Progestin supplementation appears to be a promising approach to both preventing initiation of pre-term labor and treating it once it is already established. Successful pregnancy depends on maternal tolerance of the fetal "semi-allograft". A protein called progesterone-induced blocking factor (PIBF), by inducing a Th2 dominant cytokine production mediates the immunological effects of progesterone. Over time, various attempts have been made to clarify the question, whether progestogens can contribute positively to either prevention or treatment of pre-term labor and birth. Dydrogesterone treatment of women at risk of pre-term delivery results in increased PIBF production and IL-10 concentrations, and lower concentrations of IFNγ and could be effective for prevention or treatment of pre-term labor. Further randomized studies are needed.