Peri-conceptional progesterone treatment in women with unexplained recurrent miscarriage: a randomized double-blind placebo-controlled trial.

OBJECTIVE: The current study aims to evaluate the effect of peri-conceptional progesterone started early in the luteal phase before confirmation of pregnancy in preventing miscarriage in women with history of unexplained recurrent miscarriage (RM).

MATERIALS AND METHODS: The current study was a randomized double-blind controlled trial (NCT01608347) conducted at Assiut Women's Health Hospital from 2012 through 2015 included patients of unexplained RM. Participants were randomly assigned to receive either 400 mg progesterone pessaries or placebo twice daily, started in the luteal phase and continued after a positive pregnancy test till 28 weeks of gestation. The main study outcome was the miscarriage rate.

RESULTS: Seven hundred women were enrolled (n = 350 in each group). The miscarriage rate was significantly lower in progesterone group (12.4 versus 23.3% in the placebo group, p = 0.001). There was significant improvement in rate of pregnancy continuation beyond 20 weeks as well as the live birth rate in the progesterone group in comparison to placebo group (87.6 versus 76.7% and 91.6 versus 77.4%, respectively, p < 0.05).

CONCLUSIONS: Progesterone is more effective than placebo in reducing the risk of miscarriage if administered in the luteal phase of the cycle, before confirmation of pregnancy in women with history of unexplained RM.