Characterization of endometrial immune cells during the window of implantation in infertile women with adenomyosis

Adenomyosis, characterized by the invasion of endometrial cells into the myometrium, may disrupt immune homeostasis within the eutopic endometrium, thereby impairing endometrial receptivity. This retrospective case-control study aimed to investigate the endometrial immune cell profile during the window of implantation in infertile women with adenomyosis. Total 103 controls without adenomyosis who achieved live births following in vitro fertilization-embryo transfer treatment and 227 infertile women with adenomyosis underwent endometrial biopsies on days 7-9 after the luteinizing hormone surge. Pro- and anti-inflammatory endometrial immune cells were evaluated using immunohistochemistry and quantitative analysis. Compared with control women, women with adenomyosis exhibited significantly higher percentage of endometrial CD56+ NK cells, CD163+ M2 macrophages, CD1a+ immature DCs, CD8+ cytotoxic T lymphocytes and CD57+ cells. In contrast, the percentage of Foxp3+ Tregs was significantly lower in patients with adenomyosis. No significant differences were observed for CD68+ macrophages between the two groups. After adjusting for age, BMI, hormone levels and infertility duration via multivariable linear regression analysis, adenomyosis remained significantly associated with increased proportions of CD56+ NK proportions (P＜0.001), CD163+ M2 macrophages (P＜0.001), CD1a+ immature DCs (P = 0.002), CD8+ cytotoxic T lymphocytes (P < 0.001), and CD57+ cells (P= 0.031), while with decreased proportion of Foxp3+ Tregs (P= 0.009). In conclusion, the endometria of infertile women with adenomyosis exhibit increased densities of CD56+ NK cells, CD8+ T cells, CD1a+ immature DCs, and CD163+ M2 macrophages, alongside decreased Foxp3+ Tregs, resulting in an altered immune environment.