Establishment of reference intervals of endometrial immune cells during the mid-luteal phase

Abstract

This study aimed to develop reference intervals (RIs) of endometrial immune cells in control infertile women during the mid-luteal phase, and compare with the proportion of endometrial immune cells in recurrent reproductive failure (RRF) patients. Endometrial tissue sections were obtained from 113 fertile women and 79 patients with RRF, including 40 patients who had suffered recurrent miscarriage (RM) and 39 patients with repeated implantation failure (RIF) during the mid-luteal phase of the menstrual cycle. Immunohistochemical staining and quantitative analysis of CD56⁺, Foxp3⁺, CD163⁺, CD1a⁺ and CD8⁺ cells were performed in endometriums. RIs of endometrial immune cells in control infertile women were as follows: CD56⁺ uterine natural killer cells (uNK) cells, 1.785-8.712%, forkhead box P3 (Foxp3)⁺ Tregs, 0.041-0.154%, CD163⁺ M2 macrophages, 0.298-1.492%, CD1a⁺ dendritic cells (DCs), 0.006-0.081% and CD8⁺ T cells, 0.674-2.504%. Compared with control infertile women, the percentage of endometrial CD56⁺ uNK cells, CD163⁺ M2 macrophages, CD1a⁺ DCs and CD8⁺ T cells were significantly increased in patients with RRF. Moreover, Foxp3⁺ Tregs levels were decreased in patients with RRF, and were statistically significant only in patients with RM. In conclusion, the RIs of endometrial immune cells were established in control infertile women during the mid-luteal phase, and a disordered endometrial immune microenvironment was observed in patients with RRF. The RIs of endometrial immune cells may be of important clinical significance for the treatment of RRF.

Keywords: Endometrium; Immune cells; Mid-luteal phase; Recurrent reproductive failure; Reference intervals.