Retrospective analysis of the endometrial preparation protocols for frozen-thawed embryo transfer cycles in women with endometriosis

BACKGROUND: There was inconsistency in optimal endometrial preparation protocol for frozen-thawed embryo transfer (FET) in patients with endometriosis. We conducted this study to investigate the effect of different endometrial preparation protocols on the pregnancy outcomes in patients with endometriosis undergoing FET cycles, and determine the optimal number of GnRHa injections in GnRHa-HRT protocols. METHOD(S): This was a retrospective cohort analysis of women with endometriosis who underwent FET cycles at a single university-based center. This study retrospectively analyzed 2048 FET cycles in our center from 2011 to 2020. According to the endometrial preparation protocols, patients were divided into 4 groups: gonadotropin releasing hormone agonist-hormone replacement therapy(GnRHa-HRT), hormone replacement therapy(HRT), ovulation induction(OI), and natural cycle(NC). In the GnRHa-HRT group, patients were further divided into 3 groups: one injection of GnRHa, two injections of GnRHa, and three or more injections of GnRHa. The primary outcome was the clinical pregnancy rate. Propensity score matching was used to adjust for potential non-similarities among the groups. Multivariate logistic regression analysis was performed to figure out the risk factors for pregnancy outcomes. RESULT(S): There were no statistical differences in pregnancy outcomes among the four endometrial preparation protocols in FET cycles with endometriosis patients, the results retained after propensity score matching(PSM). And in endometriosis patients complicated with adenomyosis, the results remained similar. In patients with GnRHa-HRT protocol, there were no differences in clinical pregnancy rate and live birth rate with different numbers of GnRHa injections, the early miscarriage rate were 18% in the two injections of GnRHa group and 6.5% in the one injection of GnRHa group(P = 0.017). Multifactorial logistic regression analysis showed that two injections of GnRHa before FET was associated with increased early miscarriage rate compared with one injection of GnRHa[adjusted OR (95% CI): 3.116(1.079–8.998),p = 0.036]. CONCLUSION(S): The four kinds of endometrial preparation protocols for FET, GnRHa-HRT, HRT, OI and NC had similar pregnancy outcomes in patients with endometriosis. In endometriosis patients complicated with adenomyosis, the results remained similar. In patients with endometriosis undergoing GnRHa-HRT protocol for FET, more injections of GnRHa had no more advantages in pregnancy outcomes, on the contrary, it might increase the early miscarriage rate.