Misoprostol is a common agent that is used to ripen the cervix and induce labor, yet there is no clear evidence of the optimal number of doses needed to achieve a higher rate of vaginal delivery.

Our primary objective was to compare the rate of vaginal delivery within 24 hours between a 1-dose and a multiple-dose regimen of misoprostol for the induction of labor.

A randomized controlled trial was conducted from March 2016 to March 2017 that compared a single dose to up to 4 doses of misoprostol. Randomization was stratified by parity. Women with a singleton pregnancy ≥37 weeks gestation with intact membranes who had been admitted for labor induction with a Bishop score ≤6 were included. Our primary outcome was the rate of vaginal delivery within 24 hours. Secondary outcomes included time to vaginal delivery, cesarean delivery rate, and maternal and neonatal morbidity. Based on a power of 80%, an alpha of .05, and the assumption that 50% of women in the multiple-misoprostol group would deliver vaginally in 24 hours, a sample size of 220 patients was needed to detect a 20% increase in vaginal delivery rate within 24 hours in the 1-misoprostol group. Continuous variables were compared with the use of the Mann-Whitney test. Categoric variables were compared with the use of the Fisher’s exact test. Probability values <.05 were considered statistically significant.

Two hundred fifty women were assigned randomly. Demographics and clinical characteristics were similar between groups. In the univariate analysis, there was no difference in the rate of vaginal delivery within 24 hours between the 1-misoprostol group and the multiple-dose group (41.7% vs 44.7%, respectively; P=.698) or time to vaginal delivery (1187 min vs 1321 min, respectively; P=.202). The 1-misoprostol group had a greater cesarean delivery rate (35.8% vs 22.8%; P=.034). In a Poisson regression that controlled for Bishop score before the initiation of oxytocin, parity, gestational age, body mass index, estimated fetal weight, artificial rupture of membrane at <6 cm, and Foley balloon placement, the treatment group was no longer associated with cesarean delivery rate. Instead, a Bishop score of <4 before the initiation of oxytocin and nulliparity were associated significantly with cesarean delivery rate.

In this first randomized controlled trial in the literature to compare a single with a multiple dosing of misoprostol, we found that the 1-dose regimen is an acceptable alternative for the induction for labor, especially for multiparous women and for patients with a Bishop score >4 after the first dose.