A randomized trial of mifepristone (10 mg) and levonorgestrel for emergency contraception.

OBJECTIVE: To compare the efficacy, patient acceptability and adverse effects of low-dose mifepristone (10 mg) with the levonorgestrel regimen (2 doses of 750 microg given 12 hours apart) for emergency contraception. METHODS: This randomized controlled trial compared mifepristone (10 mg) to levonorgestrel (2 doses of 750 microg given 12 hours apart) in the context of emergency contraception within 120 hours of unprotected intercourse. The primary outcome measure was unintended pregnancy. Secondary outcomes included adverse effects experienced by women, acceptability of the method of emergency contraception used, and the timing of the first menstrual cycle after treatment. RESULTS: The total number of women recruited was 2,065. The crude pregnancy rates were 1.3% and 2.0% for mifepristone and levonorgestrel (P = .46), with 77% and 64% of expected pregnancies prevented, respectively. Women receiving mifepristone were more likely to have a delayed onset of the subsequent menstrual cycle after treatment (P < .001), whereas those having levonorgestrel were more likely to have an early onset of the subsequent menstrual cycle (P < .001). Acceptability levels were high for both methods, with 94% of women receiving mifepristone and 91% receiving levonorgestrel expressing satisfaction. There was no difference in adverse effects (nausea, vomiting, breast tenderness, abdominal pain, lethargy, headache, hot flushes, and dizziness) experienced by women in the 2 groups. CONCLUSION: This study suggests that a small dose of mifepristone is not less effective than levonorgestrel for emergency contraception. Both regimens were highly acceptable to women.

Mifepristone versus the Yuzpe regimen (PC4) for emergency contraception.

OBJECTIVE: To compare side effects, women's acceptance and satisfaction with mifepristone (100 mg) versus the Yuzpe regimen for emergency contraception (EC). METHODS: A total of 1000 women requesting EC within 72 h of unprotected intercourse were randomized to receive mifepristone 100 mg or the standard Yuzpe regimen. Outcome measures included patient acceptability and satisfaction. RESULTS: A total of 620 (62%) questionnaires were returned, 64% in the mifepristone group and 60% in the Yuzpe group. Mifepristone was better tolerated than the Yuzpe regimen. The rates of nausea (P<0.0001), abdominal pain (P=0.001), tiredness (P<0.0001), lethargy (P=0.001), hot flushes (P<0.0001) and dizziness (P<0.0001) were all significantly higher in women given the Yuzpe regimen compared to those who received mifepristone. Of these 94% and 80% in the mifepristone and Yuzpe groups, respectively, were satisfied with treatment (P<0.0001). Of women in the mifepristone group, 56% (181/321) had used the Yuzpe regimen of EC in the past and of these, 93.6% (161/172) indicated they would use mifepristone in the future. A total of four women in the Yuzpe group had mifepristone in the past and all four said they would use mifepristone in the future. CONCLUSION: Mifepristone has high patient acceptability and few side effects compared to the standard Yuzpe regimen for EC.

Analgesia requirements and predictors of analgesia use for women undergoing medical abortion up to 22 weeks of gestation.

OBJECTIVE: To assess analgesia use and the predictors for requiring analgesia in women undergoing medical abortion at all gestations up to 22 weeks. DESIGN: Retrospective observational study. SETTING: Aberdeen Royal Infirmary, Scotland. POPULATION: Consecutive women undergoing medical abortion under the terms of the 1967 Abortion Act. METHODS: Analgesia requirements and characteristics of women undergoing abortion were analysed using logistic regression. MAIN OUTCOME MEASURES: The effect of age, gestation, reproductive history, route and dose of misoprostol administration on analgesia requirements. RESULTS: Of the total 4343 women included in this review, 3139 women (72%) required analgesia. Of these, 3054 women (97%) used oral analgesia, 75 women (2.4%) used opiates while 10 women (0.3%) had diclofenac sodium given rectally. There was no significant difference in analgesia use whether women used the vaginal or sublingual route of misoprostol administration. Logistic regression showed a significant positive association with gestation at termination (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.05-1.12), number of misoprostol doses used (OR 1.31, 95% CI 1.13-1.51) and induction to abortion interval (OR 1.08, 95% CI 1.03-1.12) and a negative association with the age of women undergoing abortion (OR 0.98, 95% CI 0.97-0.99) and previous live birth (OR 0.43, 95% CI 0.33-0.56). CONCLUSIONS: Analgesia requirement was significantly higher in women of younger age, higher gestation, longer induction to abortion interval and with increased number of misoprostol doses used while women with previous live birth were significantly less likely to use analgesia.

Midtrimester medical termination of pregnancy: a review of 1002 consecutive cases.

We assessed the effectiveness, safety and factors that affected the outcome of midtrimester medical termination of pregnancy at 13-21 weeks gestation. Of the 1002 women, 3 took mifepristone and decided to continue with the pregnancy, with 999 women being compliant with the regimen. Of these, 2 women aborted prior to administration of misoprostol and 970 (97.1%) aborted successfully within five doses of misoprostol. Surgical intervention was necessary to complete the abortion process in 81 (8.1%) women. Women with no previous pregnancy (p = 0.02), no previous live birth (p = 0.0001) and gestations 17-21 weeks (p = 0.001) required more prostaglandin. Younger women (p = 0.0001) and women with a previous live birth (p = 0.001) were more likely to have a successful abortion. The induction abortion interval was significantly longer with increasing gestation [95% confidence interval (CI) difference in means: -2.52 to -0.89, p = 0.0001], increasing age (p = 0.0001) and no previous live birth (95% CI difference in means: -0.25 to -1.01, p = 0.0001). Surgical intervention was more likely to be required with increasing age (p = 0.008). Mifepristone in combination with misoprostol is a safe and effective regimen for midtrimester medical abortion with younger women and those with a previous live birth more likely to have a successful abortion.

A pilot study of mifepristone in combination with sublingual or vaginal misoprostol for medical termination of pregnancy up to 63 days gestation.

Of the total women included in the study, 96 women chose to receive misoprostol 600 microg sublingually while 53 women received misoprostol 800 microg vaginally 36-48 h after receiving mifepristone 200 mg. Complete abortion occurred in 93 women (98.9%) in the sublingual and 51 women (96.2%) in the vaginal group (p = 0.27). The mean induction-to-abortion interval was 3.2 h (SD = 1.4) in the sublingual and 4.1 h (SD = 1.5) in the vaginal group (p = 0.02). The mean gestation at abortion in weeks was 7.1 (SD = 1.0) in the sublingual and 7.7 (SD = 1.3) in the vaginal group (p = 0.003). Women in the sublingual group experienced more vomiting (p = 0.03), diarrhea (p = 0.02) and unpleasant taste in their mouth (p = 0.0001) while those in the vaginal group experienced more headache (p = 0.002). Of women in the sublingual group, 77% were satisfied with the route of misoprostol administration compared to 68% in the vaginal group (p = 0.25). These findings now need to be assessed in the context of a randomized controlled trial.

Mifepristone as a late post-coital contraceptive.

This study was undertaken to assess the efficacy of mifepristone as a post-coital contraceptive beyond 72 h and up to 5 days in women who found the intrauterine contraceptive device (IUCD) unacceptable. During a 2 year period 219 consecutive women fulfilling the inclusion criteria and presenting late for emergency contraception were approached and offered a choice of methods. Fifteen (6.8%) women wished to have the IUCD fitted, but 204 (93.2%) who found this unacceptable were offered and accepted mifepristone 200 mg. In one woman there was a technical problem fitting the IUCD and mifepristone was administered. Women who had mifepristone were younger (mean age 21.4 versus 26.9 years, P = 0.004) and more likely to be nulliparous (81 versus 25 %, P < 0.001) than the IUCD group. A total of 155 (75.6%) women who had mifepristone and all 14 who had the coil fitted were followed up. There were no true failures in either group. There was one user failure in the mifepristone group, where pregnancy occurred from an act of intercourse subsequent to treatment, giving a crude pregnancy rate of 0.65%. Mifepristone prevented 85% of expected pregnancies. Most women find the IUCD an unacceptable method of post-coital contraception. Mifepristone is an effective late post-coital contraceptive, which can be offered to women who decline the IUCD.

Mifepristone versus vaginally administered misoprostol for cervical priming before first-trimester termination of pregnancy: a randomized, controlled study.

OBJECTIVE: This study was undertaken to compare the effectiveness of mifepristone orally administered at 24 or 48 hours before first-trimester vacuum aspiration abortion with that of vaginally administered misoprostol as a cervical priming agent. STUDY DESIGN: In a randomized comparative trial 90 women who requested surgical termination of pregnancy were randomly assigned to receive 200 mg mifepristone orally 24 or 48 hours before the operation or 800 microg misoprostol vaginally 2 to 4 hours before the operation. The main outcome measures were baseline cervical dilatation, cumulative force required to dilate the cervix to 9 mm, and intraoperative blood loss. RESULTS: The baseline cervical dilatation was significantly greater among women who received mifepristone 48 hours before the operation (P =.02). This group also required the least mechanical force to dilate the cervix (P =.06). There were no significant differences among the 3 groups in the intraoperative blood loss, in the operating time, or in patient acceptability. Side effects such as hot flushes and headaches were significantly higher among women who received mifepristone 24 or 48 hours before the operation than among those who received misoprostol (P =.01 and P =. 002, respectively). CONCLUSION: Mifepristone is an effective cervical priming agent when orally administered 48 hours before vacuum aspiration for termination of first-trimester pregnancy. Because of its cost and availability in comparison with misoprostol, however, selective use may have to be considered.

An effective regimen for early medical abortion: a report of 2000 consecutive cases.

A combination of the anti-progesterone mifepristone and gemeprost provides an effective non-surgical method for the induction of abortion at gestations up to 63 days, achieving complete abortion rates of over 95%. We report our experience with an alternate regimen, comprising a reduced dose of mifepristone in combination with vaginal misoprostol. A consecutive series of 2000 women requesting early medical abortion at gestations up to 63 days was studied retrospectively. Each woman received mifepristone 200 mg orally, followed 36-48 h later by misoprostol 800 microg vaginally. Of the 2000 women, 39 (2.0%) aborted completely following administration of mifepristone alone and a further 1912 experienced complete abortion following administration of misoprostol (a complete abortion rate of 97.5%). Surgical intervention was required in 49 women (2.5%): for incomplete abortion in 27 (1.4%), for missed abortion in seven (0.4%), for continuing pregnancy in 11 (0.6%) and to exclude ectopic pregnancy in four (0.2%). The surgical intervention rate was significantly higher among women at gestations > or = 49 days than among those at < or = 49 days (3.3 versus 1.5%, P = 0.0193). The regimen appears as effective, in terms of high complete abortion rate and low continuing pregnancy rate, as any published alternative. This regimen has the benefit of being less costly as the dose of mifepristone is 67% lower and misoprostol is substantially less expensive than gemeprost. Additionally, misoprostol does not require special transport or storage requirements. As such, the combination of mifepristone and misoprostol may be preferable to mifepristone and gemeprost.

Termination of pregnancy at 9-13 weeks' amenorrhoea with mifepristone and misoprostol.

PIP: The effectiveness of a combined regimen of mifepristone and vaginal misoprostol for termination of pregnancies of 9-13 weeks of gestation was investigated in 120 UK abortion patients (median age, 22.1 years; median duration of amenorrhea, 10.3 weeks). Each woman received a single oral dose of 200 mg of mifepristone 36-48 hours before admission, at which time 800 mcg of misoprostol was administered vaginally. Where indicated, a further two doses of 400 mcg of misoprostol (vaginal or oral) were provided every 3 hours. All 120 women aborted on the day of prostaglandin administration; however, 6 women (5%) required exploratory curettage after the procedure for retained placenta. The median prostaglandin dose was 1200 mcg (range, 800-1600 mcg). The median time from misoprostol administration to abortion was 4.33 hours (range, 1.3-16.0 hours). 60 women (50%) required oral analgesics and 26 (22%) received parenteral analgesia. Diarrhea occurred in 38 women (32%). The median duration of bleeding after abortion was 12.5 days (range, 3-43 days). In questionnaires administered to 73 women, only 3 (4%) expressed dissatisfaction with medical abortion, because of pain or prolonged bleeding. The relatively high dose of misoprostol used in this study and the vaginal route of administration are presumed to account for the 95% success rate. Extension of medical abortion to later gestation times would decrease the need for surgery and expand women's choice of methods of pregnancy termination.^ieng

Assessment of patients with menorrhagia: how valid is a structured clinical history as a measure of health status?

A patient-administered questionnaire for menorrhagia based on the type of questions asked when taking a gynaecological history was developed and tested using the following steps: literature reviews, devising the questions, testing responses for internal consistency and test-retest reliability and validating the questionnaire by comparing patient's scores with their responses to the SF-36 general health measure, and with family practitioner perceptions of severity. The main sample consisted of 351 women with menorrhagia, 246 referred to gynaecology ambulatory clinics and 105 from four large training practices in North-east Scotland. Following testing, two questions were discarded from the questionnaire. The final questionnaire demonstrated a good level of reliability and the resulting patient scores correlated significantly with their scores on the scales making up the general health measure. The questions asked in taking a clinical history from a woman with menorrhagia can be used to construct a valid and reliable measure of health status. This clinical measure may be a useful guide in selection for treatment and in the assessment of patient outcome following treatment.

Ectopic pregnancy in Aberdeen 1950-1985.

The reported incidence of ectopic pregnancy in Aberdeen City and suburbs (1950-1985), using as denominators maternities, pregnancies and women aged 15-44 years, has increased threefold since 1970 to 6.4/1000 pregnancies. This increased incidence persisted after the exclusion of previously sterilized women. A total of 11,128 women were sterilized in Aberdeen City and suburbs between 1960 and 1982; 36 ectopic pregnancies occurred in this sterilized population. The prevalence of ectopic pregnancy was 3.55/1000 sterilizations. This did not alter significantly over the period of study despite changes in the method of sterilization. However, due to the increased popularity of sterilization, the proportion of ectopic pregnancies in women who had been sterilized increased from 0% in the 1950s to 21% in the quinquennium 1975-1979.

PIP: The incidence of ectopic pregnancy in a stable, geographically defined population served by the Aberdeen Maternity Hospital was determined from hospital census data: it rose 3-fold from 1950-1985. Ectopic pregnancy incidence remained fairly constant from 1950-1974, ranging from 2.40-3.10/1000 pregnancies (2.87-3.40/1000 maternities, and 0.20-0.27/1000 women aged 15-44). Then incidence rose to 6.40/1000 pregnancies (8.7/1000 maternities and 0.45/1000 women aged 15-44). From 1950-1982, of 413 ectopic pregnancies, 36 were in previously sterilized women. Although the prevalence of ectopic pregnancy in sterilized women remained steady around 3.55/1000, there were 6 in women sterilized by postpartum laparotomy (1.9/1000), 6 in women having open laparotomy (2.4/1000), and 23 in women having laparoscopic tubal diathermy (5.4/1000). The preponderance of right side ectopic pregnancy (53.6%) remains unexplained. Similarly, the explanation for the rising incidence of ectopic pregnancy is unclear, although sensitive pregnancy tests and high-resolution ultrasound may have improve diagnosis.