Globally, postpartum hemorrhage (PPH) is the top cause of maternal death. Multiple uterotonic medications are available to prevent PPH; however, it is still unclear whether one is the most effective. The current study compared the efficacy and safety of intravenous carbetocin with rectal misoprostol for the active management of the third stage of labor in order to prevent PPH. Eligible studies were found utilizing digital medical sources, including the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science (WOS), PubMed, Scopus, and Google Scholar, from inception until September 2022. Only randomized controlled trials (RCTs) that matched the inclusion requirements were chosen. We used the Cochrane Risk of Bias scale (version 2) to assess the quality of the included studies. The Review Manager (version 5.4 for Windows) was used to conduct the meta-analysis. The results were summarized as mean difference (MD) or risk ratio (RR) with a 95% confidence interval (CI) in fixed- or random-effects models according to the degree of between-study heterogeneity. Collectively, we screened 621 articles after omitting duplicates and eventually included three RCTs for analysis. Overall, 404 patients were included in these studies; 202 patients were allocated to the intravenous carbetocin group whereas 202 patients were allocated to the rectal misoprostol group. Two RCTs were judged as “low” risk of bias, whereas one RCT was judged as having “some concerns” regarding the quality assessment. Regarding efficacy endpoints, the intravenous carbetocin group had significantly lower blood loss (n=3 RCTs, MD=-117.74 mL, 95% CI [-185.41, -50.07], p<0.001), need for additional uterotonics (n=2 RCTs, RR=0.06, 95% CI [0.01, 0.46], p=0.007), need for uterine massage (n=2 RCTs, RR=0.40, 95% CI [0.20, 0.80], p=0.009), and need for blood transfusion (n=2 RCTs, RR=0.38, 95% CI [0.15, 0.95], p=0.04) compared with the rectal misoprostol group. Regarding safety endpoints, the rates of diarrhea (n=3 RCTs, RR=0.18, 95% CI [0.06, 0.55], p=0.003) and chills (n=2 RCTs, RR=0.31, 95% CI [0.12, 0.83], p=0.02) were significantly lower in the intravenous carbetocin group compared with the rectal misoprostol group. However, there was no significant difference between both groups regarding the rates of headache (n=3 RCTs, RR=1.23, 95% CI [0.06, 1.91], p=0.35) and facial flushing (n=2 RCTs, RR=0.88, 95% CI [0.46, 1.68], p=0.70). In conclusion, it was discovered that intravenous carbetocin was a superior substitute for rectal misoprostol for the active management of the third stage of labor. With far fewer side effects, intravenous carbetocin decreased postpartum blood loss and further uterotonic use. For women who have a high risk of PPH, intravenous carbetocin is advised.

Leiomyomas are inherently well-vascularized neoplasms; thus, they are very vulnerable to bleedingassociated complications during myomectomy. Ascorbic acid has well-established functions in tissue healing and the prevention of bleeding tendencies. Several randomized controlled trials (RCTs) have explored the antihemorrhagic utility of ascorbic acid administration during myomectomy. This research aimed to systematically and meta-analytically summarize the clinical antihemorrhagic efficacy of ascorbic acid (i.e., the intervention arm) versus placebo/no treatment (i.e., the control arm) during myomectomy. We electronically searched six sources, i.e., PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar. Our search was from inception until October 2022. We used the Cochrane Risk of Bias Scale (version 2) to assess the quality of the included studies. We summarized the effect sizes as the mean difference (MD) or risk ratio (RR) with a 95% confidence interval (CI) in a fixedeffects or random-effects model. Overall, three RCTs met the inclusion criteria, comprising a total of 193 patients: 99 patients were allocated to the ascorbic acid arm, whereas 94 patients were allocated to the control arm. The overall study quality was "low" and "some concerns" risk of bias in two and one RCT(s), respectively. There was no significant difference between the ascorbic acid and control arms regarding the mean intraoperative blood loss (n=2 RCTs, MD = −190.29 ml, 95% CI [−626.62, 246.05], p=0.39) and mean change in hemoglobin level (n=3 RCTs, MD = −0.26 mg/dl, 95% CI [−0.56, 0.04], p=0.09), respectively. Conversely, the ascorbic acid arm had statistically significant reductions in the mean operative time (n=3 RCTs, MD = −24.10 min, 95% CI [−30.67, −17.53], p<0.001) and the rate of blood transfusion (n=3 RCTs, RR=0.36, 95% CI [0.15, 0.87], p=0.02) compared with the control arm. No serious adverse events related to ascorbic acid were identified. In conclusion, ascorbic acid administration was associated with several beneficial effects, including reductions in mean operative time and rate of blood transfusion, but without affecting the mean intraoperative blood loss and mean change in hemoglobin level. In view of the limitations of the present meta-analysis, the use of ascorbic acid as an antihemorrhagic additive among patients undergoing myomectomy is not strongly recommended.