Oral dydrogesterone treatment during the first trimester of pregnancy: the prevention of miscarriage study (PROMIS). A double-blind, prospectively randomized, placebo-controlled, parallel group trial.

OBJECTIVE: A planned study to test the hypothesis that dydrogesterone given during the first trimester of pregnancy can positively influence the immune system of women suffering from recurrent miscarriages and thereby lead to successful pregnancies. The primary objective is to show whether the administration of dydrogesterone during the first trimester of pregnancy increases the release of progesterone-induced blocking factor (PIBF) and causes a shift from Th-1 cytokines to Th-2 cytokines. Further objectives are an analysis of pregnancy outcome and to investigate the tolerability and safety of dydrogesterone use during pregnancy. METHODS: A prospectively randomized, placebo-controlled study of 20 mg dydrogesterone per day during the first trimester of pregnancy in women aged between 18 and 38 and with a history of idiopathic recurrent miscarriage. Start of treatment will be after ovulation. The study will be conducted in a two-stage adaptive design, starting with a sample size of 20 patients per treatment group. The concentrations of Th-1 and Th-2 cytokines in the serum and PIBF in the urine will be measured. Efficacy will be measured primarily by the ratio IFNgamma/IL-10. CONCLUSION: The results of this study will contribute to the discussion of a current concept of immunomodulation in pregnancy and potentially provide a treatment option for patients suffering from recurrent miscarriage.