Higher CD16-NKp46bright uterine endometrial natural killer cells may predict pregnancy success in women experiencing recurrent reproductive failure.

RESEARCH QUESTION: Could CD16-NKp46bright uterine endometrial natural killer (uNK) cells serve as a predictor of pregnancy success in women with unknown recurrent reproductive failure (URRF), and what are the underlying mechanisms involved?

DESIGN

A prospective study involving 63 women with URRF, followed up for 2 years. After age adjustment, 17 women remained in both the pregnant and non-pregnant groups. The pregnant group was further divided into the live birth (n = 10) and miscarriage (n = 4) groups, with three women lost to follow-up. Surface antigens expressed and cytokine produced in uNK cells were analysed with multicolour flow cytometry.

RESULTS

Expression NKp46+ uNK (P = 0.034), NKp46bright uNK (P = 0.045), CD16-NKp46bright uNK (P = 0.026), NKp46brightNKG2D+ uNK (P = 0.004) and NKp46+NKG2D+ uNK (P = 0.037) cells was significantly lower in the non-pregnant group compared with the pregnant group. Also, the expression of CD16-NKp46bright uNK cells was significantly (P = 0.040) higher in the live birth group compared with the non-pregnant group. The threshold 44.9% of CD16-NKp46bright uNK cells showed the largest area under the curve. Women with decreased CD16-NKp46bright uNK cells (<44.9%), produced significantly higher TNF-α+IFN-γ+ in CD56+ uNK (P = 0.014) and in CD56bright uNK cells (P = 0.013) and significantly lower TNF-α-IFN-γ- in CD56+ uNK (P = 0.039) and in CD56bright uNK cells (P = 0.017), and had an elevated risk of failing to achieve live birth or pregnancy (OR 21.60, 95% CI 2.14 to 218.58; P = 0.004 (OR 11.20, 95% CI 2.20 to 56.93; P = 0.005).

CONCLUSIONS

CD16-NKp46bright uNK cells are a protective factor as well as an appropriate candidate for predicting pregnancy success in URRF.