Clustering of Uterine Natural Killer Cells Around Uterine Glands in Women with Recurrent Implantation Failure and Recurrent Pregnancy Loss: an Immunohistochemical Study

The immunological factor of sterility, specifically the abnormal count and activity of uterine NK (uNK) cells, may represent one of the potential contributors affecting specific subgroups of sterile couples undergoing assisted reproductive treatment (ART). Therefore, the primary purpose of the present paper was to assess uNK cell count. A total of 387 endometrial biopsies from patients with recurrent implantation failure (RIF) or recurrent pregnancy loss (RPL) were analyzed to identify abnormalities in uNK cell count, using immunohistopathological evaluation. ANOVA analysis revealed a strong association with factor 0.161 with p-value < 0.01, indicating that higher uNK cell count is associated with the presence of clusters (multicellular aggregates of uNK cells). These results suggest that the formation of clusters and the spatial distribution of uNK cells are significant factors in the context of the aforementioned clinical questions. However, the actual translational potential to clinical practice has not yet been established due to several challenges, namely: 1. the constantly changing definitions and diagnostic criteria for RIF and RPL, 2. varying sampling approaches for uNK cells, and 3. the historical lack of clear differentiation between uterine and peripheral NK cells. When all these issues are resolved, the observed tendency of uNK cells to form clusters will need to be a central focus of future investigations addressing RIF and RPL, thus improving ART outcomes.