Infertility affects approximately 17.5% of couples who seek to conceive, with recurrent implantation failure (RIF) posing one of the most significant challenges. RIF is commonly defined as the repeated failure to achieve pregnancy after transferring good-quality embryos, particularly after multiple fertility treatments. Recent studies at the University of Tokyo have brought attention to chronic endometritis (CE) and endometrial dysbiosis (ED) as key contributors to RIF.
Chronic endometritis, diagnosed through hysteroscopy or the endometrial CD138 test, has been found to occur in 30-57% of RIF patients. Conversely, endometrial dysbiosis has emerged as another important factor, characterized by abnormalities in the endometrial microbiome, especially through the depletion of Lactobacillus species. Understanding the relationship among CE, ED, and their impact on embryo implantation success is pivotal for developing effective treatment strategies.
A comprehensive analysis involving 73 patients with RIF was conducted from April 2019 to March 2024 at the University of Tokyo Hospital, assessing the efficacy of the different diagnostic tests: hysteroscopy, endometrial CD138 testing, and endometrial microbiome testing. Results showed CE was diagnosed through hysteroscopy with an incidence of 56.2% and by the CD138 test at 49.3%; the overall prevalence of ED was recorded at 53.4%.
Notably, among the assessed patients, 88.9% of those diagnosed with ED achieved clinical pregnancy after treatment, which was significantly higher compared to those without ED (56.0% pregnancy rate, p = 0.021). The odds ratio indicates the strong association between ED and clinical pregnancy success (OR: 6.29, p = 0.031), providing compelling evidence for the effectiveness of the endometrial microbiome test.
Diagnosis for CE was supported by specific findings during hysteroscopy—such as hyperemia and stromal edema—and by the presence of plasma cells detected through the CD138 test. For patients identified with ED, treatment encompassed the administration of antibiotics and the use of vaginal Lactobacillus probiotics, targeting microbiome restoration. Treatment was carried out over two weeks, followed by probiotics to support the endometrial environment.
After analyzing clinical outcomes, the study found significant differences—30 patients, or 69.8%, achieved clinical pregnancy, but those treated with Lactobacillus alongside antibiotics exhibited even greater success, with pregnancy rates of 88.9% compared to 60% for antibiotic-only treatment (p = 0.045). The evidence provides new insights, encouraging combined antibiotic and probiotic treatment as effective interventions.
Despite advancements, the study revealed no observable correlations between CE diagnosed by hysteroscopy, the CD138 test, and ED. With roughly 50% positive results across all tests, the lack of overlap suggests the necessity for individualized patient assessment methods. The discordance raises questions about whether the tests could capture different populations and conditions affecting fertility.
The researchers conclude, "No correlations were observed among the test-positive individuals in these three tests," reinforcing the suggestion to incorporate the microbiome test as part of routine evaluations for RIF patients. This study's outcomes open avenues for future pregnancy success rates by utilizing the endometrial microbiome as a key indicator of reproductive health.
While this retrospective analysis presents pivotal findings, it is not without limitations. Future prospective studies are warranted to verify the established link between ED treatment and improved outcomes over varying populations, including those beyond the Japanese demographic focus of this study. The importance of continuous evaluation, particularly through re-testing protocols post-treatment for CE and ED, would also aid significantly.
Overall, these findings suggest the real potential of addressing chronic endometritis and endometrial dysbiosis to facilitate improved reproductive outcomes. By focusing on the nuances of endometrial health and leveraging microbial treatments, the prospect of enhancing fertility treatments can be realized, possibly reshaping approaches for managing recurrent implantation failures.