Endometrial immune profile: A predictor of pregnancy success

The likelihood of a successful pregnancy is influenced by a set of variables that influence endometrial receptivity, including hormonal, genetic, metabolic, age, lifestyle, and immunological factors. Among these, the endometrial immune profile has received particular attention as a critical actor of implantation and embryo tolerance. Dynamic fluctuations in immune cell populations-such as macrophages, dendritic cells, uterine natural killer cells, and regulatory T cells-across the menstrual cycle might significantly affect the endometrium's capacity to support successful implantation. Recent evidence highlights that disruptions in the quantity, phenotype, or function of these immune cells contribute to impaired endometrial receptivity in infertility-related disorders, including recurrent implantation failure, recurrent pregnancy loss, endometriosis, and polycystic ovary syndrome. This review provides a comprehensive assessment of immune cell composition and function in the healthy endometrium compared to pathological conditions, emphasizing how immune dysregulation may impair pregnancy. Furthermore, we evaluate both current and emerging diagnostic modalities-from immunohistochemistry and flow cytometry to high-resolution single-cell transcriptomics-and endometrial microbiome impact on immune profiling that enables more precise characterization of immune profile dysregulation, alongside established and investigational therapies, with particular attention to their efficacy and mechanistic rationale. By integrating these insights, a clinically oriented framework can be provided to guide the development of personalized diagnostic algorithms and targeted immune-based therapies that, ultimately, could lead to improved implantation rates and live birth outcomes in individuals facing infertility disorders with immunological causes.