A randomised study comparing a low dose of mifepristone and the Yuzpe regimen for emergency contraception. Comparison of Yuzpe regimen, danazol, and mifepristone (RU486) in oral postcoital contraception. Mifepristone (RU 486) compared with high-dose estrogen and progestogen for emergency postcoital contraception. Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Task Force on Postovulatory Methods of Fertility Regulation. Comparison of three single doses of mifepristone as emergency contraception: a randomised trial. Task Force on Postovulatory Methods of Fertility Regulation. The effect of dose of mifepristone and gestation on the efficacy of medical abortion with mifepristone and misoprostol. A randomized double-blind comparison of two single doses of mifepristone for emergency contraception. Randomized comparison of vaginal (200 microg every 3 h) and oral (400 microg every 3 h) misoprostol when combined with mifepristone in termination of second trimester pregnancy. Effect of oral prostaglandin E2 on uterine contractility and outcome of treatment in women receiving RU 486 (mifepristone) for termination of early pregnancy.
To compare 100 mg mifepristone with the standard Yuzpe regimen for emergency contraception.
                Randomised controlled trial.
                Family Planning Clinic, Aberdeen.
                One thousand women seeking emergency contraception within 72 hours after an episode of unprotected sexual intercourse.
                Women were randomised to receive either 100 mg (half tablet) of mifepristone as a single dose or the Yuzpe regimen (two tablets each with 50 microg ethinyloestradiol and 0.25 mg levonorgestrel, to be repeated 12 hours later).
                Crude pregnancy rates, proportion of pregnancies prevented, side effects and patient acceptability.
                The crude pregnancy rates (95% CI) for the Yuzpe regimen and mifepristone were 3.6% (2.3-5.7) and 0.6% (0.2-1.8), respectively, with a significant difference between the two groups (RR 6.04; 95% CI 1.75-20.75). Mifepristone prevented 92% of pregnancies and the Yuzpe regimen preventing 56%. An increasing coitus to treatment interval was associated with contraceptive failure in the Yuzpe group (P = 0.03) with no association seen with mifepristone. Following administration of mifepristone 24.5% and 13.1% given the Yuzpe regimen had a delayed period (RR 2.14; 95% CI 1.46-3.15). Overall, mifepristone was better tolerated than the Yuzpe regimen with significantly fewer side effects. More women were satisfied (P < 0.0001) with mifepristone as an emergency contraceptive and would recommend it to a friend (P = 0.02).
                Mifepristone administered in a 100 mg dose is a highly effective post-coital contraceptive with high patient acceptability and fewer side effects compared with the standard Yuzpe regimen. Delay in the onset of menstruation did not decrease patient acceptability. To compare the effectiveness and acceptability of three regimens of postcoital contraception.
                Randomised group comparison of ethinyloestradiol 100 micrograms plus levonorgestrel 500 micrograms repeated after 12 hours (Yuzpe method); danazol 600 mg repeated after 12 hours; and mifepristone 600 mg single dose.
                Community family planning clinic.
                616 consecutive women with regular cycles aged 16 to 45 years.
                Number of pregnancies, incidence of side effects, and timing of next period.
                The raw pregnancy rates (with 95% confidence intervals) for the Yuzpe, danazol, and mifepristone groups were 2.62% (0.86% to 6.00%), 4.66% (2.15% to 8.67%), and 0% (0% to 1.87%) respectively. Overall, these rates differed significantly (chi 2 = 8.988, df = 2; p = 0.011). The differences between the mifepristone and Yuzpe groups and between the mifepristone and danazol groups were also significant. Side effects were more common and more severe in the Yuzpe group (133 women (70%)) than in either the danazol group (58 (30%)) or the mifepristone group (72 (37%)). The Yuzpe regimen tended to induce bleeding early but mifepristone prolonged the cycle. Three women bled more than seven days late in the Yuzpe group compared with 49 in the mifepristone group.
                Mifepristone was effective in reducing expected pregnancy rates and the Yuzpe method also had a clinical effect. Danazol had little or no effect. A further multicentre trial is needed. Mifepristone (RU 486) is a synthetic steroid with potent antiprogestational and antiglucocorticoid properties that provides an effective medical method of inducing abortion in early pregnancy. Since progesterone is essential for implantation, we tested the use of mifepristone for emergency postcoital contraception.
                We studied 800 women and adolescents requesting emergency postcoital contraception who had had unprotected intercourse within the preceding 72 hours. A total of 398 women and adolescents were randomly assigned to treatment with 100 micrograms of ethinyl estradiol and 1 mg of norgestrel, each given twice 12 hours apart (standard therapy), and 402 women and adolescents were randomly assigned to receive 600 mg of mifepristone.
                None of the women and adolescents who received mifepristone became pregnant, as compared with four of those who received standard therapy; the difference in failure rates between the two regimens was not statistically significant. The number of pregnancies in each group was significantly lower than the number expected according to calculations based on the day of the cycle during which intercourse had taken place (P less than 0.001). In many subjects the stage of the cycle as calculated by menstrual history was inconsistent with measurements of plasma progesterone or urinary pregnanediol excretion. The subjects treated with mifepristone reported less nausea (40 percent vs. 60 percent) and vomiting (3 percent vs. 17 percent) on the day of treatment, as well as lower rates of other side effects, than the subjects treated with the standard regimen, but they were more likely to have a delay in the onset of the next menstrual period (42 percent vs. 13 percent).
                Mifepristone is a highly effective postcoital contraceptive agent that, if used more widely, could help reduce the number of unplanned and unwanted pregnancies. A previous randomised study suggested that the progestagen, levonorgestrel, given alone in two separate doses each of 0.75 mg caused nausea and vomiting in fewer women and might be more effective than the Yuzpe regimen of combined oral contraceptives for emergency contraception, although the difference was not significant. We compared these two regimens when started within 72 h of unprotected coitus.
                We enrolled in the double-blind, randomised trial 1998 women at 21 centres worldwide. Women with regular menses, not using hormonal contraception, and requesting emergency contraception after one unprotected coitus, received levonorgestrel (0.75 mg, repeated 12 h later) or the Yuzpe regimen (ethinyloestradiol 100 microg plus levonorgestrel 0.5 mg, repeated 12 h later).
                Outcome was unknown for 43 women (25 assigned levonorgestrel, 18 assigned Yuzpe regimen). Among the remaining 1955 women, the crude pregnancy rate was 1.1% (11/976) in the levonorgestrel group compared with 3.2% (31/979) in the Yuzpe regimen group. The crude relative risk of pregnancy for levonorgestrel compared with the Yuzpe regimen was 0.36 (95% CI 0.18-0.70). The proportion of pregnancies prevented (compared with the expected number without treatment) was 85% (74-93) with the levonorgestrel regimen and 57% (39-71) with the Yuzpe regimen. Nausea (23.1 vs 50.5%) and vomiting (5.6 vs 18.8%) were significantly less frequent with the levonorgestrel regimen than with the Yuzpe regimen (p<0.01). The efficacy of both treatments declined with increasing time since unprotected coitus (p=0.01).
                The levonorgestrel regimen was better tolerated and more effective than the current standard in hormonal emergency contraception. With either regimen, the earlier the treatment is given, the more effective it seems to be. Mifepristone is a highly effective and well-tolerated emergency contraceptive when given in a dose of 600 mg within 72 h of unprotected coitus. We assessed whether the same effectiveness can be achieved with lower doses of mifepristone (50 mg and 10 mg) and a longer postcoital treatment period (120 h).
                We undertook a multicentre, single-masked, randomised trial in 11 family-planning clinics in Australia, China, Finland, Georgia, the UK, and the USA. 1717 healthy women with regular menstrual cycles who requested emergency contraception within 120 h of unprotected coitus were randomly assigned to three treatment groups.
                32 women were lost to follow-up and one was pregnant before treatment. The 600 mg, 50 mg, and 10 mg groups did not differ in the proportions of pregnancies (seven [1.3%] of 559, six [1.1%] of 560, and seven [1.2%] of 565). Two pregnancies (both in the 50 mg group) were tubal. Among women without further acts of intercourse, treatment delay did not appear to influence the effectiveness. No major side-effects occurred, except a delay in the onset of next menses, significantly (p<.001) related to the mifepristone dose.
                Lowering the dose of mifepristone sixty-fold did not decrease its effectiveness as an emergency contraceptive under typical use, though a study of this size cannot exclude differences in effectiveness up to almost three-fold. Lower doses of mifepristone were associated with less disturbance of the menstrual cycle. Thus, a dose as low as 10 mg seems preferable to the 600 mg dose. Although it has been demonstrated that a combination of mifepristone and a prostaglandin is an effective method of inducing abortion in early pregnancy, the optimum dose of the antigestogen is unknown. Women (n = 220) requesting abortion in early pregnancy (< or = 63 days amenorrhoea) were randomized to receive a single dose of either 600 or 200 mg mifepristone followed 48 h later by a single dose of 600 micrograms misoprostol by mouth. The percentage of women who had a complete abortion (93.6% confidence interval 90.4-95.5%) was identical in the two groups. There was no significant difference in the number of women who passed the fetus within 4 h of receiving the prostaglandin (64 versus 74%), the days of bleeding (14.6 +/- 1.1 versus 15.3 +/- 0.9) nor in the onset of the next period (39.7 +/- 1.3 versus 36.7 +/- 1.3) respectively between the groups receiving 200 or 600 mg mifepristone. However, the complete abortion rate was significantly higher in women < or = 49 days compared to women 50-63 days amenorrhoea (97.5 versus 89.1% respectively; P < 0.02). There was no difference in any of the other parameters at different weeks of gestation. We conclude: (i) that the recommended dose of mifepristone could be reduced from 600 to 200 mg without loss of clinical efficacy, (ii) that the combination of mifepristone and 600 micrograms misoprostol is a highly effective alternative to vacuum aspiration for inducing abortion in women < 50 days amenorrhoea and (iii) at gestation > 56 days, this combination may result in too many incomplete abortions to be clinically acceptable. Previous trials have shown the potential of 10 mg of mifepristone in emergency contraception. The aim of this trial was to investigate whether 10 mg of mifepristone has the same efficacy as 25 mg.
                This double-blind, randomized trial was carried out in 10 family planning institutes and hospitals in China. Women who met recruitment criteria and requested emergency contraception within 120 h of a single act of unprotected coitus were randomized using a computer-generated list to either 10 or 25 mg of mifepristone within each centre.
                Among 3052 women enrolled, the outcome was known for 3030 women, 1516 in the 10 mg group and 1514 in the 25 mg group. Seventeen pregnancies occurred in each group, giving a pregnancy rate of 1.1%. The relative risk of pregnancy for women treated with 10 mg mifepristone compared with those treated with 25 mg was 1.0 (95% CI: 0.51-1.95) and equivalence was demonstrated within a two-fold margin. Both doses prevented 85-86% of pregnancies expected to have occurred if no treatment had been given. The pregnancy rate nearly doubled if women had further acts of intercourse. Efficacy decreased with treatment delay. Side-effects were uncommon and mild.
                A dose of 10 mg of mifepristone is sufficient for emergency contraception. Earlier treatment is preferable, although the method can be used effectively for up to 5 days after intercourse. It is known that when misoprostol is given at 200 microg every 3 h after mifepristone pretreatment, the vaginal route is more effective than the oral route. However, women prefer the oral route. This randomized study was to test our hypothesis that oral misoprostol 400 microg is as effective as vaginal misoprostol 200 microg when given every 3 h in termination of second trimester pregnancy after priming with mifepristone. A total of 142 patients was randomly assigned to group 1 (200 mg mifepristone + 400 microg oral misoprostol every 3 h up to five doses) or group 2 (200 mg mifepristone + 200 microg vaginal misoprostol every 3 h up to five doses). The incidence of side-effects and the preference study were assessed through a standardized questionnaire during and after the abortion. For the oral group, both the incidence of diarrhoea (40.0 versus 23.2%, P = 0.03) and the amount of drug used (1734 compared with 812 microg, P < 0.0001) were significantly higher than that of the vaginal group but the incidence of fever appeared to be lower (not significant). There was no significant difference in complete abortion rate: 81.4% in the oral group and 75.4% in the vaginal group. The median induction-abortion interval was similar in the two groups (10.4 versus 10.0 h). The percentage of women who aborted in 24 h was also similar: 57/70 (81.4%) in the oral group and 58/69 (87.0%) in the vaginal group. Overall, 82.0% of women preferred the oral route. Oral misoprostol (400 microg) given every 3 h up to five doses, when combined with mifepristone, was as effective as the vaginal (200 microg) route in second trimester termination of pregnancy. This regimen could also be offered to those women who found repeated vaginal administration unacceptable. It has been shown that the antiprogestin RU 486 (mifepristone) increases the sensitivity of the early pregnant human uterus to the stimulatory action of synthetic prostaglandin E (PGE) analogues. To examine if RU 486 also increases uterine sensitivity to the naturally occurring PGE2 given orally, two investigative approaches were used in the present studies: (i) direct registration of uterine contractions before and after PGE2 administration in untreated and RU 486-treated early pregnant women; and (ii) a double-blind, randomized, controlled efficacy trial involving treatment of pregnant women (amenorrhoea of less than or equal to 49 days) with RU 486 (25 mg twice daily for 4 days) and PGE2 (1 mg once or twice) or placebo on the last day of RU 486 treatment. The results indicate that oral PGE2 at the doses employed had little or no stimulatory effect on uterine contractility and that it did not improve the rate of complete abortion achieved with RU 486 alone. Overall, 25 of 42 women (59%) had a complete abortion, 15 women (36%) did not abort and the remaining two had incomplete abortions. Women with complete abortions had significantly lower pretreatment levels of progesterone and a longer duration of induced bleeding than those who did not abort. Thus oral PGE2, when given in clinically acceptable doses, is not a suitable alternative to synthetic PGE analogues for use in combination with RU 486 for termination of early pregnancy.
Intermediate-dose mifepristone (25-50 mg) was superior to LNG and Yuzpe regimens. Mifepristone low dose (< 25 mg) may be more effective than LNG (0.75 mg two doses), but this was not conclusive. UPA may be more effective than LNG. LNG proved to be more effective than the Yuzpe regimen. The copper IUD was the most effective EC method and was the only EC method to provide ongoing contraception if left in situ.