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International Journal of Gynaecology... Feb 2024Misoprostol is widely used for cervical ripening and labour induction as it is heat-stable and inexpensive. Oral misoprostol 25 μg given 2-hourly is recommended over... (Meta-Analysis)
Meta-Analysis Review
The efficacy and safety of 25 μg or 50 μg oral misoprostol versus 25 μg vaginal misoprostol given at 4- or 6-hourly intervals for induction of labour in women at or beyond term with live singleton pregnancies: A systematic review and meta-analysis.
BACKGROUND
Misoprostol is widely used for cervical ripening and labour induction as it is heat-stable and inexpensive. Oral misoprostol 25 μg given 2-hourly is recommended over vaginal misoprostol 25 μg given 6-hourly, but the need for 2-hourly fetal monitoring makes oral misoprostol impractical for routine use in high-volume obstetric units in resource-constrained settings.
OBJECTIVES
To compare the efficacy and safety of oral misoprostol initiated at 25 or 50 μg versus 25 μg vaginal misoprostol given at 4- to 6-hourly intervals for labor induction in women at or beyond term (≥ 37 weeks) with a single viable fetus and an unscarred uterus.
SEARCH STRATEGY
We identified eligible randomized, parallel-group, labor-induction trials from recent systematic reviews. We additionally searched PubMed, Cochrane CENTRAL, Epistemonikos, and clinical trials registries from February 1, 2020 to December 31, 2022 without language restrictions. Database-specific keywords for cervical priming, labor induction, and misoprostol were used.
SELECTION CRITERIA
We excluded labor-induction trials exclusively in women with ruptured membranes, in the third trimester, and those that initiated misoprostol at doses not specified in the review's objectives. The primary outcomes were vaginal birth within 24 h, cesarean section, perinatal mortality, neonatal morbidity, and maternal morbidity. The secondary outcomes were uterine hyperstimulation with fetal heart rate changes, and oxytocin augmentation.
DATA COLLECTION AND ANALYSIS
Two or more authors selected studies independently, assessed risk of bias, and extracted data. We derived pooled weighted risk ratios with 95% confidence intervals (CIs) for each outcome, subgrouping trials by the dose and frequency of misoprostol regimens. We used the I statistic to quantify heterogeneity and the random-effects model for meta-analysis when appropriate. We used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach to assess certainty (confidence) in the effect estimates.
MAIN RESULTS
Thirteen trials, from Canada, India, Iran, and the US, randomizing 2941 women at ≥37 weeks of gestation with an unfavorable cervix (Bishop score <6), met the eligibility criteria. Five misoprostol regimens were compared: 25 μg oral versus 25 μg vaginal, 4-hourly (three trials); 50 μg oral versus 25 μg vaginal, 4-hourly (five trials); 50 μg followed by 100 μg oral versus 25 μg vaginal, 4-hourly (two trials); 50 μg oral, 4-hourly versus 25 μg vaginal, 6-hourly (one trial); and 50 μg oral versus 25 μg vaginal, 6-hourly (two trials). The overall certainty in the evidence ranged from moderate to very low, due to high risk of bias in 11/13 trials (affecting all outcomes), unexplained heterogeneity (1/7 outcomes), indirectness (1/7 outcomes), and imprecision (4/7 outcomes). Vaginal misoprostol probably increased vaginal deliveries within 24 h compared with oral misoprostol (risk ratio [RR] 0.82, 95% CI 0.70-0.96; 11 trials, 2721 mothers; moderate-certainty evidence); this was more likely with 4-hourly than with 6-hourly vaginal regimens. The risk of cesarean sections did not appreciably differ (RR 1.00, 95% CI 0.80-1.26; 13 trials, 2941 mothers; very low-certainty evidence), although oral misoprostol 25 μg 4-hourly probably increased this risk compared with 25 μg vaginal misoprostol 4-hourly (RR 1.69, 95% CI 1.21-2.36; three trials, 515 mothers). The risk of perinatal mortality (RR 0.67, 95% CI 0.11-3.90; one trial, 196 participants; very low-certainty evidence), neonatal morbidity (RR 0.84, 95% CI 0.67-1.06; 13 trials, 2941 mothers; low-certainty evidence), and maternal morbidity (RR 0.83, 95% CI 0.48-1.44; 6 trials; 1945 mothers; moderate-certainty evidence) did not differ appreciably. The risk of uterine hyperstimulation with fetal heart rate changes may be lower with oral misoprostol (RR 0.70, 95% CI 0.52-0.95; 10 trials, 2565 mothers; low-certainty evidence). Oxytocin augmentation was probably more frequent with oral compared with vaginal misoprostol (RR 1.29, 95% CI 1.10-1.51; 13 trials, 2941 mothers; moderate-certainty evidence).
CONCLUSIONS
Low-dose, 4- to 6-hourly vaginal misoprostol regimens probably result in more vaginal births within 24 h and less frequent oxytocin use compared with low-dose, 4- to 6-hourly, oral misoprostol regimens. Vaginal misoprostol may increase the risk of uterine hyperstimulation with fetal heart changes compared with oral misoprostol, without increasing the risk of perinatal mortality, neonatal morbidity, or maternal morbidity. Indirect evidence indicates that 25 μg vaginal misoprostol 4-hourly may be more effective and as safe as the recommended 6-hourly vaginal regimen. This evidence could inform clinical decisions in high-volume obstetric units in resource-constrained settings.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Cervical Ripening; Cesarean Section; Labor, Induced; Misoprostol; Oxytocics; Oxytocin; Perinatal Death
PubMed: 37401143
DOI: 10.1002/ijgo.14970 -
Ugeskrift For Laeger Sep 2021Medical abortion with combined mifepristone and misoprostol is a highly effective, safe, and widely used method for medical termination of pregnancy. In this review, it... (Review)
Review
Medical abortion with combined mifepristone and misoprostol is a highly effective, safe, and widely used method for medical termination of pregnancy. In this review, it is shown that self-testing with a urine human chorionic gonadotropin stix (detection limit greater than 25 IU/l) four weeks after administration of medication is a safe, practical, and cheap method to determine successful termination.
Topics: Abortion, Induced; Drug Therapy, Combination; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Research Design
PubMed: 34596513
DOI: No ID Found -
Revista Brasileira de Ginecologia E... Jun 2023
Topics: Humans; Pregnancy; Female; Misoprostol; Obstetrics; Oxytocics; Gynecology
PubMed: 37494579
DOI: 10.1055/s-0043-1770931 -
The American Journal of Forensic... Sep 2020Misoprostol is a prostaglandin analog commonly used to induce termination of pregnancy. Clandestine home terminations complicate forensic fetal autopsy when a history of...
Misoprostol is a prostaglandin analog commonly used to induce termination of pregnancy. Clandestine home terminations complicate forensic fetal autopsy when a history of misoprostol use is withheld and the gross and histologic findings are sparse, as is often the case. One hundred thirty-two placentas with no vaginal misoprostol use, low-dose misoprostol use, and high-dose misoprostol use were reviewed for the presence, volume, and locations of microcrystalline cellulose and crospovidone, common tablet fillers in misoprostol tablets. Microcrystalline cellulose and/or crospovidone was identified in 0 (0%) of 88 cases with no vaginal administration or low-dose vaginal administration and 29 (66%) of 44 placentas with high-dose vaginal administration. When identified, microcrystalline cellulose and/or crospovidone is most commonly present on the maternal surfaces of the extraplacental membranes. The presence of microcrystalline cellulose and/or crospovidone was associated with smaller placental weight (Mann-Whitney U, P = 0.019). These fillers have a reasonable sensitivity for high-dose vaginal tablet use and are very specific. Although they are not diagnostic for misoprostol administration, they provide a finding that may prompt additional investigation into the nature of the vaginal tablet administered and the circumstances surrounding birth.
Topics: Abortifacient Agents, Nonsteroidal; Administration, Intravaginal; Cellulose; Excipients; Female; Forensic Pathology; Humans; Misoprostol; Organ Size; Placenta; Povidone; Pregnancy; Retrospective Studies
PubMed: 32649317
DOI: 10.1097/PAF.0000000000000557 -
JNMA; Journal of the Nepal Medical... Oct 2020Second trimester abortion is known as termination of pregnancy from 13- 28 weeks of gestation which can be further divided into early second trimester as 13-22 weeks and... (Review)
Review
INTRODUCTION
Second trimester abortion is known as termination of pregnancy from 13- 28 weeks of gestation which can be further divided into early second trimester as 13-22 weeks and late as 23-28 weeks. In our study we have limited up to early second trimester. We intend to see the success rate of combination of mifepristone and misoprostol for medical induction, median time required for expulsion, complication and need of dilation and evacuation in some cases. This study also aims to give a review of current literature in mid trimester abortion with respect to efficacy, complication and also to provide evidencebase recommendation for safe regimens for mid trimester pregnancy termination.
METHODS
This was hospital-based descriptive cross-sectional study conducted among 40 pregnant women at second trimester admitted for termination of pregnancy in Kathmandu medical collage teaching hospital for the period of six month. Ethical approval was taken from the Institutional Review Committee of Kathmandu Medical College (Ref: 2207202002). Convenient sampling was done. All the pregnant women who need to terminate their pregnancy at second trimester (13-22 weeks) were admitted at Kathmandu Medical College Teaching hospital for termination of pregnancy were included in the study.
RESULTS
Among the 40 women, who had termination of pregnancy at second trimester 37 (92.5%) had successful medical termination whereas 3 (7.5%) needed dilatation and evacuation.
CONCLUSIONS
The combination of Mifepristone and Misoprostol have excellent result for termination of pregnancy if appropriately used after evaluating the patient with minimal complications.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Cross-Sectional Studies; Female; Hospitals; Humans; Mifepristone; Misoprostol; Pregnancy; Pregnancy Trimester, Second
PubMed: 34504357
DOI: 10.31729/jnma.5502 -
Contraception Jun 2021To determine the time interval between mifepristone and misoprostol administration associated with the most efficacious early pregnancy loss (EPL) management. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To determine the time interval between mifepristone and misoprostol administration associated with the most efficacious early pregnancy loss (EPL) management.
STUDY DESIGN
We performed a secondary analysis of a randomized trial. Participants with EPL were instructed to take 200 mg oral mifepristone followed by 800 mcg vaginal misoprostol 24 hours later. The primary outcome was gestational sac expulsion at the first follow-up visit (1-4 days after misoprostol use) after a single dose of misoprostol and no additional intervention within 30 days after treatment. Despite specification of drug timing, participants used the medication over a range of time. We graphed sliding average estimates of success and assessed the proportion of treatment successes over time to define timing interval cohorts for analysis. We used multivariable generalized linear regression to assess the association between time interval and success.
RESULTS
Of 139 eligible participants, 70 (50.4%) self-administered misoprostol before 24 hours, and 69 (49.6%) at or after 24 hours. We defined the following time intervals: 0 to 6 hours (n = 22); 7 to 20 hours (n = 29); and 21 to 48 hours (n = 88). Success occurred in 96.6% of the 7- to 20-hour cohort compared to 54.6% and 87.5% of the cohorts self-administering misoprostol earlier or later, respectively. When adjusting for race, gestational age, diagnosis, bleeding at presentation, insurance status, and enrollment site, participants administering misoprostol between 0 and 6 hours (adjusted risk ratio 0.58, 95% CI 0.40-0.85) and 21 to 48 hours (adjusted risk ratio 0.91, 95% CI 0.72-0.99) had a lower risk of success when compared to participants administering 7 to 20 hours after mifepristone.
CONCLUSIONS
These data suggest that medical management of EPL has the highest likelihood of success when misoprostol is self-administered 7 to 20 hours after mifepristone.
IMPLICATIONS
These preliminary data suggest that patients have the highest likelihood of success when misoprostol is taken between 7 and 20 hours after mifepristone. In contrast with medical abortion, simultaneous medication administration may not be as effective as delayed. Future research is needed to confirm the optimal medication time interval.
Topics: Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Abortion, Induced; Abortion, Spontaneous; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Treatment Outcome
PubMed: 33476659
DOI: 10.1016/j.contraception.2021.01.007 -
Journal of Gynecology Obstetrics and... Jan 2022To conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) that examined the maternal and neonatal outcomes of misoprostol+isosorbide... (Meta-Analysis)
Meta-Analysis
Misoprostol plus isosorbide mononitrate versus misoprostol alone for cervical ripening during labor induction: A systematic review and meta-analysis of randomized controlled trials.
AIM
To conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) that examined the maternal and neonatal outcomes of misoprostol+isosorbide mononitrate (ISMN) versus misoprostol alone (control) in promoting cervical ripening during labor induction.
METHODS
We searched five databases from inception until 05-May-2021. We assessed risk of bias of RCTs, meta-analyzed 23 endpoints, and pooled them as mean difference or risk ratio with 95% confidence interval.
RESULTS
Overall, five RCTs met the inclusion criteria, comprising 850 patients (426 and 424 patients were allocated to misoprostol+ISMN and misoprostol group, respectively). Overall, the RCTs had a low risk of bias. Pertaining to maternal delivery-related outcomes, there was no significant difference between both groups regarding the mean interval from drug administration to delivery, rate of vaginal delivery, rate of cesarean section delivery, and rate of need for oxytocin augmentation. Pertaining to maternal drug-related side effects, the rate of maternal headache was significantly higher in disfavor of the misoprostol+ISMN compared with misoprostol alone. However, the rates of maternal nausea, hypotension, flushing, palpitation, dizziness, postpartum hemorrhage, and uterine tachysystole did not differ between both groups. Pertaining to neonatal outcomes, there was no significant difference between both groups regarding rates of NICU admission, meconium-stained amniotic fluid, and Apgar score <7 at five minutes.
CONCLUSION
Compared with misoprostol alone, co-administration of misoprostol+ISMN did not correlate with superior maternal delivery-related outcomes. The rate of maternal headache was significantly higher in disfavor of the misoprostol+ISMN group. There was no significant difference between both groups regarding neonatal endpoints.
Topics: Adult; Cervical Ripening; Female; Humans; Isosorbide; Labor, Induced; Misoprostol; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 34583026
DOI: 10.1016/j.jogoh.2021.102235 -
Clinical Pharmacology in Drug... Aug 2022Misoprostol is a synthetic prostaglandin E1 derivative that has been used to treat duodenal and gastric ulcers, and to prevent ulcers caused by nonsteroidal... (Randomized Controlled Trial)
Randomized Controlled Trial
Misoprostol is a synthetic prostaglandin E1 derivative that has been used to treat duodenal and gastric ulcers, and to prevent ulcers caused by nonsteroidal anti-inflammatory drugs in many countries. Misoprostol can also be used for medical abortion. This study aimed to investigate the pharmacokinetic profiles of misoprostol tablets (test product) by comparing them with Cytotec (200 μg) (reference product). To assess the bioequivalence between test and reference products, a two-sequence, two-period crossover study was conducted with 48 healthy Chinese subjects enrolled under fasting conditions. A validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was used to determine the concentration of misoprostol acid in plasma. A mixed model analysis of variance was used to calculate the bioequivalence of pharmacokinetic (PK) parameters. The point estimate of geometric mean ratios with 90% confidence intervals for the maximum observed concentration (C ) and the area under the concentration-time curve (AUC ) for misoprostol acid in reference and test products were 107.8% and 106.5%, respectively (range 80%-125%). Additionally, none of the secondary PK parameters presented significant differences. No severe or more than moderate adverse events were detected in the 48 subjects. However, one subject discontinued the treatment due to drug-related gastrointestinal reactions. All adverse events were mild with rates of 19.2% and 22.9% after the administration test and reference products, respectively. Overall, the bioequivalence between the two misoprostol products was demonstrated in fasting conditions, and all subjects tolerated both treatments.
Topics: China; Chromatography, Liquid; Cross-Over Studies; Healthy Volunteers; Humans; Misoprostol; Tablets; Tandem Mass Spectrometry; Therapeutic Equivalency
PubMed: 35486088
DOI: 10.1002/cpdd.1102 -
Contraception May 2020To evaluate the characteristics, clinical information, and storage instructions contained in package inserts from medical abortion commodities collected in low- and...
OBJECTIVES
To evaluate the characteristics, clinical information, and storage instructions contained in package inserts from medical abortion commodities collected in low- and middle-income countries.
STUDY DESIGN
From November 2017 to February 2018 mifepristone, misoprostol, and combined mifepristone-misoprostol (combipack) products were collected to populate the Medical Abortion Commodities Database. We extracted stated indications for use, storage instructions, and date of last revision from each package insert obtained. For those inserts listing medical abortion as an indication, we also extracted eligibility criteria, recommended regimens, side effects, and contraindications.
RESULTS
We identified 41 package inserts from 20 countries; 19 (46%) listed medical abortion as an indication including all 7 combipacks, all 7 mifepristone products, and 5/27 (19%) misoprostol products. Date of last insert revision ranged from 1991 to 2016. Gestational age limits for early medical abortion ranged from 49 days to "first trimester." Three (43%) mifepristone products recommended a 600 mg oral dose and two (29%) recommended regimens with gemeprost. Eighteen (67%) misoprostol and one (14%) combipack inserts recommended protection from moisture.
CONCLUSIONS
The characteristics, clinical information, and storage instructions in medical abortion product package inserts from a variety of field settings in low- and middle-income countries included inadequate storage instructions and outdated gestational age limits and regimens.
IMPLICATIONS
There is an urgent need to revisit approved inserts for medical abortion products in low- and middle-income countries to ensure information is accurate and reflects the current evidence base. Simultaneously, providing supplemental instructions targeted at users may fill some gaps. People have a right to accurate information to ensure a safe and effective medical abortion experience.
Topics: Abortifacient Agents; Abortion, Induced; Alprostadil; Cross-Sectional Studies; Developing Countries; Drug Therapy, Combination; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Pregnancy Trimester, First; Product Labeling; Treatment Outcome
PubMed: 32032639
DOI: 10.1016/j.contraception.2020.01.011 -
Social Science & Medicine (1982) Jan 2020Misoprostol has during the past few years become an important obstetric drug used for different purposes both within and outside hospitals in Tanzania. In this paper, we...
Misoprostol has during the past few years become an important obstetric drug used for different purposes both within and outside hospitals in Tanzania. In this paper, we analyze how misoprostol is perceived, accessed and used off-label as an abortion drug in the city and region of Dar es Salaam. The study took place in Dar es Salaam's three districts from July to November 2015, and had a qualitative explorative approach. We carried out in-depth interviews (42) with the following main categories of informants: women having undergone medical abortion (15), health care workers with experiences from post abortion care (16) and drug vendors (11). Focus group discussions (10) were carried out with young women. A client simulation study was carried out in 64 drugstores across Dar es Salaam assessing the availability of misoprostol and the advice given concerning its use. In addition, shorter qualitative interviews were carried out with representatives of NGOs and public agencies working with sexual and reproductive health issues (17). Our findings reveal that in Dar es Salaam, misoprostol is well known, available and accessed for abortion purposes through drugstores and health providers. Women tend to prefer misoprostol over other abortion methods since it allows for a private, low-cost, safer and less uncomfortable abortion experience. But, while misoprostol facilitates women's agency in the process of seeking abortion, a series of obstacles shaped by a restrictive abortion law and an unregulated pharmaceutical market hinder its safe use. Central obstacles are profit-seeking providers, suboptimal user instructions and poor provider follow-up. In the discussion of the material we draw upon Van der Geest, Hardon and Whyte's concept of the 'social life of pharmaceuticals' and indicate the ways in which misoprostol acts as an agent of change in the social relations connected to abortion.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Adult; Female; Focus Groups; Health Personnel; Humans; Interviews as Topic; Misoprostol; Off-Label Use; Pregnancy; Qualitative Research; Tanzania
PubMed: 31810016
DOI: 10.1016/j.socscimed.2019.112676