Since 1997, many more randomized controlled trials of vaginal misoprostol for third-trimester cervical ripening or induction of labor with a viable fetus have been completed. The Cochrane Pregnancy and Childbirth Group recently analyzed 45 randomized trials of sound methodological quality, which collectively included more than 5400 women. The trials included in this metanalysis compared vaginal misoprostol with placebo, oxytocin, prostaglandin E2, or oral misoprostol. Studies comparing different vaginal misoprostol-dosing regimens were also included. The primary outcomes measured were the efficacy of inducing vaginal delivery within 24 hours, the incidence of uterine hyperstimulation with associated fetal heart rate changes, the rates of cesarean delivery, and serious adverse effects for the fetus or mother.
Vaginal misoprostol (25-100 mcg) was more effective than oxytocin or vaginal prostaglandin E2 at effecting vaginal delivery within 24 hours without an increase in the frequency of uterine hyperstimulation associated with fetal heart rate changes. Compared to induction of labor with oxytocin alone, induction with misoprostol was associated with an overall reduction in cesarean delivery rates. However, cesarean rates were no different for women induced with misoprostol compared with women induced with prostaglandin E2. An earlier metanalysis from the Cochrane group suggested that labor induction with misoprostol was associated with more uterine hyperstimulation with associated fetal heart changes and more frequent meconium staining than induction of labor with prostaglandin E2. The most recent analysis found these associations still true when misoprostol was compared with intracervical prostaglandin E2 but not significant when misoprostol was compared with vaginal prostaglandin E2. The authors of this review found no differences in serious neonatal or maternal morbidity or mortality between women who received misoprostol and those who received oxytocin or prostaglandin E2. However, the incidence and relative risk of rare adverse outcomes with the use of misoprostol for induction of labor remains unknown. The Cochrane group estimated that cumulatively it would require approximately 61,000 patients enrolled in randomized controlled trials to detect a clinically significant difference in serious perinatal morbidity and mortality and approximately 155,000 patients to detect a clinically significant difference in maternal death or serious morbidity with misoprostol compared with other induction agents. This volume of data from randomized trials does not exist for misoprostol, nor does it exist for oxytocin or the other prostaglandin E2 preparations currently in use.
Dose of Misoprostol for Labor Induction
To be efficacious yet minimize the frequency of uterine hyperstimulation, recent studies have focused on low-dose vaginal misoprostol (25 mcg). In one randomized trial of 522 women, 25 mcg of vaginal misoprostol given every 3 hours was compared to the same dose given every 6 hours. Less frequent dosing resulted in a longer time to delivery and a greater need for oxytocin augmentation, but no differences in uterine hyperstimulation with fetal heart rate changes, rates of cesarean delivery, or other adverse outcomes. In another randomized trial of 200 women, 25 mcg of vaginal misoprostol given every 4 hours was compared with the dinoprostone insert (Cervidil). No differences in the time from induction of labor to delivery, the rate of uterine hyperstimulation with fetal heart rate changes, the rate of cesarean delivery, or other indexes of neonatal adverse effects between groups were found. The available data suggest that the best dose of misoprostol for induction of labor is 25 mcg vaginally every 4 to 6 hours.
J Midwifery Womens Health. 2003;48(4) © 2003 Elsevier Science, Inc.
Cite this: Induction of Labor: The Misoprostol Controversy - Medscape - Jul 01, 2003.