Misoprostol for termination of pregnancy with intrauterine fetal demise in the second and third trimester of pregnancy - a systematic review

Abstract

Background: A systematic review was conducted to compare with other methods, using the best available evidence, the benefits and risks associated with the administration of misoprostol to terminate pregnancy with fetal demise in the second and third trimesters (defined as gestational age of more than 14 weeks).

Study design: We assessed all published randomized controlled trials identified from the Cochrane Pregnancy and Childbirth Group Trials Register, MEDLINE, POPLINE, LILACS and CINHAL from 1987 to 2008 comparing misoprostol alone (vaginal, oral or sublingual administration) with placebo or no treatment or any other method of uterine evacuation (including cervical ripening with other prostaglandins administered vaginally or extra-amniotically, oxytocin, as well as mechanical methods of evacuation including extra-amniotic Foley catheter or laminaria placement) in women with diagnosis of intrauterine fetal death in the second and third trimester of pregnancy. We also evaluated the use of misoprostol alone with misoprostol plus other adjuncts such as intravenous oxytocin. Meta-analyses were performed using relative risks (RRs) as the measure of effect size for binary outcomes and weighted mean differences for continuous outcome measures. For all data, 95% confidence intervals (CIs) were also computed.

Results: Fourteen studies comparing different interventions were included. The induction regimens varied considerably in the number of applications of medication, dosages and time intervals between doses. The main outcome was uterine evacuation at 48 h. In all studies evaluated, both vaginal and oral misoprostol showed 100% success rate in achieving uterine evacuation at 48 h. We also evaluated the success at achieving uterine evacuation at 24 h. Although the differences were not statistically significant and heterogeneity was observed, vaginal misoprostol was as effective as oral administration, achieving uterine evacuation within 48 h (RR=0.96, 95% CI=0.85 to 1.09). Oral administration was associated with more side effects than vaginal administration. The mean time intervals from induction to delivery were not significantly different between the vaginal and oral treatment groups [-1.97 (95% CI=-3.22 to 0.72)], so that the clinical benefit of oral administration and avoidance of repeated vaginal administration is probably marginal. Vaginal misoprostol alone was less effective in achieving uterine evacuation at 24 h compared with vaginal misoprostol plus oxytocin. However, there was no statistically significant difference (RR=1.00, 95% CI=0.89 to 1.12) in uterine evacuation at 48 h for vaginal misoprostol either with or without oxytocin administration.

Conclusions: Overall, the body of evidence regarding induction of labor and delivery for second and third trimester of pregnancy is limited and the studies vary in methodology and selected outcome measures, making direct comparisons difficult. Vaginal misoprostol was less effective than oral misoprostol for effecting delivery within 24 h, but not within 48 h.