In vitro studies indicate that estradiol and progesterone can reduce IL-18 level in the cultured endometrial stromal cells from patients who experienced spontaneous abortion, which helps to improve the pregnant outcomes [31].This is because IL-18 is a strong enhancer of IL-12 that can behave as proinflammatory cytokine engaging in cytolytic effects of uNK cells at excessive doses to cause pregnancy loss (Fig. 1) [32]. The gene discussed is IL18; the disease is abortion.