Correlation of NK cell activation and inhibition markers with NK cytoxicity among women experiencing immunologic implantation failure after in vitro fertilization and embryo transfer

Purpose: The pivotal event in determining successful from unsuccessful cycles after in vitro fertilization is implantation. The purpose of this study was to compare the percentage of circulating NK cells expressing activation and inhibition markers between infertile and fertile control women and to determine the correlation between these markers and those of the NK cytotoxicity activation assay. Lastly, we wish to determine the ability of each of these markers to predict pregnancy outcome after IVF/ET (in vitro fertilization/embryo transfer). Methods: Blood samples from 22 infertile women undergoing IVF/ET during the November 2001 cycle were drawn on cycle Day 9 and analyzed for expression of CD69+, HLA-DR, CD161+, CD94+, and CD158a+ as well as NK cytotoxicity using immunoflluorescent labeling and flow cytometry. Results were compared with those from 26 fertile control women and correlated to pregnancy outcome that of cycle. Results: Infertile women had significantly higher expression of NK cell activation markers of CD69+ and CD161+ than fertile women. NK cytotoxicity correlated inversely with expression of NK cells bearing the inhibition marker of CD94+. None of the successfully pregnant women of that cycle had elevated levels of NK cytotoxicity whereas 50% of those experiencing a chemical pregnancy loss and those not becoming pregnant had elevated levels of NK cytotoxicity. Conclusions: Immunologic markers can identify mechanisms involved in implantation failure. Activation markers of CD69+ and CD161+ expressed on NK cells as well as NK cytotoxicity can be added to the previously reported risk factors for immunologic implantation failure.