The 2-week course of misoprostol was well tolerated by women who underwent early first trimester termination of pregnancy with mifepristone and misoprostol.
The 2-week course of misoprostol was well tolerated by women who underwent early first trimester termination of pregnancy with mifepristone and misoprostol. The earlier the treatment is given, the better it is tolerated
The 2-week course of misoprostol was well tolerated by women who underwent early first trimester termination of pregnancy with mifepristone and misoprostol. The mean baseline pain score was significantly lower than that observed with the 600 mcg of mifepristone (3 or 6 hourly).
The results of this study suggest that the two-week course of misoprostol is well tolerated by women who undergo early first trimester termination of pregnancy with mifepristone and misoprostol.
A large number of women undergoing early first trimester termination of pregnancy (less than 12 weeks) with mifepristone and misoprostol used only one dose. This study assessed a two-week treatment regimen with 800 μg mifepristone followed by 600 μg of misoprostol administered daily for three days or until complete abortion occurred. Misoprostol was well tolerated by all patients who had a follow-up visit after the procedure and proven efficacy within the 2 weeks.
Misoprostol At 2 Weeks Pregnancy Dosage
Twenty women who requested early first trimester termination of pregnancy were recruited to study the tolerability of a 2-week course of oral misoprostol after termination of pregnancy by mifepristone and vaginal misoprostol. Ten patients (50%) complained of mild diarrhea during the 2-week course of misoprostol. Otherwise, there were no other significant side effects. The 2-week course of misoprostol was well tolerated by women who underwent early first trimester termination of pregnancy with mifepristone and misoprostol.
PIP: A pilot study was conducted to assess whether prolonged use of misoprostol is well tolerated by women who have undergone termination of an early pregnancy with mifepristone and misoprostol and if this regimen increases the complete abortion rate and decreases the duration of bleeding. Enrolled were 20 women from Hong Kong and Shanghai with a menstrual delay of 21 days or less; the mean duration of pregnancy was 40.8 +or- 4.7 days. Women were given 200 mg of oral mifepristone, followed 48 hours later by 400 mcg of vaginal misoprostol. Oral misoprostol (400 mcg) was continued twice daily for 2 weeks. 11 women (55%) aborted during the initial 4-hour observation period and all had complete abortion. The mean duration of bleeding was 25.2 +or- 4.3 days. Nausea, diarrhea, and lower abdominal pain were the most common side effects of misoprostol, but all women were able to complete the 2-week course of treatment. On the basis of the findings of this pilot study, a prospective, randomized study with a larger number of patients is recommended to confirm whether a 2-week course of misoprostol can increase the abortion rate and decrease the duration of postabortal bleeding.
Misoprostol at 1 Weeks Pregnancy
To summarize available data on the effectiveness and safety of single-agent misoprostol for medical abortion in the first trimester.
We searched Medline, CABI, Cochrane, EMBASE, LILACS, and the Web of Science, and ClinicalTrials.gov for English language studies that evaluated misoprostol alone for abortion of viable pregnancy in the first trimester.
Methods of Study Selection:
Our search yielded 1562 citations, of which 38 included data from 53 trial groups that met our inclusion and exclusion criteria.
Tabulation, Integration, and Results:
We abstracted data about each trial group, including study characteristics, treatment regimen, clinical protocol, number of women treated and followed, and numbers with outcomes of interest. We used meta-analytic methods and logistic regression to examine factors associated with surgical intervention after treatment. Among all 12,829 evaluable women, 2536 (meta-analytic estimate 22.0%, 95% CI 18.8%, 25.5%) had surgical uterine evacuation. Multiple factors were significantly associated with this proportion, including misoprostol amount per dose and route of administration, loss to follow-up rate, publication date, geographic region, number of misoprostol doses, duration of dosing, and time between dosing and evaluation. Of 6359 evaluable women, 384 (meta-analytic estimate 6.8%, 95% CI 5.3%, 8.5%) had ongoing pregnancy. At most 26 of 12,184 evaluable women (meta-analytic estimate 0.7%, 95% CI 0.4%, 1.0%)were transfused or hospitalized for abortion-related reasons. In trials that provided satisfaction data, most of women were satisfied or very satisfied with the treatment (meta-analytic estimate 78%, 95% CI 71%, 85%).
Misoprostol alone is effective and safe and is a reasonable option for women seeking abortion in the first trimester. Research is indicated to further refine the regimen and to establish efficacy in the late first trimester.
Systematic Review Registration:
Treatment regimens that contain only misoprostol can be effective and safe for first-trimester medical abortion.
For early medical abortion, the primary regimens recommended by current clinical guidelines include two drugs: mifepristone and misoprostol. Because mifepristone potentiates the abortifacient action of misoprostol, the combination is highly effective, resulting in complete abortion in more than 95% of women through 63 days of gestation1,2 and 93% between 64 and 70 days.2,3 However, mifepristone is costly and is unavailable in many settings. In the United States, although the drug is approved for marketing, the Food and Drug Administration has imposed restrictions on its distribution that substantially limit both patients’ and providers’ access to it.4 For women who cannot obtain mifepristone, use of misoprostol alone, which is inexpensive and is widely used for various obstetric and gastrointestinal indications, can serve as an important alternative option. A systematic review published in 2007 found that the efficacy of misoprostol single-agent regimens at gestational ages ≤63 days ranged from 84% to 96%,5 but since then, additional studies have been published. We performed this systematic review to summarize available data on the effectiveness and safety of medical abortion with misoprostol alone in the first trimester of pregnancy. The primary outcome of our analysis was surgical evacuation of the uterus to complete the abortion; secondary outcomes were viable ongoing pregnancy after taking the prescribed misoprostol regimen, transfusions and hospitalizations.
We registered our systematic review protocol on PROSPERO (CRD42018083589) before beginning data collection and followed MOOSE guidelines6 in reporting the results. With the assistance of a librarian, we searched six databases (Medline, CABI, Cochrane, EMBASE, LILACS, and the Web of Science,) on November 17, 2017, and ClinicalTrials.gov on June 20 2018, for English language studies that evaluated misoprostol alone for medical abortion of a known or presumed viable pregnancy in the first trimester. We did not exclude studies based on study design, date, or any other criteria. Our search strategy for Medline is indicated in Box 1.
Box 1. Search strategy for Medline
(Early trimester OR less than ten weeks OR early pregnancy OR first trimester OR less than thirteen weeks) AND (Medical abortion OR medical termination OR oral medication abortion OR oral medication termination OR non-surgical abortion OR non-surgical termination OR elective abortion OR termination of pregnancy OR induced abortion OR induced termination of pregnancy) AND (misoprostol OR cytotec) AND (single agent OR single-agent OR alone OR only).
Search strategies for other databases were substantively similar. 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 (MH and EGR) separately reviewed the title, abstract, and full text if necessary of each paper identified by the search to select all language reports of studies that included women with viable pregnancies who were treated in the first trimester (91 days or less) with misoprostol alone to cause abortion. The same two authors then reviewed each selected study together and systematically abstracted relevant data about these women into a custom database. We excluded women who received abortifacient drugs other than misoprostol, women who were treated in the second trimester, women who had missed abortions or non-viable pregnancies before treatment, and women who did not take any misoprostol after study enrollment. Some studies evaluated more than one misoprostol regimen; in our abstraction process, we recorded data about women who received each regimen in each study as a separate trial group.
The primary data abstracted included the number of women treated with the misoprostol regimen in each group, details of the misoprostol regimen (specifically, the number of misoprostol doses provided, the amount of misoprostol in each dose and route of administration, and the intervals between doses), abortion outcomes (specifically, whether surgical evacuation of the uterus was performed and whether the patient had a viable ongoing pregnancy at the time of surgery), the numbers of reported hospitalizations and transfusions, and information about patient satisfaction. We also recorded data about specified factors that we postulated could cause heterogeneity or bias in assessment of efficacy and safety, including information about the trial design, conduct, and publication, the maximum gestational age and other inclusion criteria, location of misoprostol administration (facility or home), follow-up rates, and timing and method of outcome assessment. We contacted some authors to obtain additional data or to clarify details about the studies. We used our judgment to interpret certain details in some reports and to correct apparent errors and inconsistencies.
We combined data across groups to estimate the proportion of patients who had surgical evacuation of the uterus to complete the abortion and viable ongoing pregnancy using meta-analytic methods, conducted in R, version 3.5.0, with the “metafor” package, version 2.0.7,8 We applied the Freeman-Tukey double arcsine transformation, and we report p-values from the chi-square test of heterogeneity and associated I2 statistic. We calculated estimates and 95% confidence intervals using the DerSimonian-Laird random-effects model.
To explore possible explanations for heterogeneity among trial groups in the proportions who had surgery, we examined associations between this outcome and selected characteristics of the trial groups. Many of these characteristics were highly correlated across trial groups, with numerous zero cells in cross-classifications. Therefore, we opted to present only unadjusted results. We used generalized estimating equations with a logistic link and an independence working correlation matrix to control for nesting of trial groups within paper. The response for the models was the ratio of the number of surgeries to the number of evaluable patients for each trial group (conducted in SAS, version 9.4, SAS Institute, Cary, NC, USA); thus model results were weighted by trial group sample size. We included all trial groups in our examination of misoprostol amount per dose and route of administration. We restricted our examination of other factors to groups treated with an initial dose of 800 mcg misoprostol administered vaginally, the most common combination, because most characteristics did not vary across groups treated with other dose-route combinations. We categorized each characteristic considering both clinical interest and the distribution of the data, and we estimated odds ratios and 95% confidence intervals. We tested for linear trends using linear contrasts of model parameters. We made no adjustment for multiple comparisons. In reviewing the results, we focused on associations that were both substantial (odds ratio>1.5 or <0.67) and significant (p<0.05).
To further evaluate the association between number of misoprostol doses and efficacy, we estimated the proportion of women reported to have had complete abortion after taking only the doses required for all women in that trial group before any doses that were contingent on abortion status. This analysis included only those trial groups that reported these data. We estimated unadjusted odds ratios with confidence intervals and tested for linear trend as described above for amount of misoprostol in the initial dose.
We assessed safety by computing the proportion of women across all trial groups who were reported to have been hospitalized or receive transfusions after treatment. We did not abstract data on non-serious side effects because ascertainment and reporting was not standardized across studies.