Endometrial microbiota in infertile women with and without chronic endometritis as diagnosed using a quantitative and reference range-based method

Abstract

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.

Keywords: 16S ribosomal RNA; Chronic endometritis; endometrial cavity; microbiome.