total number of GnRH antagonist administration in Rel group was significantly fewer than that of Ga/Ce group (2.4±0.7 vs. 3.7±0.9, p<0.01). A total dose of HMG/FSH administration was considerably higher in Rel group, though the difference was not statistically significant (2346.3±748.8 vs. 2136.1±634.2, p=0.08). Despite no significant difference in average number of retrieved oocyte (Ga/Ce group vs. Rel group: 9.9±5.8 vs. 9.7±5.5) and MII oocyte (Ga/Ce group vs. Rel group: 7.8±4.5 vs. 7.2±4.0), maturation rate in Rel group was significantly lower than that in Ga/Ce group (73.7% vs. 81.7%, p<0.05). There were no significant differences in fertilization rate (79.1% vs. 80.0%), good day3 embryo rate (22.6% vs. 24.9%), blastocyst rate (47.0% vs. 49.9%) and good blastocyst rate (26.2% vs. 29.7%) between Ga/Ce group and Rel group. Premature LH surge was observed in one patient in Ga/Ce group, but not in Rel group. Our results suggested that relugolix, a novel orally active GnRH antagonist was effective in COH with GnRH antagonist protocol in IVF. As clinical effectiveness of relugolix is expected by less expensive and few times administration compared with ganirelix and cetrorelix, relugolix is useful for patients in cost-benefit.