Vaginal misoprostol superior to buccal route for cervical ripening at term pregnancy

Reference

Haas DM, Daggy J, flannery KM, at al. A comparison of vaginal versus buccal misoprostol for cervical ripening in women for labor induction at term (the IMPROVE trial): a triple-masked randomized controlled trial. Am J Obset Gynecol 2019;221:259.e1-16.

Synopsis

This was a high quality randomized, double-blinded trial of vaginal versus buccal route for administration of misoprostol for cervical ripening for women undergoing induction at term pregnancy. Women participants (n=300) were eligible if at least 14 years old with medically indicated induction of labor at 37 0/7 weeks or more or elective induction after 39 weeks, singleton pregnancy in cephalic presentation, and Bishop score of 6 or less. Women were excluded if they had a uterine scar, evidence of fetal compromise on electronic fetal monitoring before medication administration or known major fetal anomaly. Study protocol included misoprostol tablets (100 mcg) or identical appearing placebo for both routes of administration, cut into halves or quarters for 50 and 25 mcg doses, respectively. Tablets were supplied in packages with doses for buccal (BM) and vaginal (VM) administration included, and active medication was vaginal or buccal in 1:1 proportion. Both active medication and placebo were administered to each patient. Initial dose was 25 mcg, with subsequent doses of 50 mcg every 4 hours up to a maximum of 7 total. Medication was stopped if cervical ripening was deemed no longer needed, tachysystole or nonreassuring fetal status developed or maximum doses had been given. Vaginal delivery was achieved in 81% of cases. Median time to (vaginal) delivery was the primary efficacy measure and favored VM (20.1 h, CI 18.2-22.8 vs 28.1 h CI 24.1-31.4, P=.006). The primary safety measure was cesarean section for fetal nonreassuance, which also trended in favor of VM, (5/152 [3.3%] vs 14/148 [9.5%], P=0.33). Secondary outcomes that also favored VM were rate of vaginal delivery within 24 h (59% vs 39%, RR 1.49, CI 1.17-1.90, P=.001), doses of misoprostol to achieve active labor (median 2 vs 3, P< .001), and maximum dose of oxytocin used (4 mU/min vs 6 mU/min, P=.001). The difference in overall cesarean rate did not reach statistical significance (VM 16% vs BM 22%, P= .15), but the study was not powered for the outcome and a 6 percentage point difference would arguably be clinically significant.