Immune phenotype of the endometrium in patients with recurrent implantation failures after the transfer of genetically tested embryos in assisted reproductive technology programs.

Recurrent implantation failures (RIF) in assisted reproduction programs are one of the most challenging problems. Among the factors that can adversely affect implantation, endometrial immune structural disorders may be one of the leading causes. The aim of our work was to study the immune features of the endometrium in women with RIF after genetically tested embryo transfer in comparison with fertile gestational carriers. Immune cells in endometrial samples were studied by flow cytometry and RNA expression of IL (interleukin)15, IL18, fibroblast growth factor-inducible 14 receptor (Fn14), and tumor necrosis factor-like weak inducer of apoptosis (TWEAK) by reverse polymerase chain reaction. In one-third of the cases, a unique immune profile of the endometrium, which we called the not transformed endometrial immune phenotype, was found. It is characterized by a combination of features, such as high expression of HLA-DR on natural killers (NK), increased fraction of CD16 + , and a decreased fraction of CD56bright endometrial NK. In addition, when compared to gestational carriers, patients with RIF had a greater discrepancy between IL18 mRNA expression data, reduced mean TWEAK and Fn14 levels, and increased IL18/TWEAK and IL15/Fn14 ratios. Immune abnormalities that were found in more than half of the patients (66.7 %) may be the cause of implantation failures in genetically tested embryo transfer programs.