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Contraception Sep 2011Mifepristone combined with misoprostol for second-trimester abortion (MM) and intra-amniotic injection of ethacridine lactate (EL; Rivanol®) are the common methods for... (Comparative Study)
Comparative Study Review
Termination of second-trimester pregnancy by mifepristone combined with misoprostol versus intra-amniotic injection of ethacridine lactate (Rivanol®): a systematic review of Chinese trials.
BACKGROUND
Mifepristone combined with misoprostol for second-trimester abortion (MM) and intra-amniotic injection of ethacridine lactate (EL; Rivanol®) are the common methods for termination of second-trimester pregnancy in China. The systematic review of relevant literature was conducted to evaluate the effectiveness and safety on termination of second-trimester pregnancy using MM, introduced in 1988 in China, versus the Chinese routinely used method since 1970 -- EL. The review was conducted to evaluate mifepristone combined with the misoprostol versus intra-amniotic injection of ethacridine lactate in China for termination of second-trimester pregnancy with respect to efficacy, side effects, complications and so on.
STUDY DESIGN
The Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, POPLINE, TOXLINE, World Health Organization-Department of Reproductive Health and Research, Chinese Biomedical Literature Database, Chinese Journal Full-text Database and Chinese Science & Technology Journal Database were systematically searched. Reference lists for English and Chinese-language reports (published from 1966 to 2008) were searched. All randomized controlled trials (RCTs) on second-trimester abortion by combination of mifepristone and misoprostol versus ethacridine lactate, which conducted in China, were analyzed. Trial quality was assessed, and data extraction was made independently by two reviewers.
RESULTS
Fifteen original RCTs using MM versus EL were included. Three trials used oral misoprostol, six trials used vaginal misoprostol, and six trials used oral plus vaginal misoprostol. Failure rate of abortion was 2.0% to 5.9% in the MM group and 7.4% to 20.7% in the EL group. The incidence of postabortion curettage was similar in the two groups. The time of labor and hospitalization for abortion in the MM group were shorter compared with EL group. The blood loss within 2 h of abortion in the MM group was significantly less than that in the EL group, but the blood loss within 24 h of abortion was the same in both groups. More gastrointestinal side effects occurred with the MM regimen, whereas cervical injury occurred more often in the EL group.
CONCLUSIONS
Compared with the intra-amniotic injection of ethacridine lactate, mifepristone/misoprostol has a higher success rate and shorter time of labor with more gastrointestinal side effects for termination of second-trimester pregnancy.
Topics: Abortifacient Agents; Abortion, Induced; China; Ethacridine; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Pregnancy Trimester, Second; Randomized Controlled Trials as Topic
PubMed: 21843683
DOI: 10.1016/j.contraception.2011.01.018 -
Women's Health (London, England) Jan 2011China was the first country in the world that approved mifepristone (RU-486) for abortion. A total of 6 years after the report published in the Western world indicated... (Review)
Review
China was the first country in the world that approved mifepristone (RU-486) for abortion. A total of 6 years after the report published in the Western world indicated that mifepristone may also be effective in treating endometriosis, the first paper on the same topic was published in China in 1997. Since then, over 160 studies on this topic have been published in China. We retrieved 104 papers on clinical trials and trial-like studies conducted in China evaluating the use of mifepristone to treat endometriosis that were published in the last 11 years. We found that the quality of these studies is well below an acceptable level, making it difficult to judge whether mifepristone is truly efficacious. There are intriguing signs that these studies, as a whole, have serious anomalies. The areas that are glaringly deficient are informed consent, choice of outcome measures, the evaluation of outcome measures, data analysis and randomization. The uniformly low quality is disquieting, given the large quantity of studies, the enormous amount of resource and energy put into these studies and, above all, the weighty issue of treatment efficacy that concerns each and every patient with endometriosis. Equally disquieting are the low-quality repetition, the absence of a critical, systematic review on the subject, the lack of suggestions for multicenter clinical trials and the seemingly unnecessary duplication of clinical trials without due informed consent. In view of this, it may be time to institute changes in attitude and practice, and to change education and training programs in the methodology of clinical trials in obstetrics and gynecology research in China.
Topics: China; Clinical Trials as Topic; Endometriosis; Female; Humans; Mifepristone; Pregnancy
PubMed: 21175391
DOI: 10.2217/whe.10.79 -
The Cochrane Database of Systematic... Jan 2019Emergency contraception (EC) is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Emergency contraception (EC) is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are available for EC. Information on the comparative effectiveness, safety and convenience of these methods is crucial for reproductive healthcare providers and the women they serve. This is an update of a review previously published in 2009 and 2012.
OBJECTIVES
To determine which EC method following unprotected intercourse is the most effective, safe and convenient to prevent pregnancy.
SEARCH METHODS
In February 2017 we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, Popline and PubMed, The Chinese biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction (HRP) emergency contraception database. We also searched ICTRP and ClinicalTrials.gov as well as contacting content experts and pharmaceutical companies, and searching reference lists of appropriate papers.
SELECTION CRITERIA
Randomised controlled trials including women attending services for EC following a single act of unprotected intercourse were eligible.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. The primary review outcome was observed number of pregnancies. Side effects and changes of menses were secondary outcomes.
MAIN RESULTS
We included 115 trials with 60,479 women in this review. The quality of the evidence for the primary outcome ranged from moderate to high, and for other outcomes ranged from very low to high. The main limitations were risk of bias (associated with poor reporting of methods), imprecision and inconsistency.Comparative effectiveness of different emergency contraceptive pills (ECP)Levonorgestrel was associated with fewer pregnancies than Yuzpe (estradiol-levonorgestrel combination) (RR 0.57, 95% CI 0.39 to 0.84, 6 RCTs, n = 4750, I = 23%, high-quality evidence). This suggests that if the chance of pregnancy using Yuzpe is assumed to be 29 women per 1000, the chance of pregnancy using levonorgestrel would be between 11 and 24 women per 1000.Mifepristone (all doses) was associated with fewer pregnancies than Yuzpe (RR 0.14, 95% CI 0.05 to 0.41, 3 RCTs, n = 2144, I = 0%, high-quality evidence). This suggests that if the chance of pregnancy following Yuzpe is assumed to be 25 women per 1000 women, the chance following mifepristone would be between 1 and 10 women per 1000.Both low-dose mifepristone (less than 25 mg) and mid-dose mifepristone (25 mg to 50 mg) were probably associated with fewer pregnancies than levonorgestrel (RR 0.72, 95% CI 0.52 to 0.99, 14 RCTs, n = 8752, I = 0%, high-quality evidence; RR 0.61, 95% CI 0.45 to 0.83, 27 RCTs, n = 6052, I = 0%, moderate-quality evidence; respectively). This suggests that if the chance of pregnancy following levonorgestrel is assumed to be 20 women per 1000, the chance of pregnancy following low-dose mifepristone would be between 10 and 20 women per 1000; and that if the chance of pregnancy following levonorgestrel is assumed to be 35 women per 1000, the chance of pregnancy following mid-dose mifepristone would be between 16 and 29 women per 1000.Ulipristal acetate (UPA) was associated with fewer pregnancies than levonorgestrel (RR 0.59; 95% CI 0.35 to 0.99, 2 RCTs, n = 3448, I = 0%, high-quality evidence).Comparative effectiveness of different ECP dosesIt was unclear whether there was any difference in pregnancy rate between single-dose levonorgestrel (1.5 mg) and the standard two-dose regimen (0.75 mg 12 hours apart) (RR 0.84, 95% CI 0.53 to 1.33, 3 RCTs, n = 6653, I = 0%, moderate-quality evidence).Mid-dose mifepristone was associated with fewer pregnancies than low-dose mifepristone (RR 0.73; 95% CI 0.55 to 0.97, 25 RCTs, n = 11,914, I = 0%, high-quality evidence).Comparative effectiveness of Cu-IUD versus mifepristoneThere was no conclusive evidence of a difference in the risk of pregnancy between the Cu-IUD and mifepristone (RR 0.33, 95% CI 0.04 to 2.74, 2 RCTs, n = 395, low-quality evidence).Adverse effectsNausea and vomiting were the main adverse effects associated with emergency contraception. There is probably a lower risk of nausea (RR 0.63, 95% CI 0.53 to 0.76, 3 RCTs, n = 2186 , I = 59%, moderate-quality evidence) or vomiting (RR 0.12, 95% CI 0.07 to 0.20, 3 RCTs, n = 2186, I = 0%, high-quality evidence) associated with mifepristone than with Yuzpe. levonorgestrel is probably associated with a lower risk of nausea (RR 0.40, 95% CI 0.36 to 0.44, 6 RCTs, n = 4750, I = 82%, moderate-quality evidence), or vomiting (RR 0.29, 95% CI 0.24 to 0.35, 5 RCTs, n = 3640, I = 78%, moderate-quality evidence) than Yuzpe. Levonorgestrel users were less likely to have any side effects than Yuzpe users (RR 0.80, 95% CI 0.75 to 0.86; 1 RCT, n = 1955, high-quality evidence). UPA users were more likely than levonorgestrel users to have resumption of menstruation after the expected date (RR 1.65, 95% CI 1.42 to 1.92, 2 RCTs, n = 3593, I = 0%, high-quality evidence). Menstrual delay was more common with mifepristone than with any other intervention and appeared to be dose-related. Cu-IUD may be associated with higher risks of abdominal pain than mifepristone (18 events in 95 women using Cu-IUD versus no events in 190 women using mifepristone, low-quality evidence).
AUTHORS' CONCLUSIONS
Levonorgestrel and mid-dose mifepristone (25 mg to 50 mg) were more effective than Yuzpe regimen. Both mid-dose (25 mg to 50 mg) and low-dose mifepristone(less than 25 mg) were probably more effective than levonorgestrel (1.5 mg). Mifepristone low dose (less than 25 mg) was less effective than mid-dose mifepristone. UPA may be more effective than levonorgestrel.Levonorgestrel users had fewer side effects than Yuzpe users, and appeared to be more likely to have a menstrual return before the expected date. UPA users were probably more likely to have a menstrual return after the expected date. Menstrual delay was probably the main adverse effect of mifepristone and seemed to be dose-related. Cu-IUD may be associated with higher risks of abdominal pain than ECPs.
Topics: Contraception, Postcoital; Contraceptives, Postcoital; Drug Administration Schedule; Estradiol; Female; Humans; Intrauterine Devices, Copper; Intrauterine Devices, Medicated; Levonorgestrel; Mifepristone; Norpregnadienes; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Unsafe Sex
PubMed: 30661244
DOI: 10.1002/14651858.CD001324.pub6 -
The Cochrane Database of Systematic... Jul 2017Endometriosis is defined as the presence of endometrial tissue (glands and stroma) outside the uterine cavity. This condition is oestrogen-dependent and thus is seen... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Endometriosis is defined as the presence of endometrial tissue (glands and stroma) outside the uterine cavity. This condition is oestrogen-dependent and thus is seen primarily during the reproductive years. Owing to their antiproliferative effects in the endometrium, progesterone receptor modulators (PRMs) have been advocated for treatment of endometriosis.
OBJECTIVES
To assess the effectiveness and safety of PRMs primarily in terms of pain relief as compared with other treatments or placebo or no treatment in women of reproductive age with endometriosis.
SEARCH METHODS
We searched the following electronic databases, trial registers, and websites: the Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register of Controlled Trials, the Central Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, clinicaltrials.gov, and the World Health Organization (WHO) platform, from inception to 28 November 2016. We handsearched reference lists of articles retrieved by the search.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) published in all languages that examined effects of PRMs for treatment of symptomatic endometriosis.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as expected by the Cochrane Collaboration. Primary outcomes included measures of pain and side effects.
MAIN RESULTS
We included 10 randomised controlled trials (RCTs) with 960 women. Two RCTs compared mifepristone versus placebo or versus a different dose of mifepristone, one RCT compared asoprisnil versus placebo, one compared ulipristal versus leuprolide acetate, and four compared gestrinone versus danazol, gonadotropin-releasing hormone (GnRH) analogues, or a different dose of gestrinone. The quality of evidence ranged from high to very low. The main limitations were serious risk of bias (associated with poor reporting of methods and high or unclear rates of attrition in most studies), very serious imprecision (associated with low event rates and wide confidence intervals), and indirectness (outcome assessed in a select subgroup of participants). Mifepristone versus placebo One study made this comparison and reported rates of painful symptoms among women who reported symptoms at baseline.At three months, the mifepristone group had lower rates of dysmenorrhoea (odds ratio (OR) 0.08, 95% confidence interval (CI) 0.04 to 0.17; one RCT, n =352; moderate-quality evidence), suggesting that if 40% of women taking placebo experience dysmenorrhoea, then between 3% and 10% of women taking mifepristone will do so. The mifepristone group also had lower rates of dyspareunia (OR 0.23, 95% CI 0.11 to 0.51; one RCT, n = 223; low-quality evidence). However, the mifepristone group had higher rates of side effects: Nearly 90% had amenorrhoea and 24% had hot flushes, although the placebo group reported only one event of each (1%) (high-quality evidence). Evidence was insufficient to show differences in rates of nausea, vomiting, or fatigue, if present. Mifepristone dose comparisons Two studies compared doses of mifepristone and found insufficient evidence to show differences between different doses in terms of effectiveness or safety, if present. However, subgroup analysis of comparisons between mifepristone and placebo suggest that the 2.5 mg dose may be less effective than 5 mg or 10 mg for treating dysmenorrhoea or dyspareunia. Gestrinone comparisons Ons study compared gestrinone with danazol, and another study compared gestrinone with leuprolin.Evidence was insufficient to show differences, if present, between gestrinone and danazol in rate of pain relief (those reporting no or mild pelvic pain) (OR 0.71, 95% CI 0.33 to 1.56; two RCTs, n = 230; very low-quality evidence), dysmenorrhoea (OR 0.72, 95% CI 0.39 to 1.33; two RCTs, n = 214; very low-quality evidence), or dyspareunia (OR 0.83, 95% CI 0.37 to 1.86; two RCTs, n = 222; very low-quality evidence). The gestrinone group had a higher rate of hirsutism (OR 2.63, 95% CI 1.60 to 4.32; two RCTs, n = 302; very low-quality evidence) and a lower rate of decreased breast size (OR 0.62, 95% CI 0.38 to 0.98; two RCTs, n = 302; low-quality evidence). Evidence was insufficient to show differences between groups, if present, in rate of hot flushes (OR 0.79, 95% CI 0.50 to 1.26; two RCTs, n = 302; very low-quality evidence) or acne (OR 1.45, 95% CI 0.90 to 2.33; two RCTs, n = 302; low-quality evidence).When researchers compared gestrinone versus leuprolin through measurements on the 1 to 3 verbal rating scale (lower score denotes benefit), the mean dysmenorrhoea score was higher in the gestrinone group (MD 0.35 points, 95% CI 0.12 to 0.58; one RCT, n = 55; low-quality evidence), but the mean dyspareunia score was lower in this group (MD 0.33 points, 95% CI 0.62 to 0.04; low-quality evidence). The gestrinone group had lower rates of amenorrhoea (OR 0.04, 95% CI 0.01 to 0.38; one RCT, n = 49; low-quality evidence) and hot flushes (OR 0.20, 95% CI 0.06 to 0.63; one study, n = 55; low quality evidence) but higher rates of spotting or bleeding (OR 22.92, 95% CI 2.64 to 198.66; one RCT, n = 49; low-quality evidence).Evidence was insufficient to show differences in effectiveness or safety between different doses of gestrinone, if present. Asoprisnil versus placebo One study (n = 130) made this comparison but did not report data suitable for analysis. Ulipristal versus leuprolide acetate One study (n = 38) made this comparison but did not report data suitable for analysis.
AUTHORS' CONCLUSIONS
Among women with endometriosis, moderate-quality evidence shows that mifepristone relieves dysmenorrhoea, and low-quality evidence suggests that this agent relieves dyspareunia, although amenorrhoea and hot flushes are common side effects. Data on dosage were inconclusive, although they suggest that the 2.5 mg dose of mifepristone may be less effective than higher doses. We found insufficient evidence to permit firm conclusions about the safety and effectiveness of other progesterone receptor modulators.
Topics: Danazol; Dysmenorrhea; Dyspareunia; Endometriosis; Estrenes; Female; Gestrinone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Mifepristone; Norpregnadienes; Oximes; Prevalence; Randomized Controlled Trials as Topic; Receptors, Progesterone
PubMed: 28742263
DOI: 10.1002/14651858.CD009881.pub2 -
The Cochrane Database of Systematic... Aug 2012Emergency contraception (EC) is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Emergency contraception (EC) is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are available for EC. Information on the comparative effectiveness, safety and convenience of these methods is crucial for reproductive healthcare providers and the women they serve.
OBJECTIVES
To determine which EC method following unprotected intercourse is the most effective, safe and convenient to prevent pregnancy.
SEARCH METHODS
The search included the Cochrane Controlled Trials Register, Popline, MEDLINE, PubMed, Biosis/EMBASE, Chinese biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction (HRP) emergency contraception database (July 2011). Content experts and pharmaceutical companies were contacted.
SELECTION CRITERIA
Randomised controlled trials and controlled clinical trials including women attending services for EC following a single act of unprotected intercourse were eligible.
DATA COLLECTION AND ANALYSIS
Data on outcomes and trial characteristics were extracted in duplicate and independently by two review authors. Quality assessment was also done by two review authors independently. Meta-analysis results are expressed as risk ratio (RR) using a fixed-effect model with 95% confidence interval (CI). In the presence of statistically significant heterogeneity a random-effects model was applied.
MAIN RESULTS
One hundred trials with 55,666 women were included. Most trials were conducted in China (86/100). Meta-analysis indicated that mid-dose mifepristone (25-50 mg) (20 trials; RR 0.64; 95% CI 0.45 to 0.92) or low-dose mifepristone (< 25 mg) (11 trials; RR 0.70; 95% CI 0.50 to 0.97) were significantly more effective than levonorgestrel (LNG), but the significance was marginal when only high-quality studies were included (4 trials; RR 0.70; 95% CI 0.49 to 1.01). Low-dose mifepristone was less effective than mid-dose mifepristone (25 trials; RR 0.73; 95% CI 0.55 to 0.97). This difference was not statistically significant when only high-quality trials were considered (6 trials; RR 0.75; 95% CI 0.50 to 1.10). Ulipristal acetate (UPA) appeared more effective (2 trials; RR 0.63) than LNG at a marginal level (P = 0.09) within 72 hours of intercourse.Regarding effectiveness in relation to the time of administration, women who took LNG within 72 hours of intercourse were significantly less likely to be pregnant than those who took it after 72 hours (4 trials; RR 0.51; 95% CI 0.31 to 0.84). It was not evident that the coitus-treatment time affected the effectiveness of mifepristone and UPA.Single-dose LNG (1.5 mg) showed similar effectiveness as the standard two-dose regimen (0.75 mg 12 h apart) (3 trials; RR 0.84; 95% CI 0.53 to 1.33). This conclusion was not modified by the time elapsed from intercourse to treatment administration.Mifepristone (all doses) (3 trials; RR 0.14; 95% CI 0.05 to 0.41) and LNG (5 trials; RR 0.54; 95% CI 0.36 to 0.80) were more effective than the Yuzpe regimen in preventing pregnancy. One trial compared gestrinone with mifepristone. No significant difference of effectiveness was identified in this trial (996 women; RR 0.75; 95% CI 0.32 to 1.76).All methods of EC were safe. Nausea and vomiting occurred with oestrogen-containing EC methods and progestogen and anti-progestogen methods caused changes in subsequent menses. LNG users were more likely to have a menstrual return before the expected date, but UPA users were more likely to have a menstrual return after the expected date. Menstrual delay was the main adverse effect of mifepristone and seemed to be dose-related.
AUTHORS' CONCLUSIONS
Intermediate-dose mifepristone (25-50 mg) was superior to LNG and Yuzpe regimens. Mifepristone low dose (< 25 mg) may be more effective than LNG (0.75 mg two doses), but this was not conclusive. UPA may be more effective than LNG. LNG proved to be more effective than the Yuzpe regimen. The copper IUD was the most effective EC method and was the only EC method to provide ongoing contraception if left in situ.
Topics: Contraception, Postcoital; Contraceptives, Postcoital; Drug Administration Schedule; Female; Humans; Levonorgestrel; Mifepristone; Norpregnadienes; Randomized Controlled Trials as Topic
PubMed: 22895920
DOI: 10.1002/14651858.CD001324.pub4 -
The Cochrane Database of Systematic... Apr 2008Emergency contraception is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Emergency contraception is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are available for emergency contraception. Information on the comparative efficacy, safety and convenience of these methods is crucial for reproductive health care providers and the women they serve.
OBJECTIVES
To determine which emergency contraceptive method following unprotected intercourse is the most effective, safe and convenient to prevent pregnancy.
SEARCH STRATEGY
The search included the Cochrane Controlled Trials Register, Popline, MEDLINE, PubMed, Biosis/Embase, Chinese biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction (HRP) emergency contraception database (December 2006). Content experts and pharmaceutical companies were contacted.
SELECTION CRITERIA
Randomised controlled trials and controlled clinical trials including women attending services for emergency contraception following a single act of unprotected intercourse were eligible.
DATA COLLECTION AND ANALYSIS
Data on outcomes and trial characteristics were extracted in duplicate and independently by two reviewers. Quality assessment was also done by two reviewers independently. Meta-analysis results are expressed as relative risk (RR) using a fixed-effects model with 95% confidence interval (CI). In the presence of statistically significant heterogeneity a random-effect model was applied.
MAIN RESULTS
Eighty-one trials with 45,842 women were included. Most trials were conducted in China (70/81). There were more pregnancies with levonorgestrel compared to mid-dose (25-50 mg) (15 trials, RR: 2.01; 95% CI: 1.27 to 3.17) or low-dose mifepristone (<25 mg) (9 trials, RR: 1.43; 95% CI: 1.02 to 2.01). Low-dose mifepristone was less effective than mid-dose (20 trials, RR:0.67; 95% CI: 0.49 to 0.92), but this effect was no longer statistically significant when only high quality trials were considered (6 trials, RR: 0.75; 95% CI: 0.50 to 1.10). Single dose levonorgestrel (1.5 mg) administration seemed to have similar effectiveness as the standard 12 hours apart split-dose (0.75 mg twice) (2 trials, 3830 women; RR: 0.77, 95% CI: 0.45 to 1.30). Levonorgestrel was more effective than the Yuzpe regimen in preventing pregnancy (2 trials, RR: 0.51; 95% CI: 0.31 to 0.83). CDB-2914 (a second-generation progesterone receptor modulator) may be as effective as levonorgestrel (1 trial, 1549 women; RR:1.89; 95% CI: 0.75 to 4.64) but the confidence interval is wide and the result compatible with higher or lower effectiveness. Delay in the onset of subsequent menses was the main unwanted effect of mifepristone and seemed to be dose-related.
AUTHORS' CONCLUSIONS
Mifepristone middle dose (25-50 mg) was superior to other hormonal regimens. Mifepristone low dose (<25 mg) could be more effective than levonorgestrel 0.75 mg (two doses) but this was not conclusive. Levonorgestrel proved more effective than the Yuzpe regimen. The copper IUD was another effective emergency contraceptive that can provide ongoing contraception.
Topics: Contraception, Postcoital; Contraceptives, Oral, Combined; Contraceptives, Postcoital; Female; Humans; Levonorgestrel; Mifepristone; Randomized Controlled Trials as Topic
PubMed: 18425871
DOI: 10.1002/14651858.CD001324.pub3 -
International Journal of Gynaecology... Dec 2019Optimal dose, interval, and administration route of misoprostol with added benefit of mifepristone for management of second trimester intrauterine fetal death (IUFD) are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Optimal dose, interval, and administration route of misoprostol with added benefit of mifepristone for management of second trimester intrauterine fetal death (IUFD) are not established.
OBJECTIVES
To assess effectiveness, safety, and acceptability of medical management of second trimester IUFD.
SEARCH STRATEGY
Research databases from January 2006 to October 2018.
SELECTION CRITERIA
Randomized controlled trials with IUFD cases at 14-28 weeks of gestation.
DATA COLLECTION AND ANALYSIS
We screened and extracted data, assessed risk of bias, conducted analyses, and assessed overall certainty of the evidence.
MAIN RESULTS
Sixteen trials from 1695 citations. When misoprostol is used alone, 400 μg is more effective than 200 μg (RR 0.78; 95% CI, 0.66-0.92, moderate certainty evidence); the sublingual route is more effective than the oral route (RR 0.88; 95% CI, 0.70-1.11, low certainty evidence). There may be little to no difference between the sublingual and vaginal route (RR 0.93; 95% CI, 0.85-1.03, low certainty evidence). Certainty of evidence related to mifepristone-misoprostol regimens and safety and acceptability is very low.
CONCLUSIONS
Misoprostol 400 μg every 4 hours, sublingually or vaginally, may be effective. We cannot draw conclusions about safety and acceptability, or about the added benefits of mifepristone.
Topics: Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Abortion, Induced; Dose-Response Relationship, Drug; Female; Fetal Death; Humans; Mifepristone; Misoprostol; Pregnancy; Pregnancy Trimester, Second; Randomized Controlled Trials as Topic
PubMed: 31493314
DOI: 10.1002/ijgo.12964 -
European Journal of Obstetrics,... Dec 2015Early pregnancy failure (EPF) is a common complication of pregnancy. Surgical intervention carries a risk of complications and, therefore, medical treatment appears to... (Review)
Review
OBJECTIVE(S)
Early pregnancy failure (EPF) is a common complication of pregnancy. Surgical intervention carries a risk of complications and, therefore, medical treatment appears to be a safe alternative. Unfortunately, the current medical treatment with misoprostol alone has complete evacuation rates between 53% and 87%. Some reports suggest that sequential treatment with mifepristone and misoprostol leads to higher success rates than misoprostol alone.
STUDY DESIGN
To evaluate the added value of mifepristone to current non-surgical treatment regimens in women with EPF we performed a systematic literature search. Electronic databases were searched: PubMed, Cochrane Library, Current Controlled Trials, and ClinicalTrials.gov. Clinical studies, both randomised and non-randomised trials, reporting on the added value of mifepristone to current non-surgical treatment regimens in women with EPF were included. Data of sixteen studies were extracted using a data extraction sheet (based on the Cochrane Consumers and Communication Review Group's data extraction template). The methodological quality was assessed using the Cochrane Collaboration Risk of Bias tool.
RESULTS
In five randomised and eleven non-randomised trials, success rates of sequential treatment with mifepristone and misoprostol in case of EPF varied between 52% and 95%. Large heterogeneity existed in treatment regimens and comparators between studies.
CONCLUSION(S)
The existing evidence is insufficient to draw firm conclusions about the added value of mifepristone to misoprostol alone. A sufficiently powered randomised, double blinded placebo-controlled trial is urgently required to test whether, in EPF, the sequential combination of mifepristone with misoprostol is superior to misoprostol only.
Topics: Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Abortion, Spontaneous; Clinical Protocols; Drug Therapy, Combination; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Pregnancy Trimester, First
PubMed: 26461963
DOI: 10.1016/j.ejogrb.2015.09.027 -
The Cochrane Database of Systematic... Jan 2008Determining the optimal method of performing second-trimester abortions is important, since they account for a disproportionate amount of abortion-related morbidity and... (Review)
Review
BACKGROUND
Determining the optimal method of performing second-trimester abortions is important, since they account for a disproportionate amount of abortion-related morbidity and mortality.
OBJECTIVES
To compare surgical and medical methods of inducing abortion in the second trimester of pregnancy with regard to efficacy, side effects, adverse events, and acceptability.
SEARCH STRATEGY
We identified trials using Pub Med, EMBASE, POPLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL). We also searched the reference lists of identified studies, relevant review articles, book chapters, and conference proceedings for additional, previously unidentified studies. We contacted experts in the field for information on other published or unpublished research.
SELECTION CRITERIA
Randomised trials comparing any surgical to any medical method of inducing abortion at >/= 13 weeks' gestation were included.
DATA COLLECTION AND ANALYSIS
We assessed the validity of each study using the methods suggested in the Cochrane Handbook. Investigators were contacted as needed to provide additional information regarding trial conduct or outcomes. Two reviewers abstracted the data. Odds ratios and 95% confidence intervals were calculated for dichotomous variables using RevMan 4.2. The trials did not have uniform interventions, therefore, we were unable to combine them into a meta-analysis.
MAIN RESULTS
Two studies met criteria for this review. One compared dilation and evacuation (D&E) to intra-amniotic instillation of prostaglandin F(2) (alpha). The second study compared D&E to induction with mifepristone and misoprostol. Compared with prostaglandin instillation, the combined incidence of minor complications was lower with D&E (OR 0.17, 95% CI 0.04-0.65) as was the total number of minor and major complications (OR 0.12, 95% CI 0.03-0.46). The number of women experiencing adverse events was also lower with D&E than with mifepristone and misoprostol (OR 0.06, 95% CI 0.01-0.76). Although women treated with mifepristone and misoprostol reported significantly more pain than those undergoing D&E, efficacy and acceptability were the same in both groups. In both trials, fewer subjects randomised to D&E required overnight hospitalisation.
AUTHORS' CONCLUSIONS
Dilation and evacuation is superior to instillation of prostaglandin F(2) (alpha). The current evidence also appears to favour D&E over mifepristone and misoprostol, however larger randomised trials are needed.
Topics: Abortifacient Agents; Abortion, Induced; Dilatation and Curettage; Dinoprost; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Pregnancy Trimester, Second; Randomized Controlled Trials as Topic
PubMed: 18254113
DOI: 10.1002/14651858.CD006714.pub2 -
The Cochrane Database of Systematic... Nov 2013The introduction of a new progestin-only oral contraceptive in Europe has renewed interest in this class of oral contraceptives. Unlike the more widely used combined... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The introduction of a new progestin-only oral contraceptive in Europe has renewed interest in this class of oral contraceptives. Unlike the more widely used combined oral contraceptives containing an estrogen plus progestin, these pills contain only a progestin (progestogen) and are taken without interruption. How these pills compare to others in their class or to combined oral contraceptives is not clear.
OBJECTIVES
This review examined randomized controlled trials of progestin-only pills for differences in efficacy, acceptability, and continuation rates.
SEARCH METHODS
Through October 2013, we searched the computerized databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), POPLINE, and LILACS for studies of progestin-only pills. We also searched for current trials via ClinicalTrials.gov and ICTRP. Previous searches also included EMBASE.
SELECTION CRITERIA
We included all randomized controlled trials in any language that included progestin-only pills for contraception. We incorporated any comparison with a progestin-only pill; this could include different doses, other progestin-only pills, combined oral contraceptives, or other contraceptives.
DATA COLLECTION AND ANALYSIS
The first author abstracted the data and entered the information into RevMan 5. Another author performed a second, independent data abstraction to verify the initial data entry.We attempted to extract life-table rates (actuarial or continuous) and used the rate difference as the effect measure. Where life-table rates were not published, we used the incidence rate ratio (ratio of Pearl rates). Where only the crude number of events was published, we calculated the Peto odds ratio with 95% confidence interval (CI) using a fixed-effect model. For continuous variables, the mean difference (MD) was computed with 95% CI. Because of disparate exposures, we were not able to combine studies in meta-analysis.
MAIN RESULTS
Six trials met the inclusion criteria. We have not found any new studies since the initial review. In the trial comparing the desogestrel versus levonorgestrel progestin-only pill, desogestrel was not associated with a significantly lower risk of accidental pregnancy; the rate ratio was 0.27 (95% CI 0.06 to 1.19). However, the desogestrel progestin-only pill caused more bleeding problems, although this difference was not statistically significant. The trial comparing low-dose mifepristone versus a levonorgestrel progestin-only pill found similar pregnancy rates. In the trial comparing ethynodiol diacetate versus a combined oral contraceptive, irregular cycles occurred in all women assigned to the progestin-only pill (odds ratio 135.96; 95% CI 7.61 to 2421.02). In a trial comparing two progestin-only and two combined oral contraceptives, the progestin-only pill containing levonorgestrel 30 μg had higher efficacy than did the pill containing norethisterone 350 μg. An early trial found megestrol acetate inferior to other progestin-only pills in terms of efficacy. A study of the timing of pill initiation after birth found no important differences, but high losses to follow up undermined the trial.
AUTHORS' CONCLUSIONS
Evidence is insufficient to compare progestin-only pills to each other or to combined oral contraceptives.
Topics: Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Desogestrel; Ethynodiol Diacetate; Female; Humans; Levonorgestrel; Progestins; Randomized Controlled Trials as Topic; Uterine Hemorrhage
PubMed: 24226383
DOI: 10.1002/14651858.CD007541.pub3