Intravenous immunoglobulin (IVIG) as infertility treatment is supposed to affect the cytotoxic function of NK cells, but the underlying mechanism remains unclear. Objective: To investigate the effect of IVIG on the cytotoxicity of NK cells against target cells of K-562 line and trophoblast cells of JEG-3 line. Materials and methods: This study analyzed the cytotoxicity of NK-92 cells against K-562 cells and JEG-3 trophoblast cells in the presence of IVIG and that of peripheral blood NK cells in the mononuclear fraction against JEG-3 cells in the presence of IVIG. Mononuclear cells were obtained from the peripheral blood of healthy nonpregnant donors (group 1, n=10) and healthy nonpregnant fertile women (group 2, n=12). Results: Cell death of the JEG-3 line in the presence of mononuclear cells from Group 1 and IVIG at concentrations of 12 and 6 mg/mL was lower than that without IVIG (p<0.01 and p<0.05, respectively). Cell death of the JEG-3 line in the presence of mononuclear cells from group 2 and IVIG at concentrations of 12, 6, and 1.5 mg/ml was lower than that without IVIG (p<0.001, p<0.001, and p<0.01, respectively). Conclusion: Contact interaction between trophoblast cells and IVIG is associated with lower cytotoxicity of NK cells against trophoblast cells. More studies are needed to predict the effectiveness of IVIG therapy in patients with reproductive disorders.