A randomized trial of sublingual misoprostol to augment routine third-stage management among women at risk of postpartum hemorrhage.

OBJECTIVE: To assess whether a combination of misoprostol and oxytocin is more beneficial than oxytocin alone in reducing blood loss after vaginal delivery among women with known risk factors for postpartum hemorrhage (PPH). METHODS: A randomized, double-blind trial was conducted in a medical college in eastern India among women aged at least 18 years who had known high-risk factors for PPH. Using a computer-generated random number sequence (block size 6-8), participants were randomly assigned to receive 400 µg misoprostol or matched placebo tablets sublingually, in addition to 10 units of oxytocin, after vaginal delivery. The primary outcomes were postpartum blood loss at 1 hour and frequency of PPH. Analyses were by intention to treat. RESULTS: Both groups contained 144 participants. Postpartum blood loss at 1 hour after delivery was significantly lower among women who received misoprostol than among those who received placebo (225.8±156.7 mL vs 302.4±230.3 mL; P<0.001). The frequency of moderate PPH (500-999 mL) was significantly lower in the group receiving misoprostol than in the placebo group (5 [3.5%] vs 15 [10.4%] participants; P=0.03). CONCLUSION: As compared with oxytocin alone, misoprostol with oxytocin more effectively reduced blood loss after vaginal delivery among women at risk of PPH. Clinical Trial Registry India:CTRI/2014/03/004491.

Mifepristone and misoprostol compared with misoprostol alone for induction of labor in intrauterine fetal death: A randomized trial.

AIM: To assess whether mifepristone and misoprostol are more beneficial than misoprostol alone for the induction of labor in women with intrauterine fetal death. METHODS: A randomized double blind placebo-controlled parallel group superiority trial was conducted. One hundred and ten women who had experienced fetal death at or later than 20 weeks of gestation were randomized by computer-generated random number sequence to receive 200 mg of mifepristone or matched placebo tablets orally. Misoprostol was administered vaginally to women of both groups after 36-48 h. The main outcomes studied were the fetal-placental delivery rate within 24 hours of commencement of the first dose of misoprostol without additional intervention and the induction-delivery interval. RESULTS: Successful delivery occurred significantly more frequently in women who received mifepristone prior to misoprostol than in women who received only misoprostol (92.5% [49/53] compared with 71.2% [37/52] respectively; P = 0.001). The mean induction-delivery interval was also significantly shorter when using mifepristone plus misoprostol than using misoprostol alone (9.8 h, standard deviation, 4.4 compared with 16.3 h standard deviation, 5.7, respectively; P < 0.001). CONCLUSION: Use of a combination of mifepristone and misoprostol significantly improved the rate of successful delivery and shortened the induction-delivery interval in women who had experienced fetal death compared with the use of misoprostol alone.

Sublingual misoprostol as an adjunct to oxytocin during cesarean delivery in women at risk of postpartum hemorrhage.

OBJECTIVE: To evaluate whether a combination of misoprostol and oxytocin more effectively reduces blood loss during and after cesarean delivery than does oxytocin alone among women with known risk factors for postpartum hemorrhage (PPH). METHODS: A prospective, randomized, double-blind, placebo-controlled trial was performed at a tertiary care center in Kolkata, India, between October 2012 and December 2013. Women were eligible if they were undergoing emergency cesarean under spinal anesthesia and were at high risk for PPH. Participants were randomly assigned (1:1) to receive 400 µg misoprostol or matched placebo sublingually after delivery of the newborn using a computer-generated random number sequence (block size eight). Participants and providers were masked to assignment. All participants received 20 IU oxytocin. The primary outcomes were intraoperative and postoperative blood loss. RESULTS: Both groups contained 198 women. Mean intraoperative blood loss was significantly lower in the misoprostol group (505.4±215.5 mL) than in the placebo group (587.3±201.5 mL; P<0.001). Mean postoperative blood loss was slightly lower in the misoprostol group (96.9±57.3 mL) than in the placebo group (103.4±58.4 mL; P=0.07). Shivering and pyrexia were more frequently associated with misoprostol (P<0.05 for both). CONCLUSION: Misoprostol as an adjunct to oxytocin seemed to more effectively reduce blood loss than did oxytocin alone. Clinical Trial Registry India:CTRI/2013/05/003645.

Rectally administrated misoprostol as an alternative to intravenous oxytocin infusion for preventing post-partum hemorrhage after cesarean delivery.

AIM: With the increasing rate of cesarean delivery (CD) worldwide, there is a need for a revision of practices to prevent post-partum hemorrhage (PPH) after CD. In search of a safe, cheap and effective alternative to oxytocin for prevention of PPH during the postoperative period of CD, the present study aimed to compare rectally administrated misoprostol with i.v. oxytocin infusion. METHODS: A randomized, placebo-controlled, double-blind prospective trial was undertaken on 192 women who did not have risk factors for PPH and who had an uneventful emergency CD under spinal anesthesia. They were randomly allocated to receive either 800 mg of rectal misoprostol or an i.v. infusion of oxytocin at the end of operation. Primary outcome measures were the amount of postoperative (24 h) blood loss and incidence of PPH during the postoperative period. The secondary outcome measures were the postoperative drop in hemoglobin concentration after 24 h, need for additional uterotonic and blood transfusion, and side-effects/complications during the 24-h observation period. RESULTS: There was a significant reduction of blood loss in the misoprostol group compared with the oxytocin group (144.5 ± 100.1 vs 191.7 ± 117.1, P < 0.0001). The two groups were similar in terms of the secondary outcome parameters. CONCLUSION: Rectally administrated 800-mg misoprostol may be an effective alternative to oxytocin infusion to prevent PPH after CD.

Dosing interval of 24hours versus 48hours between mifepristone and misoprostol administration for mid-trimester termination of pregnancy.

OBJECTIVE: To compare the efficacy of a shorter interval (24hours) between misoprostol and mifepristone administration with that of the conventional dosing interval (48hours) for second-trimester termination of pregnancy (TOP). METHODS: This was a prospective randomized, controlled, open-label study of 98 healthy women opting for mid-trimester TOP. The women were randomized to receive 200mg mifepristone orally, followed 24hours (Group 1) or 48hours (Group 2) later by misoprostol (800µg, then 400µg every 3hours). The primary outcome measure was the percentage of successful abortions within 24hours. Secondary outcome measures were the induction-to-abortion interval (measured from misoprostol administration) and the frequencies of complications and adverse effects. RESULTS: The rate of successful abortions was similar with the 24-hour and 48-hour dosing intervals (95.8% and 93.6%, respectively; P=0.38). The mean induction-to-abortion interval was also comparable between the 2 groups (8.6±4.1hours versus 8.7±3.9hours; P=0.37). Nulliparous women and women with a pregnancy duration of 16weeks or more had a longer induction-to-abortion interval in both groups. CONCLUSION: The 24-hour dosing interval between misoprostol and mifepristone administration seems to be as effective as the 48-hour dosing interval for second trimester TOP. Clinical Trial Registry India: CTRI/2011/05/001770.

Effect of a single preoperative dose of sublingual misoprostol on intraoperative blood loss during total abdominal hysterectomy.

OBJECTIVE: To investigate whether use of preoperative misoprostol can reduce blood loss during total abdominal hysterectomy (TAH). METHODS: In a randomized double-blind placebo-controlled trial at a tertiary care hospital in Kolkata, India, between March 2011 and April 2012, women (n=132) undergoing TAH with or without bilateral salpingo-oophorectomy for symptomatic myomas were randomly allocated to receive either 400 µg of misoprostol or placebo 30 minutes before surgery. The primary outcome measure was intraoperative blood loss was. The secondary outcomes were postoperative drop in hemoglobin, need for blood transfusion, and incidence of adverse effects. RESULTS: The 2 groups were similar with regard to demographic and clinical characteristics. There was a significant reduction of blood loss during TAH after sublingual administration of misoprostol compared with placebo before surgery (356 mL vs 435 mL; P=0.049). The mean postoperative hemoglobin concentration was higher (10.5 g/dL vs 9.5 g/dL; P<0.001) and the postoperative drop in hemoglobin was smaller (1.1g/dL vs 1.9 g/dL; P=0.004) in the misoprostol group than in the placebo group. No significant adverse effects occurred in either group. CONCLUSION: The results showed that a single dose of misoprostol administered before abdominal hysterectomy resulted in a significant reduction of blood loss with minimal adverse effects. Clinical Trial Registry India (www.ctri.nic.in): CTRI/2011/091/000216.

Misoprostol for cervical ripening prior to gynecological transcervical procedures.

PURPOSE: Dilatation and curettage is frequently performed in gynecological practice. Aim of this prospective randomized double-blind placebo-controlled study was to evaluate the safety and efficacy of oral misoprostol to prime non-pregnant cervix before this procedure. METHOD: Women requiring dilatation and curettage were included in the study. Exclusion criteria were visible growth in cervix or vagina, pregnancy, allergy to prostaglandins, some medical disorders. Each participant was instructed to take either 400 µg of misoprostol or placebo orally 12 h before the procedure. Primary outcome measure was: diameter of the largest negotiable Hegar's dilator through internal os without any resistance at the beginning of the procedure. Secondary outcome measures were: percentage of women with initial cervical dilatation of ≥5 mm, time required for optimum cervical dilatation, percentage of failed procedures and complications. t test, Chi-square test and Fisher's test were used to compare the variables. RESULT: Misoprostol significantly increased baseline cervical diameter in the pre-menopausal group (p < 0.001), but not in post-menopausal subjects (p = 0.1) and reduced time required for cervical dilatation in both pre-and post-menopausal women. The number of patients achieving initial cervical dilatation ≥5 mm was significantly greater in pre-menopausal subjects receiving misoprostol, but not significant in post-menopausal ones. The drug was also found to be effective in both nulliparous and multiparous patients. Side effects were comparable between two groups. Only nausea and vomiting were more frequent in post-menopausal misoprostol group than placebo (p = 0.018). CONCLUSION: Four hundred micrograms of oral misoprostol 12 h prior to dilation and curettage was found to be beneficial in cervical priming in pre-menopausal subjects. It was also found to be effective irrespective of the parity of the patients.

Sublingual misoprostol versus intramuscular oxytocin for prevention of postpartum hemorrhage in low-risk women.

OBJECTIVE: To compare sublingual misoprostol with intramuscular oxytocin for prevention of postpartum hemorrhage (PPH) in low-risk vaginal birth. METHODS: In a prospective, randomized, double-blind trial, 530 women without risk of PPH were randomly allocated to receive either 400 µg of misoprostol sublingually or 10 units of oxytocin intramuscularly within 1minute of delivery. The outcome measures were incidence of PPH, postpartum blood loss, drop in hemoglobin level in 24 hours, need for additional uterotonic drug, incidence of adverse effects, and need for blood transfusion. Student t, χ(2), Mann-Whitney U, and Fisher exact tests were used for comparison. RESULTS: Incidence of postpartum hemorrhage (≥ 500 mL) and postpartum blood loss in the misoprostol group were similar to those in the oxytocin group (6% versus 5.7%, P=0.85; 153 mL versus 146 mL, P=0.36). Shivering and pyrexia were encountered more often in the misoprostol than in the oxytocin group (shivering: 19% versus 0.8%, P<0.001, relative risk [RR] 0.86, 95% confidence interval [CI] 0.82-0.90; pyrexia: 2.3% versus 0%, P=0.03, RR 0.97, 95% CI 0.95-0.99). CONCLUSION: The efficacy of 400 µg of misoprostol administered sublingually was equivalent to that of 10 units of oxytocin given intramuscularly for prevention of PPH in low-risk vaginal delivery.

Rectally administered misoprostol versus intravenous oxytocin infusion during cesarean delivery to reduce intraoperative and postoperative blood loss.

OBJECTIVE: To compare the efficacy of rectally administered misoprostol with intravenous oxytocin infusion in preventing uterine atony and blood loss during cesarean delivery. METHODS: In this prospective, randomized, double-blind trial, 200 women undergoing cesarean delivery who did not have risk factors for postpartum hemorrhage were randomly allocated to receive either 800 microg of rectal misoprostol at the time of peritoneal incision or an intravenous infusion of oxytocin after delivery of the neonate. Primary outcome measures were estimated amount of intraoperative and postoperative (8 hours) blood loss and changes in hemoglobin levels 24 hours after delivery. RESULTS: A total of 96 and 94 women were analyzed in the misoprostol and oxytocin groups, respectively. Intraoperative and postoperative blood loss was significantly lower in the misoprostol group than in the oxytocin group (503 vs 592 mL, P=0.003 and 74 vs 114 mL, P=0.045, respectively). The incidence of shivering was higher in the misoprostol group (8.3% vs 1.1%, P=0.018; RR 7.83; 95% confidence interval, 0.99-61.42). CONCLUSION: Rectal misoprostol appears to be an effective alternative to intravenous oxytocin in preventing blood loss for routine use during cesarean delivery. CLINICAL TRIALS REGISTRATION: CTRI/2009/091/000075.