Wet versus dry intravaginal misoprostol application for treatment of early pregnancy failure

Abstract

Objective: To assess if moistening misoprostol tablets with saline, when used in a dose of 800 μg vaginally, affects efficacy, side effects and acceptability of medical management of early pregnancy failure as compared to dry tablets. Design: Randomized controlled clinical trial. Materials/Methods: Approval was obtained from the FDA, NICHD, and from each participating clinical centers’ IRB. After informed consent was obtained, 80 women with embryonic/fetal demise or anembryonic pregnancies with a crown-rump length less than 41 mm or a mean sac diameter less than 46 mm were enrolled. Potential subjects were excluded if they had any contraindication to treatment with prostaglandin E1. Participants received either 800ug of misoprostol per vagina with 2 ml of saline added (Group 1) or the same without saline (Group 2) on day 1. On discharge, subjects received pain medication and a symptom diary to record drug related side effects. A transvaginal pelvic ultrasound was repeated on follow-up visit days 3, 8, and 15. The misoprostol dose was repeated on day 3 if the gestational sac was still present. D&C was performed if the gestational sac remained at day 8 or if clinically indicated. On day 15, subjects reported on their satisfaction with the treatment. Telephone interviews were conducted on day 30 to determine if any subject underwent additional medical or surgical procedures. Data were analyzed using Student t-test or chi-square test for continuous and categorical variables, respectively. We had 80% power to detect a 20% difference in success rate between the two groups. Results: Both groups had similar demographic characteristics. In Group 1, 30/41 (73%) and 34/41 (83%) subjects expelled the gestational sac by the days 3 and 8, respectively. In Group 2, 25/39 (64%) and 31/39 (79%) subjects expelled the sac by days 3 and 8, respectively. Six subjects in group 1 and seven subjects in Group 2 underwent a D&C. There was no statistical difference in success rates between the two groups. The combined success rate was 84% (95% CI: 76 - 92%). The frequency of drug related side effects was similar in both groups with an overall incidence of: pain in 97%, headaches 78%, chills 71%, and fever 40%. Nonetheless, 79% (58/73) of the women reported the treatment was acceptable and 21% (15/73) and 59% (43/73) stated that they would probably or absolutely be willing to undergo the same treatment again. Conclusions: Misoprostol (800ug) administered intravaginally is effective for pregnancy evacuation in women with failed first trimester gestations. The addition of saline does not appear to enhance drug effectiveness, nor the incidence or severity of side effects. Although drug related side effects are very common, women find misoprostol as an outpatient treatment to be acceptable. Supported by: Supported by the NIH; N01-HD-1–322(1–5).