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

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.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.