Evaluation of peripheral and uterine immune status of chronic endometritis in patients with recurrent reproductive failure

Abstract

Objective: To investigate whether chronic endometritis (CE) affects the immune status of peripheral blood and endometrium in patients with recurrent reproductive failure (RRF).

Design: Retrospective study.

Setting: Private fertility center.

Patients(s): A total of 524 RRF patients, including 324 women with recurrent miscarriage (RM) and 200 women with recurrent implantation failure (RIF).

Intervention(s): Peripheral blood and endometrium samples were collected in the midluteal phase before in vitro fertilization treatment or pregnancy. The number of peripheral T, natural killer (NK), and B cells, as well as cytotoxicity of NK cells and expression of T_H1 cytokines were analyzed with the use of flow cytometry, and uterine immune cells were subjected to immunohistochemistry.

Main outcome measure(s): Peripheral immune cells, cytokines, NK cytotoxicity, and endometrial immune cells were compared in RRF patients with versus without CE.

Result(s): The proportion and function of the analyzed immune cell subsets in peripheral blood as well as the percentages of CD56⁺ NK cells, CD163⁺ M2 macrophages, and CD1a⁺ immature dendritic cells in the endometrium were not significantly altered between non-CE and CE patients, whereas the proportions of uterine CD68⁺ macrophages, CD83⁺ mature dendritic cells, CD8⁺ T cells, and Foxp3⁺ regulatory T cells were significantly elevated in CE patients. After antibiotic treatment, the percentage of CD68⁺ macrophages, CD83⁺ mature dendritic cells, CD8⁺ T cells, and Foxp3⁺ regulatory T cells in endometrium were significantly reduced in patients with cured CE.

Conclusion(s): CE contributes to elevated endometrial infiltration levels of immune cells. The excessive presence of endometrial immune cells in CE patients may be involved in reduced endometrial receptivity and recurrent pregnancy failures.

Keywords: Chronic endometritis; immune cells; recurrent implantation failure; recurrent miscarriage.