Abstract

BACKGROUND Prophylactic administration of tranexamic acid has been associated with reduced postpartum blood loss after cesarean delivery in several small trials, but evidence of its benefit in this clinical context remains inconclusive. METHODS In a multicenter, double-blind, randomized, controlled trial, we assigned women undergoing cesarean delivery before or during labor at 34 or more gestational weeks to receive an intravenously administered prophylactic uterotonic agent and either tranexamic acid (1 g) or placebo. The primary outcome was postpartum hemorrhage, defined as a calculated estimated blood loss greater than 1000 ml or receipt of a red-cell transfusion within 2 days after delivery. Secondary outcomes included gravimetrically estimated blood loss, provider-assessed clinically significant postpartum hemorrhage, use of additional uterotonic agents, and postpartum blood transfusion. RESULTS Of the 4551 women who underwent randomization, 4431 underwent cesarean delivery, 4153 (93.7%) of whom had primary outcome data available. The primary outcome occurred in 556 of 2086 women (26.7%) in the tranexamic acid group and in 653 of 2067 (31.6%) in the placebo group (adjusted risk ratio, 0.84; 95% confidence interval [CI], 0.75 to 0.94; P = 0.003). There were no significant between-group differences in mean gravimetrically estimated blood loss or in the percentage of women with provider-assessed clinically significant postpartum hemorrhage, use of additional uterotonic agents, or postpartum blood transfusion. Thromboembolic events in the 3 months after delivery occurred in 0.4% of women (8 of 2049) who received tranexamic acid and in 0.1% of women (2 of 2056) who received placebo (adjusted risk ratio, 4.01; 95% CI, 0.85 to 18.92; P = 0.08). CONCLUSIONS Among women who underwent cesarean delivery and received prophylactic uterotonic agents, tranexamic acid treatment resulted in a significantly lower incidence of calculated estimated blood loss greater than 1000 ml or red-cell transfusion by day 2 than placebo, but it did not result in a lower incidence of hemorrhage-related secondary clinical outcomes. (Funded by the French Ministry of Health; TRAAP2 ClinicalTrials.gov number, NCT03431805.).

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

OBJECTIVE To evaluate the efficacy of carbetocin versus placebo in decreasing intraoperative blood loss and the need for blood transfusion during abdominal myomectomy. DESIGN Randomized, double-blind, placebo-controlled trial. SETTING Tertiary university hospital from September 2019 to February 2020. PATIENT(S): A total of 138 women with symptomatic leiomyoma who were candidates for abdominal myomectomy (n = 69 in each group). INTERVENTION(S): We randomized the study participants in a 1:1 ratio to carbetocin and placebo groups. Intravenous 100 μg carbetocin or placebo was administered slowly after induction of anesthesia. MAIN OUTCOME MEASURE(S): Intraoperative blood loss, need for blood transfusion, postoperative hemoglobin, operative time, length of hospitalization, and drug side-effects. RESULT(S): The baseline characteristics were similar among all groups. Carbetocin had significantly lower intraoperative blood loss compared with placebo (mean difference 184 mL). Hemoglobin level 24 hours after surgery was significantly lower in the placebo group than in the carbetocin group (9.1 ± 0.8 vs. 10.3 ± 0.6 g/dL). Eight women in the carbetocin group needed blood transfusion compared with 17 in placebo group. Operative time, length of hospitalization, and side-effects were similar in both groups. CONCLUSION(S): A single preoperative intravenous dose of 100 μg carbetocin is a simple, practical, and effective method of decreasing intraoperative blood loss and the need for blood transfusion during abdominal myomectomy, with tolerable, few, nonsignificant side-effects. CLINICAL TRIAL REGISTRATION NUMBER NCT04083625.

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

RESEARCH QUESTION Is there a difference in the ovarian reserve 1 year post-operatively in those who used a haemostatic sealant or bipolar diathermy for haemostasis during laparoscopic ovarian cystectomy for ovarian endometriomas? DESIGN This was an extended follow-up observational study of a previous randomized controlled trial where women aged 18 to 40 years with 3-8 cm unilateral or bilateral endometriomas were randomized to receive haemostasis by a haemostatic sealant or bipolar diathermy following ovarian cystectomy. The primary outcome was the ovarian reserve as assessed by antral follicle count (AFC) 1 year post-operatively. Secondary outcomes included the recurrence rate of ovarian endometrioma, the change in anti-Müllerian hormone (AMH) and FSH concentrations, and reproductive outcomes. RESULTS The significant increase in AFC at 3 months after initial surgery (P = 0.025) in the haemostatic sealant group compared with the diathermy group was sustained at 1 year (P = 0.024) but there was no difference in AMH or FSH concentrations between the groups throughout the follow-up period. The recurrence rate in the FloSeal group was 7.7% (n = 3/39) compared with 22.2% (n = 8/36) in the diathermy group (P = 0.060). The recurrence rate in women who had bilateral lesions was significantly higher than those with unilateral lesions (risk ratio 5.33, interquartile range 1.55-18.38). No difference in reproductive outcomes was found between the two groups. CONCLUSIONS Applying haemostatic sealant after laparoscopic cystectomy of ovarian endometriomas produces a significantly greater improvement in AFC, which was apparent at 3-month follow-up, and was sustained at 1-year follow-up without compromising the recurrence rate.

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

OBJECTIVES To compare the operative time, effectiveness, and patient satisfaction between ball endometrial ablation and transcervical resection of the endometrium (TCRE) using a bipolar resectoscope. MATERIALS AND METHODS Forty-four women with heavy menstrual bleeding who were unresponsive to at least 3 months' medical management were included in this randomized, controlled clinical trial. After randomization, patients underwent either TCRE or ball endometrial ablation using a bipolar resectoscope. The operative time, fluid deficit, and postoperative pain were recorded. The patients were evaluated postoperatively at 3, 6, and 12 months after surgery. Patient satisfaction, amenorrhea rate, reintervention rate, and pictorial blood-loss-assessment chart (PBAC) score were compared between the two groups. RESULTS The mean operative time in ball endometrial ablation group was 11.17 ± 2.24 min and in TCRE group was 22.33 ± 5.26 min (P < 0.001). There was no significant difference in the postoperative PBAC score, amenorrhea rates, patient satisfaction, and need for reintervention between the two groups. CONCLUSION Operative time with ball endometrial ablation is significantly less when compared to TCRE when using a bipolar resectoscope.

Abstract

OBJECTIVE The aim of the present study was to evaluate the effect of autologous platelet-rich plasma (PRP) on wound healing and pain perception after cesarean section in high-risk patients. DESIGN This was a prospective randomized controlled trial. Participants/Materials, Settings, and Methods: This was a randomized controlled trial of 200 patients who came to the outpatient clinic of Menoufia University Hospital for elective cesarean surgery. The women were randomly assigned to 2 equal groups. The intervention group received PRP subcutaneous injection in the wound after surgery; however, the control group received the usual care. Outcome variables included the redness, edema, ecchymosis, discharge, approximation (REEDA) scale, Vancouver scar scale (VSS), and in addition to the visual analog scale (VAS). RESULTS From April 2018 to July 2020, the PRP group showed a greater reduction in the REEDA score compared to the control group on day 1, day 7, and this was continued till 6 months (1.51 ± 0.90 vs. 2.49 ± 1.12, p < 0.001). Compared with the control group, the PRP group had a significantly greater reduction in the VSS and VAS scores beginning on the seventh day (3.71 ± 0.99 vs. 4.67 ± 1.25, p < 0.001) and (5.06 ± 1.10 vs. 6.02 ± 1.15, p < 0.001), respectively, and continued till 6 months. LIMITATIONS Pain was not measured by the use of analgesics, and we did not investigate the effects of varying platelet concentrations, centrifuge duration, or speed. CONCLUSIONS PRP has positive effects on wound healing and pain reduction in high-risk patients undergoing cesarean section in low-resource settings.

Abstract

The preservation of ovarian reserve during laparoendoscopic single-site (LESS) ovarian cystectomy is crucial for reproductive-age women. This study was a single-blinded, single-center, and randomized controlled trial to evaluate the effect of hemostatic agents on the preservation of ovarian reserve and hemostasis during LESS ovarian cystectomy. Patients with unilateral ovarian cyst were randomized to the hemostatic agent and coagulation groups according to the hemostasis method. Afterwards, the patients underwent LESS ovarian cystectomy, and hemostasis was performed after ovarian cyst excision according to the assigned hemostasis method. If hemostasis was not completed within 10 min. After discharge, the patients were followed until 3 months after surgery. We compared the hemoglobin, anti-Müllerian hormone (AMH) levels, and ovarian volumes before surgery, and 2 days, 1 week, and 3 months after surgery (3 M-POST), and the decline ratio between the two groups. The decline ratio of serum AMH levels was greater at 3 M-POST in the coagulation than in the hemostatic agent group (median intention-to-treat [ITT], - 36.7 vs. - 13.3%; per-protocol [PP], - 36.8 vs. - 13.3%; P < 0.05). Notably, the difference of the decline ratio of serum AMH levels was only shown in endometriosis patients (median; ITT, - 50.7 vs. - 14.4%; PP, - 50.7% vs. - 14.4%; P < 0.05), while there was no difference in non-endometriosis patients. In conclusion, Hemostatic agents may be non-inferior to bipolar coagulation for preserving ovarian reserve and hemostasis during LESS ovarian cystectomy, in particular, for endometriosis patients. (Trial registry: ClinicalTrials.gov Identifier NCT03374397).