Endometrial Microbiota in Infertile Women With and Without Chronic Endometritis as Diagnosed Using a Quantitative and Reference Range-Based Method

Objective To systematically compare the endometrial microbiota in infertile women with and without chronic endometritis (CE), as diagnosed by a quantitative and reference range-based method. Design Case-control observational study. Setting University-affiliated hospital. Patient(s) One hundred and thirty infertile women. Intervention(s) Endometrial biopsy and fluid (uterine lavage, UL) collected precisely 7 days after LH surge, with plasma cell density (PCD) determined based on Syndecan-1 (CD138)-positive cells in the entire biopsy section and culture-independent massively parallel sequencing of the 16S ribosomal RNA gene performed on both the CE and non-CE endometrial fluid samples. Main Outcome Measure(s) Relative abundance of bacterial taxa. Result(s) Chronic endometritis was diagnosed if the PCD was above the 95th percentile (>5.15 cells per 10 mm2) of the reference range in fertile control subjects. With this stringent diagnostic criterion, 12 women (9%) were diagnosed with CE. Sequencing was successfully performed on all endometrial samples obtained by UL) (CE, n = 12; non-CE, n = 118). The median relative abundance of Lactobacillus was 1.89% and 80.7% in the CE and non-CE microbiotas, respectively. Lactobacillus crispatus was less abundant in the CE microbiota (fold-change, range: 2.10–2.30). Eighteen non-Lactobacillus taxa including Dialister, Bifidobacterium, Prevotella, Gardnerella, and Anaerococcus were more abundant in the CE microbiota (fold-change, 2.10–18.9). Of these, Anaerococcus and Gardnerella were negatively correlated in relative abundance with Lactobacillus (SparCC correlation magnitude, range: 0.142–0.177). Conclusion(s) Chronic endometritis was associated with a statistically significantly higher abundance of 18 bacterial taxa in the endometrial cavity. Clinical Trials Registry Number ChiCTR-IOC-16007882.