Single versus repeat doses of misoprostol for treatment of early pregnancy loss-a randomized clinical trial

Abstract

Study question: Does repeat administration of misoprostol for early pregnancy loss increase the treatment success rate?

Summary answer: Repeat administration of misoprostol does not increase the treatment success rate, and is associated with more analgesics use.

What is known already: Misoprostol reduces the need for surgical evacuation and shortens the time to complete expulsion in patients with early pregnancy loss. However, the impact of repeat doses of misoprostol is not clear.

Study design, size, duration: A randomized clinical trial was conducted in a single tertiary hospital, recruiting women with early pregnancy loss (<12 weeks), seeking medical treatment, between August 2015 and June 2016. A sample size of 160 patients was sufficient to detect a 30% decrease in treatment success.

Participants/materials, setting, methods: Participants received 800 μg of misoprostol vaginally on Day 1, and were then randomly assigned into two groups: Patients in the single-dose group were evaluated on Day 8. Patients in the repeat-dose group were evaluated on Day 4, when they were given a repeat dose if required, and scheduled for re-evaluation on Day 8. If complete expulsion was not achieved on Day 8 (endometrial thickness >15 mm or the presence of gestational sac on transvaginal sonography), participants underwent surgical evacuation. The primary outcome was treatment success, defined as no need for surgical intervention up to Day 8.

Main results and the role of chance: Final analysis included 87 participants in the single-dose group and 84 participants in the repeat-dose group, out of whom 41 (48.8%) received a second dose. Treatment succeeded in 67 (77%) patients in the single-dose group and 64 (76%) patients in the repeat-dose group (RR 0.98; 95% CI 0.83-1.16; P = 0.89). Patients in the repeat-dose group reported more use of over the counter analgesics (82.1% versus 69.0%, P = 0.04).

Limitations, reasons for caution: The study was not blinded and our definition of complete expulsion may be debated. Follow-up time was not equal in all participants, since some had a complete expulsion on Day 4 and some underwent emergent D&C before Day 8. This, however, should not affect the primary outcome.

Wider implications of the findings: Our results suggest that a single-dose protocol is superior to a repeat-dose protocol due to a comparable success rate and more favorable outcomes regarding the need for analgesic drugs.

Study funding/competing interest(s): We did not receive funding for this study and we declare no conflict of interest.

Trial registration number: ClinicalTrials.gov (NCT02515604).

Trial registration date: 2 August 2015.

Date of first patient's enrolment: 19 August 2015.

Keywords: abortion; cost effectiveness; pregnancy; randomized controlled trial; surgery.