Does progesterone improve outcomes in unexplained recurrent miscarriage?

ASRM (2026) position: additional prospective trials are needed to determine whether progesterone supplementation improves live birth rates in RPL. Vaginal progesterone may be considered in early pregnancy in the setting of vaginal bleeding and/or recurrent unexplained miscarriage, using a shared decision-making model. The trial background. PROMISE, a large multicentre placebo-controlled randomised trial, found vaginal progesterone in the first trimester did not significantly increase live birth in unexplained recurrent miscarriage — though it was limited by starting progesterone only after pregnancy was confirmed. PRISM, in women presenting with early pregnancy bleeding, found a 3% increase in live birth that was not significant overall; in the subgroup with a history of miscarriage presenting with threatened miscarriage, the increase was 5% and reached significance, though the investigators note multiple comparisons were made without statistical adjustment and the finding requires validation. ASRM also states there is no evidence supporting checking progesterone levels in unassisted pregnancies and supplementing based on the level — a practice that remains common. On dydrogesterone: ESHRE (2026), in the luteal support context, records published reports of an association between dydrogesterone exposure and congenital malformations, noting these are potential associations that cannot be translated into a conclusion on causality. Relevant given how widely it is prescribed in India.