WHO multinational study of three misoprostol regimens after mifepristone for early medical abortion.

OBJECTIVES: To compare the side effect profiles of regimens of oral and vaginal administration of misoprostol after a single oral dose of 200 mg of mifepristone and to investigate patients' perceptions of medical abortion. DESIGN: Double-blind, randomised controlled trial. SETTING: Fifteen gynaecological clinics in 11 countries. POPULATION: A total of 2219 healthy pregnant women requesting medical abortion with < or =63 days of amenorrhoea. Two thousand women were asked about their perceptions of the method. METHODS: Mifepristone 200 mg orally on day one, followed by 0.8 mg misoprostol either orally or vaginally on day three. The oral group (O/O group) and one of the vaginal groups (V/O group) continued with 0.4 mg of oral misoprostol, and the vaginal-only group (V-only group) with oral placebo, twice daily for seven days. Side effects were recorded daily by women and reported at each visit. After misoprostol administration at the clinic, side effects were recorded at 1-hour interval up to 3 hours. Patients' perceptions were asked at the second follow up visit, six weeks after treatment. MAIN OUTCOME MEASURES: The outcome measures were the following: pregnancy-related symptoms (nausea, vomiting, breast tenderness, fatigue, dizziness, headache), drug-related side effects (diarrhoea, fever, rash and blood pressure change), side effects related to the abortion process (lower abdominal pain) and women's perceptions of the method. RESULTS: The pregnancy-related symptoms decreased in all groups after misoprostol, and breast tenderness decreased already after mifepristone. Oral administration of misoprostol was associated with a higher frequency of nausea and vomiting than vaginal administration at 1 hour after administration. With oral misoprostol, diarrhoea was more frequent at 1, 2 and at 3 hours after administration than with vaginal administration. Misoprostol induced fever during at least 3 hours after administration in up to 6% of the women, this peak being slightly higher and taking place later with the vaginal route. Lower abdominal pain peaked at 1 and 2 hours after oral misoprostol, while it did so at 2 and 3 hours after vaginal misoprostol. In the two groups that continued misoprostol, 27% of women had diarrhoea between the misoprostol visit and the two-week follow up visit, compared with 9% in the placebo group. Among the women studied, 84% would choose medical abortion again, 9% would choose surgical abortion and 7% did not know. Twenty-three percent of the women would choose to have a possible future abortion at home, 70% at a health facility and 7% did not know. CONCLUSIONS: The pregnancy-related symptoms decrease significantly with time during medical abortion. Nausea, vomiting and diarrhoea were more frequent after oral administration of misoprostol. Pain related to the abortion process occurs earlier after oral misoprostol. Should a need arise, a majority of women would choose medical abortion again and would prefer to have it at a health facility rather than at home.

WHO multinational study of three misoprostol regimens after mifepristone for early medical abortion. I: Efficacy.

OBJECTIVES: To compare the efficacy of oral and vaginal administration of misoprostol after a single oral dose of 200 mg of mifepristone and to investigate whether the efficacy can be improved and the duration of bleeding shortened by continuing oral misoprostol for one week. DESIGN: Double blind, randomised controlled trial. SETTING: Fifteen gynaecological clinics in 11 countries. POPULATION: A total of 2219 healthy pregnant women requesting medical abortion with < or =63 days of amenorrhoea. METHODS: Mifepristone 200 mg administered orally on day one, followed by 0.8 mg misoprostol either orally or vaginally on day three. The oral group and one of the vaginal groups continued with 0.4 mg of oral misoprostol twice daily for seven days. MAIN OUTCOME MEASURES: Complete abortion was the main outcome. Secondary outcomes were side effects, timing of expulsion and duration of bleeding. RESULTS: The crude complete abortion rate was 92.3% in the oral plus continued oral misoprostol group, in the vaginal-only group it was 93.5%, and it was 94.7% in the vaginal group that continued with oral misoprostol, when considering undetermined cases as failures. Among women with amenorrhoea length > or =57 days, the risk of failure of complete abortion was almost three times higher in the oral plus continued oral misoprostol group (RR = 2.8, 95% CI 1.3 to 5.8), and over two times higher in the vaginal-only group (RR = 2.2, 95% CI 1.0 to 4.7), when compared with the vaginal plus continued oral misoprostol group. Among women with amenorrhoea length < 57 days, the differences were not significant. Timing of expulsions and duration of bleeding were similar in the three groups. CONCLUSIONS: For amenorrhoea length > or =57 days, vaginal misoprostol is more effective than oral when continued with 0.4 mg oral misoprostol twice daily for seven days. Misoprostol continuation improved the efficacy in this amenorrhoea group compared with a single dose of vaginal misoprostol on day three, but it did not shorten the duration of bleeding. No differences in efficacy were observed when amenorrhoea length was < 57 days.