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Objective To compare 400 and 800 lg sublingual or vaginal misoprostol 24 hours after 200 mg mifepristone for noninferiority regarding efficacy in achieving complete abortion for pregnancy termination up to 63 days of gestation.Design Placebo-controlled, randomised, noninferiority factorial trial, stratified by centre and length of gestation. Misoprostol 400 or 800 lg, administered either sublingually or vaginally, with follow up after 2 and 6 weeks.Setting Fifteen obstetrics/gynaecology departments in ten countries.Population Pregnant women (n = 3005) up to 63 days of gestation requesting medical abortion.Methods Two-sided 95% CI for differences in failure of complete abortion and continuing pregnancy, with a 3% noninferiority margin, were calculated. Proportions of women with adverse effects were recorded.Outcome measures Complete abortion without surgical intervention (main); continuing live pregnancies, induction-toabortion interval, adverse effects, women's perceptions (secondary).Results Efficacy outcomes analysed for 2962 women (98.6%): 90.5% had complete abortion after 400 lg misoprostol, 94.2% after 800 lg. Noninferiority of 400 lg misoprostol was not demonstrated for failure of complete abortion (difference: 3.7%; 95% CI 1.8-5.6%). The 400-lg dose showed higher risk of incomplete abortion (P < 0.01) and continuing pregnancy (P < 0.01) than 800 lg. Vaginal and sublingual routes had similar risks of failure to achieve complete abortion (P = 0.47, difference in sublingual minus vaginal )0.7%, 95% CI )2.6-1.2%). A similar pattern was observed for continuing pregnancies (P = 0.21). Fewer women reported adverse effects with vaginal than sublingual administration and with the 400-lg dose than the 800-lg dose. Of the women, 94% were satisfied or highly satisfied with the regimens, 53% preferred the sublingual route and 47% preferred the vaginal route.Conclusions A 400-lg dose of misoprostol should not replace the 800-lg dose when administered 24 hours after 200 mg mifepristone for inducing abortion in pregnancies up to 63 days. Sublingual and vaginal misoprostol have similar efficacy, but vaginal administration is associated with a lower frequency of adverse effects.

Equivalence between vaginal and sublingual administration could not be demonstrated overall. Vaginal administration showed a higher effectiveness than sublingual administration in terminating second trimester pregnancies, but this result was mainly driven by nulliparous women. Fever was more prevalent with vaginal administration. Registered with International Standard Randomized Controlled Trial number ISRCTN72965671.

ObjectivesTo compare rates of unintended pregnancy, method continuation and reasons for removal among women using the 52-mg levonorgestrel (daily release 20 microg) levonorgestrel IUD (LNG-IUD) or the copper T 380 A (TCu380A) intrauterine device.Study designThis was an open-label 7-year randomized controlled trial in 20 centres, 11 of which in China. Data on 1884 women with interval insertion of the LNG-IUD and 1871 of the TCu380A were analysed using life tables with 30-day intervals and Cox proportional hazards models.ResultsThe cumulative 7-year pregnancy rate of the LNG-IUD was 0.5 (standard error 0.2) per 100, significantly lower than 2.5 (0.4) per 100 of the TCu380A, cumulative method discontinuation rates at 7 years were 70.6 (1.2) and 40.8 (1.3) per 100, respectively. Dominant reasons for discontinuing the LNG-IUD were amenorrhea (26.1 [1.3] per 100) and reduced bleeding (12.5 [1.1] per 100), particularly in Chinese women and, for the TCu380A, increased bleeding (9.9 [0.9] per 100), especially among non-Chinese women. Removal rates for pain were similar for the two intrauterine devices (IUDs). Cumulative rates of removal for symptoms compatible with hormonal side effects were 5.7 (0.7) and 0.4 (0.2) per 100 for the LNG-IUD and TCu380A, respectively, and cumulative losses to follow-up at 7 years were 26.0 (1.4) and 36.9 (1.3) per 100, respectively.ConclusionThe LNG-IUD and the TCu380A have very high contraceptive efficacy, with the LNG-IUD significantly higher than the TCu380A. Overall rates of IUD removals were higher among LNG-IUD users than TCu380A users. Removals for amenorrhea appeared culturally associated.ImplicationsThe 52-mg LNG-IUD and the TCu380A have very high contraceptive efficacy through 7 years. As an IUD, the unique side effects of the LNG-IUD are reduced bleeding, amenorrhea and symptoms compatible with hormonal contraceptives.

Objective To compare the efficacy of 100 mg and 200 mg of mifepristone and 24-and 48-hour intervals to administration of 800mg vaginal misoprostol for termination of early pregnancy.Design Placebo-controlled, randomized, equivalence trial, stratified by centre.Setting 13 departments of obstetrics and gynecology in nine countries.Population 2181 women with 63 days or less gestation requesting medical abortion.Methods Two-sided 95% CI for the risk differences of failure to complete abortion were calculated and compared with 5% equivalence margin between two doses of mifepristone and two intervals to misoprostol administration. Proportions of women with adverse effects were compared between the regimens using standard testes for proportions.Outcome measures Rates of complete abortion without surgical intervention and adverse effects associated with the regimens.Results Efficacy outcome was analysed for 2126 women (97.5%) excluding 55 lost to follow up. Both mifepristone doses were found to be similar in efficacy. The rate of complete abortion was 92.0% for women assigned 100 mg of mifepristone and 93.2% for women assigned 200 mg of mifepristone (difference 1.2%, 95% CI: -1.0 to 3.5). Equivalence was also evident for the two intervals of administration: the rate of complete abortion was 93.5% for 24-hour interval and 91.7% for the 48-hour interval (difference -1.8%, 95% CI: -4.0 to 0.5). Interaction between doses and interval to misoprostol administration was not significant (P = 0.92). Adverse effects related to treatments did not differ between the groups.Conclusions Both the 100 and 200 mg doses of mifepristone and the 24-and 48-hour intervals have a similar efficacy to achieve complete abortion in early pregnancy when mifepristone is followed by 800 micrograms of vaginally administered misoprostol.

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 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. Twentythree 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. BJOG: an International Journal of Obstetrics and GynaecologyNausea, 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 th...

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.