Comparison of pregnancy outcomes and vaginal microbiota in women with endometriosis undergoing frozen embryo transfer using letrozole combined with HMG versus hormone replacement therapy with GnRH-a pretreatmentOA

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 gonadotropin-releasing hormone agonist(GnRH-a)pretreatment—in women with endometriosis 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 nonsignificant trend toward a lower miscarriage rate(13.7%vs.19.8%,P=0.070),as well as lower observed rates of cesarean delivery(64.9%vs.75.4%,P=0.020)and hypertensive disorders of pregnancy(4.8%vs.10.1%,P=0.039).Previous evidence suggests an association between GnRH-a treatment and reproductive tract microbiota composition.Given the clinical and ethical constraints of endometrial sampling during FET,vaginal microbiota was evaluated as a non-invasive indicator of lower reproductive tract microbial composition.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 showed higher relative abundances of several low-abundance taxa,such as Escherichia-Shigella,Limosilactobacillus,and Staphylococcus.In conclusion,although both protocols achieved comparable live birth outcomes,the LE+HMG regimen was associated with lower rates of cesarean delivery and hypertensive disorders of pregnancy,while the two protocols exhibited differences in several low-abundance vaginal bacterial taxa.However,longitudinal studies incorporating baseline and repeated sampling are needed to clarify temporal relationships and causality.