Progesterone regimen impact on live birth rate and neonatal outcomes in artificial frozen-thawed embryo transfer cycles: a retrospective cohort study

Abstract

Background: Previous studies have demonstrated that singletons from frozen embryo transfer (FET) are heavier and longer-gestational-days at delivery than those from fresh embryo transfer. The amounts and routes of progesterone used in FET vary tremendously among different ART centers.Does different serum progesterone level induced by different progesterone regimens determine live birth rate and neonatal outcomes in hormone replacement therapy frozen-thawed embryo transfer (HRT-FET) cycles?Design: A cohort study of 856 HRT-FET cycles from a Chinese public fertility center. Data from patients undergoing their first FET cycles from 2015-2018 were extracted from the database. All patients had their first FET with two day2 or day3 embryos transferred. Endometrial preparation was performed with sequential administration of estrogen followed by progesterone 60mg per day intramuscularly or Crinone 90mg per day vaginally. Live birth was the primary outcome. Secondary outcome included clinical pregnancy rate, singleton birthweight, large for gestational age (LGA) rate, SGA rate and preterm delivery rate. Student's t test, Mann-Whitney U-test, Chi square analysis and multivariable logistic regression were used where appropriate. Differences were considered significant if p<0.05.Results: No significant difference of live birth rate was found between different progesterone regimens (Adjusted OR 1.128, 95%CI 0.842, 1.511, p=0.420). Neonatal outcomes like birthweight, preterm delivery rate, SGA and LGA rate were not different between two progesterone regimens.Serum P level >41.82 pmol/L at 14 day post-FET was associated with higher live birth rate than serum P level ≤41.82pmolL in HRT-FET cycles when progesterone was intramuscularly delivered (Adjusted OR 1.690, 95%CI 1.002, 2.849, p=0.049). Birthweight and gestational weeks were not different between these two different P level groups. Conclusions: Progesterone vaginally or intramuscularly didn't impact live birth rate and neonatal outcomes in artificial FET cycles. Relatively higher serum progesterone level induced by intramuscular regimen did not increase newborn birthweight or prolong gestational weeks compared to vaginal regimen. Intramuscular progesterone supplementation during HRT-FET cycles was associated with development in cows. Theriogenology 2011, 76:1594-1601. 17. Nogueira MF, Melo DS, Carvalho LM, Fuck EJ, Trinca LA, Barros CM: Do high progesterone concentrations decrease pregnancy rates in embryo recipients synchronized with PGF2alpha and eCG? Theriogenology 2004, 61:1283-1290. 18. Mitwally MF, Diamond MP, Abuzeid M: Vaginal micronized progesterone versus intramuscular progesterone for luteal support in women undergoing in vitro fertilization-embryo transfer. Fertil Steril 2010, 93:554-569. 19. Zarei A, Sohail P, Parsanezhad ME, Alborzi S, Samsami A, Azizi M: Comparison of four protocols for luteal phase support in frozen-thawed Embryo transfer progesterone on the day of embryo transfer is associated with a diminished ongoing pregnancy rate in oocyte donation ...