Progestogens in threatened miscarriage

Threatened miscarriage (bleeding during the first 20 weeks of pregnancy) may progress to miscarriage or may resolve. Progestational agents have been prescribed since the 1950s in order to prevent threatened miscarriage progressing to miscarriage. There is much theoretical data to support the use of progestogens. Progestogens affect implantation, cytokine balance, natural killer cell activity, arachidonic acid release and myometrial contractility. Therefore, the question arises whether progestogens should be used in threatened miscarriage. A recent Cochrane review found progestogens to be effective for the treatment of threatened miscarriage with no harmful effects on mother or fetus. Two trials of dydrogesterone and two trials of vaginal progesterone were compared to placebo. The overall results showed a statistically significant result in favour of progestogens. The results were not statistically different for vaginal progesterone (RR = 0.47 95 % CI, 0.17–1.30), whereas dydrogesterone was effective (RR = 0.54 CI 0.35–0.84). Based on these results, both the U.K. National Institute of Health and Care excellence (NICE) and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) have claimed that progestogens improve the prognosis, but indicated the need for further trials. The author tried to expand the figures in the Cochrane review by including less robust trials in an expanded analysis. At that time there were no further trials available on vaginal progesterone although one further trial of vaginal micronised progesterone has since been published. Three additional randomised trials were identified comparing dydrogesterone to standard management in threatened miscarriage. 660 patients were eligible for analyses. There was a 47 % reduction in the miscarriage rate (OR = 0.47 CI 0.31–0.7), there was a 13 % (44/335) miscarriage rate after dydrogesterone administration compared to 24 % in control women.