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.     

Second trimester medical abortion with mifepristone followed by unlimited dosing of buccal misoprostol in Armenia

Objectives: The aim of the study was to assess the efficacy and acceptability of a regimen using mifepristone and buccal misoprostol with unlimited dosing for second trimester abortion in Armenia.

Methods: Women seeking to terminate 13–22 week pregnancies were enrolled in the study. Participants swallowed 200?mg mifepristone in the clinic and were instructed to return to the hospital for induction 24–48?h later. During induction, women were given 400?μg buccal misoprostol every 3?h until the fetus and placenta were expelled. The abortion was considered a success if complete uterine evacuation was achieved without oxytocin or surgery.

Results: A total of 120 women with a median gestational age of 18 weeks participated in the study. All women began misoprostol induction around 24?h after taking mifepristone. Complete uterine evacuation was achieved in 119 (99.2%) women. The median induction-to-abortion interval was 10.3?h (range 4–17.4) with a mean of 9.5?±?2.5?h. A median of four misoprostol doses (range 2–6) with a mean of 4?±?1 misoprostol doses were administered. The induction-to-abortion interval, number of misoprostol doses, pain score and analgesia use increased as gestational age advanced. Acceptability of the method was high among both patients and providers.

Conclusion: The medical abortion regimen of 200?mg mifepristone followed 24?h later by induction with 400?μg buccal misoprostol administered every 3?h, with no limit on the number of doses used for the termination of pregnancies of 13–22 weeks’ gestation is an effective and acceptable option for women.     

Efficacy and safety of mifepristone and buccal misoprostol versus buccal misoprostol alone for medical abortion

Objectives  

To evaluate the efficacy and safety of mifepristone and buccal misoprostol versus buccal misoprostol alone in medical abortion of ≤56 days.     

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.     

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     

Preference and acceptability of oral versus vaginal administration of misoprostol in medical abortion with mifepristone

OBJECTIVES: To compare the experience of pain, need of analgesic interventions, preference and acceptability in medical abortion up to 49 days of amenorrhea with mifepristone and orally versus vaginally administered misoprostol. STUDY DESIGN: Ninety-seven women were randomised to oral misoprostol, n=48, or vaginal misoprostol, n=49. On day 1 of the study, both the groups received 600 mg of mifepristone. On day 3 of the study, one group received 0.4 mg of misoprostol orally and the other group received 0.8 mg of misoprostol vaginally. RESULTS: Even though oral administration of misoprostol seemed to be associated with a higher rate of gastrointestinal side effects, women in both the groups showed a clear preference towards the oral route of administration. The willingness to administer the misoprostol at home was also higher among the women in the oral group, which may in part depend on a more positive/less negative experience of the abortion. CONCLUSION: A majority of women prefer oral administration of misoprostol in early medical abortion.     

Effect of antiprogesterone mifepristone followed by misoprostol on circulating leptin in early pregnancy

BACKGROUND: To study the role of progesterone (P4) in the regulation of circulating leptin in early human pregnancy, we measured the levels of leptin before and after administration of the antiprogestin mifepristone, followed by misoprostol in early pregnancy. METHODS: Thirty-four women requesting termination of pregnancy, with < or =63 days of amenorrhea, received 200 mg of mifepristone on day 0, followed by either oral or vaginal administration of 0.8 mg of misoprostol on day 2. Five serial serum samples were assayed for leptin, human chorionic gonadotrophin (hCG), P4, estradiol (E2), cortisol, and mifepristone. RESULTS: Circulating leptin concentrations decreased by 8.7 +/- 29.7% (mean +/- standard deviation) (p < 0.05) following the ingestion of mifepristone. After misoprostol administration on day 2, a decrease of 12.6 +/- 17.0% (p < 0.05) was followed by a rebound on day 3 to 87.6 +/- 25.7% of the pretreatment values. Two weeks after mifepristone, leptin levels had declined by 25.4 +/- 30.4%. In contrast, E2, P4, and hCG concentrations continued to increase following mifepristone, followed by rapid declines from day 2 to day 3. Serum cortisol concentrations increased by 89.7% +/- 82.7% in response to mifepristone, but this increase did not correlate with the decrease in leptin. The decrease in leptin levels on day 2 correlated with the decreases in P4 (r = 0.37, p < 0.05) and in E2 (r = 0.44, p < 0.05) levels. CONCLUSIONS: The fall in leptin levels following mifepristone implies a role for P4 in the regulation of leptin in early pregnancy. Moreover, the significant correlation between the changes in leptin and those of P4 and E2 at the time of luteolysis suggests that corpus luteum may also play a role in the regulation of circulating leptin in early pregnancy.     

A randomised controlled trial of mifepristone in combination with misoprostol administered sublingually or vaginally for medical abortion up to 13 weeks of gestation

OBJECTIVE: To assess women's acceptability, the efficacy and side effects of sublingual versus vaginal administration of misoprostol in combination with mifepristone for medical abortion up to 13 weeks of gestation. DESIGN: Randomised controlled trial. SETTING: Aberdeen Royal Infirmary. POPULATION: Women undergoing medical abortion under the terms of the 1967 Abortion Act. METHODS: Mifepristone (200 mg) was given orally followed 36-48 hours later by misoprostol administration (sublingual: 600 microg; vaginal: 800 microg). A second dose of misoprostol 400 microg was given 3 hours later (sublingually or vaginally). Women between 9 and 13 weeks of gestation received a further (third) dose of misoprostol 400 microg (sublingually or vaginally), 3 hours later if abortion had not occurred. MAIN OUTCOME MEASURES: Women's acceptability, efficacy of the regimen and side effects experienced. RESULTS: A total of 340 women were recruited (171 sublingual and 169 vaginal). A total of 70% of women in the sublingual group expressed satisfaction with the route of misoprostol administration; 18% answered 'Don't know' while 12% were dissatisfied, compared with 68%, 28% and 4%, respectively, in the vaginal group (P= 0.02). There was no significant difference in the need for surgical evacuation for women in the sublingual (3/158, 1.9%) and vaginal groups (4/156, 2.6%) (P= 0.70). Women receiving misoprostol sublingually were more likely to experience diarrhoea (P < 0.01), shivering (P < 0.01) and unpleasant mouth taste (P < 0.01). CONCLUSIONS: Sublingual administration of misoprostol is an effective alternative to vaginal administration for medical abortion up to 13 weeks of gestation. The prevalence of prostaglandin-related side effects, however, was higher with this route of administration.     

Oral versus vaginal misoprostol for induction of labor: a double-blind randomized controlled trial

OBJECTIVE: To determine the efficacy of oral misoprostol (50 microg) administered every 3 hours compared to vaginal misoprostol (50 microg) administered every 6 hours for induction of labor. STUDY DESIGN: In this double-blind randomized trial, 126 women received misoprostol (50 microg) either orally every 3 hours or vaginally every 6 hours for induction of labor. Outcomes included time from induction to delivery, oxytocin augmentation, incidence of hyperstimulation and tachysystole, mode of delivery, and neonatal outcomes. RESULTS: Median time to delivery was shorter in those women who were receiving vaginal misoprostol (vaginal 14.3 hours vs oral 23.1 hours; P =.0004) and more women in the oral group required oxytocin augmentation of labor (73% vs 42%) (RR, 1.98; 95% CI, 1.29 to 3.06). The incidence of hyperstimulation was similar between the groups, but there was an increased incidence of tachysystole in the vaginal group (26.5% vs 9.7%)(RR, 2.74; 95% CI, 1.16 to 6.51). There was no difference between the groups with respect to mode of delivery or neonatal outcome. CONCLUSION: Vaginal misoprostol administered every 6 hours is more effective for induction of labor than oral misoprostol administered every 3 hours. The higher rates of tachysystole with use of vaginal misoprostol in the current study warrant further investigation.     

Alternatives to mifepristone for early medical abortion.

OBJECTIVE: To review published reports of first-trimester medical abortion regimens that do not include mifepristone. METHODS: Reports listed in Pubmed and Medline on prospective and controlled trials of the efficacy of misoprostol, alone or associated with methotrexate, for first-trimester abortion were analyzed if they included more than 100 participants and were published since 1990. RESULTS: The efficacy of regimens using misoprostol alone ranged from 84% to 96%, and when misoprostol was used with methotrexate the efficacy ranged from 70% to 97%. Efficacy rates were influenced by follow-up interval. Treatment for infection, bleeding, and incomplete abortion were infrequent with both methods (0.3%-5%). CONCLUSION: Alone or in combination with methotrexate, misoprostol is an efficacious alternative to mifepristone for the medical termination of pregnancy.     

Gemeprost versus misoprostol for cervical priming before first-trimester abortion: a randomized controlled trial

OBJECTIVE: To compare the efficacy of 400 microg of misoprostol with that of 1 mg of gemeprost as cervical priming agents when administered vaginally 3 to 4 hours before first-trimester vacuum aspiration abortion. METHODS: In a prospective controlled trial 90 nulliparous women who requested termination of pregnancy before 12 weeks' gestation were randomized to receive vaginally either misoprostol or gemeprost for cervical priming. The force to dilate the cervix was measured by the use of a cervical tonometer connected to Hegar dilators from 3 to 10 mm. The main outcome measures were baseline cervical dilation; the peak force to dilate the cervix at 8, 9, and 10 mm; and the cumulative force to dilate the cervix to 10 mm. RESULTS: Baseline cervical dilation did not differ significantly between the women who received misoprostol and those who were treated with gemeprost. Neither the peak force required to dilate the cervix at 8, 9, and 10 mm nor the cumulative force to dilate the cervix to 10 mm showed any significant difference between the two groups. CONCLUSION: Vaginally administered misoprostol (400 microg) is as effective as gemeprost (1 mg) for cervical priming 3 to 4 hours before surgical termination of first-trimester pregnancies.     

Randomized comparison of dry tablet insertion versus gel form of vaginal misoprostol for second trimester pregnancy termination

AIM: To compare the effectiveness of vaginal misoprostol between dry tablet insertion and gel form for second trimester pregnancy termination. METHODS: A non-blinded block randomized controlled trial was conducted on 148 pregnant women with live fetuses in the second trimester undergoing pregnancy termination. They were randomly allocated to receive vaginal misoprostol (400 microg) either dry tablet insertion (n=72) or gel form (n=76). The same dose was then repeated every 3 h if adequate uterine contraction was not achieved until 48 h after the initiation of misoprostol. If abortion did not occur within this period, the treatment was considered a failure and other technique of termination was then given based on the decision of the attending physicians and the cervical status. RESULTS: The mean induction-abortion interval in group 1 (20.9+/-12.3 h) was not significantly different from that in group 2 (17.7+/-10.2 h). The mean total dose of misoprostol was also not significantly different between the two groups (group 1, 1556.9 microg; group 2, 1350.9 microg), but the adverse effects of misoprostol (chill and diarrhoea) were more common in the gel group. CONCLUSION: Tablet insertion or gel form of vaginal misoprostol have similar effectiveness but the gel form was associated with more common adverse effects.