Misoprostol for induction of labour: a systematic review


  • An electronic version of this review has been published in the Cochrane Library as two separate reviews.

Correspondence: Dr A. Metin Gülmezoglu, Medical Officer, UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, World Health Organisation, Geneva 27, Switzerland CH-1211.


Objective To determine, from the best available evidence, the effectiveness and safety of misoprostol administered vaginally or orally for third trimester cervical ripening or induction of labour.

Methods Clinical trials of misoprostol used for cervical ripening or labour induction in the third trimester were identified from the register of randomised trials maintained by the Cochrane Pregnancy and Childbirth Group. All identified trials were considered for inclusion in the review according to a prespecified protocol. Primary outcomes were chosen to address clinical effectiveness (delivery within 24 hours) and safety (uterine hyperstimulation, caesarean section, serious maternal and neonatal morbidity) and were determined a priori. All meta-analyses were based on the intentionto-treat principle. In the absence of heterogeneity the summary statistics have been expressed as typical relative risk (RR) and 95% confidence interval (CI).

Results Vaginal misoprosrol: one small study showed that the use of misoprostol results in more effective cervical ripening and reduced need for oxytocin when compared with placebo. When compared with oxytocin, vaginal misoprostol was more effective for labour induction. The relative risk of failure to achieve vaginal delivery within 24 hours was 0.48 (95% CI 0.35 to 0.66). However, the relative risks for uterine hyperstimulation with and without fetal heart rate abnormalities were 2.54 (95% CI 1.12 to 5.77) and 2.96 (95% CI 2.11 to 4.14), respectively. In three out of four trials which studied women with intact membranes and unfavourable cervices, failure to achieve vaginal delivery within 24 hours was reduced with misoprostol when compared with other prostaglandins (RR 0.71,95% CI 0.62 to 0.81). Vaginal misoprostol was associated with increased uterine hyperstimulation both without fetal heart rate changes (RR 1.67, 95% CI 1.30 to 2.14) and with associated fetal heart rate changes (RR 1.45, 95% CI 1.04 to 2.04). There was also an increase in meconium stained amniotic fluid following vaginal misoprostol (RR 1.38,95% CI 1.06 to 1.79). Oral misoprostol: one small trial suggests that, when compared with placebo, oral misoprostol reduces the need for oxytocin and shortens the time between induction and delivery. Compared with other prostaglandins one small trial showed a reduced need for oxytocin with oral misoprostol. No trials compared oral with vaginal misoprostol using different doses. No significant differences were evident.

Conclusions Overall, misoprostol appears to be more effective than conventional methods of cervical ripening and labour induction. Although no differences in perinatal outcome were shown, the studies were not sufficiently large to exclude the possibility of uncommon serious adverse effects. In particular the increase in uterine hyperstimulation with fetal heart rate changes following misoprostol is a matter for concern. It is possible that, if sufficient numbers are studied, an unacceptably high number of serious adverse events including uterine rupture and asphyxia1 fetal deaths may occur. The data at present are not robust enough to address the issue of safety. Thus, though misoprostol shows promise as a highly effective, inexpensive and convenient agent for labour induction, it cannot be recommended for routine use at this stage. Lower dose misoprostol regimens should be investigated further.