Sublingual Versus Vaginal Misoprostol In Medical Treatment of First Trimestric Missed Miscarriage: A Randomized Controlled Trial.

Abstract

Medical treatment of first trimester missed miscarriage has been shown to be reasonable effective alternative to surgical evacuation. Although surgical evacuation was introduced to reduce risk of hemorrhage, it is reported to be associated with many complications including cervical trauma, perforation of the uterus and endometritis. In addition, uterine synechia, reduced fertility, tubal damage, and pelvic pain have been reported as long-term complications. Medical methods’ of uterine evacuation are safer and accepted by the patients. Many other studies had discussed the efficacies of different doses, routes, and timing of follow up. The present study has been designed to compare the safety and efficacy aspect of sublingual versus vaginal misoprostol for medical treatment of first trimester missed miscarriage. This randomized controlled trial was carried out in Ain Shams University Maternity Hospital in the period from February to August 2016. The study enrolled a total 214 of those attending the outpatient clinic or reception room who were diagnosed with missed miscarriage, 14 were excluded as 11 did not meet the inclusion criteria and 3 declined to participate. The study group was divided into two groups: patients were randomly assigned to one of the two groups. Group A: 100 patients were given sublingual misoprostol, group B: 100 patients were given vaginal misoprostol. Each patient was instructed to take 800μg misoprostol (4 tablets of Misotac®) either sublingual or vaginal every four hours for three doses. The follow up was by ultrasonography on day 7, day 14 and day 30 or after next menstruation provided that there was no heavy bleeding or signs of pelvic infection. Each patient was instructed to report any adverse effects as pain “ VAS 01-10”, bleeding “ using PBLAC”, shivering, gastrointestinal side effects and unpleasant taste. The overall success rate in our study was 60% on day 7 (70% in sublingual group and 50% in vaginal group) that increased to 76% (83% in sublingual group and 69% in vaginal group) on day 14 and increased to 82.5% (87% in sublingual group and 78% in vaginal group) on day 30 or after next menstruation. The effectiveness of treatment with misoprostol also depends on the time interval to follow up. To avoid unnecessary intervention the assessment of success should be delayed for at least 7 to 14 days or even after 30 days or next menstruation as long as patient is vitally stable and no signs or symptoms of infection. In the current study, sublingual misoprostol reduces the risk of incomplete abortion by 40% compared to vaginal misoprostol (P=0.005, RR= 0.6, 95% CI 0.42 to 0.86). In addition, sublingual misoprostol reduces the risk of surgical evacuation by 91% while vaginal misoprostol reduces it by 85%. The cause of surgical evacuation was nearly the same between the study groups in which the most common indication of surgical evacuation was inevitable abortion followed by patient request and then retained gestational sac after second course of misoprostol administration. The current study found that the expulsion rate was shorter among sublingual group than among vaginal group. The Mean interval was 12 hours ± 3.1 in sublingual group and 16.4 hours ± 4.2 in vaginal group. While the duration of bleeding was slightly shorter among the sublingual group than vaginal group, the difference was statistically non significant (P=0.113).Mean was 14.6 days ±2.5 SD in the sublingual group and 15.2 days ±2.9 SD in the vaginal group. In the current study, post-abortive drop in hemoglobin was higher among the vaginal group and represents 1 gm/dL ±0.3 SD in sublingual group and 1.5 gm/dL ± 0.3 SD in vaginal group (p<0.001). The incidence of side effects in our study was more common among the sublingual group as compared to the vaginal group but most of patients consider it were tolerable, transient and decreased gradually after the first day of treatment. The most common side effects were unpleasant taste among sublingual group representing 62% of cases followed by pain that is gradedaccording to VAS0-10 to 7.1±1.4 SD in sublingual group while 6.4 ±1.3 SD in the vaginal group. Other side effects include gastrointestinal side effects; nausea, vomiting and diarrhea and all are more common among sublingual group. This increased frequency of side effects may be explained by the higher bioavailability of sublingual misoprostol. The risk of blood transfusion represents only 1% among both study groups due to significant blood loss affecting patient general condition causing marked drop in hemoglobin level. From these results, we can conclude that sublingual misoprostol for the medical management of first trimester missed miscarriage is more effective and associated with less duration of bleeding and drop of hemoglobin level than vaginal misoprostol. However, it showed more adverse effects than vaginal misoprostol.