Progesterone Intramuscularly or Vaginally Administration May Not Change Live Birth Rate or Neonatal Outcomes in Artificial Frozen-Thawed Embryo Transfer Cycles

Abstract

BackgroundsPrevious studies suggested that singletons from frozen-thawed embryo transfer (FET) were associated with higher risk of large, post-date babies and adverse obstetrical outcomes compared to fresh transfer and natural pregnancy. No data available revealed whether the adverse perinatal outcomes were associated with aberrantly high progesterone level from different endometrium preparations in HRT-FET cycle. This study aimed to compare the impact of progesterone intramuscularly and vaginally regimens on neonatal outcomes in HRT-FET cycles.MethodsA total of 856 HRT-FET cycles from a fertility center from 2015 to 2018 were retrospectively analyzed. All patients had their first FET with two cleavage-staged embryos transferred. Endometrial preparation was performed with sequential administration of estrogen followed by progesterone intramuscularly 60 mg per day or vaginal gel Crinone 90 mg per day. Pregnancy outcomes including live birth rate, singleton birthweight, large for gestational age (LGA) rate, small for gestational age (SGA) rate, and preterm delivery rate were analyzed. 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.ResultsNo 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 singleton birthweight (p = 0.744), preterm delivery rate (Adjusted OR 1.920, 95% CI 0.603, 6.11, p = 0.269), SGA (Adjusted OR 0.227, 95% CI 0.027, 1.934, p = 0.175), and LGA rate (Adjusted OR 0.862, 95% CI 0.425, 1.749, p=0.681) 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 ≤41.82 pmol/L in HRT-FET cycles when progesterone was intramuscularly delivered (Adjusted OR 1.690, 95% CI 1.002, 2.849, p = 0.049). But singleton birthweight, preterm delivery rate, SGA and LGA rate were not different between these two groups.ConclusionsRelatively higher serum progesterone level induced by intramuscular regimen did not change live birth rate or neonatal outcomes compared to vaginal regimen. Monitoring serum progesterone level and optimizing progesterone dose of intramuscular progesterone as needed in HRT-FET cycles has a role in improving live birth rate without impact on neonatal outcomes.

Estradiol on Trigger Day was Irrelevant to Live Birth Rates of Fresh Cycles but Positively Associated with Cumulative Live Birth Rates: A Multicenter Retrospective Study

“…Hence, the impact of E2 on live birth rates could not be accurately assessed. Furthermore, the live birth rates reported in that study were much lower than those in the present study (45.4%) and other research (which were within 35.6%-45.6% [27][28][29][30]). Consequently, other factors, except for the E2 on trigger day, might interfere with the live birth rates for FET cycles in the study conducted by Duan.…”

Short (seven days) versus standard (fourteen days) oestrogen administration in a programmed frozen embryo transfer cycle: a retrospective cohort study

“…Now, the route of clinical progesterone administration is intramuscular injection, oral and vaginal administration, or a combination regimen. Current studies suggest that the mode of progesterone administration does not affect pregnancy rates [25][26][27] . Despite these limitations, our study still provides valuable data with reference for clinicians to use exible programmed cycle protocols.…”

Low Luteal Serum Progesterone Levels Are Associated With Lower Ongoing Pregnancy and Live Birth Rates in ART: Systematic Review and Meta-Analyses

“…The main characteristics of the included studies are reported in Supplementary Table 1. The included women were recruited during their first or second cycle (19)(20)(21)(22)(23), all of them (24)(25)(26)(27)(28)(29)(30) or not specified (11,14,(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46). Studies concerned either autologous cycles (13, 14, 19, 21, 22, 25, 27, 29-32, 36, 38-43, 45, 47), oocyte donation (20,44) or not specified (11, 21, 23, 26, 28, 33-35, 37, 46).…”

“…Studies concerned either autologous cycles (13, 14, 19, 21, 22, 25, 27, 29-32, 36, 38-43, 45, 47), oocyte donation (20,44) or not specified (11, 21, 23, 26, 28, 33-35, 37, 46). Studies included single-embryo transfers (11,13,22,28,33,35,40,41), single-or double-embryo transfers (19,20,26,27,30,31,34,37,46), transfers of two to three embryos (24), transfers of three to four embryos (38,39,44) and not reported (14,21,23,25,29,36,43,45,47). Transferred embryos were cleaved embryos (21,24,27,29,34,39), blastocyst embryos (11,13,14,19,20,22,23,26,…”

“…Studies included single-embryo transfers (11,13,22,28,33,35,40,41), single-or double-embryo transfers (19,20,26,27,30,31,34,37,46), transfers of two to three embryos (24), transfers of three to four embryos (38,39,44) and not reported (14,21,23,25,29,36,43,45,47). Transferred embryos were cleaved embryos (21,24,27,29,34,39), blastocyst embryos (11,13,14,19,20,22,23,26,31,35,40,41,46), both (28,30,…”