-
The Cochrane Database of Systematic... Mar 2023Mechanical methods were the first methods developed to ripen the cervix and induce labour. During recent decades they have been substituted by pharmacological methods.... (Review)
Review
BACKGROUND
Mechanical methods were the first methods developed to ripen the cervix and induce labour. During recent decades they have been substituted by pharmacological methods. Potential advantages of mechanical methods, compared with pharmacological methods may include reduction in side effects that could improve neonatal outcomes. This is an update of a review first published in 2001, last updated in 2012.
OBJECTIVES
To determine the effectiveness and safety of mechanical methods for third trimester (> 24 weeks' gestation) induction of labour in comparison with prostaglandin E2 (PGE2) (vaginal and intracervical), low-dose misoprostol (oral and vaginal), amniotomy or oxytocin.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies (9 January 2018). We updated the search in March 2019 and added the search results to the awaiting classification section of the review.
SELECTION CRITERIA
Clinical trials comparing mechanical methods used for third trimester cervical ripening or labour induction with pharmacological methods. Mechanical methods include: (1) the introduction of a catheter through the cervix into the extra-amniotic space with balloon insufflation; (2) introduction of laminaria tents, or their synthetic equivalent (Dilapan), into the cervical canal; (3) use of a catheter to inject fluid into the extra-amniotic space (EASI). This review includes the following comparisons: (1) specific mechanical methods (balloon catheter, laminaria tents or EASI) compared with prostaglandins (different types, different routes) or with oxytocin; (2) single balloon compared to a double balloon; (3) addition of prostaglandins or oxytocin to mechanical methods compared with prostaglandins or oxytocin alone.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and assessed risk of bias. Two review authors independently extracted data and assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
This review includes a total of 112 trials, with 104 studies contributing data (22,055 women; 21 comparisons). Risk of bias of trials varied. Overall, the evidence was graded from very-low to moderate quality. All evidence was downgraded for lack of blinding and, for many comparisons, the effect estimates were too imprecise to make a valid judgement. Balloon versus vaginal PGE2: there may be little or no difference in vaginal deliveries not achieved within 24 hours (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.82 to 1.26; 7 studies; 1685 women; low-quality evidence) and there probably is little or no difference in caesarean sections (RR 1.00, 95% CI 0.92 to 1.09; 28 studies; 6619 women; moderate-quality evidence) between induction of labour with a balloon catheter and vaginal PGE2. A balloon catheter probably reduces the risk of uterine hyperstimulation with fetal heart rate (FHR) changes (RR 0.35, 95% CI 0.18 to 0.67; 6 studies; 1966 women; moderate-quality evidence), serious neonatal morbidity or perinatal death (RR 0.48, 95% CI 0.25 to 0.93; 8 studies; 2757 women; moderate-quality evidence) and may slightly reduce the risk of aneonatal intensive care unit (NICU) admission (RR 0.82, 95% CI 0.65 to 1.04; 3647 women; 12 studies; low-quality evidence). It is uncertain whether there is a difference in serious maternal morbidity or death (RR 0.20, 95% CI 0.01 to 4.12; 4 studies; 1481 women) or five-minute Apgar score < 7 (RR 0.74, 95% CI 0.49 to 1.14; 4271 women; 14 studies) because the quality of the evidence was found to be very low and low, respectively. Balloon versus low-dose vaginal misoprostol: it is uncertain whether there is a difference in vaginal deliveries not achieved within 24 hours between induction of labour with a balloon catheter and vaginal misoprostol (RR 1.09, 95% CI 0.85 to 1.39; 340 women; 2 studies; low-quality evidence). A balloon catheter probably reduces the risk of uterine hyperstimulation with FHR changes (RR 0.39, 95% CI 0.18 to 0.85; 1322 women; 8 studies; moderate-quality evidence) but may increase the risk of a caesarean section (RR 1.28, 95% CI 1.02 to 1.60; 1756 women; 12 studies; low-quality evidence). It is uncertain whether there is a difference in serious neonatal morbidity or perinatal death (RR 0.58, 95% CI 0.12 to 2.66; 381 women; 3 studies), serious maternal morbidity or death (no events; 4 studies, 464 women), both very low-quality evidence, and five-minute Apgar score < 7 (RR 1.00, 95% CI 0.50 to 1.97; 941 women; 7 studies) and NICU admissions (RR 1.00, 95% CI 0.61 to 1.63; 1302 women; 9 studies) both low-quality evidence. Balloon versus low-dose oral misoprostol: a balloon catheter probably increases the risk of a vaginal delivery not achieved within 24 hours (RR 1.28, 95% CI 1.13 to 1.46; 782 women, 2 studies, and probably slightly increases the risk of a caesarean section (RR 1.17, 95% CI 1.04 to 1.32; 3178 women; 7 studies; both moderate-quality evidence) when compared to oral misoprostol. It is uncertain whether there is a difference in uterine hyperstimulation with FHR changes (RR 0.81, 95% CI 0.48 to 1.38; 2033 women; 2 studies), serious neonatal morbidity or perinatal death (RR 1.11, 95% CI 0.60 to 2.06; 2627 women; 3 studies), both low-quality evidence, serious maternal morbidity or death (RR 0.50, 95% CI 0.05 to 5.52; 2627 women; 3 studies), very low-quality evidence, five-minute Apgar scores < 7 (RR 0.71, 95% CI 0.38 to 1.32; 2693 women; 4 studies) and NICU admissions (RR 0.82, 95% CI 0.58 to 1.17; 2873 women; 5 studies) both low-quality evidence.
AUTHORS' CONCLUSIONS
Low- to moderate-quality evidence shows mechanical induction with a balloon is probably as effective as induction of labour with vaginal PGE2. However, a balloon seems to have a more favourable safety profile. More research on this comparison does not seem warranted. Moderate-quality evidence shows a balloon catheter may be slightly less effective as oral misoprostol, but it remains unclear if there is a difference in safety outcomes for the neonate. When compared to low-dose vaginal misoprostol, low-quality evidence shows a balloon may be less effective, but probably has a better safety profile. Future research could be focused more on safety aspects for the neonate and maternal satisfaction.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Cesarean Section; Dinoprostone; Labor, Induced; Misoprostol; Oxytocin; Perinatal Death
PubMed: 36996264
DOI: 10.1002/14651858.CD001233.pub4 -
The Cochrane Database of Systematic... Jun 2021Misoprostol given orally is a commonly used labour induction method. Our Cochrane Review is restricted to studies with low-dose misoprostol (initially ≤ 50 µg), as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Misoprostol given orally is a commonly used labour induction method. Our Cochrane Review is restricted to studies with low-dose misoprostol (initially ≤ 50 µg), as higher doses pose unacceptably high risks of uterine hyperstimulation.
OBJECTIVES
To assess the efficacy and safety of low-dose oral misoprostol for labour induction in women with a viable fetus in the third trimester of pregnancy.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (14 February 2021) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised trials comparing low-dose oral misoprostol (initial dose ≤ 50 µg) versus placebo, vaginal dinoprostone, vaginal misoprostol, oxytocin, or mechanical methods; or comparing oral misoprostol protocols (one- to two-hourly versus four- to six-hourly; 20 µg to 25 µg versus 50 µg; or 20 µg hourly titrated versus 25 µg two-hourly static).
DATA COLLECTION AND ANALYSIS
Using Covidence, two review authors independently screened reports, extracted trial data, and performed quality assessments. Our primary outcomes were vaginal birth within 24 hours, caesarean section, and hyperstimulation with foetal heart changes.
MAIN RESULTS
We included 61 trials involving 20,026 women. GRADE assessments ranged from moderate- to very low-certainty evidence, with downgrading decisions based on imprecision, inconsistency, and study limitations. Oral misoprostol versus placebo/no treatment (four trials; 594 women) Oral misoprostol may make little to no difference in the rate of caesarean section (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.59 to 1.11; 4 trials; 594 women; moderate-certainty evidence), while its effect on uterine hyperstimulation with foetal heart rate changes is uncertain (RR 5.15, 95% CI 0.25 to 105.31; 3 trials; 495 women; very low-certainty evidence). Vaginal births within 24 hours was not reported. In all trials, oxytocin could be commenced after 12 to 24 hours and all women had pre-labour ruptured membranes. Oral misoprostol versus vaginal dinoprostone (13 trials; 9676 women) Oral misoprostol probably results in fewer caesarean sections (RR 0.84, 95% CI 0.78 to 0.90; 13 trials, 9676 women; moderate-certainty evidence). Subgroup analysis indicated that 10 µg to 25 µg (RR 0.80, 95% CI 0.74 to 0.87; 9 trials; 8652 women) may differ from 50 µg (RR 1.10, 95% CI 0.91 to 1.34; 4 trials; 1024 women) for caesarean section. Oral misoprostol may decrease vaginal births within 24 hours (RR 0.93, 95% CI 0.87 to 1.00; 10 trials; 8983 women; low-certainty evidence) and hyperstimulation with foetal heart rate changes (RR 0.49, 95% CI 0.40 to 0.59; 11 trials; 9084 women; low-certainty evidence). Oral misoprostol versus vaginal misoprostol (33 trials; 6110 women) Oral use may result in fewer vaginal births within 24 hours (average RR 0.81, 95% CI 0.68 to 0.95; 16 trials, 3451 women; low-certainty evidence), and less hyperstimulation with foetal heart rate changes (RR 0.69, 95% CI 0.53 to 0.92, 25 trials, 4857 women, low-certainty evidence), with subgroup analysis suggesting that 10 µg to 25 µg orally (RR 0.28, 95% CI 0.14 to 0.57; 6 trials, 957 women) may be superior to 50 µg orally (RR 0.82, 95% CI 0.61 to 1.11; 19 trials; 3900 women). Oral misoprostol probably does not increase caesarean sections overall (average RR 1.00, 95% CI 0.86 to 1.16; 32 trials; 5914 women; low-certainty evidence) but likely results in fewer caesareans for foetal distress (RR 0.74, 95% CI 0.55 to 0.99; 24 trials, 4775 women). Oral misoprostol versus intravenous oxytocin (6 trials; 737 women, 200 with ruptured membranes) Misoprostol may make little or no difference to vaginal births within 24 hours (RR 1.12, 95% CI 0.95 to 1.33; 3 trials; 466 women; low-certainty evidence), but probably results in fewer caesarean sections (RR 0.67, 95% CI 0.50 to 0.90; 6 trials; 737 women; moderate-certainty evidence). The effect on hyperstimulation with foetal heart rate changes is uncertain (RR 0.66, 95% CI 0.19 to 2.26; 3 trials, 331 women; very low-certainty evidence). Oral misoprostol versus mechanical methods (6 trials; 2993 women) Six trials compared oral misoprostol to transcervical Foley catheter. Misoprostol may increase vaginal birth within 24 hours (RR 1.32, 95% CI 0.98 to 1.79; 4 trials; 1044 women; low-certainty evidence), and probably reduces the risk of caesarean section (RR 0.84, 95% CI 0.75 to 0.95; 6 trials; 2993 women; moderate-certainty evidence). There may be little or no difference in hyperstimulation with foetal heart rate changes (RR 1.31, 95% CI 0.78 to 2.21; 4 trials; 2828 women; low-certainty evidence). Oral misoprostol one- to two-hourly versus four- to six-hourly (1 trial; 64 women) The evidence on hourly titration was very uncertain due to the low numbers reported. Oral misoprostol 20 µg hourly titrated versus 25 µg two-hourly static (2 trials; 296 women) The difference in regimen may have little or no effect on the rate of vaginal births in 24 hours (RR 0.97, 95% CI 0.80 to 1.16; low-certainty evidence). The evidence is of very low certainty for all other reported outcomes.
AUTHORS' CONCLUSIONS
Low-dose oral misoprostol is probably associated with fewer caesarean sections (and therefore more vaginal births) than vaginal dinoprostone, and lower rates of hyperstimulation with foetal heart rate changes. However, time to birth may be increased, as seen by a reduced number of vaginal births within 24 hours. Compared to transcervical Foley catheter, low-dose oral misoprostol is associated with fewer caesarean sections, but equivalent rates of hyperstimulation. Low-dose misoprostol given orally rather than vaginally is probably associated with similar rates of vaginal birth, although rates may be lower within the first 24 hours. However, there is likely less hyperstimulation with foetal heart changes, and fewer caesarean sections performed due to foetal distress. The best available evidence suggests that low-dose oral misoprostol probably has many benefits over other methods for labour induction. This review supports the use of low-dose oral misoprostol for induction of labour, and demonstrates the lower risks of hyperstimulation than when misoprostol is given vaginally. More trials are needed to establish the optimum oral misoprostol regimen, but these findings suggest that a starting dose of 25 µg may offer a good balance of efficacy and safety.
Topics: Administration, Intravaginal; Administration, Oral; Apgar Score; Cesarean Section; Dinoprostone; Drug Administration Schedule; Female; Heart Rate, Fetal; Humans; Intensive Care, Neonatal; Labor, Induced; Misoprostol; Oxytocics; Oxytocin; Parturition; Placebos; Pregnancy; Randomized Controlled Trials as Topic; Time Factors; Uterus
PubMed: 34155622
DOI: 10.1002/14651858.CD014484 -
Obstetrics and Gynecology Jun 2021To assess the comparative effectiveness and potential harms of cervical ripening in the outpatient compared with the inpatient setting, or different methods of ripening... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the comparative effectiveness and potential harms of cervical ripening in the outpatient compared with the inpatient setting, or different methods of ripening in the outpatient setting alone.
DATA SOURCES
Searches for articles in English included MEDLINE, EMBASE, CINAHL, Cochrane Library, ClinicalTrials.gov, and reference lists (up to August 2020).
METHODS OF STUDY SELECTION
Using predefined criteria and DistillerSR software, 10,853 citations were dual-reviewed for randomized controlled trials (RCTs) and cohort studies of outpatient cervical ripening using prostaglandins and mechanical methods in pregnant women at or beyond 37 weeks of gestation.
TABULATION, INTEGRATION, AND RESULTS
Using prespecified criteria, study data abstraction and risk of bias assessment were conducted by two reviewers, random-effects meta-analyses were conducted and strength of evidence was assessed. We included 30 RCTs and 10 cohort studies (N=9,618) most generalizable to women aged 25-30 years with low-risk pregnancies. All findings were low or insufficient strength of evidence and not statistically significant. Incidence of cesarean delivery was not different for any comparison of inpatient and outpatient settings, or comparisons of different methods in the outpatient setting (most evidence available for single-balloon catheters and dinoprostone). Harms were inconsistently reported or inadequately defined. Differences were not found for neonatal infection (eg, sepsis) with outpatient compared with inpatient dinoprostone, birth trauma (eg, cephalohematoma) with outpatient compared with inpatient single-balloon catheter, shoulder dystocia with outpatient dinoprostone compared with placebo, maternal infection (eg, chorioamnionitis) with outpatient compared with inpatient single-balloon catheters or outpatient prostaglandins compared with placebo, and postpartum hemorrhage with outpatient catheter compared with inpatient dinoprostone. Evidence on misoprostol, hygroscopic dilators, and other outcomes (eg, perinatal mortality and time to vaginal birth) was insufficient.
CONCLUSION
In women with low-risk pregnancies, outpatient cervical ripening with dinoprostone or single-balloon catheters did not increase cesarean deliveries. Although there were no clear differences in harms when comparing outpatient with inpatient cervical ripening, the certainty of evidence is low or insufficient to draw definitive conclusions.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42020167406.
Topics: Ambulatory Care; Catheters; Cervical Ripening; Cesarean Section; Dilatation; Dinoprostone; Female; Hospitalization; Humans; Labor, Induced; Obstetric Labor Complications; Oxytocics; Pregnancy
PubMed: 33752219
DOI: 10.1097/AOG.0000000000004382 -
The Cochrane Database of Systematic... Aug 2014Benign smooth muscle tumours of the uterus, known as fibroids or myomas, are often symptomless. However, about one-third of women with fibroids will present with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Benign smooth muscle tumours of the uterus, known as fibroids or myomas, are often symptomless. However, about one-third of women with fibroids will present with symptoms that are severe enough to warrant treatment. The standard treatment of symptomatic fibroids is hysterectomy (that is surgical removal of the uterus) for women who have completed childbearing, and myomectomy for women who desire future childbearing or simply want to preserve their uterus. Myomectomy, the surgical removal of myomas, can be associated with life-threatening bleeding. Excessive bleeding can necessitate emergency blood transfusion. Knowledge of the effectiveness of the interventions to reduce bleeding during myomectomy is essential to enable evidence-based clinical decisions. This is an update of the review published in The Cochrane Library (2011, Issue 11).
OBJECTIVES
To assess the effectiveness, safety, tolerability and costs of interventions to reduce blood loss during myomectomy.
SEARCH METHODS
In June 2014, we conducted electronic searches in the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO, and trial registers for ongoing and registered trials.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) that compared potential interventions to reduce blood loss during myomectomy to placebo or no treatment.
DATA COLLECTION AND ANALYSIS
The two authors independently selected RCTs for inclusion, assessed the risk of bias and extracted data from the included RCTs. The primary review outcomes were blood loss and need for blood transfusion. We expressed study results as mean differences (MD) for continuous data and odds ratios for dichotomous data, with 95% confidence intervals (CI). We assessed the quality of evidence using GRADE methods.
MAIN RESULTS
Eighteen RCTs with 1250 participants met our inclusion criteria. The studies were conducted in hospital settings in low, middle and high income countries.Blood lossWe found significant reductions in blood loss with the following interventions: vaginal misoprostol (2 RCTs, 89 women: MD -97.88 ml, 95% CI -125.52 to -70.24; I(2) = 43%; moderate-quality evidence); intramyometrial vasopressin (3 RCTs, 128 women: MD -245.87 ml, 95% CI -434.58 to -57.16; I(2) = 98%; moderate-quality evidence); intramyometrial bupivacaine plus epinephrine (1 RCT, 60 women: MD -68.60 ml, 95% CI -93.69 to -43.51; low-quality evidence); intravenous tranexamic acid (1 RCT, 100 women: MD -243 ml, 95% CI -460.02 to -25.98; low-quality evidence); gelatin-thrombin matrix (1 RCT, 50 women: MD -545.00 ml, 95% CI -593.26 to -496.74; low-quality evidence); intravenous ascorbic acid (1 RCT, 102 women: MD -411.46 ml, 95% CI -502.58 to -320.34; low-quality evidence); vaginal dinoprostone (1 RCT, 108 women: MD -131.60 ml, 95% CI -253.42 to -9.78; low-quality evidence); loop ligation of the myoma pseudocapsule (1 RCT, 70 women: MD -305.01 ml, 95% CI -354.83 to -255.19; low-quality evidence); and a fibrin sealant patch (1 RCT, 70 women: MD -26.50 ml, 95% CI -44.47 to -8.53; low-quality evidence). We found evidence of significant reductions in blood loss with a polyglactin suture (1 RCT, 28 women: MD -1870.0 ml, 95% CI -2547.16 to 1192.84) or a Foley catheter (1 RCT, 93 women: MD -240.70 ml, 95% CI -359.61 to -121.79) tied around the cervix. However, pooling data from these peri-cervical tourniquet RCTs revealed significant heterogeneity of the effects (2 RCTs, 121 women: MD (random) -1019.85 ml, 95% CI -2615.02 to 575.32; I(2) = 95%; low-quality evidence). There was no good evidence of an effect on blood loss with oxytocin, morcellation or clipping of the uterine artery.Need for blood transfusion We found significant reductions in the need for blood transfusion with vasopressin (2 RCTs, 90 women: OR 0.15, 95% CI 0.03 to 0.74; I(2) = 0%; moderate-quality evidence); peri-cervical tourniquet (2 RCTs, 121 women: OR 0.09, 95% CI 0.01 to 0.84; I(2) = 69%; low-quality evidence); gelatin-thrombin matrix (1 RCT, 100 women: OR 0.01, 95% CI 0.00 to 0.10; low-quality evidence) and dinoprostone (1 RCT, 108 women: OR 0.17, 95% CI 0.04 to 0.81; low-quality evidence), but no evidence of effect on the need for blood transfusion with misoprostol, oxytocin, tranexamic acid, ascorbic acid, loop ligation of the myoma pseudocapsule and a fibrin sealant patch.There were insufficient data on the adverse effects and costs of the different interventions.
AUTHORS' CONCLUSIONS
At present there is moderate-quality evidence that misoprostol may reduce bleeding during myomectomy, and low-quality evidence that bupivacaine plus epinephrine, tranexamic acid, gelatin-thrombin matrix, a peri-cervical tourniquet, ascorbic acid, dinoprostone, loop ligation and a fibrin sealant patch may reduce bleeding during myomectomy. There is no evidence that oxytocin, morcellation and temporary clipping of the uterine artery reduce blood loss. Further well designed studies are required to establish the effectiveness, safety and costs of different interventions for reducing blood loss during myomectomy.
Topics: Blood Loss, Surgical; Blood Transfusion; Female; Hemostasis, Surgical; Hemostatics; Humans; Leiomyoma; Randomized Controlled Trials as Topic; Tourniquets; Uterine Neoplasms
PubMed: 25125317
DOI: 10.1002/14651858.CD005355.pub5 -
The Cochrane Database of Systematic... Apr 2015Hysteroscopy is an operation in which the gynaecologist examines the uterine cavity using a small telescopic instrument (hysteroscope) inserted via the vagina and the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hysteroscopy is an operation in which the gynaecologist examines the uterine cavity using a small telescopic instrument (hysteroscope) inserted via the vagina and the cervix. Almost 50% of hysteroscopic complications are related to difficulty with cervical entry. Potential complications include cervical tears, creation of a false passage, perforation, bleeding, or simply difficulty in entering the internal os (between the cervix and the uterus) with the hysteroscope. These complications may possibly be reduced with adequate preparation of the cervix (cervical ripening) prior to hysteroscopy. Cervical ripening agents include oral or vaginal prostaglandin, which can be synthetic (e.g misoprostol) or natural (e.g. dinoprostone) and vaginal osmotic dilators, which can be naturally occurring (e.g. laminaria) or synthetic.
OBJECTIVES
To determine whether preoperative cervical preparation facilitates cervical dilatation and reduces the complications of operative hysteroscopy in women undergoing the procedure for any condition.
SEARCH METHODS
In August 2014 we searched sources including the Menstrual Disorders and Subfertility Group (MDSG) Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, ClinicalTrials.gov and reference lists of relevant articles. We searched for published and unpublished studies in any language.
SELECTION CRITERIA
Two review authors independently selected randomised controlled trials (RCTs) of cervical ripening agents used before operative hysteroscopy in pre- and postmenopausal women. Cervical ripening agents could be compared to each other, placebo or no treatment.
DATA COLLECTION AND ANALYSIS
Data extraction and quality assessment were conducted independently by two review authors. The primary review outcomes were effectiveness of cervical dilatation (defined as the proportion of women requiring mechanical cervical dilatation) and intraoperative complications. Secondary outcomes were mean time required to dilate the cervix, preoperative pain, cervical width, abandonment of the procedure, side effects of dilating agents and duration of surgery. We calculated odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, with 95% confidence intervals ( CIs). Data were statistically pooled where appropriate. Heterogeneity was assessed using the I(2) statistic. The overall quality of the evidence was assessed using GRADE methods.
MAIN RESULTS
Nineteen RCTs with a total of 1870 participants were included. They compared misoprostol with no treatment or placebo, dinoprostone or osmotic dilators.Misoprostol was more effective for cervical dilatation than placebo or no intervention, with fewer women requiring mechanical dilatation (OR 0.08, 95% CI 0.04 to 0.16, five RCTs, 441 participants, I(2)=0%, moderate quality evidence). This suggests that in a population in which 80% of women undergoing hysteroscopy require mechanical dilatation without use of preoperative ripening agents, use of misoprostol will reduce the need for mechanical dilatation to between 14% and 39%. Misoprostol was associated with fewer intraoperative complications (OR 0.37, 95% CI 0.18 to 0.77, 12 RCTs, 901 participants, I(2)=0%, moderate quality evidence). This suggests that in a population in which 3% of women undergoing hysteroscopy experience intraoperative complications without use of preoperative ripening agents, use of misoprostol will reduce the risk of complications to 2% or less.When specific complications were considered, the misoprostol group had a lower rate of cervical laceration or tearing (OR 0.25, 95% CI 0.11 to 0.57, nine RCTS, 669 women, I(2)=0%, moderate quality evidence) or false track formation (OR 0.34, 95% CI 0.12 to 0.97, seven RCTs, 560 participants, I(2)=0%, moderate quality evidence). There was no evidence of a difference between the groups in rates of uterine perforation (0.42, 95% CI 0.13 to 1.38, seven RCTs, 455 participants, I(2)=0%, low quality evidence) or uterine bleeding (OR 0.51, 95% CI 0.10 to 2.49, four RCTs, 340 participants, I(2)=0%, low quality evidence). Some treatment side effects (mild abdominal pain, vaginal bleeding, and increased body temperature) were more common in the misoprostol group.Compared with dinoprostone, misoprostol was associated with more effective cervical dilatation, with fewer women requiring mechanical dilatation (OR 0.58; 95% CI 0.34 to 0.98; one RCT, 310 participants, low quality evidence) and with fewer intraoperative complications (OR 0.32; 95% CI 0.12 to 0.83, one RCT, 310 participants, low quality evidence). However treatment side effects were more common in the misoprostol arm.Compared to osmotic dilatation (laminaria), misoprostol was associated with less effective cervical dilatation, with more women in the misoprostol group requiring mechanical dilatation (OR 5.96, 95% CI 2.61 to 13.59, one RCT, 110 participants, low quality evidence). There was no evidence of a difference between misoprostol and osmotic dilators in intraoperative complication rates (OR 5.14, 95% CI 0.24 to 109.01, three RCTs, 354 participants, low quality evidence), with only two events reported altogether.The overall quality of the evidence ranged from low to moderate. The main limitations in the evidence were imprecision and poor reporting of study methods.
AUTHORS' CONCLUSIONS
There is moderate quality evidence that use of misoprostol for preoperative ripening of the cervix before operative hysteroscopy is more effective than placebo or no treatment and is associated with fewer intraoperative complications such as lacerations and false tracks. However misoprostol is associated with more side effects, including preoperative pain and vaginal bleeding. There is low quality evidence to suggest that misoprostol has fewer intraoperative complications and is more effective than dinoprostone.There is also low quality evidence to suggest that laminaria may be more effective than misoprostol, with uncertain effects for complication rates. However the possible benefits of laminaria need to be weighed against the inconvenience of its insertion and retention for one to two days.
Topics: Cervical Ripening; Cervix Uteri; Dilatation; Dinoprostone; Female; Humans; Hysteroscopy; Laminaria; Misoprostol; Oxytocics; Pregnancy; Preoperative Care; Randomized Controlled Trials as Topic
PubMed: 25906113
DOI: 10.1002/14651858.CD005998.pub2 -
BJOG : An International Journal of... Aug 2016To compare the clinical effectiveness and cost-effectiveness of labour induction methods. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To compare the clinical effectiveness and cost-effectiveness of labour induction methods.
METHODS
We conducted a systematic review of randomised trials comparing interventions for third-trimester labour induction (search date: March 2014). Network meta-analysis was possible for six of nine prespecified key outcomes: vaginal delivery within 24 hours (VD24), caesarean section, uterine hyperstimulation, neonatal intensive care unit (NICU) admissions, instrumental delivery and infant Apgar scores. We developed a decision-tree model from a UK NHS perspective and calculated incremental cost-effectiveness ratios, expected costs, utilities and net benefit, and cost-effectiveness acceptability curves.
MAIN RESULTS
In all, 611 studies comparing 31 active interventions were included. Intravenous oxytocin with amniotomy and vaginal misoprostol (≥50 μg) were most likely to achieve VD24. Titrated low-dose oral misoprostol achieved the lowest odds of caesarean section, but there was considerable uncertainty in ranking estimates. Vaginal (≥50 μg) and buccal/sublingual misoprostol were most likely to increase uterine hyperstimulation with high uncertainty in ranking estimates. Compared with placebo, extra-amniotic prostaglandin E2 reduced NICU admissions. There were insufficient data to conduct analyses for maternal and neonatal mortality and serious morbidity or maternal satisfaction. Conclusions were robust after exclusion of studies at high risk of bias. Due to poor reporting of VD24, the cost-effectiveness analysis compared a subset of 20 interventions. There was considerable uncertainty in estimates, but buccal/sublingual and titrated (low-dose) misoprostol showed the highest probability of being most cost-effective.
CONCLUSIONS
Future trials should be designed and powered to detect a method that is more cost-effective than low-dose titrated oral misoprostol.
TWEETABLE ABSTRACT
New study ranks methods to induce labour in pregnant women on effectiveness and cost.
Topics: Administration, Intravaginal; Administration, Intravenous; Administration, Sublingual; Amniotomy; Apgar Score; Cesarean Section; Cost-Benefit Analysis; Delivery, Obstetric; Dinoprostone; Extraction, Obstetrical; Female; Humans; Intensive Care Units, Neonatal; Labor, Induced; Misoprostol; Network Meta-Analysis; Oxytocics; Oxytocin; Pregnancy
PubMed: 27001034
DOI: 10.1111/1471-0528.13981 -
PloS One 2016Marine-derived n-3 polyunsaturated fatty acids (PUFA) may have a beneficial effect on inflammation via lowering pro-inflammatory eicosanoid concentrations. We aimed to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Marine-derived n-3 polyunsaturated fatty acids (PUFA) may have a beneficial effect on inflammation via lowering pro-inflammatory eicosanoid concentrations. We aimed to assess the effect of marine-derived n-3 PUFA on prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and leukotriene B4 (LTB4) through systematic review and meta-analysis of randomized controlled trials.
METHOD AND FINDINGS
A structured search strategy on PubMed, Web of Science and Cochrane up to November 2015 was undertaken in this meta-analysis. Standard mean difference was used to calculate the effect size of marine-derived n-3 PUFA on PGE2, TXB2 and LTB4 in a random-effect model. A total of 18 RCTs with 826 subjects were included in this systematic review and meta-analysis. Supplementation of marine-derived n-3 PUFA significantly decreased concentrations of TXB2 in serum/plasma in subjects with high risk of cardiovascular diseases (SMD:-1.26; 95% CI: -1.65, -0.86) and LTB4 in neutrophils in unhealthy subjects (subjects with non-autoimmune chronic diseases or auto-immune diseases) (SMD:-0.59: 95% CI: -1.02, -0.16). Subgroup analyses showed a significant reduction of LTB4 in subjects with rheumatoid arthritis (SMD: -0.83; 95% CI: -1.37, -0.29), but not in non-autoimmune chronic disease patients (SMD: -0.33; 95% CI: -0.97, 0.31). No significant publication bias was shown in the meta-analysis.
CONCLUSIONS
Marine-derived n-3 PUFA had a beneficial effect on reducing the concentration of TXB2 in blood of subjects with high risk of CVD as well as LTB4 in neutrophils in unhealthy subjects, and that subjects with RA showed lower LTB4 content with supplementation of marine-derived n-3 PUFA.
Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Chronic Disease; Dietary Supplements; Dinoprostone; Dose-Response Relationship, Drug; Eicosanoids; Fatty Acids, Omega-3; Fish Oils; Humans; Leukotriene B4; Randomized Controlled Trials as Topic; Research Design; Thromboxane B2; Treatment Outcome
PubMed: 26808318
DOI: 10.1371/journal.pone.0147351 -
The Cochrane Database of Systematic... Sep 2017Induction of labour is carried out for a variety of indications and using a range of methods. For women at low risk of pregnancy complications, some methods of induction... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Induction of labour is carried out for a variety of indications and using a range of methods. For women at low risk of pregnancy complications, some methods of induction of labour or cervical ripening may be suitable for use in outpatient settings.
OBJECTIVES
To examine pharmacological and mechanical interventions to induce labour or ripen the cervix in outpatient settings in terms of effectiveness, maternal satisfaction, healthcare costs and, where information is available, safety.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2016) and reference lists of retrieved studies.
SELECTION CRITERIA
We included randomised controlled trials examining outpatient cervical ripening or induction of labour with pharmacological agents or mechanical methods. Cluster trials were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed evidence using the GRADE approach.
MAIN RESULTS
This updated review included 34 studies of 11 different methods for labour induction with 5003 randomised women, where women received treatment at home or were sent home after initial treatment and monitoring in hospital.Studies examined vaginal and intracervical prostaglandin E₂ (PGE₂), vaginal and oral misoprostol, isosorbide mononitrate, mifepristone, oestrogens, amniotomy and acupuncture, compared with placebo, no treatment, or routine care. Trials generally recruited healthy women with a term pregnancy. The risk of bias was mostly low or unclear, however, in 16 trials blinding was unclear or not attempted. In general, limited data were available on the review's main and additional outcomes. Evidence was graded low to moderate quality. 1. Vaginal PGE₂ versus expectant management or placebo (5 studies)Fewer women in the vaginal PGE₂ group needed additional induction agents to induce labour, however, confidence intervals were wide (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.27 to 0.99; 150 women; 2 trials). There were no clear differences between groups in uterine hyperstimulation (with or without fetal heart rate (FHR) changes) (RR 3.76, 95% CI 0.64 to 22.24; 244 women; 4 studies; low-quality evidence), caesarean section (RR 0.80, 95% CI 0.49 to 1.31; 288 women; 4 studies; low-quality evidence), or admission to a neonatal intensive care unit (NICU) (RR 0.32, 95% CI 0.10 to 1.03; 230 infants; 3 studies; low-quality evidence).There was no information on vaginal birth within 24, 48 or 72 hours, length of hospital stay, use of emergency services or maternal or caregiver satisfaction. Serious maternal and neonatal morbidity or deaths were not reported. 2. Intracervical PGE₂ versus expectant management or placebo (7 studies) There was no clear difference between women receiving intracervical PGE₂ and no treatment or placebo in terms of need for additional induction agents (RR 0.98, 95% CI 0.74 to 1.32; 445 women; 3 studies), vaginal birth not achieved within 48 to 72 hours (RR 0.83, 95% CI 0.68 to 1.02; 43 women; 1 study; low-quality evidence), uterine hyperstimulation (with FHR changes) (RR 2.66, 95% CI 0.63 to 11.25; 488 women; 4 studies; low-quality evidence), caesarean section (RR 0.90, 95% CI 0.72 to 1.12; 674 women; 7 studies; moderate-quality evidence), or babies admitted to NICU (RR 1.61, 95% CI 0.43 to 6.05; 215 infants; 3 studies; low-quality evidence). There were no uterine ruptures in either the PGE₂ group or placebo group.There was no information on vaginal birth not achieved within 24 hours, length of hospital stay, use of emergency services, mother or caregiver satisfaction, or serious morbidity or neonatal morbidity or perinatal death. 3. Vaginal misoprostol versus placebo (4 studies)One small study reported on the rate of perinatal death with no clear differences between groups; there were no deaths in the treatment group compared with one stillbirth (reason not reported) in the control group (RR 0.34, 95% CI 0.01 to 8.14; 77 infants; 1 study; low-quality evidence).There was no clear difference between groups in rates of uterine hyperstimulation with FHR changes (RR 1.97, 95% CI 0.43 to 9.00; 265 women; 3 studies; low-quality evidence), caesarean section (RR 0.94, 95% CI 0.61 to 1.46; 325 women; 4 studies; low-quality evidence), and babies admitted to NICU (RR 0.89, 95% CI 0.54 to 1.47; 325 infants; 4 studies; low-quality evidence).There was no information on vaginal birth not achieved within 24, 48 or 72 hours, additional induction agents required, length of hospital stay, use of emergency services, mother or caregiver satisfaction, serious maternal, and other neonatal, morbidity or death.No substantive differences were found for other comparisons. One small study found that women who received oral misoprostol were more likely to give birth within 24 hours (RR 0.65, 95% CI 0.48 to 0.86; 87 women; 1 study) and were less likely to require additional induction agents (RR 0.60, 95% CI 0.37 to 0.97; 127 women; 2 studies). Women who received mifepristone were also less likely to require additional induction agents (average RR 0.59, 95% CI 0.37 to 0.95; 311 women; 4 studies; I² = 74%); however, this result should be interpreted with caution due to high heterogeneity. One trial each of acupuncture and outpatient amniotomy were included, but few review outcomes were reported.
AUTHORS' CONCLUSIONS
Induction of labour in outpatient settings appears feasible and important adverse events seem rare, however, in general there is insufficient evidence to detect differences. There was no strong evidence that agents used to induce labour in outpatient settings had an impact (positive or negative) on maternal or neonatal health. There was some evidence that compared to placebo or no treatment, induction agents administered on an outpatient basis reduced the need for further interventions to induce labour, and shortened the interval from intervention to birth.We do not have sufficient evidence to know which induction methods are preferred by women, the interventions that are most effective and safe to use in outpatient settings, or their cost effectiveness. Further studies where various women-friendly outpatient protocols are compared head-to-head are required. As part of such work, women should be consulted on what sort of management they would prefer.
Topics: Acupuncture Therapy; Ambulatory Care; Cesarean Section; Dinoprostone; Feasibility Studies; Female; Humans; Intensive Care, Neonatal; Labor, Induced; Misoprostol; Oxytocics; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 28901007
DOI: 10.1002/14651858.CD007701.pub3 -
Medicine Nov 2018Successful labor induction depends on the cervical status at the time of induction. Currently, both a Foley catheter and a dinoprostone insert are used for effective... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Successful labor induction depends on the cervical status at the time of induction. Currently, both a Foley catheter and a dinoprostone insert are used for effective cervical ripening. This study compared the efficacy and safety of the intracervical Foley catheter and dinoprostone insert for cervical ripening to achieve successful labor induction.
METHODS
PubMed, Embase, and the Cochrane Library were searched from January 2000 to February 2017 for relevant articles. Only published randomized, controlled trials comparing the dinoprostone insert with the Foley catheter were included.
RESULTS
Eight trials including 1191 women who received the intracervical Foley catheter balloon and 1199 who received the dinoprostone insert were used for this study. There was no significant difference between the 2 groups regarding the induction-to-delivery (I-D) interval in a random effect model (mean difference, 0.71 hours; 95% confidence interval [CI], -2.50 to 3.91; P = .67). The highly significant heterogeneity (I = 97%) could be explained by the subgroup analysis of the type of Foley catheter and balloon volume. There was no significant difference between the 2 methods regarding the cesarean delivery rate (relative risk, 0.91; 95% CI, 0.78-1.07; P = .24), Apgar score, or side effects, including maternal infection rate, postpartum hemorrhage, and hyperstimulation. No obvious publication bias was found.
CONCLUSIONS
According to the cesarean delivery rate, the intracervical Foley catheter balloon was as efficient as the dinoprostone insert. A moderate balloon volume (30 mL) and higher dose of dinoprostone (≥6 mg) were related to shorter I-D intervals. Additionally, there was no significant difference between the two methods regarding maternal or neonatal safety.
Topics: Catheters; Cervical Ripening; Dinoprostone; Drug Delivery Systems; Female; Humans; Labor, Induced; Oxytocics; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 30508911
DOI: 10.1097/MD.0000000000013251 -
The Cochrane Database of Systematic... Dec 2016Sometimes it is necessary to bring on labour artificially because of safety concerns for the mother or baby. This review is one of a series of reviews of methods of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sometimes it is necessary to bring on labour artificially because of safety concerns for the mother or baby. This review is one of a series of reviews of methods of labour induction using a standardised protocol.
OBJECTIVES
To determine the effects of NO donors (isosorbide mononitrate (ISMN), isosorbide dinitrate (ISDN), nitroglycerin and sodium nitroprusside) for third trimester cervical ripening or induction of labour, in comparison with placebo or no treatment or other treatments from a predefined hierarchy.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register (15 August 2016) and the reference lists of trial reports.
SELECTION CRITERIA
Clinical trials comparing NO donors for cervical ripening or labour induction with other methods listed above it on a predefined list of methods of labour induction. Interventions include NO donors (isosorbide mononitrate, isosorbide dinitrate, nitroglycerin and sodium nitroprusside) compared with other methods listed above it on a predefined list of methods of labour induction.
DATA COLLECTION AND ANALYSIS
This review is part of a series of reviews focusing on methods of induction of labour, based on a generic protocol. Three review authors independently assessed trials for inclusion, assessed risk of bias and extracted data. In this update, the quality of the evidence for the main comparison was assessed using the GRADE approach.
MAIN RESULTS
We included 23 trials (including a total of 4777 women). Included studies compared NO donors with placebo, vaginal prostaglandin E2 (PGE2), intracervical PGE2, vaginal misoprostol and intracervical Foley catheter. The majority of the included studies were assessed as being at low risk of bias. Nitric oxide versus placebo There was no evidence of a difference for any of the primary outcomes analysed: vaginal delivery not achieved in 24 hours (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.83 to 1.15; one trial, 238 women; low-quality evidence), uterine hyperstimulation with fetal heart rate (FHR) changes (RR 0.09, 95% CI 0.01 to 1.62; two trials, 300 women; low-quality evidence), caesarean section (RR 0.99, 95% CI 0.88 to 1.11; nine trials, 2624 women; moderate-quality evidence) or serious neonatal morbidity/perinatal death (average RR 1.61, 95% CI 0.08 to 33.26; two trials, 1712 women; low-quality evidence). There were no instances of serious maternal morbidity or death (one study reported this outcome).There was a reduction in an unfavourable cervix at 12 to 24 hours in women treated with NO donors (average RR 0.78, 95% CI 0.67 to 0.90; four trials, 762 women), and this difference was observed in both subgroups of standard release and slow release formulation. Women who received NO donors were less likely to experience uterine hyperstimulation without FHR rate changes (RR 0.05, 95% CI 0.00 to 0.80; one trial, 200 women), and more likely to experience side effects, including nausea, headache and vomiting. Nitric oxide donors versus vaginal prostaglandins There was no evidence of any difference between groups for uterine hyperstimulation with FHR changes or caesarean section (RR 0.97, 95% CI 0.78 to 1.21; three trials, 571 women). Serious neonatal morbidity and serious maternal morbidity were not reported. There were fewer women in the NO donor group who did not achieve a vaginal delivery within 24 hours (RR 0.63, 95% CI 0.47 to 0.86; one trial, 400 primiparae women). Nitric oxide donors versus intracervical prostaglandins One study reported a reduction in the number of women who had not achieved a vaginal delivery within 24 hours with NO donors (RR 0.63, 95% CI 0.47 to 0.86; one trial, 400 women). This result should be interpreted with caution as the information was extracted from an abstract only and a full report of the study is awaited. No differences were observed between groups for uterine hyperstimulation with FHR changes (RR 0.33, 95% CI 0.01 to 7.74; one trial, 42 women) or serious neonatal morbidity/perinatal death (RR 0.33, 95% CI 0.01 to 7.74; one trial, 42 women). Fewer women in the NO donor group underwent a caesarean section in comparison to women who received intracervical prostaglandins (RR 0.63, 95% CI 0.44 to 0.90; two trials, 442 women). No study reported on the outcome serious maternal morbidity or death. Nitric oxide donors versus vaginal misoprostol There was a reduction in the rate of uterine hyperstimulation with FHR changes with NO donors (RR 0.07, 95% CI 0.01 to 0.37; three trials, 281 women). There were no differences in caesarean section rates (RR 1.00, 95% CI 0.82 to 1.21; 761 women; six trials) and no cases of serious neonatal morbidity/perinatal death were reported. One study found that women in the NO donor group were more likely to not deliver within 24 hours (RR 5.33, 95% CI 1.62 to 17.55; one trial, 150 women). Serious maternal morbidity or death was not reported.In terms of secondary outcomes, there was an increase in cervix unchanged/unfavourable with NO (RR 3.43, 95% CI 2.07 to 5.66; two trials, 151 women) and an increase in the need for oxytocin augmentation with NO induction (RR 2.67, 95% CI 1.31 to 5.45; 7 trials; 767 women), although there was evidence of significant heterogeneity which could not be fully explained. Uterine hyperstimulation without FHR was lower in the NO group, as was meconium-stained liquor, Apgar score less than seven at five minutes and analgesia requirements. Nitric oxide donors versus intracervical catheter There was no evidence on any difference between the effects of NO and the use of a Foley catheter for induction of labour for caesarean section (RR 1.00, 95% CI 0.39 to 2.59; one trial, 80 women). No other primary outcomes were reported. One study of 75 participants did not contribute any data to the review.For all comparisons, women who received NO donors were more likely to experience side effects such as headache, nausea or vomiting.
AUTHORS' CONCLUSIONS
Available data suggests that NO donors can be a useful tool in the process of induction of labour causing the cervix to be more favourable in comparison to placebo. However, additional data are needed to assess the true impact of NO donors on all important labour process and delivery outcomes.
Topics: Administration, Intravaginal; Cervical Ripening; Dinoprostone; Female; Humans; Labor, Induced; Misoprostol; Nitric Oxide Donors; Oxytocics; Pregnancy; Randomized Controlled Trials as Topic; Urinary Catheterization
PubMed: 27918616
DOI: 10.1002/14651858.CD006901.pub3