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Journal of General Internal Medicine Aug 2020Abortion and miscarriage are common, affecting millions of US women each year. By age 45, one in four women in the USA will have had an abortion, and at least as many... (Review)
Review
Abortion and miscarriage are common, affecting millions of US women each year. By age 45, one in four women in the USA will have had an abortion, and at least as many will have had a miscarriage. Most individuals seeking abortion services do so before 10 weeks' gestation when medication abortions are a safe and effective option, using a regimen of oral mifepristone followed by misoprostol tablets. When a pregnancy is non-viable before 13 weeks' gestation, it is referred to as an early pregnancy loss or miscarriage and can be managed using the same mifepristone and misoprostol regimen. Given their safety and efficacy, mifepristone and misoprostol can be offered in ambulatory settings without special equipment or on-site emergency services. As more patients find it difficult to access clinical care when faced with an undesired pregnancy or a miscarriage, it is important for general internists and primary care providers to become familiar with how to use medications to manage these common conditions. We summarize the most recent evidence regarding the use of mifepristone with misoprostol for early abortion and miscarriage. We discuss clinical considerations and resources for integrating mifepristone and misoprostol into clinical practice. By learning to prescribe mifepristone and misoprostol, clinicians can expand access to time-sensitive health services for vulnerable populations.
Topics: Abortion, Induced; Abortion, Spontaneous; Female; Gestational Age; Humans; Middle Aged; Mifepristone; Misoprostol; Pregnancy
PubMed: 32410127
DOI: 10.1007/s11606-020-05836-9 -
Journal of Veterinary Internal Medicine Nov 2018The gastrointestinal (GI) mucosal barrier is continuously exposed to noxious toxins, reactive oxygen species, microbes, and drugs, leading to the development of...
The gastrointestinal (GI) mucosal barrier is continuously exposed to noxious toxins, reactive oxygen species, microbes, and drugs, leading to the development of inflammatory, erosive, and ultimately ulcerative lesions. This report offers a consensus opinion on the rational administration of GI protectants to dogs and cats, with an emphasis on proton pump inhibitors (PPIs), histamine type-2 receptor antagonists (H RAs), misoprostol, and sucralfate. These medications decrease gastric acidity or promote mucosal protective mechanisms, transforming the management of dyspepsia, peptic ulceration, and gastroesophageal reflux disease. In contrast to guidelines that have been established in people for the optimal treatment of gastroduodenal ulcers and gastroesophageal reflux disease, effective clinical dosages of antisecretory drugs have not been well established in the dog and cat to date. Similar to the situation in human medicine, practice of inappropriate prescription of acid suppressants is also commonplace in veterinary medicine. This report challenges the dogma and clinical practice of administering GI protectants for the routine management of gastritis, pancreatitis, hepatic disease, and renal disease in dogs and cats lacking additional risk factors for ulceration or concerns for GI bleeding. Judicious use of acid suppressants is warranted considering recent studies that have documented adverse effects of long-term supplementation of PPIs in people and animals.
Topics: Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Gastrointestinal Agents; Gastrointestinal Diseases; Misoprostol; Proton Pump Inhibitors; Sucralfate
PubMed: 30378711
DOI: 10.1111/jvim.15337 -
Lancet (London, England) Sep 2020The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of mifepristone and misoprostol is more effective than administering misoprostol alone. We investigated whether treatment with mifepristone plus misoprostol would result in a higher rate of completion of missed miscarriage compared with misoprostol alone.
METHODS
MifeMiso was a multicentre, double-blind, placebo-controlled, randomised trial in 28 UK hospitals. Women were eligible for enrolment if they were aged 16 years and older, diagnosed with a missed miscarriage by pelvic ultrasound scan in the first 14 weeks of pregnancy, chose to have medical management of miscarriage, and were willing and able to give informed consent. Participants were randomly assigned (1:1) to a single dose of oral mifepristone 200 mg or an oral placebo tablet, both followed by a single dose of vaginal, oral, or sublingual misoprostol 800 μg 2 days later. Randomisation was managed via a secure web-based randomisation program, with minimisation to balance study group assignments according to maternal age (<30 years vs ≥30 years), body-mass index (<35 kg/mvs ≥35 kg/m), previous parity (nulliparous women vs parous women), gestational age (<70 days vs ≥70 days), amount of bleeding (Pictorial Blood Assessment Chart score; ≤2 vs ≥3), and randomising centre. Participants, clinicians, pharmacists, trial nurses, and midwives were masked to study group assignment throughout the trial. The primary outcome was failure to spontaneously pass the gestational sac within 7 days after random assignment. Primary analyses were done according to intention-to-treat principles. The trial is registered with the ISRCTN registry, ISRCTN17405024.
FINDINGS
Between Oct 3, 2017, and July 22, 2019, 2595 women were identified as being eligible for the MifeMiso trial. 711 women were randomly assigned to receive either mifepristone and misoprostol (357 women) or placebo and misoprostol (354 women). 696 (98%) of 711 women had available data for the primary outcome. 59 (17%) of 348 women in the mifepristone plus misoprostol group did not pass the gestational sac spontaneously within 7 days versus 82 (24%) of 348 women in the placebo plus misoprostol group (risk ratio [RR] 0·73, 95% CI 0·54-0·99; p=0·043). 62 (17%) of 355 women in the mifepristone plus misoprostol group required surgical intervention to complete the miscarriage versus 87 (25%) of 353 women in the placebo plus misoprostol group (0·71, 0·53-0·95; p=0·021). We found no difference in incidence of adverse events between the study groups.
INTERPRETATION
Treatment with mifepristone plus misoprostol was more effective than misoprostol alone in the management of missed miscarriage. Women with missed miscarriage should be offered mifepristone pretreatment before misoprostol to increase the chance of successful miscarriage management, while reducing the need for miscarriage surgery.
FUNDING
UK National Institute for Health Research Health Technology Assessment Programme.
Topics: Abortion, Missed; Adult; Double-Blind Method; Drug Therapy, Combination; Humans; Mifepristone; Misoprostol; Oxytocics; Treatment Outcome
PubMed: 32853559
DOI: 10.1016/S0140-6736(20)31788-8 -
American Family Physician Feb 2022Induction of labor is a common obstetric procedure, and approximately one-fourth of pregnant patients undergo the procedure. Although exercise and nipple stimulation can...
Induction of labor is a common obstetric procedure, and approximately one-fourth of pregnant patients undergo the procedure. Although exercise and nipple stimulation can increase the likelihood of spontaneous labor, sexual intercourse may not be effective. Acupuncture has been used for labor induction; however, it has not been shown to increase vaginal delivery rates. There is strong evidence that membrane sweeping can increase the likelihood of spontaneous labor within 48 hours. Cervical preparation or ripening is often needed before induction. Some evidence shows that the use of nonpharmacologic approaches such as osmotic dilators and cervical ripening balloons reduce time to delivery. The effect of amniotomy on labor is uncertain. Pharmacologic intervention with oxytocin or prostaglandins is effective for cervical ripening and induction of labor. Combining a balloon catheter with misoprostol is a common practice and has been shown to decrease time to delivery in a small study.
Topics: Cervical Ripening; Female; Humans; Labor, Induced; Misoprostol; Oxytocics; Oxytocin; Pregnancy
PubMed: 35166491
DOI: No ID Found -
Obstetrics and Gynecology May 2022To compare immediate initiation with delayed initiation of medication abortion among patients with an undesired pregnancy of unknown location.
OBJECTIVE
To compare immediate initiation with delayed initiation of medication abortion among patients with an undesired pregnancy of unknown location.
METHODS
This retrospective cohort study used electronic medical record data from the Planned Parenthood League of Massachusetts (2014-2019) for patients who requested medication abortion with a last menstrual period (LMP) of 42 days or less and pregnancy of unknown location (no gestational sac) on initial ultrasonogram. Clinicians could initiate medication abortion with mifepristone followed by misoprostol while simultaneously excluding ectopic pregnancy with serial serum human chorionic gonadotropin (hCG) testing (same-day-start group) or establish a diagnosis with serial hCG tests and repeat ultrasonogram before initiating treatment (delay-for-diagnosis group). We compared primary safety outcomes (time to diagnosis of pregnancy location [rule out ectopic], emergency department visits, adverse events, and nonadherence with follow-up) between groups. We also reported secondary efficacy outcomes: time to complete abortion, successful medication abortion (no uterine aspiration), and ongoing pregnancy.
RESULTS
Of 5,619 medication abortion visits for patients with an LMP of 42 days or less, 452 patients had pregnancy of unknown location (8.0%). Three patients underwent immediate uterine aspiration, 55 had same-day start, and 394 had delay for diagnosis. Thirty-one patients (7.9%), all in the delay-for-diagnosis group, were treated for ectopic pregnancy, including four that were ruptured. Among patients with no major ectopic pregnancy risk factors (n=432), same-day start had shorter time to diagnosis (median 5.0 days vs 9.0 days; P=.005), with no significant difference in emergency department visits (adjusted odds ratio [aOR] 0.90, 95% CI 0.43-1.88) or nonadherence with follow-up (aOR 0.92, 95% CI 0.39-2.15). Among patients who proceeded with abortion (n=270), same-day start had shorter time to complete abortion (median 5.0 days vs 19.0 days; P<.001). Of those who had medication abortion with known outcome (n=170), the rate of successful medication abortion was lower (85.4% vs 96.7%; P=.013) and the rate of ongoing pregnancy was higher (10.4% vs 2.5%; P=.041) among patients in the same-day-start group.
CONCLUSION
In patients with undesired pregnancy of unknown location, immediate initiation of medication abortion is associated with more rapid exclusion of ectopic pregnancy and pregnancy termination but lower abortion efficacy.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Abortion, Spontaneous; Chorionic Gonadotropin; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Pregnancy, Ectopic; Retrospective Studies
PubMed: 35576336
DOI: 10.1097/AOG.0000000000004756 -
The New England Journal of Medicine Jun 2018Medical management of early pregnancy loss is an alternative to uterine aspiration, but standard medical treatment with misoprostol commonly results in treatment... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Medical management of early pregnancy loss is an alternative to uterine aspiration, but standard medical treatment with misoprostol commonly results in treatment failure. We compared the efficacy and safety of pretreatment with mifepristone followed by treatment with misoprostol with the efficacy and safety of misoprostol use alone for the management of early pregnancy loss.
METHODS
We randomly assigned 300 women who had an anembryonic gestation or in whom embryonic or fetal death was confirmed to receive pretreatment with 200 mg of mifepristone, administered orally, followed by 800 μg of misoprostol, administered vaginally (mifepristone-pretreatment group), or 800 μg of misoprostol alone, administered vaginally (misoprostol-alone group). Participants returned 1 to 4 days after misoprostol use for evaluation, including ultrasound examination, by an investigator who was unaware of the treatment-group assignments. Women in whom the gestational sac was not expelled were offered expectant management, a second dose of misoprostol, or uterine aspiration. We followed all participants for 30 days after randomization. Our primary outcome was gestational sac expulsion with one dose of misoprostol by the first follow-up visit and no additional intervention within 30 days after treatment.
RESULTS
Complete expulsion after one dose of misoprostol occurred in 124 of 148 women (83.8%; 95% confidence interval [CI], 76.8 to 89.3) in the mifepristone-pretreatment group and in 100 of 149 women (67.1%; 95% CI, 59.0 to 74.6) in the misoprostol-alone group (relative risk, 1.25; 95% CI, 1.09 to 1.43). Uterine aspiration was performed less frequently in the mifepristone-pretreatment group than in the misoprostol-alone group (8.8% vs. 23.5%; relative risk, 0.37; 95% CI, 0.21 to 0.68). Bleeding that resulted in blood transfusion occurred in 2.0% of the women in the mifepristone-pretreatment group and in 0.7% of the women in the misoprostol-alone group (P=0.31); pelvic infection was diagnosed in 1.3% of the women in each group.
CONCLUSIONS
Pretreatment with mifepristone followed by treatment with misoprostol resulted in a higher likelihood of successful management of first-trimester pregnancy loss than treatment with misoprostol alone. (Funded by the National Institute of Child Health and Human Development; PreFaiR ClinicalTrials.gov number, NCT02012491 .).
Topics: Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Abortion, Spontaneous; Administration, Intravaginal; Administration, Oral; Adult; Drug Therapy, Combination; Embryo, Mammalian; Female; Fetal Death; Gestational Sac; Hemorrhage; Humans; Mifepristone; Misoprostol; Pregnancy; Pregnancy Trimester, First; Ultrasonography
PubMed: 29874535
DOI: 10.1056/NEJMoa1715726 -
Health Technology Assessment... Feb 2019Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic drugs can reduce blood loss and are routinely recommended....
BACKGROUND
Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic drugs can reduce blood loss and are routinely recommended. There are several uterotonic drugs for preventing PPH, but it is still debatable which drug or combination of drugs is the most effective.
OBJECTIVES
To identify the most effective and cost-effective uterotonic drug(s) to prevent PPH, and generate a ranking according to their effectiveness and side-effect profile.
METHODS
The Cochrane Pregnancy and Childbirth's Trials Register (1 June 2015), ClinicalTrials.gov and the World Health Organization (WHO)'s International Clinical Trials Registry Platform (ICTRP) were searched for unpublished trial reports (30 June 2015). In addition, reference lists of retrieved studies (updated October 2017) were searched for randomised trials evaluating uterotonic drugs for preventing PPH. The study estimated relative effects and rankings for preventing PPH, defined as blood loss of ≥ 500 ml and ≥ 1000 ml. Pairwise meta-analyses and network meta-analysis were performed to determine the relative effects and rankings of all available drugs and combinations thereof [ergometrine, misoprostol (Cytotec; Pfizer Inc., New York, NY, USA), misoprostol plus oxytocin (Syntocinon; Novartis International AG, Basel, Switzerland), carbetocin (Pabal; Ferring Pharmaceuticals, Saint-Prex, Switzerland), ergometrine plus oxytocin (Syntometrine; Alliance Pharma plc, Chippenham, UK), oxytocin, and a placebo or no treatment]. Primary outcomes were stratified according to the mode of birth, prior risk of PPH, health-care setting, drug dosage, regimen and route of drug administration. Sensitivity analyses were performed according to study quality and funding source, among others. A model-based economic evaluation compared the relative cost-effectiveness separately for vaginal births and caesareans with or without including side effects.
RESULTS
From 137 randomised trials and 87,466 women, ergometrine plus oxytocin, carbetocin and misoprostol plus oxytocin were found to reduce the risk of PPH blood loss of ≥ 500 ml compared with the standard drug, oxytocin [ergometrine plus oxytocin: risk ratio (RR) 0.69, 95% confidence interval (CI) 0.57 to 0.83; carbetocin: RR 0.72, 95% CI 0.52 to 1.00; misoprostol plus oxytocin: RR 0.73, 95% CI 0.6 to 0.9]. Each of these three strategies had 100% cumulative probability of being ranked first, second or third most effective. Oxytocin was ranked fourth, with an almost 0% cumulative probability of being ranked in the top three. Similar rankings were noted for the reduction of PPH blood loss of ≥ 1000 ml (ergometrine plus oxytocin: RR 0.77, 95% CI 0.61 to 0.95; carbetocin: RR 0.70, 95% CI 0.38 to 1.28; misoprostol plus oxytocin: RR 0.90, 95% CI 0.72 to 1.14), and most secondary outcomes. Ergometrine plus oxytocin and misoprostol plus oxytocin had the poorest ranking for side effects. Carbetocin had a favourable side-effect profile, which was similar to oxytocin. However, the analysis was restricted to high-quality studies, carbetocin lost its ranking and was comparable to oxytocin. The relative cost-effectiveness of the alternative strategies is inconclusive, and the results are affected by both the uncertainty and inconsistency in the data reported on adverse events. For vaginal delivery, when assuming no adverse events, ergometrine plus oxytocin is less costly and more effective than all strategies except carbetocin. The strategy of carbetocin is both more effective and more costly than all other strategies. When taking adverse events into consideration, all prevention strategies, except oxytocin, are more costly and less effective than carbetocin. For delivery by caesarean section, with and without adverse events, the relative cost-effectiveness is different, again because of the uncertainty in the available data.
LIMITATIONS
There was considerable uncertainty in findings within the planned subgroup analyses, and subgroup effects cannot be ruled out.
CONCLUSIONS
Ergometrine plus oxytocin, carbetocin and misoprostol plus oxytocin are more effective uterotonic drug strategies for preventing PPH than the current standard, oxytocin. Ergometrine plus oxytocin and misoprostol plus oxytocin cause significant side effects. Carbetocin has a favourable side-effect profile, which was similar to oxytocin. However, most carbetocin trials are small and of poor quality. There is a need for a large high-quality trial comparing carbetocin with oxytocin; such a trial is currently being conducted by the WHO. The relative cost-effectiveness is inconclusive, and results are affected by uncertainty and inconsistency in adverse events data.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42015020005; Cochrane Pregnancy and Childbirth Group (substudy) reference number 0871; PROSPERO-Cochrane (substudy) reference number CRD42015026568; and sponsor reference number ERN_13-1414 (University of Birmingham, Birmingham, UK).
FUNDING
Funding for this study was provided by the National Institute for Health Research Health Technology Assessment programme in a research award to the University of Birmingham and supported by the UK charity Ammalife (UK-registered charity 1120236). The funders of the study had no role in study design, data collection, data synthesis, interpretation or writing of the report.
Topics: Clinical Trials as Topic; Delivery, Obstetric; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Ergonovine; Female; Humans; Misoprostol; Network Meta-Analysis; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy
PubMed: 30821683
DOI: 10.3310/hta23090 -
CMAJ : Canadian Medical Association... Jun 2018
Topics: Abortifacient Agents, Steroidal; Abortion, Induced; Canada; Drug Therapy, Combination; Family Planning Services; Female; Guidelines as Topic; Humans; Insurance Coverage; Mifepristone; Misoprostol; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second
PubMed: 29866894
DOI: 10.1503/cmaj.180047 -
The Cochrane Database of Systematic... Nov 2020Postpartum haemorrhage (PPH), defined as a blood loss of 500 mL or more after birth, is the leading cause of maternal death worldwide. The World Health Organization... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postpartum haemorrhage (PPH), defined as a blood loss of 500 mL or more after birth, is the leading cause of maternal death worldwide. The World Health Organization (WHO) recommends that all women giving birth should receive a prophylactic uterotonic agent. Despite the routine administration of a uterotonic agent for prevention, PPH remains a common complication causing one-quarter of all maternal deaths globally. When prevention fails and PPH occurs, further administration of uterotonic agents as 'first-line' treatment is recommended. However, there is uncertainty about which uterotonic agent is best for the 'first-line' treatment of PPH.
OBJECTIVES
To identify the most effective uterotonic agent(s) with the least side-effects for PPH treatment, and generate a meaningful ranking among all available agents according to their relative effectiveness and side-effect profile.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (5 May 2020), and the reference lists of all retrieved studies.
SELECTION CRITERIA
All randomised controlled trials or cluster-randomised trials comparing the effectiveness and safety of uterotonic agents with other uterotonic agents for the treatment of PPH were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed all trials for inclusion, extracted data and assessed each trial for risk of bias. Our primary outcomes were additional blood loss of 500 mL or more after recruitment to the trial until cessation of active bleeding and the composite outcome of maternal death or severe morbidity. Secondary outcomes included blood loss-related outcomes, morbidity outcomes, and patient-reported outcomes. We performed pairwise meta-analyses and indirect comparisons, where possible, but due to the limited number of included studies, we were unable to conduct the planned network meta-analysis. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
Seven trials, involving 3738 women in 10 countries, were included in this review. All trials were conducted in hospital settings. Randomised women gave birth vaginally, except in one small trial, where women gave birth either vaginally or by caesarean section. Across the seven trials (14 trial arms) the following agents were used: six trial arms used oxytocin alone; four trial arms used misoprostol plus oxytocin; three trial arms used misoprostol; one trial arm used Syntometrine® (oxytocin and ergometrine fixed-dose combination) plus oxytocin infusion. Pairwise meta-analysis of two trials (1787 participants), suggests that misoprostol, as first-line treatment uterotonic agent, probably increases the risk of blood transfusion (risk ratio (RR) 1.47, 95% confidence interval (CI) 1.02 to 2.14, moderate-certainty) compared with oxytocin. Low-certainty evidence suggests that misoprostol administration may increase the incidence of additional blood loss of 1000 mL or more (RR 2.57, 95% CI 1.00 to 6.64). The data comparing misoprostol with oxytocin is imprecise, with a wide range of treatment effects for the additional blood loss of 500 mL or more (RR 1.66, 95% CI 0.69 to 4.02, low-certainty), maternal death or severe morbidity (RR 1.98, 95% CI 0.36 to 10.72, low-certainty, based on one study n = 809 participants, as the second study had zero events), and the use of additional uterotonics (RR 1.30, 95% CI 0.57 to 2.94, low-certainty). The risk of side-effects may be increased with the use of misoprostol compared with oxytocin: vomiting (2 trials, 1787 participants, RR 2.47, 95% CI 1.37 to 4.47, high-certainty) and fever (2 trials, 1787 participants, RR 3.43, 95% CI 0.65 to 18.18, low-certainty). According to pairwise meta-analysis of four trials (1881 participants) generating high-certainty evidence, misoprostol plus oxytocin makes little or no difference to the use of additional uterotonics (RR 0.99, 95% CI 0.94 to 1.05) and to blood transfusion (RR 0.95, 95% CI 0.77 to 1.17) compared with oxytocin. We cannot rule out an important benefit of using the misoprostol plus oxytocin combination over oxytocin alone, for additional blood loss of 500 mL or more (RR 0.84, 95% CI 0.66 to 1.06, moderate-certainty). We also cannot rule out important benefits or harms for additional blood loss of 1000 mL or more (RR 0.76, 95% CI 0.43 to 1.34, moderate-certainty, 3 trials, 1814 participants, one study reported zero events), and maternal mortality or severe morbidity (RR 1.09, 95% CI 0.35 to 3.39, moderate-certainty). Misoprostol plus oxytocin increases the incidence of fever (4 trials, 1866 participants, RR 3.07, 95% CI 2.62 to 3.61, high-certainty), and vomiting (2 trials, 1482 participants, RR 1.85, 95% CI 1.16 to 2.95, high-certainty) compared with oxytocin alone. For all outcomes of interest, the available evidence on the misoprostol versus Syntometrine® plus oxytocin combination was of very low-certainty and these effects remain unclear. Although network meta-analysis was not performed, we were able to compare the misoprostol plus oxytocin combination with misoprostol alone through the common comparator of oxytocin. This indirect comparison suggests that the misoprostol plus oxytocin combination probably reduces the risk of blood transfusion (RR 0.65, 95% CI 0.42 to 0.99, moderate-certainty) and may reduce the risk of additional blood loss of 1000 mL or more (RR 0.30, 95% CI 0.10 to 0.89, low-certainty) compared with misoprostol alone. The combination makes little or no difference to vomiting (RR 0.75, 95% CI 0.35 to 1.59, high-certainty) compared with misoprostol alone. Misoprostol plus oxytocin compared to misoprostol alone are compatible with a wide range of treatment effects for additional blood loss of 500 mL or more (RR 0.51, 95% CI 0.20 to 1.26, low-certainty), maternal mortality or severe morbidity (RR 0.55, 95% CI 0.07 to 4.24, low-certainty), use of additional uterotonics (RR 0.76, 95% CI 0.33 to 1.73, low-certainty), and fever (RR 0.90, 95% CI 0.17 to 4.77, low-certainty).
AUTHORS' CONCLUSIONS
The available evidence suggests that oxytocin used as first-line treatment of PPH probably is more effective than misoprostol with less side-effects. Adding misoprostol to the conventional treatment of oxytocin probably makes little or no difference to effectiveness outcomes, and is also associated with more side-effects. The evidence for most uterotonic agents used as first-line treatment of PPH is limited, with no evidence found for commonly used agents, such as injectable prostaglandins, ergometrine, and Syntometrine®.
Topics: Bias; Blood Transfusion; Confidence Intervals; Drug Therapy, Combination; Ergonovine; Female; Humans; Misoprostol; Network Meta-Analysis; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 33232518
DOI: 10.1002/14651858.CD012754.pub2 -
The Cochrane Database of Systematic... Jan 2017Miscarriage occurs in 10% to 15% of pregnancies. The traditional treatment, after miscarriage, has been to perform surgery to remove any remaining placental tissues in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Miscarriage occurs in 10% to 15% of pregnancies. The traditional treatment, after miscarriage, has been to perform surgery to remove any remaining placental tissues in the uterus ('evacuation of uterus'). However, medical treatments, or expectant care (no treatment), may also be effective, safe, and acceptable.
OBJECTIVES
To assess the effectiveness, safety, and acceptability of any medical treatment for incomplete miscarriage (before 24 weeks).
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register (13 May 2016) and reference lists of retrieved papers.
SELECTION CRITERIA
We included randomised controlled trials comparing medical treatment with expectant care or surgery, or alternative methods of medical treatment. We excluded quasi-randomised trials.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the studies for inclusion, assessed risk of bias, and carried out data extraction. Data entry was checked. We assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
We included 24 studies (5577 women). There were no trials specifically of miscarriage treatment after 13 weeks' gestation.Three trials involving 335 women compared misoprostol treatment (all vaginally administered) with expectant care. There was no difference in complete miscarriage (average risk ratio (RR) 1.23, 95% confidence interval (CI) 0.72 to 2.10; 2 studies, 150 women, random-effects; very low-quality evidence), or in the need for surgical evacuation (average RR 0.62, 95% CI 0.17 to 2.26; 2 studies, 308 women, random-effects; low-quality evidence). There were few data on 'deaths or serious complications'. For unplanned surgical intervention, we did not identify any difference between misoprostol and expectant care (average RR 0.62, 95% CI 0.17 to 2.26; 2 studies, 308 women, random-effects; low-quality evidence).Sixteen trials involving 4044 women addressed the comparison of misoprostol (7 studies used oral administration, 6 studies used vaginal, 2 studies sublingual, 1 study combined vaginal + oral) with surgical evacuation. There was a slightly lower incidence of complete miscarriage with misoprostol (average RR 0.96, 95% CI 0.94 to 0.98; 15 studies, 3862 women, random-effects; very low-quality evidence) but with success rate high for both methods. Overall, there were fewer surgical evacuations with misoprostol (average RR 0.05, 95% CI 0.02 to 0.11; 13 studies, 3070 women, random-effects; very low-quality evidence) but more unplanned procedures (average RR 5.03, 95% CI 2.71 to 9.35; 11 studies, 2690 women, random-effects; low-quality evidence). There were few data on 'deaths or serious complications'. Nausea was more common with misoprostol (average RR 2.50, 95% CI 1.53 to 4.09; 11 studies, 3015 women, random-effects; low-quality evidence). We did not identify any difference in women's satisfaction between misoprostol and surgery (average RR 1.00, 95% CI 0.99 to 1.00; 9 studies, 3349 women, random-effects; moderate-quality evidence). More women had vomiting and diarrhoea with misoprostol compared with surgery (vomiting: average RR 1.97, 95% CI 1.36 to 2.85; 10 studies, 2977 women, random-effects; moderate-quality evidence; diarrhoea: average RR 4.82, 95% CI 1.09 to 21.32; 4 studies, 757 women, random-effects; moderate-quality evidence).Five trials compared different routes of administration, or doses, or both, of misoprostol. There was no clear evidence of one regimen being superior to another. Limited evidence suggests that women generally seem satisfied with their care. Long-term follow-up from one included study identified no difference in subsequent fertility between the three approaches.
AUTHORS' CONCLUSIONS
The available evidence suggests that medical treatment, with misoprostol, and expectant care are both acceptable alternatives to routine surgical evacuation given the availability of health service resources to support all three approaches. Further studies, including long-term follow-up, are clearly needed to confirm these findings. There is an urgent need for studies on women who miscarry at more than 13 weeks' gestation.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Incomplete; Administration, Intravaginal; Administration, Oral; Diarrhea; Extraction, Obstetrical; Female; Gestational Age; Humans; Misoprostol; Nausea; Pregnancy; Pregnancy Trimester, First; Randomized Controlled Trials as Topic; Vomiting; Watchful Waiting
PubMed: 28138973
DOI: 10.1002/14651858.CD007223.pub4