Effects of endometrial stimulation timings and techniques on pregnancy outcomes in patients without prior embryo transfer: A systematic review and meta-analysis

Objective: To investigate the effects of endometrial stimulation timings and techniques on pregnancy outcomes in patients without prior embryo transfer (ET). Methods: We included a total of 10 studies related to the impact of endometrial stimulation on the pregnancy outcome of infertile patients with the first ET from 2010 to 2019. These studies were found by searching databases including China Science and Technology Journal Database (VIP), Chinese Biological Med (CBM), Chinese Medical Current Content (CMCC), China National Knowledge Internet (CNKI), WanFang Med Online, Cochrane Library, Web of Science, PubMed, Medline, ScienceDirect, and EMBASE. A total of 1,983 cycles were included, of which 725 were cycles with endometrial stimulation. Clinical outcomes included clinical pregnancy, implantation, abortion, multiple pregnancy, and live birth rate. Results: The implantation rate (IR) was higher in the fresh cycle endometrial stimulation group than in the control group (relative risk [RR] = 1.21, 95% confidence interval [CI] = 1.03-1.42; P = 0.02), but there were no significant between-group differences in the live birth rate (LBR) and abortion rate (AR). Subgroup analysis showed that whether follicular or luteal endometrial stimulation was performed before the ET cycle had no effect on the clinical pregnancy outcome, and endometrial stimulation on the day of oocyte retrieval reduced the clinical pregnancy rate (CPR) (RR = 0.37, 95% CI = 0.19-0.75; P = 0.005). Whether the technique involved the use of a curette or catheter, there was no significant between-group difference in CPR. Conclusions: Fresh cycle endometrial stimulation can improve the embryo IR in patients without prior ET, but it cannot increase CPR, LBR, or AR. Subgroup analysis showed that different endometrial stimulation timings and techniques did not significantly improve CPR and that endometrial stimulation on the day of oocyte retrieval reduced CPR.