Elevated NK cell cytotoxicity, CD158a expression in NK cells and activated T lymphocytes in peripheral blood of women with IVF failures.

PROBLEM: The aim of this study was to evaluate the role of elevated natural killer cytotoxicity (NKc) in women with multiple implantation failures (IF) in vitro fertilization-embryo transfer (IVF-ET) cycles.

METHODS OF STUDY: Seventy-nine antiphospholipid antibodies-negative women with IF including 33 women with elevated NKc were selected for investigation. K-562 cell line was used to evaluate NKc. Lymphocyte subsets, intracellular cytokines [interferon (IFN)-gamma, interleukin (IL)-4, tumour necrosis factor, IL-10], expression of activating markers [CD69, human leukocyte antigen (HLA)-DR], CD8, KIR (CD158a), CD95, and chemokine receptors (CXCR3, CCR4) were estimated by flow cytometry.

RESULTS

In women with IF, levels of NKc were higher than in IVF successful women. IF was associated with higher expression of CD8, CD158a, and HLA-DR in NK cells, activating markers in T lymphocytes, and lower levels of CCR4+ and IL-4+ T lymphocyte subsets. Predictive value of single elevated NKc for IVF success was 0.85, but addition of two other abnormal parameters resulted in its decrease to <0.39.

CONCLUSIONS

Elevated NKc is negative factor, though not critical for implantation in IVF cycles. Immune mechanism of IVF failure includes not only elevated NKc but also some other factors, such as elevated expression of CD8 and CD158a on NK cells, T lymphocyte activation, and diminished T helper 2 parameters.