Abstract

OBJECTIVE To synthesize available evidence on intravenous (IV) oxytocin dosing regimens for the prevention of postpartum hemorrhage (PPH) at cesarean section (CS). DATA SOURCES We searched Medline/OVID, Embase, Global Index Medicus, CINAHL, CENTRAL, ClinicalTrials.gov, and ICTRP for eligible studies published until Feb 2020. STUDY ELIGIBILITY CRITERIA We included any randomized or non-randomized study published in peer-reviewed journals that compared at least two different dosing regimens of IV oxytocin for PPH prevention in women undergoing CS. STUDY APPRAISAL AND SYNTHESIS METHODS Two authors independently assessed eligibility, extracted data, and assessed risk of bias. Primary outcome was incidence of PPH ≥ 1000 mL. Other review outcomes included use of additional uterotonics, blood loss, and adverse maternal events. Data were analyzed based on type of IV administration (bolus only, infusion only, bolus plus infusion) and oxytocin dose. Meta-analysis was performed using randomized trials and reported using risk ratios or mean difference with 95% confidence intervals. GRADE was used to rate the certainty of evidence. Findings from dose-finding trials and non-randomized studies were reported narratively. RESULTS Thirty-five studies (7,333 women) met our inclusion criteria, including 30 randomized trials and five non-randomized studies. There were limited data from trials for most outcomes, and results were not conclusive. Compared to bolus plus infusion regimens, bolus only regimens probably result in slightly higher mean blood loss (MD 52 mL, 95% CI 0.4-104 mL, moderate certainty). Amongst bolus plus infusion regimens, initial bolus doses < 5 IU may reduce nausea (RR 0.26, 95% CI 0.11-0.63, low certainty) as compared to 5-9 IU. Total oxytocin doses 5-9 IU versus 10-19 IU may increase use of additional uterotonics (RR 13.00, 95% CI 1.75-96.37, low certainty). Effects on other outcomes were generally inconclusive. CONCLUSION There are limited data comparing IV oxytocin regimens for PPH prevention at CS. Bolus plus infusion regimens may lead to minor reductions in mean blood loss, and initial bolus doses of < 5 IU may minimize nausea. Bolus only regimens of 10 IU versus 5 IU may decrease use of additional uterotonics, however further comparative trials are required to understand effects on other key outcomes, particularly hypotension.

Abstract

BACKGROUND Bleeding is the leading cause of maternal mortality in the world. Tranexamic acid reduces bleeding in trauma and surgery. Several systematic reviews of randomized trials have investigated tranexamic acid in the prevention of bleeding in caesarean delivery. However, the conclusions from systematic reviews are conflicting. This overview aims to summarize the evidence and explore the reasons for conflicting conclusions across the systematic reviews. METHODS A comprehensive literature search of Medline, Embase, and Cochrane Database of Systematic Reviews was conducted from inception to April 2021. Screening, data extraction, and quality assessments were performed by two independent reviewers. A Measurement Tool to Assess Reviews 2 and the Risk of Bias Assessment Tool for Systematic Reviews were used for study appraisal. A qualitative synthesis of evidence is presented. RESULTS Fourteen systematic reviews were included in our analysis. Across these reviews, there were 32 relevant randomized trials. A modest reduction in blood transfusions and bleeding outcomes was found by most systematic reviews. Overall confidence in results varied from low to critically low. All of the included systematic reviews were at high risk of bias. Quality of evidence from randomized trials was uncertain. CONCLUSIONS Systematic reviews investigating prophylactic tranexamic acid in caesarean delivery are heterogeneous in terms of methodological and reporting quality. Tranexamic acid may reduce blood transfusion and bleeding outcomes, but rigorous well-designed research is needed due to the limitations of the included studies. Data on safety and adverse effects is insufficient to draw conclusions.

Abstract

INTRODUCTION Despite the fact that endometrial ablation/resection is a very successful treatment for women with heavy menstrual bleeding, re-intervention with additional surgery is needed in 12-25% of the cases. Introducing a levonorgestrel-intrauterine system (LNG-IUS) immediately after ablation could preserve the integrity of the uterine cavity and suppress the regenerated or non-ablated endometrial tissue. Therefore, this combined treatment can perhaps lower the re-intervention rate. The aim of this systematic review was to assess the impact of the combined treatment. MATERIAL AND METHODS The MEDLINE, EMBASE and Cochrane library were systematically searched. No language restrictions were applied. All types of studies were included reporting on the results of endometrial ablation or resection combined with immediate insertion of LNG-IUS for treatment of heavy menstrual bleeding. The primary outcome was the number of hysterectomies after the ablation procedure. Secondary outcomes included re-intervention rates, removals of LNG-IUS, bleeding pattern, patient satisfaction, side-effects and complications. Our protocol was registered in PROSPERO, an international prospective register of systematic reviews under registration number CRD42020151384. RESULTS Six studies with a retrospective design and one case series with a follow up duration varying from 6 to 55 months were included. In total, 427 women were treated with the combined treatment. The studies described a lower hysterectomy and re-intervention rate after combined treatment compared to treatment with endometrial ablation/resection alone. Hysterectomy rate varied from 0-11% after combined treatment versus 9.4-24% after endometrial ablation/resection alone. Bleeding patterns and patient satisfaction appeared to be in favour of the combined treatment group. No intra or post operation complications or complications in the removal of LNG-IUS were described. Most described side effects after combined treatment were weight gain, mood changes and head-aches. An additional eleven studies with only an abstract available substantiated these findings. All the included studies had poor methodologic quality. CONCLUSIONS Based on the available literature inserting an LNG-IUS immediately after endometrial ablation/resection seems to lower the hysterectomy and re-intervention rates compared to ablation/resection alone. However, since only limited observational studies of low methodological quality are available, high quality research is necessary to confirm the findings of this systematic review.

Abstract

OBJECTIVE To assess the efficacy and safety of prophylactic tranexamic acid administration in comparison with standard uterotonic agents alone among women undergoing cesarean delivery. DATA SOURCES Medline, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov and Google Scholar were systematically searched from inception to June 30, 2021. STUDY ELIGIBILITY CRITERIA Randomized controlled trials comparing intravenous tranexamic acid administration to placebo in women undergoing cesarean delivery and receiving standard prophylactic uterotonic agents were held eligible. STUDY APPRAISAL AND SYNTHESIS METHODS The risk of bias of individual studies was appraised with the RoB-2 tool. Meta-analysis was conducted by fitting random-effects models using restricted maximum likelihood. Subgroup analysis was performed based on country, protocol availability, double-blinding, risk of bias, sample size and tranexamic acid dose. One-stage meta-analysis was performed as a sensitivity analysis. The credibility of outcomes was appraised with the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS Overall, 36 studies with 10,659 women were included. Tranexamic acid administration was associated with significantly lower total blood loss (Mean difference-MD: -189.44 ml, 95% confidence intervals-CI: -218.63; -160.25), lower hemoglobin drop (MD: 8.22%, 95% CI: 5.54; 10.90), decreased risk of blood loss >1000 ml (Odds ratio-OR: 0.37, 95% CI: 0.22; 0.60), transfusion requirement (OR: 0.41, 95% CI: 0.26; 0.65) and need of additional uterotonics (OR: 0.36, 95% CI: 0.25; 0.52). Subgroup analysis indicated a greater effect of tranexamic acid on total blood loss reduction in low-middle income countries. The outcomes remained stable by separately evaluating women at low bleeding risk. One-stage meta-analysis demonstrated similar outcomes with the primary analysis. The quality of evidence was judged to be moderate regarding total blood loss and hemoglobin percentage change and low for the other outcomes. CONCLUSIONS This meta-analysis suggests that prophylactic tranexamic acid administration is effective among women undergoing cesarean delivery in lowering postpartum blood loss and limiting hemoglobin drop. Further research is needed to test its efficacy in high-risk populations and to verify its safety profile.

Abstract

BACKGROUND There is no consensus on the best timing for prophylactic oxytocin administration during cesarean section (CS) to prevent post-partum hemorrhage (PPH). OBJECTIVES Assess the effects of administrating prophylactic oxytocin at different times during CS. METHODS We searched nine databases to identify relevant randomized controlled trials (RCT). We pooled results and calculated average risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI). We used GRADE to assess the overall evidence certainty. RESULTS We screened 13,389 references and included four trials. We found no statistically significant differences between oxytocin given before versus after fetal delivery on PPH (RR 0.60, 95%CI 0.15-2.47; 1 RCT, N = 300) or nausea/vomiting (RR 1.21, 95%CI 0.69-2.13; 1 RCT, N = 300). There was a significant reduction in the need for additional uterotonics when oxytocin was given immediately before uterine incision versus after fetal delivery (RR 0.37, 95%CI 0.18-0.73; I2 = 0%; 2 RCTs; N = 301). Oxytocin given before fetal delivery significantly reduced intra-operative blood loss (MD -146.77mL, 95%CI -168.10 to -125.43; I2 = 0%; 3 RCTs, N = 601) but did not change the incidence of blood transfusion (RR 0.50, 95%CI 0.13-1.95; I2 = 0%; 2 RCTs, N = 301) or hysterectomy (RR 3.00; 95%CI 0.12-72.77; I2 = 0%; 2 RCTs, N = 301). One trial (N = 100) compared prophylactic oxytocin before versus after placental separation and found no significant differences on PPH, additional uterotonics, or nausea/vomiting. CONCLUSIONS In women having pre-labor CS, there is limited evidence indicating no significant differences between prophylactic oxytocin given before versus after fetal delivery on PPH, nausea/vomiting, blood transfusion, or hysterectomy. Earlier oxytocin administration may reduce the volume of blood loss and need for additional uterotonics. There is very limited evidence suggesting no significant differences between prophylactic oxytocin given before versus after placental separation on PPH, need for additional uterotonic, or nausea/vomiting. The overall certainty of the evidence was mostly low or very low due to imprecision. Protocol: CRD42020186797.

Abstract

Newer minimally invasive techniques provide treatment options for symptomatic uterine fibroids while allowing uterus preservation. The objective of this review was to analyze the efficacy of uterine-preserving, minimally invasive treatment modalities in reducing fibroid-related bleeding. A comprehensive search was conducted of PubMed, Embase, PsycINFO, ClinicalTrials.gov, Scopus, and Cochrane Library databases from inception to July 2020. English-language publications that evaluated premenopausal women with fibroid-related bleeding symptoms before and after treatment were considered. Randomized controlled trials were assessed for bias with the established Cochrane Risk of Bias Tool 2.0 and observational studies were assessed for quality under the New Castle-Ottawa Scale guidelines. Eighty-four studies were included in the review, including 10 randomized controlled trials and 74 observational studies. Six studies on myomectomy demonstrated overall bleeding symptom improvement in up to 95.9% of patients, though there was no significant difference between mode of myomectomy. Forty-one studies on uterine artery embolization reported significant reduction of fibroid-related bleeding, with symptomatic improvement in 79 to 98.5% of patients. Three studies suggested that embolization may be superior to myomectomy in reducing fibroid-related bleeding. Six studies reported that laparoscopic uterine artery occlusion combined with myomectomy led to greater reduction of bleeding than myomectomy alone. Fifteen studies demonstrated significantly reduced bleeding severity after radiofrequency ablation (RFA). Additional research is needed to establish the superiority of these modalities over one another. Long-term evidence is limited in current literature for magnetic resonance-guided focused ultrasound surgery, cryomyolysis, microwave ablation, and laser ablation.

Abstract

OBJECTIVE Minimizing intraoperative blood loss during hysterectomy is crucial to lessen associated perioperative morbidity. The aim of this investigation is to conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) that compared vasopressin versus normal saline in controlling intraoperative blood loss during hysterectomy. DATA SOURCES We screened five major databases (PubMed, Scopus, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials) from inception till July 18, 2021. We used the following query search in all databases: (vasopressin OR arginine vasopressin OR argipressin OR antidiuretic hormone) AND (hysterectomy) AND (saline OR placebo OR control OR no treatment) AND (randomized OR randomised OR randomly). There was no language restriction during database screening. METHODS OF STUDY SELECTION We considered all studies that met the following evidence-based criteria: (i) Patients: individuals undergoing hysterectomy for any indication, (ii) Intervention: vasopressin, (iii) Comparator: normal saline, placebo, or no treatment, (iv) Outcomes: reliable extraction of any of our endpoints, and (v) Study design: RCTs. We assessed risk of bias of included studies and pooled endpoints as mean difference (MD) or risk ratio (RR) with 95% confidence interval (CI). We performed statistical analysis using the Review Manager software, version 5.4.0. TABULATION, INTEGRATION, AND RESULTS Seven RCTs with an overall low risk of bias met the inclusion criteria. This meta-analysis included a total of 455 patients; 232 and 223 patients were allocated to vasopressin and control group, respectively. The majority of RCTs were vaginal hysterectomy (n=5) with few abdominal hysterectomy (n=2) and no laparoscopic hysterectomy. The mean estimated intraoperative blood loss was significantly lower in favor of the vasopressin group compared with the control group (n=6 RCTs, MD=-119.85 ml, 95% CI [-177.55, -62.14], p<0.001). However, there was no significant difference between both groups regarding mean operating time, mean change in postoperative hemoglobin, mean hospital stay, rate of febrile morbidity, rate of pelvic infection, rate of perioperative blood transfusion, and rate of perioperative complications. CONCLUSION Compared with normal saline, vasopressin significantly reduced the estimated blood loss during hysterectomy, but did not change any clinically significant outcomes. Additionally, vasopressin was safe and did not correlate with an increase in the rates of febrile morbidity or pelvic infection.

Abstract

BACKGROUND Hypotension is a common complication caused by spinal anesthesia (SA), which may have adverse impacts on the condition of the parturient and fetus. Liquid infusion was found to be relatively effective for reducing the incidence of hypotension. However, the question of whether colloid preload can optimize hemodynamic variables in the cesarean section remains controversial. This study aims to determine the effects of colloid preload on the incidence of hypotension induced by SA in elective cesarean section. METHODS Related keywords were searched on PubMed, EMBASE, and Cochrane Library from inception dates to May 2020. Studies included were evaluated for eligibility and quality. The primary outcome was the intra-operative incidence of hypotension and severe hypotension. The secondary outcomes included the lowest intra-operative systolic blood pressure, the maximal intra-operative heart rate, the intra-operative needs of ephedrine and phenylephrine, the incidence of maternal nausea and/or vomiting, and neonatal outcomes (umbilical artery pH and Apgar scores). Apart from the above, RevMan 5.3 was used for the data analysis. RESULTS Altogether nine randomized controlled trials were included in the meta-analysis. There were no significant differences in the incidence of intra-operative hypotension, severe hypotension, or neonatal outcomes between the colloid preload group and control group, except for the umbilical artery pH. CONCLUSION This meta-analysis suggests that colloid preload does not significantly reduce the incidence of hypotension associated with SA in elective cesarean section.

Abstract

BACKGROUND Heavy menstrual bleeding (HMB) is common in otherwise healthy women of reproductive age, and can affect physical health and quality of life. Surgery is usually a second-line treatment of HMB. Endometrial resection/ablation (EA/ER) to remove or ablate the endometrium is less invasive than hysterectomy. Hysterectomy is the definitive treatment and can be via open (laparotomy) approach, or via minimally invasive approaches (vaginally or laparoscopically). Each approach has its own advantages and risk profile. OBJECTIVES To compare the effectiveness, acceptability and safety of endometrial resection or ablation versus different routes of hysterectomy (open, minimally invasive hysterectomy, or unspecified route) for the treatment of HMB. SEARCH METHODS We searched the Cochrane Gynaecology and Fertility specialised register, CENTRAL, MEDLINE, Embase and PsycINFO (July 2020), and reference lists, grey literature and trial registers. SELECTION CRITERIA Randomised controlled trials (RCTs) that compared techniques of endometrial resection/ablation with hysterectomy (by any technique) for the treatment of HMB in premenopausal women. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. MAIN RESULTS We included 10 RCTs (1966 participants) comparing EA/ER to hysterectomy (open (abdominal), minimally invasive (laparoscopic or vaginal), or unspecified (or at surgeon's discretion) route of hysterectomy). The results were rated as moderate-, low- and very low-certainty evidence. Endometrial resection/ablation versus open hysterectomy We found two trials. Women having EA/ER are probably less likely to perceive an improvement in HMB compared to women having open hysterectomy (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.84 to 0.95; 2 studies, 247 women; moderate-certainty evidence) and probably have a 13% risk of requiring further surgery for treatment failure (compared to 0 on the open hysterectomy group; 2 studies, 247 women; moderate-certainty evidence). Both treatments probably lead to similar quality of life at two years (mean difference (MD) -5.30, 95% CI -11.90 to 1.30; 1 study, 155 women; moderate-certainty evidence) and satisfaction rate at one year (RR 0.91, 95% CI 0.82 to 1.00; 1 study, 194 women; moderate-certainty evidence). There may be no difference in serious adverse events (RR 1.29, 95% CI 0.32 to 5.20; 2 studies, 247 women; low-certainty evidence). EA/ER probably reduces time to return to normal activity compared to open hysterectomy (MD -21.00 days, 95% CI -24.78 to -17.22; 1 study, 197 women; moderate-certainty evidence). Endometrial resection/ablation versus minimally invasive hysterectomy We found five trials. The proportion of women with perception of improvement in HMB at two years may be similar between groups (RR 0.97, 95% CI 0.90 to 1.04; 1 study, 79 women; low-certainty evidence). Blood loss may be higher in the EA/ER group when assessed using the Pictorial Blood Assessment Chart (MD 44.00, 95% CI 36.09 to 51.91; 1 study, 68 women; low-certainty evidence). Quality of life is probably lower in the EA/ER group compared to the minimally invasive hysterectomy group at two years according to the 36-item Short Form (SF-36) (MD -10.71, 95% CI -15.11 to -6.30; 2 studies, 145 women; moderate-certainty evidence) and Menorrhagia Multi-Attribute Scale (RR 0.82, 95% CI 0.70 to 0.95; 1 study, 616 women; moderate-certainty evidence). EA/ER probably increases the risk of further surgery for HMB compared to minimally invasive hysterectomy (RR 7.70, 95% CI 2.54 to 23.32; 4 studies, 922 women; moderate-certainty evidence) and treatments probably have similar rates of any serious adverse events (RR 0.75, 95% CI 0.35 to 1.59; 4 studies, 809 women; moderate-certainty evidence). Women with EA/ER are probably less likely to be satisfied with treatment at one year (RR 0.90, 95% CI 0.85 to 0.94; 1 study, 558 women; moderate-certainty evidence). We were unable to pool data for time to return to work or normal life because of extreme heterogeneity (99%); however, the three studies reporting this all had the same direction of effect favouring EA/ER. Endometrial resection/ablation versus unspecified route of hysterectomy We found three trials. EA/ER may lead to a lower perception of improvement in HMB compared to unspecified route of hysterectomy (RR 0.89, 95% CI 0.83 to 0.95; 2 studies, 403 women; low-certainty evidence). Although EA/ER may lead to similar quality of life using the SF-36 General Health Perception at two years' follow-up (MD -1.90, 95% CI -8.67 to 4.87; 1 study, 209 women; low-certainty evidence), the proportion of women with improvement in general health at one year may be lower (RR 0.85, 95% CI 0.77 to 0.95; 1 study, 185 women; low-certainty evidence). EA/ER probably has a risk of 5.4% of requiring further surgery for treatment failure (compared to 0 with total hysterectomy; 2 studies, 374 women; moderate-certainty evidence) and reduces the proportion of women with any serious adverse event (RR 0.21, 95% CI 0.06 to 0.80; 2 studies, 374 women; moderate-certainty evidence). Both treatments probably lead to a similar satisfaction rate at one year' follow-up (RR 0.96, 95% CI 0.88 to 1.04; 3 studies, 545 women; moderate-certainty evidence). EA/ER may lead to shorter time to return to normal activity (MD -18.90 days, 95% CI -24.63 to -13.17; 1 study, 172 women; low-certainty evidence). AUTHORS' CONCLUSIONS Endometrial resection/ablation (EA/ER) offers an alternative to hysterectomy as a surgical treatment for HMB. Effectiveness varies with EA/ER compared to different hysterectomy approaches. The perception of improvement in HMB with EA/ER is probably lower compared to open and unspecified route of hysterectomy, but may be similar compared to minimally invasive. Quality of life with EA/ER is probably similar to open and unspecified route of hysterectomy, but lower compared to minimally invasive hysterectomy. Further surgery for treatment failure is probably more likely with EA/ER compared to all routes of hysterectomy. Satisfaction rates also vary. EA/ER probably has a similar rate of satisfaction compared to open and unspecified route of hysterectomy, but a lower rate of satisfaction compared to minimally invasive hysterectomy. The proportion having any serious adverse event appears similar in all groups, but specific adverse events did reported difference between EA/ER and different routes. We were unable to draw conclusions about the time to return to normal activity, but the direction of effect suggests it is likely to be shorter with EA/ER.

Abstract

Background and aim  Studies evaluating the role of prophylactic hemoclips (HC) in prevention of delayed post-polypectomy bleeding (DPPB) have reported conflicting results. We conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the role of prophylactic HC placement in prevention of DPPB for polyps ≥ 1 cm in size. Methods  We reviewed several databases to identify RCTs evaluating the role of HC in prevention of DPPB. The outcomes assessed included prevention of DPPB with polyps 1 to 1.9 cm, ≥ 2 cm, any polyp ≥ 1 cm, proximal colon polyps, distal colon polyps, and perforation. We analyzed data using a fixed effect model and reported summary pooled risk ratios (RR) with 95 % confidence intervals (CI). We assessed heterogeneity with the I (2) statistic. Results  We included nine RCTs with 4550 patients. For polyps ≥ 2 cm, there was a statistically significantly lower risk of DPPB with use of HC; RR 0.55, 95 % CI 0.36, 0.86. There was also a statistically significantly lower risk for proximal colon polyps ≥ 2 cm; RR 0.41 (0.24, 0.70) but no significant difference for distal polyps; RR 1.23 (0.45, 3.32). There was also no significant difference in risk for polyps 1 to 1.9 cm; RR 1.07 (0.59, 1.97). There was no significant reduction in risk of perforation with HC use for any polyp size. Conclusions  Prophylactic HC placement is effective in prevention of DPPB from proximal colon polyps ≥ 2 cm, but of no significant benefit for polyps 1 to 1.9 cm in size or for distal colon polyps ≥ 2 cm.