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The dose of mifepristone approved by most government agencies for medical abortion is 600 mg. Our aim was to summarize extant data on the effectiveness and safety of regimens using the widely recommended lower mifepristone dose, 200 mg, followed by misoprostol in early pregnancy and to explore potential correlates of abortion failure.
Study Design
To identify eligible reports, we searched Medline, reviewed reference lists of published reports, and contacted experts to identify all prospective trials of any design of medical abortion using 200 mg mifepristone followed by misoprostol in women with viable pregnancies up to 63 days' gestation. Two authors independently extracted data from each study. We used logistic regression models to explore associations between 15 characteristics of the trial groups and, separately, the rates of medical abortion failure and of ongoing pregnancy.
Results
We identified 87 trials that collectively included 120 groups of women treated with a regimen of interest. Of the 47,283 treated subjects in these groups, abortion outcome data were reported for 45,528 (96%). Treatment failure occurred in 2,192 (4.8%) of these evaluable subjects. Ongoing pregnancy was reported in 1.1% (499/45,150) of the evaluable subjects in the 117 trial groups reporting this outcome. The risk of medical abortion failure was higher among trial groups in which at least 25% of subjects had gestational age >8 weeks, the specified interval between mifepristone and misoprostol was less than 24 h, the total misoprostol dose was 400 mcg (rather than higher), or the misoprostol was administered by the oral route (rather than by vaginal, buccal, or sublingual routes). Across all trials, 119 evaluable subjects (0.3%) were hospitalized, and 45 (0.1%) received blood transfusions.
Conclusions
Early medical abortion with mifepristone 200 mg followed by misoprostol is highly effective and safe.
Since mifepristone was introduced in France and China more than two decades ago, medical abortion with this antiprogestin has expanded rapidly throughout the world. Mifepristone is now registered in 50 countries (www.gynuity.org, accessed 14 December 2011). In the United States, about one fifth of all outpatient abortions are performed medically [
Although medical abortion regimens approved by most government regulatory agencies specify 600 mg mifepristone, in practice, a dose of 200 mg is standard worldwide [
]. A prostaglandin, misoprostol, is administered after the mifepristone to enhance success. The dose, route, and timing of administration of misoprostol are not standardized. In the United States, affiliates of Planned Parenthood Federation of America provide 800 mcg buccally 24���48 h after the mifepristone [
], which also recommend oral dosing at gestational ages up to 49 days. Lower doses, divided doses, oral administration, and a shorter or longer interval between the two drugs also have been used clinically or evaluated in research studies.
The purpose of this review is to summarize published data on the effectiveness and safety of regimens including 200 mg mifepristone followed by misoprostol for early medical abortion. We also explore whether variation among studies in the frequency of medical abortion failure could be explained by characteristics of the study designs, treatment protocols, or study populations.
2. Materials and methods
We searched Medline using PubMed on 7 July 2011 for studies of medical abortion using mifepristone and misoprostol. Our search strategy was as follows: (abortion OR pregnancy termination OR termination of pregnancy) AND (mifepristone OR RU 486 OR RU-486 OR RU486 OR Mifegyne OR Mifeprex OR Medabon) AND (misoprostol OR prostaglandin). In addition, we reviewed the reference lists of relevant articles, and we contacted experts in the field for information about any published or unpublished trials not discovered in our search.
Two authors (E.G.R., C.S.) independently examined the search results (titles and as necessary abstracts and full publications) and other available information to identify all English language reports of prospective trials that included at least one group of women with viable first trimester pregnancies who were treated with a specified abortion regimen consisting of 200 mg mifepristone followed by misoprostol. These trials included randomized trials, cohort studies, and case series studies. For each group of interest in these reports, the same two authors separately abstracted data, including information about the study design and treatment protocol, the number and characteristics of women treated, and the numbers who had medical abortion failure, medical abortion failure with a diagnosed ongoing (viable) pregnancy, hospitalization, and blood transfusion. We contacted some authors to obtain additional data or to clarify details about the studies. We resolved discrepancies by discussion.
In some reports, the effectiveness analyses excluded subjects who initiated treatment but failed to complete the full prescribed medical abortion regimen. Our analyses included all pregnant women in each trial group who received at least mifepristone and who had a gestational age of 63 days or less, were not known to have an ectopic pregnancy, and had a reported abortion outcome. Most trials defined medical abortion failure as need for surgical intervention to complete the abortion, but a few used other definitions, such as failure to abort within 24 h after the misoprostol [
]. Of necessity, we used the authors' definitions, but when possible, we also included as failures ongoing pregnancies that were continued at the patient's choice after ingestion of mifepristone.
In abstracting data about protocols and study populations, we combined the original authors' categories that were similar but not necessarily identical; for example, in recording gestational age ranges, we considered ���<63 days���, ������63 days���, ���<9 weeks���, and ������9 weeks��� all to be equivalent, and we considered subjects who had had no live births to be nulliparous if the report did not describe parity (including both live births and stillbirths). In recording parity and the gestational age distribution, we accepted figures for either the entire enrolled trial population or the analyzed population, as provided by the authors. We used our judgment to resolve internal inconsistencies and to correct frank errors noted in a few reports.
Our analysis considered each group from each trial (regardless of study design) as a separate case-series. We combined data across trial groups to calculate the proportion of subjects who had medical abortion failure and the proportion who had ongoing pregnancy. We used exact Pearson chi-square goodness-of-fit tests, calculated using StatXact, Version 8.0 (Cytel Inc., Cambridge, MA, USA), to assess heterogeneity across trial groups in both outcomes. To explore possible explanations for heterogeneity, we used logistic regression to examine associations between selected characteristics of the trial groups and, separately, medical abortion failure rate and ongoing pregnancy rate. The models controlled for nesting of groups within trial using generalized estimating equations with an independence working correlation matrix. The response for the models was the ratio of the number of events to the number of evaluable patients for each trial group (conducted in SAS, version 9.2, SAS Institute, Cary NC, USA); thus, model results were weighted by trial group sample size. We used ���missing��� categories to include trial groups with missing predictor data wherever relevant. The models included interaction terms for misoprostol dose and route of first dose. We excluded from both models one trial group of 4 women treated with 200 mcg misoprostol [
] because no ongoing pregnancies occurred in any groups with that dose/route combination. For one study in which the misoprostol dose was increased from 400 to 800 mcg partway through [
], we estimated the number of women and events in each of the two respective trial groups by assuming that the enrollment rate was constant over the course of the study. In reviewing the results, we focused on associations that were both substantial (odds ratio >1.5 or <0.67) and significant (p<.05).
A previously published protocol for this systematic review does not exist.
3. Results
The Medline search yielded 860 citations. Of these, 81 included at least one group of women who were treated with an abortion regimen that used 200 mg mifepristone followed by misoprostol in viable first trimester pregnancy [
Increasing women's choices in medical abortion: a study of misoprostol 400 microg swallowed immediately or held sublingually following 200 mg mifepristone.
Eur J Contracept Reprod Health Care.2009; 14: 169-175
A multicentre randomized comparative clinical trial of 200 mg RU486 (mifepristone) single dose followed by either 5 mg 9-methylene PGE(2) gel (meteneprost) or 600 microg oral PGE(1) (misoprostol) for termination of early pregnancy within 28 days of missed menstrual period. ICMR Task Force Study. Indian Council of Medical Research.
Mifepristone plus vaginal misoprostol vs vaginal misoprostol alone for medical abortion in gestation 63 days or less in Nepalese women: a quasi-randomized controlled trial.
Early abortion induction by a combination of mifepristone and oral misoprostol: a comparison between two dose regimens of misoprostol and their effect on blood pressure.
Randomised controlled trial comparing the efficacy of same-day administration of mifepristone and misoprostol for termination of pregnancy with the standard 36 to 48 hour protocol.
A randomised controlled trial of mifepristone in combination with misoprostol administered sublingually or vaginally for medical abortion up to 13 weeks of gestation.
A prospective randomized, double-blinded, placebo-controlled trial comparing mifepristone and vaginal misoprostol to vaginal misoprostol alone for elective termination of early pregnancy.
Comparison of 400 mcg buccal and 400 mcg sublingual misoprostol after mifepristone medical abortion through 63 days' LMP: a randomized controlled trial.
Two-pill regimens of misoprostol after mifepristone medical abortion through 63 days' gestational age: a randomized controlled trial of sublingual and oral misoprostol.
Termination of early pregnancy by two regimens of mifepristone with misoprostol and mifepristone with PG05 ��� a multicentre randomized clinical trial in China.
A prospective, randomized, placebo-controlled trial on the use of mifepristone with sublingual or vaginal misoprostol for medical abortions of less than 9 weeks gestation.
A randomized double-blind placebo-controlled study to assess the effect of oral contraceptive pills on the outcome of medical abortion with mifepristone and misoprostol.
A prospective randomized study on the measured blood loss in medical termination of early pregnancy by three different misoprostol regimens after pretreatment with mifepristone.
The effect of contraceptive pills on the measured blood loss in medical termination of pregnancy by mifepristone and misoprostol: a randomized placebo controlled trial.
Two mifepristone doses and two intervals of misoprostol administration for termination of early pregnancy: a randomised factorial controlled equivalence trial.
Can midlevel health-care providers administer early medical abortion as safely and effectively as doctors? A randomised controlled equivalence trial in Nepal.
]. In addition, we became aware of six reports of unpublished trials (M. Pena and S. Raghavan, Gynuity Health Projects, personal communication) that met these criteria.
The 87 trials included 36 randomized trials and 51 prospective cohort or case series studies conducted at 314 sites in 35 countries (Table��1). Sixty-three of the trials were performed between 1994 and 2011; the other 24 reports did not provide dates of data collection. Inclusion criteria for the trials were similar and broad: in general, any woman who requested medical abortion, did not have contraindications to the abortion drugs, and was within a specified gestational age range (determined by ultrasound or clinically) was eligible. Some trials had age restrictions and/or excluded women with multiple gestations.
Table��1Characteristics of trial groups, subjects, medical abortion failures and ongoing pregnancies
Dates of mifepristone registration in each country obtained from www.gynuity.org, accessed 17 August 2011. Coded as ���before mifepristone registration��� if the year that data collection ended was not more than 1 year after the registration year and otherwise as ���after��� if the data collection started in the year after the registration year or later. This variable is missing for trials conducted in multiple countries and studies that provided insufficient information about dates of data collection.
Before mifepristone registration
42 (41)
13,859 (13,608)
744
5.4
140
1.0
After mifepristone registration
44 (42)
22,029 (21,902)
864
3.9
245
1.1
Missing
34
9,640
584
6.1
114
1.2
Geographic region
Europe
31 (30)
10,772 (10,745)
378
3.5
88
0.8
Americas
36
16,598
564
3.4
123
0.7
Other
53 (51)
18,158 (17,807)
1,250
6.9
288
1.6
Number of study sites
1
59 (57)
12,071 (11,944)
452
3.7
102
0.9
>1
61 (60)
33,457 (33,206)
1,740
5.2
397
1.2
Prescribed interval between mifepristone and misoprostol
<23 h
11
2,018
108
5.4
20
1.0
23���72 h
109 (106)
43,510 (43,132)
2,084
4.8
479
1.1
Protocol specified additional dose of misoprostol for selected subjects
No
67 (64)
20,512 (20,134)
1,335
6.5
276
1.4
Yes
53
25,016
857
3.4
223
0.9
Protocol required all subjects to take misoprostol in clinic
Total misoprostol dose and route of first dose if multiple doses were administered.
200 mcg oral
1
4
1
25.0
1
25.0
400 mcg buccal
1
272
8
2.9
4
1.5
400 mcg oral
21
9,299
737
7.9
215
2.3
400 mcg sublingual
10
2,875
126
4.4
30
1.0
400 mcg vaginal
5
1,116
86
7.7
20
1.8
600 mcg oral
9
1,608
132
8.2
22
1.4
600 mcg sublingual
4
540
7
1.3
0
0.0
600 mcg vaginal
1
242
18
7.4
9
3.7
���800 mcg buccal
6
2,205
71
3.2
16
0.7
���800 mcg oral
10 (8)
2449 (2,322)
158
6.5
38
1.6
���800 mcg sublingual
4
1,003
52
5.2
5
0.5
���800 mcg vaginal
43 (42)
19,210 (18,959)
653
3.4
99
0.5
Varied or missing
5
4,705
143
3.0
40
0.9
a Number in all groups (number in groups in which ongoing pregnancy was reported, if different).
b Percent of subjects in trial groups reporting outcome.
c Dates of mifepristone registration in each country obtained from www.gynuity.org, accessed 17 August 2011. Coded as ���before mifepristone registration��� if the year that data collection ended was not more than 1 year after the registration year and otherwise as ���after��� if the data collection started in the year after the registration year or later. This variable is missing for trials conducted in multiple countries and studies that provided insufficient information about dates of data collection.
d Total misoprostol dose and route of first dose if multiple doses were administered.
The 87 trials included 120 groups of women treated with a regimen of interest: 62 trials studied a single such regimen, 18 studied two, six studied three, and one studied four (Appendix). The total prescribed dose of misoprostol in the regimens studied varied from 200���6400 mcg. In most trial groups, the misoprostol was delivered in one administration, but 13 groups received the total dose in divided increments over 1���7 days. Routes of administration included vaginal, oral, buccal and sublingual. The two most commonly studied regimens used 800 mcg misoprostol vaginally or 400 mcg orally. The interval between the mifepristone and the misoprostol ranged from 0 to 72 h. Some protocols required that all subjects receive the misoprostol in the clinic, whereas others allowed most or all women to take the misoprostol at home. In nearly half the groups, the treatment protocol specified that selected subjects who did not abort after the initial treatment should be offered one or more additional doses of misoprostol rather than immediate surgical evacuation.
The timing of the initial follow-up evaluation of abortion success varied from 1���21 days after mifepristone administration. In about half the trial groups, ultrasound was used routinely at the follow-up visit to determine whether the medical abortion regimen resulted in complete abortion and, if not, whether the pregnancy was ongoing. In other groups, outcome assessment, including the diagnosis of ongoing pregnancy, relied primarily or solely on patient symptoms and/or clinical examination. Some trials allowed collection of outcome information by telephone or by review of outside records. No trial had explicit criteria for hospitalization and transfusion of subjects.
The 120 trial groups included a total of 47,283 treated subjects, of whom 45,528 (96%) provided evaluable data for our effectiveness analyses (Table��1). The median proportion of treated subjects with missing outcome data was 1.3% (range 0���19%). The number of evaluable subjects in the 120 groups ranged from 4 to 4,132.
Among all evaluable subjects, 2,192 (4.8%) had medical abortion failure (Table��2). Across trial groups, the proportion with this outcome ranged from 0 to 40% (Fig.��1A ). Half the groups had failure rates of 4.8% or less, and more than 90% of the evaluable subjects were in trial groups in which the failure proportion was 8.8% or less.
Table��2Associations between trial and population characteristics and rates of medical abortion failure and ongoing pregnancy
Dates of mifepristone registration in each country obtained from www.gynuity.org, accessed 17 August 2011. Coded as ���before mifepristone registration��� if the year that data collection ended was not more than 1 year after the registration year and otherwise as ���after��� if the data collection started in the year after the registration year or later. This variable is missing for trials conducted in multiple countries and studies that provided insufficient information about dates of data collection.
Before mifepristone registration
1.2
(0.8���1.6)
0.7
(0.3���1.5)
After mifepristone registration
1
1
Geographic region
Europe
0.7
(0.4���1.3)
0.6
(0.3���1.3)
Americas
1
1
Other
1.0
(0.7���1.5)
0.9
(0.4���1.7)
Number of study sites
1
0.9
(0.7���1.3)
0.8
(0.5���1.2)
>1
1
1
Prescribed interval between mifepristone and misoprostol
<23 h
2.1
(1.4���3.2)
1.2
(0.5���2.9)
23-72 h
1
1
Protocol specified additional dose of misoprostol for selected subjects
Yes
0.7
(0.5���1.1)
1.1
(0.6���2.0)
No
1
1
Protocol required all subjects to take misoprostol in clinic
Total misoprostol dose and route of first dose if multiple doses were administered.
Oral route
���800 mcg
0.7
(0.5���0.9)
0.6
(0.3���1.1)
600 mcg
0.9
(0.7���1.3)
0.6
(0.3���1.2)
400 mcg
1
1
Vaginal route
���800 mcg
0.6
(0.4���0.9)
0.3
(0.2���0.6)
600 mcg
0.7
(0.4���1.2)
3.6
(1.2���11.5)
400 mcg
1
1
Sublingual route
���800 mcg
0.8
(0.6���1.1)
0.4
(0.2���0.8)
600 mcg
0.3
(0.2���0.6)
���
400 mcg
1
1
Buccal route
���800 mcg
0.7
(0.5���1.2)
0.4
(0.2���0.8)
400 mcg
1
1
a Analyses of medical abortion failure used 119 trial groups; analyses of ongoing pregnancy used 112 trial groups (see text).
b Dates of mifepristone registration in each country obtained from www.gynuity.org, accessed 17 August 2011. Coded as ���before mifepristone registration��� if the year that data collection ended was not more than 1 year after the registration year and otherwise as ���after��� if the data collection started in the year after the registration year or later. This variable is missing for trials conducted in multiple countries and studies that provided insufficient information about dates of data collection.
c Total misoprostol dose and route of first dose if multiple doses were administered.
Fig.��1Size of trial group by percentage of subjects with medical abortion failure and ongoing pregnancy at follow-up assessment. 50% of trial groups are to the left of dashed line; 90% of subjects are to the left of solid line. One group of 4 subjects with one ongoing pregnancy is omitted from both panels; panel A also omits one group of 20 subjects with 8 medical abortion failures. (A) Medical abortion failure. (B) Ongoing pregnancy.
In 84 trials (117 groups), researchers noted whether or not each patient with medical abortion failure was diagnosed with ongoing pregnancy at the time of the failure ascertainment (Table��2). Of the 45,150 evaluable subjects in these trials, 499 (1.1%) had ongoing pregnancies. Across these groups, the median percentage of subjects with ongoing pregnancies was 0.7%, and 90% of the subjects were in groups in which less than 2.9% of subjects had ongoing pregnancy (Fig.��1B). The 499 ongoing pregnancies constituted 23% of the 1,976 medical abortion failures in these groups.
We found strong evidence of heterogeneity across trial groups in both the proportion of subjects who had medical abortion failure and the proportion who had ongoing pregnancy (p<.001 for both outcomes). Logistic regression models included as independent variables all the characteristics listed in Table��2. These models found few associations that were both substantial and significant. After adjustment for other characteristics included in the model, groups in which at least 25% of the women were in the ninth week of pregnancy had higher medical abortion failure rates than groups in which fewer women were so advanced in gestation (OR 1.5; 95% CI 1.1���2.0). Groups instructed to take the misoprostol <23 h after the mifepristone also had higher medical abortion failure rates than other groups (OR 2.1; 95% CI 1.4���3.2). At each total misoprostol dose level, oral administration was associated with higher medical abortion failure rates than each of the other three routes, but no substantial differences were noted among the other routes. Similarly, for each route, 400 mcg misoprostol was associated with higher failure rates than higher doses, although not all of these associations were significant.
Associations of misoprostol dose and route with ongoing pregnancy were mostly consistent with the associations with failure of all types; that is, both the oral route and the 400 mcg dose of misoprostol were generally associated with higher ongoing pregnancy rates than other doses and other routes. Ongoing pregnancy was twice as common in groups in which ultrasound was not routinely used to confirm success than in groups in which it was used in all women (OR 2.0, 95% CI 1.0���3.9). No notable associations were apparent between ongoing pregnancy rates and of any of the other group characteristics, however.
Across all trials, 119 of 45,528 evaluable subjects (0.3%) were hospitalized; of these, 46 hospitalizations (38%) occurred in a single trial [
] which included 4,132 treated women. Most of the hospitalizations were for vaginal bleeding, pelvic pain, or infection; some were for ectopic pregnancy or other conditions unrelated to the abortion. Forty-five women (0.1%) received blood transfusions. Hospitalizations and blood transfusions were less common in trials in which women were permitted to take the misoprostol at home (0.15% and 0.08%, respectively) than in trials in which clinic administration was required (0.45% and 0.14%, respectively).
4. Discussion
Medical abortion using mifepristone 200 mg followed by misoprostol in the first 63 days of gestation is remarkably effective and safe. In trials that together included more than 45,000 women conducted in disparate settings over nearly two decades using a variety of regimens and treatment protocols, fewer than 5% of subjects required surgery to complete termination of the pregnancy. The proportion who had ongoing pregnancy at follow-up ��� the outcome of greatest concern to clinicians ��� was 1.1%. Serious complications requiring hospitalization or transfusion occurred in less than 0.4% of patients.
Some random variability in results is expected in any collection of research studies. However, our analysis found strong evidence of statistical heterogeneity across trials in both medical abortion failure rates and rates of ongoing pregnancy. This finding indicates that the non-uniformity in these outcomes was due to underlying differences among the studies rather than simply to chance. We identified a few practices that were associated with a lower risk of medical abortion failure: an interval of at least 24 h between the mifepristone and misoprostol, use of misoprostol doses higher than 400 mcg and administration of misoprostol by a buccal, vaginal, or sublingual rather than oral route. The last of these is consistent with the conclusions of a recent Cochrane review of first trimester medical abortion, which included only randomized trials [
]. As cited previously, most current guidelines for medical abortion incorporate these practices.
We also found slightly higher risks of medical abortion failure in groups that had a high proportion (>25%) of women in the 9th week of pregnancy: after adjustment for other factors, these groups overall had a 50% higher odds of medical abortion failure. However, we did not find a higher risk of ongoing pregnancy in these groups. Given the low overall risk of medical abortion failure and the relative ease of treating failure using surgical evacuation (which would have been the treatment for all subjects had medical abortion not been attempted), offering medical abortion to women at this gestational age seems reasonable.
We observed no significant association between abortion failure rates and the timing of the follow-up evaluation. The data thus are inconclusive with respect to the theory that high surgical intervention rates are in part attributable to impatience among providers and patients [
]. Moreover, although routine ultrasound evaluation at follow-up was associated with a lower risk of diagnosis of ongoing pregnancy, we found no evidence for or against an effect of this practice on overall medical abortion failure rates ��� that is, the need for surgical intervention. Prompt confirmation of completeness of the abortion and clinical assessment without routine ultrasound may enhance women's satisfaction with the procedure.
We found no evidence that allowing women to take the misoprostol at home increased the rates of abortion failure or serious complications. Most women prefer this option [
], and it is presumably substantially more efficient for the health care system than requiring patients to return to the provider for administration of the prostaglandin. This requirement, which is law in some countries such as the United Kingdom [
This analysis has some limitations. Our data allowed us to explore heterogeneity across patient populations, not across individual patients; therefore, we may have missed some associations that would have been identified in an individual-level analysis. Missing data on some characteristics of some groups may have affected the direction or strength of associations, and we acknowledge that including ���missing��� categories for predictor variables would not have been preferred had we analyzed individual-level data [
]. Because none of the 540 women in the four groups that received misoprostol 600 mcg sublingual had ongoing pregnancies, these groups were excluded for technical reasons from our regression analysis of that outcome; this omission may have affected the apparent associations of other factors with ongoing pregnancy. Undetected publication bias is always possible; we attempted to minimize this problem by consulting experts likely to be aware of relevant unpublished studies through their many years of work in this field. We had information on only selected characteristics of the studies, and unmeasured confounding was not controlled by randomization. We evaluated many potential associations without any adjustment for multiple comparisons; however, we fit only a single model for each outcome. In 5 of the 120 trial groups, at least 10% of subjects were lost to follow-up. However, the overall follow-up success was high, and even if we made the extreme assumption that all the subjects who were lost had abortion failures, the overall medical abortion failure rate would still have been low (8.3%).
The large quantity of data presented in this review demonstrates that currently used medical abortion regimens are so effective and safe that additional research aimed at further clinical improvement will have little public health benefit. Future investigations should focus on service delivery issues: increasing access, reducing cost, enhancing patient comfort and ensuring availability of ancillary services such as contraception that can aid women in reaching their reproductive goals.
Acknowledgments
Financial support for this review was provided by an anonymous charitable foundation.
Reprints will not be available.
Appendix. Selected data from 120 trial groups
Tabled
1
Ref
Country
Date
Dose/route
Delay
Treated
Evaluable
Medical abortion failure
Ongoing pregnancy
N
N
N
%
N
%
11
Ethiopia
2009
800 mg vag
48
251
251
13
5.2
n/a
n/a
87
USA
2006���2007
800 mg buc
24 to 36
482
421
16
3.8
4
1.0
87
USA
2006���2007
800 mg oral
24 to 36
480
426
37
8.7
15
3.5
86
Nepal
2009���2010
800 mg vag
48
1077
1032
34
3.3
5
0.5
85
Multiple
2003���2005
800 mg vag
48
545
532
40
7.5
4
0.8
85
Multiple
2003���2005
800 mg vag
24
542
529
32
6.0
4
0.8
84
Multiple
2007���2008
400 mg SL
24
751
741
63
8.5
14
1.9
84
Multiple
2007���2008
400 mg vag
24
751
738
77
10.4
18
2.4
84
Multiple
2007���2008
800 mg SL
24
752
739
45
6.1
4
0.5
84
Multiple
2007���2008
800 mg vag
24
751
744
41
5.5
8
1.1
83
Multiple
1998���2000
800 mg oral then 400 mg oral bid��7 d
36 to 48
740
730
47
6.4
9
1.2
83
Multiple
1998���2000
800 mg vag then 400 mg oral bid��7 d
36 to 48
741
731
29
4.0
1
0.1
83
Multiple
1998���2000
800 mg vag
36 to 48
738
729
39
5.3
2
0.3
82
Taiwan
2000
400 mg, route n/a
48
20
20
8
40.0
1
5.0
82
Taiwan
2000
600 mg, route n/a
48
20
20
3
15.0
2
10.0
81
N. Korea
2007���2008
400 mg SL
48
199
199
8
4.0
0
0.0
80
UK
n/a
600 mg oral
48
100
100
8
8.0
3
3.0
79
China
n/a
400 mg vag
48
100
98
3
3.1
1
1.0
78
China
n/a
800 mg SL
48
100
99
5
5.1
1
1.0
77
China
n/a
800 mg oral then 400 mg oral bid��7 d
48
50
48
3
6.3
0
0.0
77
China
n/a
800 mg vag then 400 mg oral bid��7 d
48
50
50
3
6.0
2
4.0
77
China
n/a
800 mg vag
48
50
47
1
2.1
0
0.0
76
China
n/a
400 mg vag
48
200
200
3
1.5
1
0.5
75
China
n/a
400 mg vag then 400 mg oral bid��14 d
48
20
20
0
0.0
0
0.0
74
China
n/a
800 mg SL
48
112
112
2
1.8
0
0.0
74
China
n/a
800 mg vag
48
112
112
7
6.3
3
2.7
73
India
n/a
600 mg oral
48
51
50
11
22.0
0
0.0
14
India
n/a
200 mg SL��3 q6h
24
40
40
0
0.0
0
0.0
72
Nepal
2009
600 mg oral
48
50
50
3
6.0
0
0.0
71
USA
2001���2003
400 mg oral
48
376
354
30
8.5
13
3.7
70
Canada
2001
400 mg oral
24 to 48
319
319
17
5.3
0
0.0
70
Canada
2001
600 mg oral
24 to 48
319
317
21
6.6
1
0.3
70
Canada
2001
800 mg vag
24 to 48
318
317
18
5.7
0
0.0
69
USA
n/a
800 mg vag
0
80
80
7
8.8
0
0.0
66
USA
1998���1999
800 mg vag
24
745
708
15
2.1
5
0.7
66
USA
1998���1999
800 mg vag
72
772
699
28
4.0
8
1.1
66
USA
1998���1999
800 mg vag
48
778
745
16
2.1
3
0.4
67
USA
2000
400 mg oral��2 q2h
48
279
270
15
5.6
2
0.7
67
USA
2000
400 mg oral
48
228
223
21
9.4
2
0.9
67
USA
2000
800 mg vag
48
538
528
12
2.3
2
0.4
68
USA
1999���2000
400 mg oral��2 q2h
24
561
548
29
5.3
6
1.1
68
USA
1999���2000
800 mg vag
24
607
596
4
0.7
0
0.0
65
USA
1997���1999
800 mg vag
48
1137
1121
34
3.0
5
0.4
64
USA
1999
800 mg vag
48
30
27
2
7.4
2
7.4
63
USA
1996���1997
800 mg vag
48
933
928
21
2.3
6
0.6
62
China
n/a
600 mg oral
48
149
148
7
4.7
3
2.0
61
Moldova
2005���2006
400 mg oral
24
240
233
14
6.0
5
2.1
61
Moldova
2005���2006
400 mg SL
24
240
238
3
1.3
1
0.4
60
Moldova
2007���2009
400 mg buc
24
277
272
8
2.9
4
1.5
60
Moldova
2007���2009
400 mg SL
24
273
267
7
2.6
4
1.5
59
USA
n/a
800 mg vag
6 to 8
40
40
1
2.5
0
0.0
58
USA
1998���2000
800 mg vag
48
28
28
0
0.0
0
0.0
57
USA
2008
800 mg vag or buc
0 to 72
139
135
8
5.9
4
3.0
10
UK
n/a
200 mg oral
48
4
4
1
25.0
1
25.0
10
UK
n/a
400 mg oral
48
10
10
2
20.0
1
10.0
10
UK
n/a
600 mg oral
48
7
7
0
0.0
0
0.0
56
Vietnam
2001
400 mg oral
48
1601
1577
182
11.5
44
2.8
55
Vietnam
2007���2008
800 mg buc
24
201
201
7
3.5
3
1.5
54
USA
2003
800 mg vag
0
40
40
2
5.0
0
0.0
53
India
2004���2005
400 mg SL
48
149
144
2
1.4
1
0.7
52
USA
2001���2004
800 mg buc
24 to 48
223
216
11
5.1
2
0.9
52
USA
2001���2004
800 mg vag
24 to 48
219
213
14
6.6
4
1.9
51
UK
n/a
600 mg oral
48
110
110
7
6.4
1
0.9
50
USA
2006
800 mg buc
0
120
117
5
4.3
0
0.0
15
Taiwan
2002���2005
600 mg SL
48
356
355
5
1.4
0
0.0
49
Taiwan
2005���2009
600 mg vag
0
254
242
18
7.4
9
3.7
48
Taiwan
2005���2006
800 mg vag
0
90
90
2
2.2
0
0.0
47
Sweden
2004���2007
800 mg vag
36 to 48
395
395
10
2.5
4
1.0
46
Nepal
2007���2008
400 mg oral
48
400
367
32
8.7
9
2.5
45
USA
n/a
800 mg vag
48
125
121
5
4.1
0
0.0
18
Finland
2000���2002
400 or 800 mg vag
24, 48, or 72
1289
1238
67
5.4
9
0.7
16
UK
2002���2003
600 mg SL
36 to 48
49
49
1
2.0
0
0.0
44
UK
2002���2003
600 mg SL then 400 mg SL 3 h later
36 to 48
57
53
0
0.0
0
0.0
44
UK
2002���2003
800 mg vag then 400 mg vag 3 h later
36 to 48
72
69
1
1.4
0
0.0
17
UK
n/a
600 mg SL
36 to 48
96
96
1
1.0
0
0.0
17
UK
n/a
800 mg vag
36 to 48
53
53
2
3.8
0
0.0
43
Tunisia
2000���2001
400 mg oral
48
332
323
14
4.3
5
1.5
42
UK
2003���2005
800 mg vag
6
210
210
21
10.0
5
2.4
42
UK
2003���2005
800 mg vag
36 to 48
215
215
8
3.7
3
1.4
41
India
2009���2010
400 mg vag
0
40
40
2
5.0
0
0.0
41
India
2009���2010
400 mg vag
24
40
40
1
2.5
0
0.0
40
USA
n/a
800 mg vag
6 to 8
80
80
1
1.3
0
0.0
39
Tunisia
2007���2008
400 mg oral
48
126
126
7
5.6
1
0.8
38
Vietnam, Tunisia
1997���1998
400 mg oral
48
315
306
25
8.2
4
1.3
37
UK
n/a
400 mg oral��2 q2h
36 to 48
75
75
6
8.0
3
4.0
37
UK
n/a
800 mg oral
36 to 48
75
75
4
5.3
2
2.7
36
USA
1998���1999
800 mg vag
24, 48, or 72
138
138
4
2.9
0
0.0
8
India
n/a
400 mg oral
24
48
48
6
12.5
1
2.1
8
India
n/a
400 mg SL
24
45
45
2
4.4
0
0.0
35
India
n/a
800 mg vag
48
50
50
1
2.0
0
0.0
34
USA
2004���2006
800 mg vag
0
567
554
27
4.9
4
0.7
34
USA
2004���2006
800 mg vag
23 to 25
561
546
17
3.1
1
0.2
33
USA
2000���2001
800 mg vag
24 to 48
148
145
5
3.4
0
0.0
9
USA
2002���2003
800 mg vag
23 to 25
539
531
10
1.9
1
0.2
9
USA
2002���2003
800 mg vag
6 to 8
539
525
22
4.2
2
0.4
32
India
2004���2005
400 mg oral��2 q3h
48
150
150
12
8.0
1
0.7
32
India
2004���2005
400 mg oral
48
150
147
20
13.6
10
6.8
12
France
2001���2002
400 mg oral��2 q24h
24
30
27
1
3.7
n/a
n/a
31
USA
2005���2007
800 mg vag, oral or buc
6 to 72
4087
3292
57
1.7
24
0.7
30
Nepal
2004���2005
400 mg oral
48
112
107
16
15.0
2
1.9
29
Nepal
2005���2006
800 mg vag
48
50
50
3
6.0
0
0.0
27
Albania
2001���2003
400 mg oral
48
409
404
12
3.0
3
0.7
28
India
2007���2008
400 mg oral
48
599
574
60
10.5
5
0.9
26
Curacao
2009���2010
800 mg buc
24 to 36
304
281
6
2.1
1
0.4
25
Tunisia
1999���2000
400 mg oral
48
222
213
11
5.2
4
1.9
24
India
n/a
600 mg oral
48
450
440
54
12.3
5
1.1
23
UK
n/a
800 mg vag
48
500
459
6
1.3
1
0.2
22
UK
n/a
600 mg oral
48
400
386
21
5.4
9
2.3
21
UK
1994���2001
800 mg vag
36 to 48
4132
4132
95
2.3
14
0.3
13
India
2003���2004
800 mg oral
24
100
100
4
4.0
n/a
n/a
20
Turkey
2004���2005
400 mg oral
48
161
161
6
3.7
3
1.9
20
Turkey
2004���2005
400 mg SL
48
46
46
4
8.7
1
2.2
19
Turkey
2000���2001
400 mg oral
48
208
207
33
15.9
3
1.4
88
multiple
n/a
400 mg oral
48
792
775
68
8.8
22
2.8
U1
Mexico
2010���2011
800 mg buc
24 to 48
998
969
26
2.7
6
0.6
U2
Ukraine
2005���2007
400 mg oral
48
439
436
13
3.0
4
0.9
U3
Uzbekistan
2008���2009
400 mg SL
24
450
450
21
4.7
5
1.1
U4
Moldova
2007
400 mg SL
24
300
295
8
2.7
1
0.3
U5
Vietnam
2006���2008
400 mg oral
48
2400
2389
148
6.2
74
3.1
U6
Ukraine
2007���2009
400 mg SL
24
450
450
8
1.8
3
0.7
n/a: data not available.
Ref indicates reference number. U1-U6 are unpublished studies.
Date indicates dates of data collection.
Dose/route indicates dose and route of misoprostol. SL, sublingual; vag, vaginal; buc, buccal; q, every; h, hours; d, days.
Delay indicates prescribed interval between mifepristone and misoprostol, in hours.
Evaluable indicates number of subjects with known abortion outcome.
Failures indicates number and percent of evaluable subjects with abortion failure.
Ongoing pregnancy indicates number and percent of evaluable subjects with abortion failures that were ongoing pregnancies.
Increasing women's choices in medical abortion: a study of misoprostol 400 microg swallowed immediately or held sublingually following 200 mg mifepristone.
Eur J Contracept Reprod Health Care.2009; 14: 169-175
A multicentre randomized comparative clinical trial of 200 mg RU486 (mifepristone) single dose followed by either 5 mg 9-methylene PGE(2) gel (meteneprost) or 600 microg oral PGE(1) (misoprostol) for termination of early pregnancy within 28 days of missed menstrual period. ICMR Task Force Study. Indian Council of Medical Research.
Mifepristone plus vaginal misoprostol vs vaginal misoprostol alone for medical abortion in gestation 63 days or less in Nepalese women: a quasi-randomized controlled trial.
Early abortion induction by a combination of mifepristone and oral misoprostol: a comparison between two dose regimens of misoprostol and their effect on blood pressure.
Randomised controlled trial comparing the efficacy of same-day administration of mifepristone and misoprostol for termination of pregnancy with the standard 36 to 48 hour protocol.
A randomised controlled trial of mifepristone in combination with misoprostol administered sublingually or vaginally for medical abortion up to 13 weeks of gestation.
A prospective randomized, double-blinded, placebo-controlled trial comparing mifepristone and vaginal misoprostol to vaginal misoprostol alone for elective termination of early pregnancy.
Comparison of 400 mcg buccal and 400 mcg sublingual misoprostol after mifepristone medical abortion through 63 days' LMP: a randomized controlled trial.
Two-pill regimens of misoprostol after mifepristone medical abortion through 63 days' gestational age: a randomized controlled trial of sublingual and oral misoprostol.
Termination of early pregnancy by two regimens of mifepristone with misoprostol and mifepristone with PG05 ��� a multicentre randomized clinical trial in China.
A prospective, randomized, placebo-controlled trial on the use of mifepristone with sublingual or vaginal misoprostol for medical abortions of less than 9 weeks gestation.
A randomized double-blind placebo-controlled study to assess the effect of oral contraceptive pills on the outcome of medical abortion with mifepristone and misoprostol.
A prospective randomized study on the measured blood loss in medical termination of early pregnancy by three different misoprostol regimens after pretreatment with mifepristone.
The effect of contraceptive pills on the measured blood loss in medical termination of pregnancy by mifepristone and misoprostol: a randomized placebo controlled trial.
Two mifepristone doses and two intervals of misoprostol administration for termination of early pregnancy: a randomised factorial controlled equivalence trial.
Can midlevel health-care providers administer early medical abortion as safely and effectively as doctors? A randomised controlled equivalence trial in Nepal.
���E.G.R. and C.S. conducted literature searches and abstracted data. M.A.W. performed statistical analyses. All authors contributed equally to interpretation and manuscript preparation. No authors have any conflicts of interest.
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