Age- and endometrial microbiota-related delay in development of endometrial receptivity.

Purpose: We evaluated factors affecting the development of endometrial receptivity according to age and changes in the endometrial microbiota.

Methods: We recruited patients with infertility who underwent transcriptomic analyses of endometrial receptivity and the endometrial microbiome prior to frozen embryo transfer. An endometrial biopsy was performed 108 h after initial progesterone administration.

Results: In 185 tests from 185 eligible patients, the results of endometrial receptivity analysis were receptive in 111 (60.0%) patients and pre-receptive in 74 (40.0%) patients. Compared with receptive patients, pre-receptive patients had significantly older ages (36.0 ± 0.5 vs. 38.2 ± 0.5, p = 0.0021), a smaller proportion of normal Lactobacillus-dominant microbiota (27.9% vs. 12.2%), and a greater proportion of microbiota with ultralow biomass (22.5% vs. 41.9%) (p = 0.0074). Patient age (adjusted odds ratio: 1.08, 95% confidence interval: 1.01-1.16, p = 0.0351) and a microbiome with ultralow biomass (adjusted odds ratio: 3.82, 95% confidence interval: 1.49-9.82, p = 0.0039) were independent predictive factors for pre-receptive endometrium.

Conclusions: Older age was accompanied by a decrease in Lactobacillus-dominant microbiota; aging and endometrial microbiota with ultralow biomass were significantly associated with pre-receptive endometrium. Our findings suggest that the quantity (rather than proportion) of Lactobacillus in the endometrium is important in the development of endometrial receptivity.