Key takeaways:
- Women whose cervical microbiome showed lower β‑diversity were more likely to achieve a pregnancy after frozen embryo transfer.
- Distinct bacterial signatures differentiate outcomes – Successful pregnancies were linked to higher abundances of Eubacterium halli and Myxococcales, whereas implantation failures featured Peptostreptococcales‑tissierellales, Haemophilus, and Streptococcus.
- Endometriosis dramatically raises infertility risk – Approximately 40 %–50 % of endometriosis patients are infertile, representing a 20‑fold increase compared with women without the disease.
- Significant differences in both cervical and vaginal microbial communities (Shannon, Simpson, and β‑diversity indices) were observed between the successful‑pregnancy and failed‑implantation groups.
- The authors propose prospective studies to determine whether correcting the identified microbial imbalances can improve FET outcomes in endometriosis patients.
Taxonomic and functional patterns associated with frozen embryo transfer (FET) success in endometriosis patients are present within a continuous cervicovaginal microbial ecosystem, according to a recent study published in Frontiers in Medicine.1
Infertility occurs in approximately 40% to 50% of endometriosis patients, indicating a 20-fold increase in risk vs women without the condition.2 While treatments may provide symptom relief, a complete cure is often difficult, with assisted reproductive technology (ART) often utilized to achieve fertility.3
“Despite technical advances in ART, implantation failure remains a major obstacle in endometriosis-associated infertility, suggesting that factors beyond embryo quality—particularly the uterine microenvironment—are critical determinants of success,” wrote investigators.
Exploring microbial signatures
The trial was conducted to evaluate distinct microbial patterns associated with implantation outcomes among women with endometriosis. Participants included 22 women receiving FET because of endometriosis-related infertility at the Reproductive Medicine Center Hospital of Wuxi Maternal and Child Health Hospital.
Of these patients, 11 were classified as successful pregnancy vs 11 as failed transplantation. Vaginal and cervical samples were obtained on the day of transplantation. Additional eligibility criteria included being aged more than 20 but less than 40 years, body mass index (BMI) above 18.5 but below 23.9, stage 3 or greater endometriosis, and no recent contraception or antibiotic use.
Investigators performed vaginal and cervical sampling before irrigation and transportation. Samples were taken from the vaginal wall and from 2 to 3 cm into the cervix. A D3142 kit (Guangzhou Meji Biotechnology Co., LTD., China) was used to extract DNA.
The mathematical difference between the populational median of the inter-individual BC distance of a genus and the median of the intra-individual BC distance was defined as the degree of microbial individuality (DMI). A bootstrap resampling technique was used to evaluate the robustness and variability of DMI estimates.
Microbial patterns and FET success
Age, BMI, anti-Müllerian hormone, follicle-stimulating hormone, estradiol, luteinizing hormone, prolactin, testosterone, and clinical characteristics did not significantly differ between the 2 groups. However, significant differences in cervical microbial communities were observed based on the Shannon index and Simpson index.
Welch's t-test indicated significant variations in the β diversity of cervical and vaginal microbiota between patients with successful pregnancy vs failed implantation. Specifically, a significant increase in the β-diversity index was reported among the latter group vs the former group.
According to investigators, this indicates successful pregnancy may be more likely in patients with reduced β-diversity. Additionally, the distribution of vaginal and cervical microbiota significantly differed based on pregnancy success.
Other notable bacterial variations
During comparative analysis, significantly increased abundances of Eubacterium halli and Myxococcales were reported in the successful pregnancy group. In those with transplant failure, the most common bacteria observed were Peptostreptococcales-tissierellales and Haemophilus.
Additional bacteria differing based on pregnancy success included Bacteroidaceae bacterium Ms4, Methylobacterium, Mycoplasmatales, Mycoplasmataceae, Prevotella buccalis, and Ureaplasma. Patients with endometriosis and infertility most often reported Firmicutes, Actinobacteriota, and Bacteroidota at the phylum level.
In the successful pregnancy group, the main bacteria present included Lactobacillus, Gardnerella, Atopobium, Bifidobacterium, and Prevotella. In comparison, the failure group mainly presented with Lactobacillus, Gardnerella, Atopobium, Streptococcus, and Prevotella. Overall, the results highlighted different bacterial cultures based on pregnancy success status.
“In the next step, a prospective intervention study should be designed to examine whether correcting the microbiota based on these signatures can effectively improve pregnancy outcomes, which would be the ultimate test of its clinical relevance,” wrote investigators.
References
- Li Y,Chen D, Feng Y, et al. A pilot study of cervicovaginal microbiome patterns associated with embryo implantation outcomes in endometriosis-associated infertility. Frontiers in Medicine. 2025. doi:10.3389/fmed.2025.1642770
- Horne AW, Zhang L. Treatment strategies of endometriosis related infertility. J Reprod Med. 2018;27:5. doi:10.3969/j.issn.1004-3845.2018.08.023
