Recent meta-analyses have shown significantly lower pregnancy rates, serum estradiol levels on hCG day, and number of oocytes retrieved in GnRH antagonist (GnRHant) cycles compared with GnRH agonist cycles. Thus possible extrapituitary actions of GnRHant have been thought to affect controlled ovarian hyperstimulation (COH) outcomes and to be one of the causes of lower pregnancy rates. Withdrawal of GnRHant could immediately reverse antagonizing effect, therefore cessation of GnRHant administration on hCG day could remove the possible detrimental effect of GnRHant on final oocyte maturation. This is the first study that compared COH outcomes according to whether or not GnRHant was administrated on hCG day in GnRHant multiple-dose protocols for COH. Retrospective comparative study. A total of 92 eligible IVF cycles were included. All patients underwent COH with recombinant FSH and GnRHant flexible multiple-dose protocol. GnRHant, cetrorelix 0.25mg, was added when leading follicle reached a diameter of 14 mm and continued daily until the day of hCG administration (Group A, n = 66) or the day before hCG administration (Group B, n = 26). Data were analyzed and compared between the two groups. The duration of COH, total dose of gonadotropins, estradiol levels on hCG day, and number of oocytes retrieved were not significantly different between the two groups. Total dose of GnRHant was significantly lower in Group B compared to Group A (2.7 ± 0.8 vs. 3.2 ± 0.9 ampules, P=0.036). No case showed premature luteinization in Group B. The ratio of mature to total retrieved oocytes, fertilization rate of mature and total oocytes were significantly higher in Group B compared to Group A (71.4 vs. 61.7%, P=0.019; 85.4 vs. 75.3%, P=0.023; 78.6 vs. 65.8%, P=0.001, respectively). Embryo grade score was significantly higher in Group B (3.8 ± 1.0 vs. 3.0 ± 1.3, P=0.004). There were no significant differences in implantation and clinical pregnancy rates.Table 1Clinical characteristics and outcomes of controlled ovarian hyperstimulation and IVF-ET between the two groupsGroup A (n = 66)Group B (n = 26)P-valueAge (years)34.7 ± 4.832.9 ± 5.5NSBody mass index (kg/m2)21.4 ± 1.820.8 ± 2.2NSBasal FSH (mlU/mL)6.9 ± 5.67.1 ± 3.2NSCause of infertility (%)NS Tubal47.0 (31/66)61.5 (16/26) Male28.8 (19/66)26.9 (7/26) Unexplained24.2 (16/66)11.5 (3/26)Duration of COH (days)9.4 ± 1.89.4 ± 1.4NSDose of gonadotropins used (amp)24.2 ± 6.421.9 ± 10.2NSDose of GnRH antagonist used (amp)3.2 ± 0.92.7 ± 0.80.036Serum estradiol on hCG day (pg/mL)1095.0 ±751.81017.2 ± 559.5NSCycles with premature luteinization (%)∗Premature luteinization: LH ≥ 10 mIU/mL, and progesterone ≥ 1.0 mg/mL, on hCG day.1.5 (1/66)0 (0/26)NSNo. of mature follicles on hCG dayMature follicles: follicle of diameter ≥ 15 mm.6.7 ± 2.96.8 ± 3.3NSNo. of oocytes retrieved7.8 ± 4.57.0 ± 4.0NSRatio of mature oocytes (%)61.7 (316/512)71.4 (130/182)0.019Fertilization rate of mature oocyte (%)75.3 (238/316)85.4 (111/130)0.023Fertilization rate of total oocytes (%)65.8 (337/512)78.6 (143/182)0.001Embryo grade score∗Embryo quality was evaluated and scored according to their morphologies and cleavage rates.3.0 ± 1.33.8 ± 1.00.004No. of transferred embryos2.7 ± 0.73.0 ± 1.0NSImplantation rate (%)14.8 (24/162)13.3 (10/75)NSClinical pregnancy rate (%)26.3 (16/61)28.0 (7/25)NSMean ± S.D.; Data were analyzed using Chi-square test, Fisher's exact test, and Student t-test.COH: controlled ovarian hyperstimulation; amp: ampules.∗ Premature luteinization: LH ≥ 10 mIU/mL, and progesterone ≥ 1.0 mg/mL, on hCG day.∗∗ Mature follicles: follicle of diameter ≥ 15 mm.∗∗∗ Embryo quality was evaluated and scored according to their morphologies and cleavage rates. Open table in a new tab Mean ± S.D.; Data were analyzed using Chi-square test, Fisher's exact test, and Student t-test. COH: controlled ovarian hyperstimulation; amp: ampules. Our results suggest that cessation of GnRHant on hCG trigger day during flexible multiple-dose protocol could reduce total dose of GnRHant and improve oocyte and embryo quality without inducing premature luteinization.