Timing of endometrial biopsy for chronic endometritis diagnosis: CD138 + and CD56 + cell variability throughout the menstrual cycle

Purpose To evaluate the variability in the distribution of uterine plasma cells CD138+ and Natural Killer (NK) CD56+ cells throughout the menstrual cycle in patients with Recurrent Implantation Failure (RIF) or Recurrent Pregnancy Loss (RPL) undergoing endometrial biopsy for Chronic Endometritis (CE) diagnosis.Materials and methods A retrospective cohort study was conducted on women with RIF or RPL undergoing diagnostic workup between 2018 and 2025. Endometrial biopsies were performed during either the proliferative or secretive phase of the menstrual cycle.Results 249 women were included. According to histology, 117 (47%) samples were collected in the proliferative phase and 132 (53%) in the secretive phase. Univariate and multivariate analyses showed no significant differences in CD138+ positivity between phases, both using a more restrictive cut-off (>5/10 HPFs) (5.98% vs. 7.58%, OR (95% CI) 1.29 (0.47; 3.5), p = 0.620; aOR (95% CI) 1.49 (0.51; 4.69), p = 0.474) and a broader one (≥1/10 HPFs) (17.09% vs. 12.12%, OR (95% CI) 0.67 (0.33; 1.36), p = 0.267; aOR (95% CI) 0.74 (0.33; 1.61), p = 0.450). Likewise, NK CD56+ positivity did not significantly differ between groups using either a stricter cut-off (>10%) (25.66 vs. 29.55%, OR (95% CI) 1.21 (0.69; 2.13), p = 0.499; aOR 1.34, 95% CI: 0.73–2.51, p = 0.350) or a more comprehensive one (>4.5%) (68.14% vs. 68.94%, OR (95% CI) 1.04 (0.6;1.78), p = 0.893; aOR 0.88, 95% CI: 0.49–1.59, p = 0.679).Conclusions In patients with RPL or RIF, endometrial biopsy shows similar CD138+ and CD56+ positivity rates in both proliferative and secretive phases. These findings suggest that biopsy timing may not substantially affect detection rates.