米索前列醇口服与舌下含服对药物流产结局的影响

目的:探讨米索前列腺醇口服与舌下含服对药物流产结局的影响。方法:分别采用口服(341例)和舌下含服(343例)米索前列腺醇的给药方法,比较药物流产者胎囊排出时间,流产结局以及副作用。结果:口服组中有248例排出胎囊,时间为167.26±99.80min,舌下组中234例排出胎囊,时间为165.71±134.41min,差异无统计学意义(t=-0.145,P=0.885)。两组完全流产和流产失败所占比例差异均有统计学意义(χ2=6.988,P=0.008和χ2=9.631,P=0.002)。两组腹痛程度差异无统计学意义(χ2=5.103,P=0.078)。两组阴道流血情况差异无统计学意义(χ2=2.689,P=0.261)。两组呕吐、腹泻次数差异有统计学意义(Z=-2.090,P=0.037和Z=-2.370,P=0.018)。结论:米索前列醇舌下含服的完全流产率高,给药便捷,不明显增加副作用,是一种较好的给药方式。     

Pilot study on the use of sublingual misoprostol in termination of pregnancy up to 7 weeks gestation

BACKGROUND: This study was conducted to assess the efficacy and incidence of side effects of a regimen of repeated doses of 400 microg sublingual misoprostol for termination of pregnancy of <7 weeks gestation. METHOD: Fifty women were given 400 microg sublingual misoprostol every 3 h for three doses. Two additional doses were given if necessary. RESULTS: Forty-three women (86%) had a complete abortion. Two women (4%) had incomplete abortion and 5 (10%) had an ongoing pregnancy. The median interval between the first dose of misoprostol and the passage of tissue mass was 14.1 h (3.25-561.6 h). The median duration of vaginal bleeding was 20 days (8-85 days). Side effects were mild and there was no significant drop in hemoglobin level. CONCLUSIONS: Our preliminary results on sublingual misoprostol show that it is a promising method for medical termination of pregnancy of <7 weeks. It may be used as an alternative for women who do not want surgical evacuation and who live in an area where mifepristone is not available.     

Mifepristone dose in the regimen with misoprostol for medical abortion

Medical abortion with the antiprogesterone mifepristone followed by a prostaglandin is highly effective and widely used. The mifepristone dose registered is a single dose of 600 mg followed by a suitable prostaglandin analogue 36-48 h later. The 600-mg dose was chosen arbitrarily, and later studies have proven one third of this dose to be equally effective when combined with a prostaglandin analogue. This report reviews published data on the efficacy of mifepristone in different doses and demonstrates that there are no differences neither clinically nor in pharmacokinetics if the dose is reduced to 200 mg.     

Two-pill regimens of misoprostol after mifepristone medical abortion through 63 days' gestational age: a randomized controlled trial of sublingual and oral misoprostol

Background

A 400 mcg dose of sublingual misoprostol has high efficacy and few side effects when used with 200 mg mifepristone for medical abortion through 63 days' gestation.

Study Design

Eligible and consenting women (n=480) were randomized to 400 mcg of misoprostol sublingually or orally, 24 h after 200 mg of mifepristone. Abortion status was assessed two weeks later.

Results

Complete abortion occurred in 98.7% of the sublingual group and 94.0% of the oral group (p value=.006, RR: 1.05, 95% CI=1.01--1.09). Over 90% of women in both arms expressed high satisfaction with the method. Side effects were similar in both groups, with only fever or chills reported by significantly more women in the sublingual arm.

Conclusions

The sublingual route appears superior to the regimen of 400 mcg misoprostol used orally and may be a good option for mifepristone medical abortion.     

Analgesia during at-home use of misoprostol as part of a medical abortion regimen

The objective of this study was to identify predictors of narcotic analgesic use during medical abortion. Two-thousand-seven-hundred-forty-seven women with pregnancies of 63 days gestational age or less received 200 mg mifepristone followed by at-home use of 800 μg vaginal misoprostol in two consecutive clinical trials in the United States, and also reported their use of analgesics. Overall, 79% of these subjects used narcotic analgesics. Women in the 2nd of the two studies were randomized to use misoprostol 24, 48, or 72 h after mifepristone. Those who were randomized to 24 h were more likely to use narcotic analgesics than those who were randomized to 48 or 72 h. In both studies, the use of narcotic analgesia during medical abortion was less prevalent among parous women and Asian women, and among those with a gestational age of 56 days or less. The clinic providing care for the patient was the most important determinant of narcotic analgesia use, even though the analgesia was used at home. Use of narcotic analgesics in these women undergoing medical abortion at home was more prevalent than use reported in previous studies where women underwent medical abortion in a clinical setting.     

Comparing two early medical abortion regimens: mifepristone+misoprostol vs. misoprostol alone

Background

Nonsurgical abortion methods have the potential to improve access to high-quality abortion care. Until recently, availability and utilization of mifepristone medical abortion in low-resource countries were restricted due to the limited availability and perceived high cost of mifepristone, leading some providers and policymakers to support use of misoprostol-only regimens. Yet, this may not be desirable if misoprostol-only regimens are considerably less effective and ultimately more costly for health care systems. This study sought to document the differences in efficacy between two nonsurgical abortion regimens.

Study Design

This double-blind randomized placebo-controlled trial enrolled women with gestational ages up to 63 days seeking early medical abortion from August 2007 to March 2008 at a large tertiary hospital in Ho Chi Minh City, Vietnam. Eligible consenting women received either (1) two doses of 800 mcg buccal misoprostol 24 h apart or (2) 200 mg mifepristone and 800 mcg buccal misoprostol 24 h later. Participants self-administered all study drugs and returned to the hospital for follow-up 1 week later. The trial is registered at ClinicalTrials.gov as NCT00680394.

Results

Four hundred women were randomized to either misoprostol-only (198) or mifepristone+misoprostol (202). Complete abortion occurred for 76.2% (n=147) of women allocated to misoprostol-only vs. 96.5% (n=194) of those given mifepristone+misoprostol (RR 0.79, 95% CI 0.73–0.86). Ongoing pregnancy was documented for 16.6% (32) of misoprostol-only users and 1.5% (3) of mifepristone+misoprostol users (1.62, 0.68–3.90). Side effects were generally similar for both groups, although significantly more women allocated to misoprostol-only reported diarrhea.

Conclusions

Mifepristone+misoprostol is significantly more effective than use of misoprostol-alone for early medical abortion. The number of ongoing pregnancies documented with misoprostol-only warranted an early end of the trial after unblinding of the study at interim analysis. Policymakers should advocate for greater access to mifepristone. Future research should prioritize misoprostol-only regimens with shorter dosing intervals.     

Acceptability of home-use of misoprostol in medical abortion

INTRODUCTION: Home-use of misoprostol would reduce the number of visits and improve access to medical abortion. We evaluated acceptance of home-use of misoprostol among women and their partners. MATERIALS AND METHODS: One hundred women with up to 49 days of amenorrhea were given mifepristone, followed by misoprostol taken at home. RESULTS: Women chose home-use of misoprostol because it felt more natural, private and allowed the presence of a partner/friend. Two women had a vacuum aspiration due to incomplete abortion. Five unscheduled visits occurred. Ninety-six women were satisfied with their choice of home-use. The male partners were generally satisfied with their partner's choice of home-use and felt that their presence and support had been valuable. DISCUSSION: Our study shows a high acceptability among women and their partners and confirms the safety and efficacy of home-use of misoprostol. Women should be offered this choice to allow more flexibility and privacy in their abortions.     

A two-pill sublingual misoprostol outpatient regimen following mifepristone for medical abortion through 70 days' LMP: a prospective comparative open-label trial

Objective

To test the effectiveness and acceptability of an outpatient medical abortion protocol with 200 mg mifepristone and 400 mcg sublingual misoprostol at 64–70 days' last menstrual period (LMP) and compare it to the already known efficacy of the 57–63 days' LMP gestational age range.

Study Design

We conducted a prospective, comparative open-label trial in six hospitals and clinics in Ukraine, Georgia, India and Tunisia. We enrolled 714 reproductive age women with pregnancies 57 to 70 days who presented requesting abortion. Medical abortions were managed with the current service delivery protocol (200 mg oral mifepristone followed in 24–48 h by 400 mcg sublingual misoprostol). Data on safety, efficacy and acceptability were collected. The main outcome measure was complete abortion without surgical intervention at any point.

Results

A total of 703 cases were analyzable for efficacy. Success rates did not differ significantly in the two groups [57–63-day group: 94·8%; 64–70-day group: 91.9%; Relative Risk (RR): 0.79 (0.61–1.04)]. Ongoing pregnancy rates also did not differ significantly (57–63 days: 1.8%; 64–70 days: 2.2%; RR: 1.10 (0.65–1.87)].

Conclusion

A medical abortion regimen of 200 mg mifepristone followed in 24–48 h by 400 mcg sublingual misoprostol is effective through 70 days' gestation and may be offered within existing outpatient abortion services.

Implications

A regimen of 200 mg mifepristone followed in 24–48 h by 400 mcg sublingual misoprostol is effective up to 70 days' LMP. The findings have important implications for expanding access to outpatient medical abortion services in settings where the cost of misoprostol is of concern or a two-pill misoprostol regimen is the standard of care.     

2017–19 governmental decisions to allow home use of misoprostol for early medical abortion in the UK

Home use of misoprostol for early medical abortion has long been an established practice in several countries. It is a safe, effective, and dignified means of obtaining a legal abortion, with a low risk of complications. In the UK, however, the practice has only recently been permitted. Prior to the change, women were required to attend a clinic to be observed taking the drug, before being discharged to go home and see through the process. The requirement to attend a clinic was a result of political rather than medical reasoning; a desire not to provoke pro-life groups. It also highlighted an inconsistency whereby misoprostol was prescribed for home use to women who had suffered an incomplete miscarriage. Failure to permit home use of misoprostol for early medical abortion has caused women to suffer trauma when experiencing the effects of the drug when returning home from clinics, in addition to acting as an obstacle to access for women living in remote areas with no nearby clinic. Through an overview of recent developments in UK abortion policy, I demonstrate the lack of good, medical reasons for the delayed change. Further, I suggest appropriate future steps to be taken by policymakers.     

A prospective double-blinded, randomized, placebo-controlled trial on the use of letrozole pretreatment with misoprostol for second-trimester medical abortion

BackgroundThe aim of this randomized trial was to evaluate the abortion rate of combined regimen of letrozole and misoprostol in second-trimester abortion.Study DesignThis was a randomized, double-blinded, placebo-controlled trial of 130 women requesting legal termination of pregnancy at gestational age between 12 and 20 weeks. Letrozole 7.5 mg or placebo were given for 3 days, followed by misoprostol 400 mcg vaginally every 3 h up to a maximum of five doses on the third day.ResultsThe abortion rate in 24 and 48 h were similar for the letrozole and placebo groups (24 h: 93.8% vs. 90.8%, respectively, p=.718; 48 h: 98.5% vs. 95.4%, respectively, p=.496). The median induction-to-abortion interval was also similar for the letrozole and placebo groups (9.6 h vs. 10.6 h, p=.145). All the side effects were comparable between the two groups.ConclusionThe use of letrozole pretreatment (7.5 mg daily for 3 days) with misoprostol in second-trimester abortion does not significantly improve the abortion rate of the misoprostol-only regimen.     

A prospective double-blinded,randomized, placebo-controlled trial on the use of letrozole pretreatment with misoprostol for second-trimester medical abortion

BackgroundThe aim of this randomized trial was to evaluate the abortion rate of combined regimen of letrozole and misoprostol in second-trimester abortion.Study DesignThis was a randomized, double-blinded, placebo-controlled trial of 130 women requesting legal termination of pregnancy at gestational age between 12 and 20 weeks. Letrozole 7.5 mg or placebo were given for 3 days, followed by misoprostol 400 mcg vaginally every 3 h up to a maximum of five doses on the third day.ResultsThe abortion rate in 24 and 48 h were similar for the letrozole and placebo groups (24 h: 93.8% vs. 90.8%, respectively, p=.718; 48 h: 98.5% vs. 95.4%, respectively, p=.496). The median induction-to-abortion interval was also similar for the letrozole and placebo groups (9.6 h vs. 10.6 h, p=.145). All the side effects were comparable between the two groups.ConclusionThe use of letrozole pretreatment (7.5 mg daily for 3 days) with misoprostol in second-trimester abortion does not significantly improve the abortion rate of the misoprostol-only regimen.     

Simultaneous very low dose mifepristone and vaginal misoprostol for medical abortion

OBJECTIVE: This pilot study was designed to evaluate the outcome of medical abortion following simultaneous mifepristone (100 mg) and misoprostol (800 microg). METHODS: Enrollees had gestational ages up to 56 days and desired a medical abortion. They received 100 mg of mifepristone orally and 800 microg of misoprostol vaginally. Follow-up examination occurred in 2-7 days. A phone call 3 weeks later assessed symptoms and acceptability. A 95% success rate, as seen in higher dose studies, gives a 95% confidence interval of 88-100% for 40 subjects. RESULTS: Forty women were enrolled; 39 women had follow-up visits. Completed medical abortion was confirmed for 35 (90%) of 39 women. Four women had uterine aspiration. Two patients required repeat misoprostol. Median time from medication to abortion was 7 h. Most women (92%) strongly preferred taking all medications in the clinic. CONCLUSIONS: The simultaneous administration of vaginal misoprostol with 100 mg of oral mifepristone had the outcome of completed abortion within the predicted confidence interval. In addition, simultaneous dosing was highly acceptable.     

米非司酮配伍米索前列醇不同给药方式终止早孕的临床随机比较研究

目的研究米非司酮配伍米索前列醇舌下含服及口服的药物流产效果。方法将158例早孕妇女(停经≤56天)随机分为2组,连续口服米非司酮2天,3次/d,每次25mg,第3天上午使用米索前列醇(本文简称米索)口服400μg同时阴道给400μg(组Ⅰ),或者舌下含400μg同时阴道给400μg(组Ⅱ)以终止妊娠。结果总体完全流产率为94.9%,组I为92.5%,组Ⅱ为97.4%,两组无显著性差异(P>0.05);总体不全流产率为4.43%,组I为7.5%(6/80),高于组Ⅱ1.28%(1/78),但两组无显著性差异(P>0.05);总体失败率为0.63%,其中组Ⅰ为0,组Ⅱ为1.28%,两组亦无显著性差异(P>0.05);组Ⅰ从应用米索至孕囊排出时间为(2.39±1.20)h,明显低于组Ⅱ(2.98±1.33)h(P<0.01)。结论组I终止早孕的不全流产率高于组Ⅱ(但无明显组间差异,可能与样本较小有关),可能与舌下含服米索可使有效血药浓度维持时间较长,生物利用度较高有关,故在药物流产中米非司酮配伍舌下含服米索是1种很有前景的用药方法。     

Ovulation resumption after medical abortion with mifepristone and misoprostol

Background

As an antiprogestin, mifepristone may have an impact on the return to ovulation in a manner that is not only attributable to its abortifacient activity. Our aim was to measure the time-to-ovulation in women who received mifepristone 200 mg orally and misoprostol 800 mcg vaginally for abortion up to 63 days of gestation.

Study Design

This planned substudy was part of a multicenter randomized trial of mifepristone 200 mg followed immediately or 24 h later by misoprostol 800 mcg vaginally. Women who had successful expulsion of the gestational sac based on ultrasound examination 1 week after mifepristone treatment were enrolled. All subjects used nonhormonal contraception until study completion. Baseline serum progesterone (P) levels were drawn on day 8±1 after mifepristone administration and then twice weekly until the P level was >3 ng/mL, consistent with ovulation. The mean time-to-ovulation was calculated using interval censored regression to address the censoring due to participant discontinuation.

Results

Fourteen (52%) of 27 enrolled women completed the substudy. The longest period of time that a subject who did not complete the study was followed was 29 days. Ovulation occurred 20.6±5.1 (range 8–36) days after mifepristone administration. Time-to-ovulation was not affected by participant age, gestational age, study arm, body mass index or presence or absence of human chorionic gonadotropin.

Conclusions

Return to ovulation following medical abortion with mifepristone and misoprostol occurs on average 3 weeks postabortion. Mifepristone 200 mg does not appear to have a lasting effect on ovarian function. Our results should be contextualized by the small sample size, although this is one of the larger studies on return to ovulation after abortion.     

Home self-administration of misoprostol for medical abortion up to 56 days' gestation

OBJECTIVE: Studies from the USA have suggested the feasibility and acceptability of home medical abortion, however the issue has not been addressed in the UK. This study aimed to assess the feasibility, efficacy and acceptability of home self-administration of misoprostol for medical abortion up to 56 days' gestation. METHODS: Mifepristone 200 mg was given orally in hospital under nursing supervision. Women were provided with misoprostol tablets 600 microg and advised to take them sublingually 36-48 hours later. The main outcome measures were (1) feasibility, assessed through successful completion of abortion at home without the need for hospital admission, (2) efficacy, assessed through complete uterine evacuation without the need for further medical or surgical intervention and (3) women's acceptability of the procedure as assessed by questionnaire. RESULTS: A total of 49 women participated in this study. Of these, 48 women aborted at home while one opted to be admitted to hospital after receiving misoprostol at home. One woman underwent surgical evacuation 5 weeks following abortion for excessive bleeding and retained products of conception. A total of 43/44 (98%) women were satisfied with having the abortion at home. Side effects experienced by women included nausea [32/40 (80%], vomiting [17/41 (42%)], diarrhoea [17/41 (42%)], shivering [26/40 (65%)], tiredness [32/40 (80%)], headache [12/39 (31%)], hot flushes [14/40 (35%)], dizziness [24/39 (62%)] and unpleasant mouth taste [19/38 (50%)]. CONCLUSIONS: This study suggests the feasibility and acceptability of home self-administration of misoprostol for medical abortion up to 56 days' gestation. These findings need to be assessed in the context of a randomised trial.     

Early abortion with buccal versus sublingual misoprostol alone: a multicenter,randomized trial

ObjectiveTo compare efficacy, safety/side effects and acceptability of buccal versus sublingual administration of a misoprostol-only regimen commonly used for early medical abortion.Study designWe conducted a randomized trial at six clinics in two Latin American countries. We randomized women seeking early abortion to buccal or sublingual administration of three doses of misoprostol 800 mcg repeated every 3 h. At initial follow-up (7–14 days after misoprostol), we offered women without a complete abortion aspiration or additional misoprostol plus waiting 7 more days. The primary outcome was continuing pregnancy at initial follow-up. Secondary outcomes included continuing pregnancy at final follow-up, incomplete abortion, successful abortion, side effects, acceptability and complications. We analyzed all outcomes as intention to treat.ResultsWe enrolled 401 women and randomized 202 into the buccal arm and 199 into the sublingual arm. Continuing pregnancy at initial follow-up occurred in 11/201 (5.5%) and 2/189 (1.1%) women, respectively (p=.02). Additional misoprostol at follow-up increased success, defined as complete abortion, from 170/201 (84.6%) to 184/199 (92.5%) in the buccal arm and 165/189 (87.3%) to 177/189 (93.7%) in the sublingual arm. We found no differences by gestational age. Women reported similar acceptability and side effects across groups except for chills and fever, which women using sublingual misoprostol reported more frequently (p<.05).ConclusionsSublingual administration was superior to buccal administration in reducing continuing pregnancy risk after a three-dose regimen of 800 mcg misoprostol. Complete abortion rates were comparable across groups, and in both cases, additional misoprostol at follow-up increased success.ImplicationsIf the primary goal is to avoid continuing pregnancy, sublingual administration of misoprostol 800 mcg every 3 h for three doses should be recommended. If chills or fever are a concern and the primary goal is to avoid surgery, buccal administration may be preferable. For either route, additional misoprostol can be given for incomplete abortion or continuing pregnancy.     

Mifepristone-misoprostol medical abortion: home administration of misoprostol in Guadeloupe

Mifepristone-misoprostol medical abortion promises to revolutionize reproductive health-care. Several simplifications of the standard three clinic visit regimen may be possible, however. Particularly in developing countries, access to the method can be greatly increased by eliminating the longest clinic visit. Indeed, shortly after mifepristone's introduction in Guadeloupe, a semi-developed Caribbean territory administered by France, in 1991, two of the authors conducted a small prospective study of a one treatment-visit regimen. The study regimen was subsequently adopted as the standard of care for medical abortion on the island. Women (n = 92) with amenorrhea of < or = 49 days received 600 mg mifepristone under clinical supervision and were given 400 micrograms oral misoprostol for home administration 2 days later, returning 2 weeks later for follow-up. The success rate (95.4%) is comparable to rates found when both drugs are administered in the clinic and to rates from a similar study conducted recently in the United States. Adverse events were also comparable to protocols requiring in-clinic administration of misoprostol. Protocol adherence appeared to be excellent and loss to follow-up was rare. We suggest that home administration of misoprostol can be safe and effective in most nonindustrialized settings.