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

Jie Zhang, Lei Dai, Chunyan Jiang, Yuxin Zhao, Yang Zhao, Xiang Ma, Yugui Cui, Jiayin Liu
Journal of biomedical research · 2025 · vol. 39 , pp. 1 · doi:10.7555/jbr.39.20250205 · PMID:40462414 · W4411044158
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

Letrozole combined with HMG resulted in fewer obstetric complications and a more favorable vaginal microbiota compared to GnRH-a HRT for endometriosis patients undergoing frozen embryo transfer, despite similar live birth rates.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-09 ⓘ

This retrospective cohort study evaluated pregnancy and perinatal outcomes and vaginal microbiota in women with endometriosis undergoing frozen embryo transfer (FET) using either letrozole plus HMG or hormone replacement therapy (HRT) with GnRH-a pretreatment. After 1:1 propensity score matching, 770 FET cycles were analyzed, and live birth and clinical pregnancy rates were similar between protocols; however, the letrozole + HMG group had fewer cesarean deliveries and hypertensive disorders of pregnancy, with a non-significant trend toward lower miscarriage. A prospective substudy analyzed vaginal samples from 55 women in the letrozole + HMG arm and 50 in the GnRH-a HRT arm using 16S rRNA sequencing and droplet digital PCR, finding no differences in Lactobacillus or Gardnerella abundance but higher enrichment of potential pathogens (e.g., Escherichia-Shigella and Staphylococcus) in the GnRH-a HRT group. The authors note ethical constraints prevented endometrial sampling during FET, so vaginal microbiota was used as a surrogate rather than direct endometrial assessment. This paper is centrally about endometriosis — it compares endometrial preparation protocols (letrozole + HMG vs GnRH-a HRT) in endometriosis patients receiving FET, including outcomes and vaginal microbiota differences.

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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.

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MUSA

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endometriosis

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