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Background:Termination of pregnancy in the second trimester using prostaglandins has been shown to be safe and effective. Misoprostol has multiple routes of administration; oral, vaginal, buccal, rectal and sublingual.Objective:The study aims to compare the efficacy and safety of intrauterine extra-amniotic and vaginal misoprostol in a dose of 200 microgram every 4 hours for the termination of pregnancy in cases of second trimester miscarriage.Materials and Methods:A prospective randomized open labeled clinical trial included 180 women with missed miscarriage in gestational age between 13 and 24 wks. Patients were randomized to receive subsequent doses of 200 µg misoprostol every 4 hrs either intra uterine extra-amniotic by Foley catheter or vaginally administered. Randomization was completed using a computer-generated random table. The primary outcome of this study was the mean duration from the initial misoprostol dose until complete fetal expulsion (induction-expulsion interval).Results: The mean gestational age was 17.74 wks. The mean time to complete miscarriage in the intra uterine extra-amniotic group was 5.27 hrs, which was significantly lower than the vaginal group (9.92 hrs, p=0.001). Side effects were more common in vaginal group.Conclusion: Intra uterine extra-amniotic misoprostol with a dose of 200 µg every 4 hrs appears to be more effective and safer than vaginal misoprostol in induction of second trimester miscarriage.

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