The Role of Endometrial CD16+ Natural Killer Cells in Unexplained Infertility A Controlled Clinical Trial

Abstract

Unexplained infertility refers to the absence of a definable cause for a couple's failure to achieve pregnancy after 12 months of attempting conception despite a thorough evaluation, or after six months in women 35. Unexplained infertility is one of the most common diagnoses in a fertility clinic. The lack of an accurate diagnosis in reproductive medicine leads to treatment failure. Among potential biochemical diagnostic markers, cytokines and immune cells constitute important tools to differentiate treatment groups. Moreover, natural killer (NK) cells count is one of the best characterized immunological marker in reproductive failure. For this reason, new treatments are designed to modulate the number and function of these cells in infertile patients. However, more studies need to be conducted to characterize and differentiate endometrial NK cells in different reproductive pathologies such as recurrent spontaneous abortion and implantation failure. Most published data based on abnormal counts of NK cell were performed in peripheral blood of patients with recurrent abortions. Furthermore, functional parameters should be tested to associate NK cell counts with NK cell activity. In this sense, previously postulated that the switch from an inflammatory to an antiinflammatory response may modulate the ratio between CD16+/CD16 NK cell count. Thus we here in our study investigated the possible role of uterine cytotoxic CD16+ NK cells and unexplained infertility using flowcytometry that provide a much better analysis of NK cell populations than most studies that was performed by histological evaluation, where differences in NK cell subsets are limited.