Can letrozole plus HMG protocol improve pregnancy outcomes in frozen-thawed embryo transfer? An RCT

Abstract

Background:There are different methods in endometrial preparation for frozen-thawed embryo transfer (FET).Objective:The purpose of this study was to compare the live birth rate in the artificial FET protocol (estradiol/ progesterone with GnRH-agonist) with stimulated cycle FET protocol (letrozole plus HMG).Materials and Methods:This randomized clinical trial included 100 women (18-42 years) randomly assigned to two groups based on Bernoulli distribution. Group I received GnRH agonist [Bucerelin, 500μg subcutaneously] from the previous midlutea lcycle, Then estradiol valerat [2 mg/ daily orally] was started on the second day and was increased until the observation of 8mm endometrial thickness. Finally progesterone [Cyclogest, 800 mg, vaginally] was started. Group II received letrozole on the second day of the cycle for five days, then HMG 75 IU was injected on the7th day. After observing [18 mm folliclhCG10000 IU was injected for ovulation induction. Trans cervical embryo transfer was performed in two groups. The main outcome was the live birth rate. The rate of live birth, implantation, chemical, and clinical pregnancy, abortion, cancellation and endometrial thickness were compared between two groups.Results:Implantation rate was significantly higher in group I. Live birth rate was slightly increased in group I without significant difference (30% vs. 26%). The rate of chemical and clinical pregnancy was similar in two groups. The abortion rate was lower in letrozole protocol but the difference was not statistically significant. The mean endometrial thickness was not different between two groups. Conclusion:Letrozole plus HMG method cannot improve pregnancy outcomes in frozen-thawed embryo transfer but it has only one injection compare to daily injections in artificial method.

The effect of letrozole versus artificial hormonal endometrial preparation on pregnancy outcome after frozen-thawed embryos transfer cycles: a randomized clinical trial

“…To the best of our knowledge, five retrospective [2,11,12,19,20] and two clinical trial studies [9,14] have evaluated the effects of letrozole utilization for endometrial preparation before FET; however, only one of the previously published clinical trials [14] possessed a registration number in the specific clinical trial cites. The recent retrospective study, by Zhang et al in 2019 evaluated a total of 2664 patients with PCOS undergoing FET cycles, reporting that letrozole stimulation during FET cycles significantly improved live birth rates with a decrease in the pregnancy loss rate.…”

“…Since then, several studies have compared the reproductive outcomes of endometrial preparation with stimulated cycles using gonadotropin and clomiphene or letrozole or both, with the artificial cycles. Notably, a number of studies have shown positive results involving ovarian stimulation (OS) for endometrial preparation in frozen embryo transfer cycles in PCOS patients [2,[8][9][10][11][12], and some studies have not found any differences compared with hormonal endometrial preparation [13,14].…”

Pregnancy Outcomes Following Letrozole Use in Frozen-thawed Embryo Transfer Cycles: A Systematic Review and Meta-analysis

“…In one study, HMG was added to the letrozole cycle [20]. In this study, CPR (OR 1.11, 95 % CI: 0.46-2.68) (▶ Fig.…”

“…The average quality of the included studies was low. Of the 10 included studies, only 1 study was an RCT (level of evidence: 2b) 20 . The other studies included 1 prospective cohort study 21 , 7 retrospective cohort studies 22 , 23 , 24 , 25 , 26 , 27 , 28 and 1 case-control study (level of evidence: 2b–4) 29 .…”

“…A total of 3 studies representing a total of 3314 cycles were included for comparisons between letrozole and AC + GnRH-a 20 , 21 , 22 . No significant differences were identified with respect to CPR (OR 1.11, 95% CI: 0.78 – 1.59) ( Fig.…”