Comparison of Pregnancy Outcomes and Vaginal Microbiota in Endometriosis Patients Undergoing Frozen Embryo Transfer Using Letrozole Combined HMG Versus Hormone Replacement Therapy with GnRH-a Pretreatment.

Abstract

This study investigated differences in reproductive outcomes and vaginal microbiota profiles between two endometrial preparation protocols-letrozole (LE) combined with human menopausal gonadotropin (HMG) and hormone replacement therapy (HRT) with GnRH-a pretreatment-in women with endometriosis (EMs) undergoing frozen embryo transfer (FET). Following 1∶1 propensity score matching, a total of 770 FET cycles were analyzed. No statistically significant differences were observed in live birth rates or clinical pregnancy rates between the two groups. However, the LE + HMG group showed a lower miscarriage trend (13.7% vs. 19.8%, P = 0.070) and significantly fewer cesarean deliveries (64.9% vs. 75.4%, P = 0.020) and hypertensive disorders of pregnancy (4.8% vs. 10.1%, P = 0.039). Recent evidence suggests that GnRH-a treatment may disrupt reproductive tract microbiota. Given ethical constraints on endometrial sampling during FET, vaginal microbiota was used as a surrogate to explore microbial differences between protocols. In the prospective arm, vaginal samples from 55 women in the LE + HMG group and 50 in the GnRH-a HRT group were analyzed using 16S rRNA sequencing and droplet digital PCR. While no significant differences were observed in Lactobacillus or Gardnerella abundance, the GnRH-a HRT group exhibited enrichment of potential pathogens, such as Escherichia-Shigella and Staphylococcus. In conclusion, although both protocols achieved comparable live birth outcomes, the LE + HMG regimen was associated with fewer obstetric complications and a more favorable vaginal microbiota profile compared to GnRH-a HRT.