ABSTRACT: Endometrial uNK cells are proposed to have roles in endometrial angiogenesis, embryo implantation, spiral artery remodelling, trophoblast invasion, placental formation and pregnancy success. While there is no clear definition of what ‘normal’ endometrial uNK cell numbers are and a clear lack of conclusive evidence, uNK cell numbers are often used as a prognostic criterion for immunosuppressive intervention in women undergoing IVF. This study was designed to quantify uNK cells and determine their spatial distribution in relation to endometrial arterioles in patients with RIF and implantation success (IS).
METHODS: Endometrial pipelle biopsies were collected 6-8 days post-LH surge in natural cycles from women with RIF (n=14), women with implantation success (IS) (n=11) and women with potential RIF (PRIF) at the time of the study (n=9) from 2013 to 2015. uNK cell numbers and spatial distribution were investigated by standard immunohistochemistry protocols and quantified by deconvolution for single cell quantification using a Gaussian Blur and Yen algorithm.
RESULTS: uNK cell numbers and distribution was not significantly different in women with RIF compared to women with IS. uNK cell density was higher in regions distal to arterioles in both patient groups and this density was reduced with increasing POD. Furthermore, a significant reduction in uNK cell density was observed in women who had a previous pregnancy compared to those who had not, regardless of their current implantation status.
CONCLUSIONS: Our results demonstrated uNK cell numbers and their spatial distribution relative to endometrial arterioles were not altered in women with RIF compared to IS. Our data also demonstrated uNK cell density was significantly influenced by POD and prior pregnancy. Combined, these findings do not support the clinical value of using uNK cell numbers as a prognostic indicators of implantation success due to significant hormonal and immune influences such as POD and pregnancy.