Regimens of misoprostol with mifepristone for early medical abortion: a randomised trial

OBJECTIVE: To compare the efficacy, adverse effects and acceptability of the three most common misoprostol regimens used with mifepristone for medical abortion. DESIGN: Randomised nonblinded trial. SETTING: Three clinics associated with major research universities in Canada; two in major urban areas and one in a periurban area. POPULATION: Women of reproductive age. METHODS: Consenting women presenting for abortion services with gestations less than 56 days and who met inclusion criteria were given 200 mg mifepristone orally and then randomised into three misoprostol study groups: (group I) 400 micrograms of oral misoprostol, (group II) 600 micrograms of oral misoprostol, and (group III) 800 micrograms of vaginal misoprostol. Misoprostol was self-administered at home 24-48 hours following mifepristone, and participants were instructed to take a second similar misoprostol dose at 24 hours after the initial dose if bleeding was less than a normal menstrual period. MAIN OUTCOME MEASURES: Successful abortion without surgery was 94.1%, with no significant differences across the three study groups (94.7% in group I, 93.4% in group II, and 94.3% in group III; P= 0.975). RESULTS: Efficacy and adverse effects did not differ significantly across the three study groups. Pain increased significantly across the study and the gestational age groups and was associated with lower acceptability. CONCLUSIONS: There appears to be a range of safe and effective options for early medical abortion with mifepristone including a choice between oral and vaginal administration of misoprostol.     

米非司酮配伍米索前列醇行药物流产的安全性评价

目的　评价米非司酮配伍米索前列醇行药物流产的安全性。方法　检索国内外 9个医学数据库及 9种中文期刊。采用循证医学的方法对收集有关药物流产安全性研究的文献 ,进行质量评价和数据提取 ;对数据不能合并进行分析时 ,则行定性系统评价。结果　共收集、纳入文献 10 1篇 ,病例 136 4例。其中为药物严重不良反应 115例 ( 8 4 3% ) ,包括药物过敏性和失血性休克、药物中毒性心律失常、抽搐及胎儿畸形等 ;一般不良反应 10 15例 ( 74 4 1% ) ,包括异常出血和轻、中度过敏反应等。系统评价提示 ,药物流产后出血量过多、腹痛、发热和眩晕的发生率比手术流产高 ,相对危险度(RR)及 95 %可信限 (CI)范围分别为 3 2 7,1 14～ 9 38;1 6 3,1 14～ 2 34;1 5 8,1 0 3～ 2 4 4 ;和1 36 ,1 0 6～ 1 75。药物流产后的出血时间比手术流产长 ,加权均数差 (WMD)为 6 4 9,95 %CI为6 0 8～ 7 80。药物流产有并发症者 177例 ( 12 98% ) ,包括滋养细胞疾病、宫腔粘连和继发不孕。为异位妊娠而误用药物流产者 5 7例 ( 4 18% )。结论　药物流产的严重不良反应发生率较低 ,不影响药物流产的临床应用 ,但需要健全监测药物流产不良反应的制度 ;减少药物流产后出血 ,是需要进一步研究的课题     

Risk factors for unsuccessful medical abortion with mifepristone and misoprostol

BACKGROUND: The aim of this study was to determine the effectiveness of medical abortions with mifepristone and misoprostol following the approval of medical abortion in Israel. METHODS: A retrospective review of 377 consecutive medical records at an ambulatory care unit of a university medical centre was performed, screening all women undergoing medical abortion with mifepristone and misoprostol. Transvaginal ultrasonographic study and serum beta hCG measurement were performed 14-20 days after the procedure. The clinical outcome was defined as complete expulsion of intrauterine contents with (failed group) or without (successful group) surgical intervention. RESULTS: Surgical intervention was performed in 7.4% of patients. Residual products of conception were confirmed in 89%. Older age, previous spontaneous abortions, multigravidity, and earlier follow-up visit were independently associated with unsuccessful medical abortion. Significant differences were found in mean serum beta hCG and mean endometrial thickness in the successful versus failed procedure groups. CONCLUSIONS: Medical termination of pregnancy with mifepristone and misoprostol is >90% effective. High risk group for failure of the procedure can be characterised. An algorithm of follow up using follow-up visit date, serum beta hCG and sonographic endometrial stripe is suggested to define high risk patients for failed medical abortion.     

A randomised study of misoprostol and gemeprost in combination with mifepristone for induction of abortion in the second trimester of pregnancy

Objective To compare the effectiveness of gemeprost and misoprostol as prostaglandins used in combination with mifepristone for induction of mid-trimester termination.
Design Randomised trial.
Setting Scottish teaching hospital.
Sample One hundred women undergoing abortion between 12 and 20 weeks.
Methods Each woman received 200 mg mifepristone and 36–48 hours later either 1 mg gemeprost vaginal pessary every 6 hours for 18 hours or  4 × 200 μg  misoprostol tablets vaginally followed by  2 × 200 μg  misoprostol tablets orally every 3 hours for 12 hours. Success was defined as the percentage of women aborted within 24 hours of the first administration of prostaglandin.
Main outcome measures Prostaglandin–abortion interval and side effects.
Results There were no significant differences in median prostaglandin–abortion interval between gemeprost (6.6 hours 95% CI 6.0–10.7) and misoprostol (6.1 hours 95% CI 5.5–7.5) (   P = 0.22  ). The cumulative abortion rates at 24 hours (96% vs 94%, respectively), the surgical evacuation rates (12% and 10%) and the incidence of vomiting, diarrhoea and pain were similar.
Conclusion Two hundred milligrammes of mifepristone followed 36–48 hours later by either vaginal gemeprost or misoprostol is a highly effective way of inducing abortion in the second trimester of pregnancy.     

Randomized comparison of 3 misoprostol protocols for abortion induction at 13-20 weeks of gestation

OBJECTIVE: To evaluate the induction-to-abortion time of 3 pharmacokinetic-based protocols at 13-20 weeks of gestation. STUDY DESIGN: A randomized trial was conducted on 153 patients. The oral group (n = 51) received 100 microg misoprostol orally every 2 hours, the vaginal group (n = 51) received 200 microg misoprostol vaginally every 4 hours, and the sublingual group (n = 51) received 100 microg misoprostol sublingually every 2 hours. RESULTS: The mean induction-to-delivery time was shorter in the sublingual group (mean, 651 +/- 507) as compared to the vaginal group (mean, 1,056 +/- 634, p = 0.01). The number of patients who delivered within 12 hours was significantly higher in the sublingual group (n = 39, 78%) as compared to the oral (n = 26, 52%) and vaginal (n = 20, 40%) groups (p < 0.001). The numbers of patients who delivered within 24 hours were comparable in the sublingual (n = 47, 94%) and oral (n = 46, 92%) groups but higher than in the vaginal group (n = 39, 78%; p = 0.02). The total misoprostol dose was 543 +/- 422 microg in the sublingual group, 878 +/- 533 microg in the vaginal group and 741 +/- 413 microg in the oral group (p < 0.001). CONCLUSION: A pharmacokinetic-based application of 100 microg of sublingual misoprostol every 4 hours is more effective for induction of second-trimester abortion as compared to 100 microg oral misoprostol every 2 hours and 200 microg vaginal misoprostol every 4 hours.     

A comparison of orally administered misoprostol with vaginally administered misoprostol for cervical ripening and labor induction.

OBJECTIVE: Our purpose was to compare orally administered with vaginally administered misoprostol for cervical ripening and labor induction. MATERIAL AND METHODS: Two hundred twenty subjects with medical or obstetric indications for labor induction and undilated, uneffaced cervices were randomly assigned to receive orally administered or vaginally administered misoprostol. Fifty micrograms of oral misoprostol or 25 microgram of vaginal misoprostol was given every 4 hours. If cervical ripening (Bishop score of >/=8 or cervical dilatation of >/=3) or active labor did not occur, repeated doses were given to a maximum of 6 doses or 24 hours. Thereafter, oxytocin was administered intravenously by a standardized incremental infusion protocol to a maximum of 22 mU/min. RESULTS: Of the 220 subjects evaluated, 110 received orally administered misoprostol and 110 received vaginally administered misoprostol. Fewer subjects who received the oral preparation (34/110, 30.9%) were delivered vaginally within 24 hours of initiation of induction, in comparison with those who received the vaginal preparation (52/110, 47.3%) (P =.01). The average interval from start of induction to vaginal delivery was nearly 6 hours longer in the oral treatment group (mean and SD 1737.9 +/- 845.7 minutes) than in the vaginal treatment group (mean and SD 1393.2 +/- 767.9) (P =.005, log-transformed data). Orally treated patients required significantly more doses than vaginally treated patients (orally administered doses: mean and SD 3.3 +/- 1.7; vaginally administered doses: mean and SD 2.3 +/- 1.2) (P <.0001). Oxytocin administration was necessary in 83 (75.4%) of 110 orally treated subjects and in 65 (59.1%) of 110 vaginally treated subjects (P =.01, relative risk 1. 28, 95% confidence interval 1.06-1.54). Vaginal delivery occurred in 95 (86.4%) orally treated subjects and in 85 (77.3%) vaginally treated subjects (P =.08, relative risk 1.12, 95% confidence interval 0.99-1.27), with the remainder undergoing cesarean delivery. There was no difference in the incidence of uterine contractile abnormalities (tachysystole, hypertonus, or hyperstimulation), intrapartum complications, or neonatal outcomes between the 2 groups. CONCLUSIONS: Oral administration of 50-microgram doses of misoprostol appears less effective than vaginal administration of 25-microgram doses of misoprostol for cervical ripening and labor induction. Further investigation is needed to determine whether orally administered misoprostol should be used for cervical ripening and labor induction.     

Randomized, double-blind, controlled trial of mifepristone in capsule versus tablet form followed by misoprostol for early medical abortion

OBJECTIVE: To compare the efficacy and side-effects of mifepristone 75 mg in capsule form versus 150 mg in tablet form followed by misoprostol for medical termination of early pregnancy. STUDY DESIGN: In a prospective randomized, double-blind, placebo-controlled trial, a total of 480 women who were 49 days or less pregnant were randomized by means of a random number table to receive either two tablets in the morning and one tablet 12 h later for 2 days (group A) or three capsules orally twice daily for 2 days, the first dose being double all subsequent doses (group B). After a further 48 h, 600 microg misoprostol was given orally. Successful abortion was defined as complete abortion with no need for surgical aspiration. RESULTS: There were no significant differences between the two study groups in the rates of complete abortion (95.4% in group A versus 96.3% in group B), incomplete abortion (3.8% in group A, 3.3% in group B) and continued pregnancy (0.8% in group A, 0.4% in group B). No significant difference in the duration and amount of vaginal bleeding was observed. The incidence of side-effects, such as vomiting, nausea, headache, diarrhea and lower abdominal pain was similar in the two groups. CONCLUSIONS: Our results indicate that 75 mg mifepristone in capsule form combined with 600 microg misoprostol is as effective and safe as 150 mg mifepristone in tablet form for the termination of pregnancy up to 49 days.     

A randomised trial of two regimens of vaginal misoprostol to manage termination of pregnancy of up to 16 weeks

OBJECTIVE: The purpose of this study was to compare the efficacy and side-effects of two regimens of vaginal misoprostol for pregnancy termination of up to 16 weeks. METHODS: A randomised clinical trial of medical pregnancy termination of up to 16 weeks was conducted. A hundred pregnant women requesting legal termination of pregnancy were randomised into two groups to receive either 200 microg (50 women) or 400 microg (50 women)--vaginal misoprostol every six hours up to four doses. Outcome of abortion and side-effects were assessed. RESULTS: The groups were similar in maternal age, gestational age, parity and indication for pregnancy termination. There were no statistically significant differences between the two groups in abortion (P = 0.084) and mean induction to abortion time (P = 0.35). However, the side-effects in the 400 microg group were significantly higher than in the 200 microg group (P = 0.000). Conclusion: In pregnancy termination of up to 16 weeks, 200 microg vaginal misoprostol every six hours up to four doses was as effective as 400 microg, but side-effects were more common in 400 microg regimen.     

Acceptability and feasibility of medical abortion with mifepristone and misoprostol in Nigeria

Objective

To examine the acceptability and feasibility of medical abortion in Nigeria.

Methods

In total, 250 women who were eligible for legal pregnancy termination with a gestational age of up to 63 days since last menstrual period were enrolled in Benin City and Zaria between May 2005 and October 2006. Participants received 200 mg of oral mifepristone in the clinic and then took 400 μg of oral misoprostol 2 days later—choosing to either return to the clinic or take it at home. Women returned 2 weeks later for an assessment of abortion status.

Results

The vast majority (96.3%) of women had successful complete abortions. Ultrasound was used to determine outcome in less than one-third (28.9%) of participants. Most women (83.2%) took the misoprostol at home. Almost all (96.2%) participants were satisfied or very satisfied with the abortion method.

Conclusion

The introduction of medical abortion with mifepristone and misoprostol could greatly expand current method options and improve the quality of reproductive health care in Nigeria and other settings in which access to legal abortion services is limited.     

Psychological sequelae of medical and surgical abortion at 10-13 weeks gestation

BACKGROUND: Although not much research comparing the emotional distress following medical and surgical abortion is available, few studies have compared psychological sequelae following both methods of abortion early in the first trimester of pregnancy. The aim of this review was to assess the psychological sequelae and emotional distress following medical and surgical abortion at 10-13 weeks gestation. METHODS: Partially randomized patient preference trial in a Scottish Teaching Hospital was conducted. The hospital anxiety and depression scales were used to assess emotional distress. Anxiety levels were also assessed using visual analog scales while semantic differential rating scales were used to measure self-esteem. A total of 368 women were randomized, while 77 entered the preference cohort. RESULTS: There were no significant differences in hospital anxiety and depression scales scores for anxiety or depression between the groups. Visual analog scales showed higher anxiety levels in women randomized to surgery prior to abortion (P < 0.0001), while women randomized to surgical treatment were less anxious after abortion (P < 0.0001). Semantic differential rating scores showed a fall in self-esteem in the randomized medical group compared to those undergoing surgery (P = 0.02). CONCLUSIONS: Medical abortion at 10-13 weeks is effective and does not increase psychological morbidity compared to surgical vacuum aspiration and hence should be made available to all women undergoing abortion at these gestations.     

Lowering the doses of mifepristone and gemeprost for early abortion: a randomised controlled trial

Objective To test the efficacy of lower doses of mifepristone and gemeprost for medical induction of early abortion.Design Randomised controlled trial. Participants were blinded as to the therapy and physicians to the dose of mifepristone.Setting Thirteen hospital gynaecological units in different continents.Participants 1224 healthy pregnant women requesting medical abortion at <57 days from last menses.Intervention Random allocation to one of four regimens: mifepristone 50 mg by mouth followed by either 0.5 mg or 1.0 mg gemeprost vaginally on day 3; mifepristone 200 mg by mouth followed by either 0.5 mg or 1.0 mg gemeprost vaginally. We concealed the allocation sequence from clinicians enrolling participants, and maintained double blinding throughout.Main outcome measures Incidence of complete abortion; subordinate outcome measures included side effects such as vomiting and fall in haemoglobin, as well as the need for emergency curettage and blood transfusion.Results The success rate was significantly related to the dose of mifepristone. The relative risk of failure to have a complete abortion with the lower dose of mifepristone was 1.6 (95% CI: 1.1-2.3) times that with the higher dose. The relative risk of failure with the lower dose of gemeprost (1.3; 95% CI: 0.9-1.8) did not reach statistical significance.Conclusions A single dose of mifepristone 50 mg followed by gemeprost is inadequate for early medical abortion. There was no significant difference in side effects between the four treatment groups.     

Management of missed abortion: comparison of medical treatment with either mifepristone + misoprostol or misoprostol alone with surgical evacuation. A multi-center trial in Copenhagen county,Denmark

OBJECTIVE: To compare the efficacy of two different medical treatment regimens: mifepristone 600 mg orally + misoprostol 0.4 mg vaginally (Mf + Ms) or misoprostol 0.4 mg vaginally (Ms) with conventional surgical evacuation (SE) in women with missed abortion. MATERIALS AND METHODS: Prospective crossover study with alternating regimens every 4 months. The three university clinics of Obstetrics and Gynecology in Gentofte, Herlev and Glostrup of Copenhagen County. During the period October 1999 to October 2000, 176 women with missed abortion accepted to participate in the study. RESULTS: The proportion of women who needed surgical evacuation after medical treatment, number of women who needed re-evacuation after primary surgical evacuation, duration of vaginal bleeding, treated infections, need of analgesics, and the subjective experiences from the participating women. Fifty-four, 73 and 49 patients were randomized to Mf + Ms, Ms and SE, respectively. Within 1 week, complete expulsion occurred in 40 (74%), 52 (71%), 47 (96%) of the three arms, respectively. Duration of bleeding was 6.9, 7.1 and 2.5 days in the three arms, respectively (p < 0.01). Women with an initial plasma chorionic gonadotrophine (p-hCG) between 2000 and 20 000 IU/l and a gestational age less than 75 days had a significantly better response to the medical treatment than those not fulfilling these two criteria. Initial p-progesterone did not correlate with success of medical treatment. MAIN OUTCOME MEASURES: Proportion of women who needed surgical evacuation after medical treatment, and the number of women who needed re-evacuation after primary surgical evacuation, duration of vaginal bleeding, treated infections, the need of analgesics, and subjective experiences from participating women. CONCLUSION: Vaginal misoprostol 0.4-0.6 mg is effective in most patients with missed abortion. Pre-treatment with the antiprogesterone mifepristone does not increase the success rate. The selection of women with missed abortion for medical treatment based on gestational age and initial p-hCG level may increase the success of medical treatment significantly.