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

Abstract

Objective 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. Design Controlled clinical study. Setting Research unit of a university hospital. Patient(s) Thirty-five women with repeated implantation failure after ET in IVF and 12 fertile control patients. Intervention(s) Ultrasound evaluation and endometrial biopsy on day 20. Main outcome measure(s) The balance between IL-12 and IL-18, the number of NK cells, and the vascular status among fertile and implantation failure patients. Result(s) 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. Conclusion(s) Distinctions between the different local dysregulations of the cytokine network may provide clues for further exploration and treatment.