Oral Prostaglandins for Labor Induction

Are oral prostaglandins as safe and effective as oxytocin for induction of labor in pregnant patients with rupture of membranes at term but before labor onset (ie, premature rupture of membranes [PROM])?

In pregnant patients with PROM, oral prostaglandins (eg, misoprostol) are as effective as intravenous (IV) oxytocin infusion for achieving vaginal delivery within 24 hours of initiation. (Strength of Recommendation [SOR]: A, meta-analyses of randomized controlled trials [RCTs] and subsequent RCTs.) Use of oral misoprostol is associated with similar risks of uterine hyperstimulation, tachysystole, need for cesarean delivery, and meconium-stained amniotic fluid as use of IV oxytocin. (SOR: A, meta-analysis of RCTs.)

A 2014 systematic review and meta-analysis broadly assessed use of oral misoprostol for labor induction in the third trimester. A subgroup analysis compared oral misoprostol with oxytocin in pregnant patients with PROM. Patients in this group were predominantly nulliparous with initial Bishop scores of 4.5 to 6.0. Trials were conducted in a variety of predominantly tertiary care settings in multiple countries. Misoprostol regimens varied, with most dosages between 50 and 100 mcg every 4 or 6 hours.¹

Researchers found no significant difference between the misoprostol and oxytocin groups for several outcomes. These included delivery after 24 hours (three trials; n = 265; relative risk [RR] = 0.95; 95% CI, 0.56–1.64), uterine hyperstimulation causing fetal heart rate changes (six trials; n = 749; RR = 1.0; 95% CI, 0.33–3.05), or cesarean delivery rates (six trials; n = 758; RR = 0.92; 95% CI, 0.66–1.28). Four trials (n = 648) found no statistical difference in the rate of meconium-stained amniotic fluid. One trial (n = 40) assessed the outcome of serious maternal and neonatal morbidity or death with no events in either group. There were high risks of performance and detection bias, and significant heterogeneity of the misoprostol dosing regimens.¹

A 2020 systematic review analyzed the effectiveness of oral misoprostol for labor induction in patients with PROM. Six trials (three were included in the previously cited review and three were published afterward) compared various regimens of oral misoprostol with IV oxytocin (per local protocol) in term pregnant patients with singleton gestations, no contraindication to vaginal delivery, and confirmed PROM who were not yet in labor.²

Two trials that compared 100 mcg of misoprostol every 6 hours with oxytocin infusion (n = 405) found the rate of vaginal delivery was similar in the two groups (79.9% vs 80.1%; RR = 1.18; 95% CI, 0.81–1.73). Four trials used different dosages of misoprostol (ie, 20 mcg every 2 hours, 25 mcg every 4 hours, 75 mcg every 4 hours, and 100 mcg every 4 hours) and all reported similar rates of vaginal delivery between treatment groups. The authors noted that the rate of uterine hyperstimulation was similar between treatment groups in the eight studies that evaluated this outcome. The authors rated the quality of all trials in the review as moderate or high. One limitation was the inclusion of a single study that used sublingual rather than oral misoprostol. Also, for reasons not evident in the published search methodology, two relevant published trials that were included in the previously cited review were not included in this analysis.²