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The Lancet. Global Health Oct 2022To address the knowledge gaps in the provision of post-abortion care by midwives for women in the second trimester, we investigated the effectiveness and safety of... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of the effectiveness and safety of treatment of incomplete second trimester abortion with misoprostol provided by midwives and physicians: a randomised, controlled, equivalence trial in Uganda.
BACKGROUND
To address the knowledge gaps in the provision of post-abortion care by midwives for women in the second trimester, we investigated the effectiveness and safety of treatment for incomplete second trimester abortion with misoprostol, comparing care provision by midwives with that provided by physicians in Uganda.
METHODS
Our multicentre, randomised, controlled, equivalence trial undertaken in 14 health facilities in Uganda recruited women with incomplete abortion of uterine size 13-18 weeks. We randomly assigned (1:1) women to clinical assessment and treatment by either midwife or physician. The randomisation sequence was computer generated, in blocks of four to 12, and stratified for study site. Participants received sublingual misoprostol (400 μg once every 3 h for up to five doses). The study was not concealed from the health-care providers and study participants. Primary outcome was complete abortion within 24 h that did not require surgical evacuation. Analysis was per-protocol and intention to treat; the intention-to-treat population consisted of women who were randomised, received at least one dose of misoprostol, and reported primary outcome data, and the per-protocol population excluded women with unexplained discontinuation of treatment. We used generalised mixed-effects models to obtain the risk difference. The predefined equivalence range was -5% to 5%. The trial was registered at ClinicalTrials.gov, NCT03622073.
FINDINGS
Between Aug 14, 2018, and Nov 16, 2021, 1191 eligible women were randomly assigned to each group (593 women to the midwife group and 598 to the physician group). 1164 women were included in the per-protocol analysis, and 530 (92%) of 577 women in the midwife group and 553 (94%) of 587 women in the physician group had a complete abortion within 24 h. The model-based risk difference for the midwife versus physician group was -2·3% (95% CI -4·4 to -0·3), and within our predefined equivalence range (-5% to 5%). Two women in the midwife group received blood transfusion.
INTERPRETATION
Clinical assessment and treatment of second trimester incomplete abortion with misoprostol provided by midwives was equally effective and safe as when provided by physicians. In low-income settings, inclusion of midwives in the medical management of uncomplicated second trimester incomplete abortion has potential to increase women's access to safe post-abortion care.
FUNDING
Swedish Research Council and THRiVE-2.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Incomplete; Abortion, Induced; Female; Humans; Midwifery; Misoprostol; Physicians; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Uganda
PubMed: 36030801
DOI: 10.1016/S2214-109X(22)00312-6 -
The Cochrane Database of Systematic... Jan 2011With the improvement of ultrasound technology, the likelihood of detection of major fetal structural anomalies in mid-pregnancy has increased considerably. Upon the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
With the improvement of ultrasound technology, the likelihood of detection of major fetal structural anomalies in mid-pregnancy has increased considerably. Upon the detection of serious anomalies, women typically are offered the option of pregnancy termination. Additionally, there are still many reasons other than fetal anomalies why women seek abortion in the mid-trimester.
OBJECTIVES
To compare different methods of second trimester medical termination of pregnancy for their efficacy and side-effects.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, Popline and reference lists of retrieved papers and other sources.
SELECTION CRITERIA
All randomised controlled trials (RCTs) examining medical regimens for termination of pregnancy of a singleton living fetus between 12-28 weeks' gestation were analysed. The outcome measures were the induction to abortion interval, abortion rate within 24 hours, need for surgical evacuation, blood loss, uterine rupture, pain, and side-effects.Trials including >20% fetal death, multiple pregnancies, previous uterine scars and regimens which involved cervical preparation were excluded.
DATA COLLECTION AND ANALYSIS
Two authors selected the trials and three authors extracted data.
MAIN RESULTS
Fourty RCTs were included, addressing various agents for pregnancy termination and methods of administration. When used alone, misoprostol was an effective inductive agent, though it appeared to be more effective in combination with mifepristone. However, the evidence from RCTs is limited.Misoprostol was preferably administered vaginally, although among multiparous women sublingual administration appeared equally effective. A range of doses of vaginally administered misoprostol has been used. No randomised trials comparing doses of misoprostol were identified; however low doses of misoprostol appear to be associated with fewer side-effects while moderate doses appear to be more efficient in completing abortion. Four RCTs showed that the induction to abortion interval with 3-hourly vaginal administration of prostaglandins is shorter than 6-hourly administration without an increase in side-effects.Many studies reported the need for surgical evacuation. Indications for surgical evacuation include retained products of the placenta and heavy vaginal bleeding. Fewer women required surgical evacuation when misoprostol was administrated vaginally compared with women receiving intra-amniotical PGF(2a) . Mild, self-limiting diarrhoea was more common among women who received misoprostol compared to other agents.
AUTHORS' CONCLUSIONS
Medical abortion in the second trimester using the combination of mifepristone and misoprostol appeared to have the highest efficacy and shortest abortion time interval. Where mifepristone is not available, misoprostol alone is a reasonable alternative. The optimal route for administering misoprostol is vaginally, preferably using tablets at 3-hourly intervals. Apart from pain, the side-effects of vaginal misoprostol are usually mild and self limiting. Conclusions from this review are limited by the gestational age ranges and variable medical regimens, including dosing, administrative routes and intervals of medication, of the included trials.
Topics: Abortifacient Agents; Abortion, Induced; Administration, Intravaginal; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Pregnancy Trimester, Second; Prostaglandins A; Randomized Controlled Trials as Topic
PubMed: 21249669
DOI: 10.1002/14651858.CD005216.pub2 -
BioMed Research International 2022To compare the maternal and neonatal outcomes of pregnant women who had labor induction with intravaginal misoprostol or had spontaneous labor in our clinic. . The...
PURPOSE
To compare the maternal and neonatal outcomes of pregnant women who had labor induction with intravaginal misoprostol or had spontaneous labor in our clinic. . The records of 213 pregnant women, who were followed up in Acibadem Maslak University Hospital for vaginal delivery between June 2021 and December 2021, were retrospectively evaluated. The pregnant women, who gave birth, were divided into 3 groups as follows: spontaneous labor (SL), those induced by a single dose of misoprostol (SDM), and those induced by multiple doses of misoprostol (MDM). The groups were compared in terms of delivery type, the vaginal birth rate within 12 hours, need for intervention, duration of the second stage of labor, cesarean section ratio due to fetal distress, time from the last dose to delivery, and 1st and 5th minute APGAR scores.
RESULTS
Among the primiparous pregnant women, 84.7% of SL group, 65.2% of SDM group, and 37% MDM group delivered vaginally within 12 hours ( < 0.05). The time from the last misoprostol dose to delivery was also statistically significantly shorter in pregnant women, who received a single dose of misoprostol (483 vs. 720 min, respectively). When the hospitalization time was evaluated, in the SDM group, the MDM group, and the SL group, it was found to be 611, 831, and 379 min, respectively. In multiparous pregnant women, the hospitalization time was 735 min in the SDM group, 494 min in the MDM group, and 261.5 min in the SL group ( < 0.05). Other than the hospitalization time, when the aforementioned variables were studied in multiparous pregnant women, no statistically significant difference among groups was observed ( > 0.05).
CONCLUSION
Intravaginal misoprostol seems to be a promising medical agent for labor induction due to its high delivery rates within 12 hours and the absence of negative fetal outcomes, its ease of storage, and affordable cost.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Misoprostol; Oxytocics; Cesarean Section; Retrospective Studies; Pregnancy Outcome; Administration, Intravaginal; Labor, Induced
PubMed: 36531654
DOI: 10.1155/2022/2826927 -
Journal of Medical Economics 2022Various methods exist for the induction of labor (IOL), and there is limited consensus as to optimal methods. Off-label misoprostol is recommended by the World Health... (Review)
Review
BACKGROUND
Various methods exist for the induction of labor (IOL), and there is limited consensus as to optimal methods. Off-label misoprostol is recommended by the World Health Organization (WHO) for IOL but preparing it into doses suitable for IOL lacks precision, with potential adverse outcomes if dosing is inaccurate. This study explores potential outcomes and costs associated with increased uptake of a low-dose (25 µg) oral misoprostol formulation (Angusta; Norgine BV, Amsterdam) approved for IOL, in France, Belgium, and the Netherlands.
METHODS
A literature review was undertaken to derive probabilities of delivery outcomes (vaginal, instrumental, and cesarean sections) for IOL methods, from published meta-analyses. Outcomes for oral misoprostol tablets (25 µg) were unavailable in the meta-analyses, so were estimated using data from two published retrospective cohort studies. A model was developed to predict the frequency of IOL outcomes and associated costs at the national level, across multiple scenarios. Scenarios were tested using a moderate, medium, and high increase in oral misoprostol tablet (25 µg) uptake. Market shares, costs, and induction rates were defined for each country using multiple data sources.
RESULTS
Increased uptake of oral misoprostol tablets (25 µg) was estimated to be associated with a slightly increased rate of routine vaginal deliveries, and concurrent decreases in instrumental vaginal deliveries and cesarean sections. Since routine vaginal deliveries are less costly than other delivery outcomes, increased uptake of oral misoprostol tablets (25 µg) within the IOL market has the potential to be cost-saving. These trends were predicted using 25 µg oral misoprostol tablet outcomes informed by both retrospective studies.
CONCLUSION
Preliminary outcomes suggest that oral misoprostol tablets at 25 µg per dose may improve outcomes in IOL and be cost-saving. Further study is required to validate these findings and assess the comparative efficacy of IOL methods, including oral misoprostol tablets (25 µg).
Topics: Administration, Oral; Costs and Cost Analysis; Female; Humans; Labor, Induced; Misoprostol; Oxytocics; Pregnancy; Retrospective Studies; Tablets
PubMed: 35297743
DOI: 10.1080/13696998.2022.2053432 -
Drug Design, Development and Therapy 2015Induction of labor is one of the most commonly performed obstetric procedures and will likely become more common as the reproductive population in developed nations... (Review)
Review
Induction of labor is one of the most commonly performed obstetric procedures and will likely become more common as the reproductive population in developed nations changes. As the proportion of women undergoing induction grows, there is a constant search for more efficacious ways to induce labor while maintaining fetal and maternal safety as well as patient satisfaction. With almost half of induced labors requiring cervical ripening, methods for achieving active labor and vaginal delivery are constantly being investigated. Prostaglandins have been shown to be effective induction agents, and specifically vaginal misoprostol, used off-label, have been widely utilized to initiate cervical ripening and active labor. The challenge is to administer this medication accurately while maintaining the ability to discontinue the medication when needed. The misoprostol vaginal insert initiates cervical ripening utilizing a delivery system that controls medication release and can be rapidly removed. This paper reviews the design, development, and clinical utility of the misoprostol vaginal insert for induction of labor as well as patient considerations related to the delivery system.
Topics: Administration, Intravaginal; Adult; Cervical Ripening; Chemistry, Pharmaceutical; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Delivery Systems; Drug Implants; Female; Humans; Labor, Induced; Misoprostol; Oxytocics; Pregnancy
PubMed: 25960635
DOI: 10.2147/DDDT.S64227 -
BMC Pregnancy and Childbirth Nov 2015While inferior to oxytocin injection in both efficacy and safety, orally administered misoprostol has been included in the World Health Organization Model List of... (Review)
Review
BACKGROUND
While inferior to oxytocin injection in both efficacy and safety, orally administered misoprostol has been included in the World Health Organization Model List of Essential Medicines for use in the prevention of postpartum haemorrhage (PPH) in low-resource settings. This study evaluates the costs and health outcomes of use of oral misoprostol to prevent PPH in settings where injectable uterotonics are not available.
METHODS
A cost-consequences analysis was conducted from the international health system perspective, using data from a recent Cochrane systematic review and WHO's Mother-Baby Package Costing Spreadsheet in a hypothetical cohort of 1000 births in a mixed hospital (40% births)/community setting (60% births). Costs were estimated based on 2012 US dollars.
RESULTS
Using oxytocin in the hospital setting and misoprostol in the community setting in a cohort of 1000 births, instead of oxytocin (hospital setting) and no treatment (community setting), 22 cases of PPH could be prevented. Six fewer women would require additional uterotonics and four fewer women a blood transfusion. An additional 130 women would experience shivering and an extra 42 women fever. Oxytocin/misoprostol was found to be cost saving (US$320) compared to oxytocin/no treatment. If misoprostol is used in both the hospital and community setting compared with no treatment (i.e. oxytocin not available in the hospital setting), 37 cases of PPH could be prevented; ten fewer women would require additional uterotonics; and six fewer women a blood transfusion. An additional 217 women would experience shivering and 70 fever. The cost savings would be US$533. Sensitivity analyses indicate that the results are sensitive to the incidence of PPH-related outcomes, drug costs and the proportion of hospital births.
CONCLUSIONS
Our findings confirm that, even though misoprostol is not the optimum choice in the prevention of PPH, misoprostol could be an effective and cost-saving choice where oxytocin is not or cannot be used due to a lack of skilled birth attendants, inadequate transport and storage facilities or where a quality assured oxytocin product is not available. These benefits need to be weighed against the large number of additional side effects such as shivering and fever, which have been described as tolerable and of short duration.
Topics: Administration, Oral; Cost-Benefit Analysis; Female; Fever; Humans; Labor Stage, Third; Misoprostol; Oxytocics; Oxytocin; Parturition; Postpartum Hemorrhage; Pregnancy; Shivering
PubMed: 26596797
DOI: 10.1186/s12884-015-0749-z -
Equine Veterinary Journal May 2019Misoprostol is an E prostanoid (EP) 2, 3 and 4 receptor agonist that is anecdotally used to treat and prevent NSAID-induced GI injury in horses. Misoprostol elicits...
BACKGROUND
Misoprostol is an E prostanoid (EP) 2, 3 and 4 receptor agonist that is anecdotally used to treat and prevent NSAID-induced GI injury in horses. Misoprostol elicits anti-inflammatory effects in vivo in men and rodents, and inhibits TNFα production in equine leucocytes in vitro.
OBJECTIVE
Define the pharmacokinetic parameters of oral misoprostol in horses, and determine the inhibitory effect of oral misoprostol administration on equine leucocyte TNFα production in an ex vivo inflammation model.
STUDY DESIGN
Pharmacokinetic study, ex vivo experimental study.
METHODS
Six healthy adult horses of mixed breeds were used. In phase one, horses were given 5 μg/kg misoprostol orally, and blood was collected at predetermined times for determination of misoprostol free acid (MFA) by UHPLC-MS/MS. Pharmacokinetic parameters were calculated. In phase two, horses were dosed as in phase one, and blood was collected at T0, 0.5, 1 and 4 h following misoprostol administration for leucocyte isolation. Leucocytes were stimulated with 100 ng/mL LPS, and TNFα mRNA concentrations were determined via quantitative real-time PCR.
RESULTS
About 5 μg/kg oral misoprostol produced a rapid time to maximum concentration (T ) of 23.4 ± 2.4 min, with a maximum concentration (C ) of 0.29 ± 0.07 ng/mL and area under the curve (AUC ) of 0.4 ± 0.12 h ng/mL. LPS stimulation of equine leucocytes ex vivo significantly increased TNFα mRNA concentrations, and there was no significant effect of misoprostol even at the T .
MAIN LIMITATIONS
Only a single dose was used, and sample size was small.
CONCLUSIONS
Misoprostol is rapidly absorbed following oral administration in horses, and a single 5 μg/kg dose had no significant inhibitory effect on ex vivo LPS-stimulated TNFα mRNA production in leucocytes. Further studies analysing different dosing strategies, including repeat administration or combination with other anti-inflammatory drugs, are warranted.
Topics: Abortifacient Agents, Nonsteroidal; Administration, Oral; Animals; Area Under Curve; Cells, Cultured; Horse Diseases; Horses; Inflammation; Leukocytes; Misoprostol
PubMed: 30256450
DOI: 10.1111/evj.13024 -
Contraception Apr 2023We conducted a pilot study to evaluate a single dose of letrozole 30 mg prior to misoprostol 800 mcg buccally for medication abortion STUDY DESIGN: We enrolled 40...
OBJECTIVES
We conducted a pilot study to evaluate a single dose of letrozole 30 mg prior to misoprostol 800 mcg buccally for medication abortion STUDY DESIGN: We enrolled 40 participants seeking medication abortion up to 63 days' gestation at a site in Salt Lake City, UT. Participants received a single dose of letrozole 30 mg in-clinic followed 2 days later by misoprostol 800 mcg buccally at home. They took a second dose of misoprostol if they had no bleeding within 24 hours of the first. Participants returned 7 to 10 days later for assessment of abortion outcome and side effects RESULTS: Thirty-seven participants (93%) returned for follow-up and 2 (5%) went to another facility from which research staff obtained outcome data. Three-fourths (29/39, 74%, 95% CI: 60%-89%) had a complete abortion; 4 (10%, 95% CI: 0.3%-20%) had an incomplete abortion and opted for aspiration, and 6 (15%, 95% CI: 4%-27%) had an ongoing pregnancy. All subjects with follow-up reported taking the first dose of misoprostol. Ten (27%) took the second dose as well; only three did so due to no bleeding. Nineteen participants (51%) reported side effects after letrozole prior to misoprostol and two people (5%) rated these effects as severe. Side effects following misoprostol occurred in 33 participants (89%) and were as expected based on previous literature. No serious adverse events were reported CONCLUSION: A single dose of letrozole 30 mg followed by misoprostol had lower than desirable efficacy and does not warrant further study.
IMPLICATIONS
A single dose of letrozole does not appear to be an effective adjunct to misoprostol for medication abortion.
Topics: Pregnancy; Female; Humans; Misoprostol; Letrozole; Pilot Projects; Abortifacient Agents, Nonsteroidal; Abortion, Induced; Mifepristone; Administration, Intravaginal
PubMed: 36529240
DOI: 10.1016/j.contraception.2022.109924 -
The Cochrane Database of Systematic... Oct 2004This is one of a series of reviews of cervical ripening and labour induction using standardised methodology. Misoprostol administered by the oral and sublingual routes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is one of a series of reviews of cervical ripening and labour induction using standardised methodology. Misoprostol administered by the oral and sublingual routes have the advantage of rapid onset of action, while the sublingual and vaginal routes have the advantage of prolonged activity and greatest bioavailability.
OBJECTIVES
To determine the effectiveness and safety of misoprostol administered buccally or sublingually for third trimester cervical ripening and induction of labour.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group trials register (8 December 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), and bibliographies of relevant papers.
SELECTION CRITERIA
Randomised controlled trials comparing buccal or sublingual misoprostol used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods.
DATA COLLECTION AND ANALYSIS
A generic strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. Data were extracted onto standardized forms, checked for accuracy, and analysed using RevMan software.
MAIN RESULTS
Three studies (502 participants) compared buccal/sublingual misoprostol respectively with a vaginal regimen (200 microg versus 50 microg) and with oral administration (50 versus 50 microg and 50 versus 100microg).The buccal route was associated with a trend to fewer caesarean sections than with the vaginal route (18/73 versus 28/79; relative risk (RR) 0.70; 95% confidence interval (CI) 0.42 to 1.15). There were no significant differences in any other outcomes. When the same dosage was used sublingually versus orally, the sublingual route was associated with less failures to achieve vaginal delivery within 24 hours (12/50 versus 19/50; RR 0.63, 95% CI 0.34 to 1.16), reduced oxytocin augmentation (17/50 versus 23/50; RR 0.74, 95% CI 0.45 to 1.21) and reduced caesarean section (8/50 versus 15/50; RR 0.53, 95% CI 0.25 to 1.14), but the differences were not statistically significant. When a smaller dose was used sublingually than orally, there were no differences in any of the outcomes.
REVIEWERS' CONCLUSIONS
Based on only three small trials, sublingual misoprostol appears to be at least as effective as when the same dose is administered orally. There are inadequate data to comment on the relative complications and side-effects. Sublingual or buccal misoprostol should not enter clinical use until its safety and optimal dosage have been established by larger trials.
Topics: Administration, Oral; Administration, Sublingual; Cervical Ripening; Female; Humans; Labor, Induced; Misoprostol; Oxytocics; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 15495088
DOI: 10.1002/14651858.CD004221.pub2 -
What do healthcare providers think of the quality of uterotonics? A mixed-methods systematic review.BMJ Open Oct 2023To synthesise evidence on the perceptions of healthcare providers (HCPs) about the quality of oxytocin and misoprostol available in their settings, and their actions as...
OBJECTIVES
To synthesise evidence on the perceptions of healthcare providers (HCPs) about the quality of oxytocin and misoprostol available in their settings, and their actions as a result of these perceptions.
DESIGN
Mixed-methods systematic review.
ELIGIBILITY CRITERIA
We included quantitative and qualitative studies reporting HCPs' perceptions about oxytocin or misoprostol quality.
DATA SOURCES
We searched CINAHL, Cochrane Library, Ebscohost, Embase, PubMed, Global Index Medicus, Portal regional BVS, PsycNET, Scopus and Web of Science from inception to 31 March 2022 and grey literature.
RISK OF BIAS
We used the Center for Evidence-Based Management critical appraisal tool for surveys. For qualitative studies, we used the Critical Appraisal Skills Programme tool.
DATA EXTRACTION AND SYNTHESIS
Two independent reviewers performed study selection, data extraction and quality assessment. We conducted separate quantitative and qualitative syntheses and integrated the evidence into a narrative synthesis (convergent segregated review design).
RESULTS
We included five (three quantitative and two qualitative) studies, of moderate or high quality, conducted in low-income and middle-income countries (LMICs). In the three quantitative studies (N=7065 participants), 8.2-21.3% of HCPs had experienced problems due to known/suspected low-quality oxytocin and 3.3% due to low-quality misoprostol. In the two qualitative studies, perception of oxytocin quality varied. In quantitative studies, when confronted with suspected/known low-quality oxytocin, 29-78% of HCPs would inform a supervisor, 62% would document this in writing, 45-54% would change to another drug and 5-37% would double the dose of oxytocin. Qualitative evidence suggests that many HCPs do not formally report suspected low-quality oxytocin or misoprostol, and use higher doses or additional uterotonics.
CONCLUSIONS
A proportion of HCPs from LMICs perceive oxytocin to be of low quality. There is very limited evidence on their perceptions about misoprostol. Many HCPs do not report suspected low-quality uterotonics but change to another medicine or double the dose of oxytocin.
PROSPERO REGISTRATION NUMBER
CRD42022323812.
Topics: Female; Humans; Oxytocin; Misoprostol; Postpartum Hemorrhage; Health Personnel
PubMed: 37899165
DOI: 10.1136/bmjopen-2022-068442