Background:Luteal support is a key to patients undergoing in vitro fertilization and embryo transfer (IVF-ET) with gonadotropin-releasing hormone (GnRH)-antagonist protocol.This study aimed to compare the effect between vaginal progesterone (VP) and intramuscular progesterone (IMP) with GnRH-antagonist protocol after IVF-ET.Methods:A total of 1760 patients (18 years ≤ age ≤35 years) undergoing IVF-ET with GnRH-antagonist protocol were studied retrospectively between September 2014 and August 2015 in Peking University Third Hospital.In the patients,1341 patients received VP (VP group) and 419 patients received IMP (IMP group) as luteal support.We compared clinical outcomes between these two groups.The primary objective of the study was the live birth rate.Measurement data between the two groups were conducted using independent samples t-test.The variables in line with non-normal distribution were expressed as median (p25 and p75) and were compared using nonparametric Mann-Whitney U-test.Results:Live birth rate in VP group was 38.55％,significantly higher than that in the IMP group,which was 30.79％ (x2 =8.287,P =0.004).The clinical intrauterine pregnancy rate and implantation rate in VP group were also significantly higher than those in the IMP group (clinical intrauterine pregnancy rate 47.35％ vs.41.29％,x2 =4.727,P =0.030;implantation rate 30.99％ vs.25.26％,x2 =14.546,P ＜ 0.001).Any statistically significant differences in ectopic pregnancy and abortion rates between two groups were not observed.Conclusion:Luteal support with VP had better clinical outcomes for young women undergoing IVF-ET with GnRH-antagonist protocol.