The effect of progesterone treatment on natural killer cell functional activity and progesterone-induced blocking factor secretion in pregnant women with a history of recurrent pregnancy loss

BACKGROUND: Progesterone is a steroid hormone that plays a crucial role in regulating reproductive processes in women. Its decreased secretion can increase the risk of miscarriage. Progesterone-induced blocking factor is a protein that acts as a mediator of progesterone’s effects. In cases of spontaneous miscarriages, the serum concentration of this protein is lower than during normal pregnancies. It is believed that progesterone-induced blocking factor may affect the functional activity of natural killer cells, which are essential for early pregnancy development. However, studies that thoroughly evaluate the effects of different forms of progesterone on natural killer cell functional activity in reproductive failure are lacking.

AIM: The aim of this study was to evaluate the effects of micronized progesterone and dydrogesterone on the functional activity of natural killer cells and progesterone-induced blocking factor levels in pregnant women with a history of recurrent pregnancy loss.

METHODS: The levels of progesterone and progesterone-induced blocking factor were measured in the peripheral blood serum of pregnant women with a history of miscarriage who received micronized progesterone (group 1) or dydrogesterone (group 2). We also assessed the content of natural killer cells in the peripheral blood, their functional activity as measured by the CD107a degranulation marker, and their cytotoxic activity against JEG-3 trophoblast cells. The parameters were measured twice: at 8–10 weeks (first visit) and 13–15 weeks (second visit).

RESULTS: At the first visit, group 1 showed lower cytotoxicity of natural killer cells compared to group 2 (p = 0.018). Both groups showed an increase in progesterone levels at the second visit compared to the first visit. Against the background of micronized progesterone administration, we observed an increase in PC-induced activated CD107a⁺ natural killer cells (p = 0.019). At the second visit, a negative correlation was found in group 1 between progesterone levels and the cytotoxic effect of natural killer cells on trophoblast cells (r = −0.94, p = 0.008). A similar correlation was found in group 2 between progesterone levels and the content of PC-induced activated CD107a⁺(i) natural killer cells (r = −0.724, p = 0.044). We observed no changes in the blood serum concentration of progesterone-induced blocking factor in the study groups.

CONCLUSION: The effects of micronized progesterone and dydrogesterone preparations on the functional activity of natural killer cells in pregnant women with a history of recurrent pregnancy loss have been established. Research into the effects of progesterone preparations on production of pregnancy-induced blocking factor and the functional activity of natural killer cells could lead to the pathologically justified use of this type of treatment to prevent miscarriage in women with recurrent pregnancy loss.