Abstract: We included three trials, involving 244 women. The studies were considered to be at high risk of bias. The prostaglandins used were PG E2 analogue (sulprostone) in 50 participants and PG E1 analogue (misoprostol) in 194 participants at a dose of 250 mcg and 800 mcg respectively. The prostaglandins compared with placebo, were not superior in reducing the rate of manual removal of placenta (average risk ratio (RR) 0.82; 95% confidence interval (CI) 0.54 to 1.27), severe postpartum haemorrhage (RR 0.80; 95% CI 0.55 to 1.15), need for blood transfusion (RR 0.72; 95% CI 0.43 to 1.22), mean blood loss (mean difference (MD) -205.26 mL; 95% CI -536.31 to 125.79, random-effects) and the mean time from injection to placental removal (MD -7.00 minutes; 95% CI -21.20 to 7.20). Side-effects were no different between groups (vomiting, headache, pain and nausea between injection and discharge from the labour ward), with the exception of shivering, which was more frequent in women receiving prostaglandins (RR 10.00; 95% CI 1.40 to 71.49). We did not obtain any data for the primary outcomes of maternal mortality and the need to add another therapeutic uterotonic. Currently there is limited, very low-quality evidence relating to the effectiveness and the safety using prostaglandins for the management of retained placenta. Use of prostaglandins resulted in less need for manual removal of placenta, severe postpartum haemorrhage and blood transfusion but none of the differences reached statistical significance. Much larger, adequately powered studies are needed to confirm that these clinically important beneficial effects are not just chance findings. Similarly, no differences were detected between prostaglandins and placebo in mean blood loss or the mean time from injection to placental removal (minutes) or side-effects (vomiting, headache, pain and nausea between injection and discharge from the labour ward) except for 'shivering' which was more frequent in women who received prostaglandin. The included studies were of poor quality and there is little confidence in the effect estimates; the true effect is likely to be substantially different. We can not make any recommendations about changes to clinical practice. More high-quality research in this area is needed.

Plain-language summary: The review identified three randomised controlled studies (involving 244 women) that compared the use of prostaglandins with placebo. Currently there is limited, very low-quality evidence relating to the effectiveness and the safety using prostaglandins for the management of retained placenta. Use of prostaglandins resulted in less need for manual removal of placenta, severe postpartum haemorrhage and need for blood transfusion but none of the differences reached statistical significance. Much larger, adequately powered studies are needed to confirm that these clinically important beneficial effects are not just chance findings. Similarly, no differences were detected between prostaglandins and placebo in mean blood loss or the mean time from injection to placental removal (minutes). The prostaglandin was administered by intravenous infusion (E2 analogue sulprostone) in one study including 50 women and was orally or sublingually administered (E1 analogue misoprostol) in the other two studies including 194 women. Shivering was more frequent in women receiving the prostaglandin but there were no clear differences in vomiting, headache, maternal pain or nausea compared with placebo. The trials were small and of poor methodological quality. The quality of evidence is very low due to study limitations, inconsistency and imprecise results (few women and outcome events with wide confidence intervals). Two studies were stopped early due to an apparent benefit.