Quantitative and functional changes in peripheral natural killer cells in women with reproductive failure after artificial insemination with donor sperm

Considerable evidence indicates that quantitative and/or functional abnormalities of natural killer (NK) cells are associated with reproductive failure. The objective of this study was to determine if peripheral NK percentage and activity are altered in women with reproductive failure after artificial insemination by donor (AID), and which parameters can best discriminate women with AID failure and normal controls. A case–control study of 20 fertile controls, 25 patients undergoing more than four treatment cycles without success (Group I), 25 experiencing biochemical pregnancy loss (Group II), and 25 undergoing embryo growth arrest or miscarriage (Group III) was performed. The peripheral NK percentage and cytotoxicity was evaluated by flow cytometry. Our results showed that a significantly increased percentage of NK cell cytotoxicity (NKCC) was detected in all study groups compared with the controls. The percentage of CD56+ NK cells was elevated in Groups II and III compared with the controls. The percentage of CD56+CD16+ NK cells in the study groups was higher than that in the controls. By using receiver operating characteristic curve and logistic regression analysis, we found that NKCC combined with CD56+CD16+ NK percentage had good predictive power. The overall predicted percentage correct was 0.89. These results suggest that enhanced NKCC and an elevated cytotoxic NK percentage may be associated with AID failure and can be biomarkers for predicting AID-induced failure.