Ascorbic Acid for Prevention of Intraoperative Blood Loss and Related Complications During Myomectomy: A Systematic Review and Meta- Analysis of Randomized Controlled Trials

Leiomyomas are inherently well-vascularized neoplasms; thus, they are very vulnerable to bleeding -associated 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 fixed -effects 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.