Abstract
Maternal immune tolerance to semi-allogeneic fetus is essential for a successful implantation and pregnancy. Growing evidence indicated that low cytotoxic activity of γδ-T cells, which is mediated by activation and inhibitory receptors, is important for establishment of maternal immune tolerant microenvironment. However, the correlation between receptors on peripheral blood γδ-T cells, such as NKG2D, CD158a, and CD158b, and pregnancy outcome in patients with unexplained repeated implantation failure (uRIF) remains unclear. In this study, the association between the expression level of these receptors and pregnancy outcome in patients with uRIF was investigated. Thirty-eight women with uRIF were enrolled and divided into two groups: successful group and failed group, according to the pregnancy outcome on different gestational periods. The percentage of NKG2D+ γδ-T cells in lymphocytes was significantly higher in uRIF patients who had failed clinical pregnancy in subsequent cycle, compared with those who had successful clinical pregnancy. However, there were no differences about the frequencies of CD158a+ and CD158b+ γδ-T cells between the successful and failed groups. The receiver operating characteristic curve exhibited that the optimal cut-off value of NKG2D+ γδ-T cells was 3.24%, with 92.3% sensitivity and 66.7% specificity in predicting clinical pregnancy failure in uRIF patients. The patients with uRIF were further divided into two groups, group 1 (NKG2D+ γδ-T cells <3.24%) and group 2 (NKG2D+ γδ-T cells ≥3.24%), based on the cut-off value. The live birth rate of patients in the group 1 and group 2 were 61.5 and 28.0%, respectively. Kaplan-Meier survival curve further suggested that the frequency of NKG2D+ γδ-T cells in lymphocytes negatively correlated with live birth rate in patients with uRIF. In conclusion, our study demonstrated that the frequency of peripheral blood NKG2D+ γδ-T cells among lymphocytes is a potential predictor for pregnancy outcome in uRIF patients.
Highlights
The current clinical definition of infertility is the state of a diminished capacity to conceive after 12 months of regular sexual intercourse
Our study demonstrated that the frequency of peripheral NKG2D+ γδ-T cells in lymphocytes was significantly increased in the unexplained repeated implantation failure (uRIF) patients with failure of implantation or clinical pregnancy compared to that in the uRIF patients with corresponding successful pregnancy
These results suggest that the NKG2D on γδ-T cell is a potential biochemical predictor for pregnancy outcome in uRIF patients
Summary
The current clinical definition of infertility is the state of a diminished capacity to conceive after 12 months of regular sexual intercourse. Assisted reproductive technologies helped numerous infertile couples in achieving a successful pregnancy, 10–15% of the infertile couples who were subjected to assisted reproductive technology treatment experienced failure to conceive after multiple in vitro fertilization-embryo transfer (IVF-ET) cycles [2]. These patients are defined as repeated implantation failure (RIF) patients. After ruling out the RIF patients with above common etiology, there are still some patients with unknown etiology. These RIF patients are defined as unexplained RIF (uRIF) patients
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