A new role for natural killer cells, interleukin (IL)-12, and IL-18 in repeated implantation failure after in vitro fertilization

To investigate the endometrial immunohistochemical staining of interleukin (IL)-12 and IL-18 and to quantify the CD56 bright natural killer (NK) cells in relation to Doppler vascular disorders. Controlled clinical study. Research unit of a university hospital. Thirty-five women with repeated implantation failure after ET in IVF and 12 fertile control patients. Ultrasound evaluation and endometrial biopsy on day 20. The balance between IL-12 and IL-18, the number of NK cells, and the vascular status among fertile and implantation failure patients. The control patients displayed normal vascular parameters, a weak anti–IL-12 staining, a consistent moderate stromal anti–IL-18 staining, and fewer than 15 NK cells/field. This pattern was observed among only 17% (6/35) of the implantation failure group. The remaining patients fit into one of two patterns: [1] 37% (13/35) had more than 40 NK cells/field with a strong anti–IL-12 and/or anti–IL-18 staining, and [2] the remaining 46% (16/35) had a marked local depletion of IL-18 and IL-12. Respectively, 85% and 31% of two groups displayed abnormal vascular parameters. Distinctions between the different local dysregulations of the cytokine network may provide clues for further exploration and treatment.