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Abstract Objectives: The aim of the study is to compare the efficacy and safety of preoperative intravenous carbetocin versus rectal misoprostol in reducing blood loss during open myomectomy. Design: A prospective randomized controlled clinical trial. Setting: Obstetrics and Gynecology department, Cairo University, Egypt. During period time from July 2019 to March 2021. Methods: A total of 63 female patients with uterine fibroids fulfilling the inclusion criteria were subjected to do abdominal myomectomy. Patients were randomized and allocated into three groups with a 1:1:1 ratio, groups coded A, B and C (A for carbitocin group, B for misoprostol group and C for control group) (n=21 in each group). In the three groups the following was studied: the estimated blood loss (EBL) during open myomectomy, need for blood transfusion, operative time, postoperative hematocrit, Post-operative hemoglobin, side effects of cabetocin and misoprostol, DROP in hemoglobin and DROP in hematocrit. Interventions: the patient in Carbetocin group will receive 100 og IV Carbetocin (1ml) in 5ml saline before skin incision, in misoprostol group patient will receive 400 micrograms of misoprostol trans-rectally one hour preoperatively and in control group will not receive any medication before skin incision. Results: Our results showed highly statistically significant difference between groups regarding estimated blood loss (EBL) carbetocin was superior to misoprostol and control groups (P- value = 0.024) (P- value < 0.001) respectively, postoperative hematocrit was significantly higher in carbetocin and misoprostol groups compared to control group (P- value < 0.001) (P- value = 0.004) respectively, but no significant difference between them, operative time was shorter in carbetocin and misoprostol groups compared to control group (P- value < 0.001) (P- value = 0.002) respectively, but also there was no statistically significant difference between them |