IFN-γ+ NK cells as a potential predictor of pregnancy loss in unexplained recurrent pregnancy loss

Natural Killer (NK) cells are the largest population of lymphocytes in the endometrium during early pregnancy and play a key regulatory role in trophoblast cell invasion and embryo implantation at the maternal-fetal interface. Previous studies on the roles of NK cells with distinct phenotypes in pregnancy loss were based on NK cells derived from the peripheral blood or decidua, and it is difficult to determine whether the reported changes in decidual NK cells are causes or consequences of pregnancy loss.

We aimed at exploring the functional NK cells during the implantation window and their associations with pregnancy outcome.

Using flow cytometry, we assessed the expression of functional markers including Interferon-gamma (IFN-γ) and CD107a in NK cells from unexplained recurrent pregnancy loss (uRPL) patients following coculture with HTR-8/SVneo trophoblast cells during the implantation window, then the associations of functional NK cells with early pregnancy outcomes (≤12 weeks) were explored.

In this exploratory cohort, we found that an increase in the frequency of CD3^-CD56⁺IFN-γ⁺ uNK cells was associated with the recurrence of pregnancy loss in uRPL.

Elevated CD3⁻CD56⁺IFN-γ⁺ uNK cells during the implantation window were associated with early pregnancy loss (≤12 weeks) in women with uRPL, suggesting a potential biomarker that requires validation in larger studies.