Vaginal Progesterone as Maintenance Treatment After an Episode of Preterm Labour (PROMISE) Study: A Multicentre, Double-blind, Randomised, Placebo-Controlled Trial

A large proportion of both short-term neonatal morbidity and mortality and long-term disability is associated with preterm birth. Women with previous preterm delivery, a short cervical length atmidgestation, a twin pregnancy, and an episode of preterm labor arrested with tocolytic medication all have an increased risk of preterm delivery. Progestogens reduce preterm birth in women with previous preterm delivery or with a short cervix, but not in women carrying twins. It has been observed that maintenance tocolytic therapy after treatment of preterm labor does not reduce the incidence of preterm delivery or improve perinatal outcome. Hence, a multicenter, double-blind, randomized, placebo-controlled clinical trial was conducted to determine the use of vaginal progesterone as a maintenance treatment in women with arrested preterm labor (PROMISE study) to prevent preterm delivery after hospital discharge. The results noted that there were no statistically significant differences between the progesterone and placebo groups regarding the primary outcome of preterm delivery before 34 (7.1% vs 7.6%) and 37 weeks (28.6% vs 22%) of gestation. No differences were observed between the 2 groups at randomization when the 2 strata of gestational age at 34 and 37 (10.5% vs 11.5%) weeks of gestation or cervical length were evaluated. There was no difference between the 2 groups in the secondary outcomes of the study (discharge-to-delivery time, readmissions because of preterm labor, emergency service availed, or neonatal morbidity and mortality). Robust design and the use of a placebo were strengths of the study; however, low sample size due to discontinuance of insurance funding was a limiting factor to this study. In conclusion, a maintenance treatment of 200 mg/d of natural micronized progesterone in women discharged home after arrested preterm labor and with a cervical length of less than 25 mm did not reduce the rate of preterm birth at less than 34 and less than 37 weeks of gestation.