Buccal misoprostol to decrease blood loss after vaginal delivery: a randomized trial

OBJECTIVE: To assess the efficacy of buccal misoprostol to decrease bleeding after vaginal delivery. METHODS: This was a randomized study of patients between 22 weeks and 42 weeks of gestation with anticipated vaginal delivery. Patients were given either a 200-mug misoprostol tablet or placebo in the buccal space at the time of cord clamping. A continuous dilute intravenous oxytocin infusion was given to all patients at delivery of the placenta. Postpartum hemorrhage was defined as blood loss exceeding 500 mL. Sample size calculations based on previous studies assumed a 13% incidence of postpartum hemorrhage in the control group. To show a statistically significant reduction of postpartum hemorrhage a total of 1,604 patients would be required in each group. RESULTS: A total of 848 patients were enrolled and 756 randomly assigned, 377 in the misoprostol group and 379 in the placebo group. Demographic, antepartum, and intrapartum characteristics were similar between the groups. The incidence of postpartum hemorrhage, 3% compared with 5%, (relative risk 0.65, 95% confidence interval 0.33-1.29, P = .22), mean estimated blood loss, 322 compared with 329 mL, (P = .45), and mean minutes of the third stage of labor, 6.7 compared with 6.9 (P = .52) were similar between the groups, misoprostol and placebo, respectively. Hemoglobin difference before and after delivery, need for second or third uterotonic agent, and all measured neonatal variables including birth weights, and umbilical cord pH were similar between the groups. CONCLUSION: Buccal misoprostol at cord clamping is no more effective than placebo in reducing postpartum hemorrhage.     

Prospective randomized clinical trial of inpatient cervical ripening with stepwise oral misoprostol vs vaginal misoprostol

OBJECTIVE: The purpose of this study was to compare the efficacy and safety of stepwise oral misoprostol vs vaginal misoprostol for cervical ripening before induction of labor. STUDY DESIGN: Two hundred and four women between 32 to 42 weeks of gestation with an unfavorable cervix (Bishop score < or = 6) and an indication for labor induction were randomized to receive oral or vaginal misoprostol every 4 hours up to 4 doses. The oral misoprostol group received 50 microg initially followed by 100 microg in each subsequent dose. The vaginal group received 25 microg in each dose. The primary outcome was the interval from first misoprostol dose to delivery. Patient satisfaction and side effects were assessed by surveys completed after delivery. RESULTS: Ninety-three (45.6%) women received oral misoprostol; 111 (54.4%) received vaginal misoprostol. There was no difference in the average interval from the first dose of misoprostol to delivery in the oral (21.1 + 7.9 hrs) and vaginal (21.5 + 11.0 hrs, P = NS) misoprostol groups. The incidence of hyperstimulation in the oral group was 2.2% vs 5.4% in the vaginal group, P = NS. Eighteen patients in the oral group (19.4%) and 36 (32.4%) in the vaginal group underwent cesarean section (P < .05). This difference was attributed to better tolerance of more doses of misoprostol by the women in the oral group. There was no difference in side effects (nausea, vomiting, diarrhea, shivering) between groups. Fourteen percent of women in the vaginal group versus 7.5% in the oral group were dissatisfied with the use of misoprostol (P = NS). CONCLUSION: Stepwise oral misoprostol (50 microg followed by 100 microg) appears to be as effective as vaginal misoprostol (25 microg) for cervical ripening with a low incidence of hyperstimulation, no increase in side effects, a high rate of patient satisfaction, and is associated with a lower cesarean section rate.     

A randomized clinical trial comparing vaginal misoprostol versus cervical Foley plus oral misoprostol for cervical ripening and labor induction

We compared labor induced by vaginal misoprostol versus a supracervical Foley catheter and oral misoprostol. Singleton pregnancies at > or = 24 weeks' gestation were randomized to either an initial 25-microg dose of intravaginal misoprostol, followed by 50-microg intravaginal doses at 3- to 6-hour intervals, or a supracervical Foley balloon and 100 microg of oral misoprostol at 4- to 6-hour intervals. Primary outcome was time from induction to delivery. One hundred twenty-six women were randomized to vaginal misoprostol alone (group I) and 106 women to Foley and oral misoprostol (group II). The groups were similar in age, weight, gestational age, parity, indication for induction of labor, and oxytocin use. Cesarean delivery rates at 37% and cesarean indications were similar ( P = 0.25). The time from induction to delivery in group II (12.9 hours) was significantly shorter than that in group I (17.8 hours, P < 0.001). Uterine tachysystole occurred less often in the vaginal misoprostol group (21% versus 39%, P = 0.015). Compared with vaginal misoprostol, delivery within 24 hours was significantly more likely with a Foley balloon and oral misoprostol. The use of terbutaline and peripartum outcomes were similar in the two groups.     

Low-dose vaginal misoprostol in the management of intrauterine fetal death

Objectives.?To assess the effectiveness and side effects of vaginal misoprostol (Vagiprost® tablet) termination of second and third trimester pregnancy complicated with intrauterine fetal death (IUFD).

Design.?A prospective observational cohort study.

Setting.?Tanta University Hospital.

Patients.?The study carried out on 324 women with fetal demise in the second and third trimesters, from January 2008 to December 2009.

Intervention.?All patients were subjected to history taking, physical examination, and the Bishop Scoring. Application of 25?μg misoprostol in the posterior fornix of the vagina, this was repeated every 4 h over 24 h. We assessed the adverse effects, progress, and outcomes.

Results.?The success rate was 90% and 45% in women in the third and second trimesters, respectively. The mean induction-termination interval was 8.95?±?2.63 and 15.3?±?5.37 h for women in the third and second trimesters, respectively. The induction termination interval correlated negatively with the duration of gestation. Approximately, 90% of second trimester and 55% of third trimester women required oxytocin augmentation. The mean value of total required dose of misoprostol was 166.3?±?7.5 and 120?±?28.79?μg for women in the second and third trimesters, respectively.

Conclusion.?Vagiprost appears to be a safe, effective, practical, and inexpensive method for termination of third trimester pregnancy complicated with of IUFD.     

A comparison of oral misoprostol with vaginal misoprostol administration in second-trimester pregnancy termination for fetal abnormality

OBJECTIVE: To compare the clinical efficacy and side effects of oral misoprostol with vaginal misoprostol for second-trimester pregnancy termination. METHODS: A randomized clinical trial of medical pregnancy termination between 14 and 26 weeks' gestation was conducted. Three misoprostol regimens were compared: 400 microg vaginally at 6-hour intervals (group 1), 400 microg orally at 3-hour intervals (group 2), and a loading dose of 600 microg vaginally followed by 200 microg orally at 3-hour intervals (group 3). A sample size of 225 women was required for equivalence of the three regimens, with an interim safety analysis planned at 80 women. RESULTS: A significant difference between the groups was evident at the interim safety analysis and the study ceased. The subset of 84 women recruited before the study closure is described. There was a significant difference in the median time to achieve delivery among the three groups: group 1, 14.5 hours (95% confidence interval 12.0, 16.9), versus group 2, 25.5 hours (13.5, 23.8), versus group 3, 16.4 hours (interquartile range 14.2-37.3) (P =.042). Within 24 hours of commencement 85.7% of women in group 1, 44.8% in group 2, and 74.1% in group 3 delivered (P =.003). At 48 hours 0% in group 1, 20.7% in group 2, and 3.7% in group 3 were undelivered (P =.011). There was no difference in women's perceptions of the termination process. CONCLUSION: In second-trimester pregnancy termination, a vaginal misoprostol regimen of 400 microg every 6 hours was 1.9 times more likely to result in delivery within 24 hours from commencement than an oral regimen of 400 microg every 3 hours.     

A randomized trial that compared intravaginal misoprostol and dinoprostone vaginal insert in pregnancies at high risk of fetal distress

OBJECTIVE: The purpose of this study was to compare the safety and efficacy of misoprostol and dinoprostone in pregnancies at high risk of fetal distress. STUDY DESIGN: Medical indications for the induction of labor with postdate pregnancy or intrauterine growth restriction were randomized. A sequential design that was based on the triangular test was used. RESULTS: At the fourth interim analysis, which included 140 patients, the trial was stopped because no significant difference was found in neonatal safety between misoprostol and dinoprostone, which was assessed on arterial cord pH <7.20 (14.3% vs 10.0%, respectively; P=.60). Neonatal tolerance was similar in the 2 groups, with no difference in the cesarean delivery rate for fetal distress or in the incidence of meconium-stained amniotic fluid. Time to vaginal delivery was shortened by misoprostol (P=.03). CONCLUSION: Misoprostol and dinoprostone are equally safe for the induction of labor in pregnancies that are at high risk of fetal distress; however, misoprostol allowed the earlier induction of labor than did dinoprostone.     

Titrated oral compared with vaginal misoprostol for labor induction: a randomized controlled trial

OBJECTIVE: To compare the efficacy and safety of titrated oral misoprostol and vaginal misoprostol for labor induction. METHODS: Women between 34 and 42 weeks of gestation with an unfavorable cervix (Bishop score less than or equal to 6) and an indication for labor induction were randomLy assigned to receive titrated oral or vaginal misoprostol. The titrated oral misoprostol group received a basal unit of 20 mL misoprostol solution (1 mcg/mL) every 1 hour for four doses and then were titrated against individual uterine response. The vaginal group received 25 mcg every 4 hours until attaining a more favorable cervix. Vaginal delivery within 12 hours was the primary outcome. The data were analyzed by intention-to-treat. RESULTS: Titrated oral misoprostol was given to 101 (48.8%) women and vaginal misoprostol to 106 (51.2%) women. Completed vaginal delivery occurred within 12 hours in 75 (74.3%) women in the titrated oral group and 27 (25.5%) women in the vaginal group (relative risk [RR] 8.44, 95% confidence interval [CI] 4.52-15.76). The incidence of hyperstimulation was 0.0% in the titrated oral group compared with 11.3% in the vaginal group (RR 0.08, 95% CI 0.01-0.61). Although more women experienced nausea (10.9%) in the titrated oral group (RR 27.07, 95% CI 1.57-465.70), fewer infants had Apgar scores of less than 7 at 1 minute in the titrated oral group than in the vaginal group (RR 0.10, 95% CI 0.01-0.76). CONCLUSION: Titrated oral misoprostol is associated with a lower incidence of uterine hyperstimulation and a lower cesarean delivery rate than vaginal misoprostol for labor induction in patients with unfavorable cervix. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00529295 LEVEL OF EVIDENCE: I.     

The effect of prophylactic oral tranexamic acid plus buccal misoprostol on blood loss after vaginal delivery: a randomized controlled trial

Objective: The objective of this study is to evaluate the effect of prophylactic oral tranexamic acid (TA) plus buccal misoprostol on the amount of blood loss after vaginal delivery in women at low risk for post-partum hemorrhage (PPH).

Materials and methods: The study was a randomized open label clinical trial conducted in a tertiary University Hospital between January 2016 and June 2017. We included women who delivered vaginally with a singleton pregnancy. They were randomized into three groups: group I (women received 10?IU oxytocin IV after delivery of the baby), group II (women received 600?µg buccal misoprostol after delivery of the baby), and group III (women received 1000?mg oral TA at the end of the first stage of labor plus 600 µg buccal misoprostol after delivery of the baby). In each group, pre- and post-delivery pulse rate, blood pressure, temperature, and hemoglobin level were evaluated. Additionally, the amount of blood loss, need for blood transfusion, need for additional uterotonics, and side effects of the study medications were recorded.

Results: There was a statistically significant lower hemoglobin level and higher blood loss in the misoprostol group compared with oxytocin group and TA plus misoprostol group (p?=?.0001). There was a statistically significant higher hemoglobin level and lower blood loss in the TA plus misoprostol group compared with the oxytocin group (p?=?.004 and .043, respectively). PPH occurred in 16.7% of women in the misoprostol group compared 1.7% in the oxytocin group and no cases of PPH in the TA plus misoprostol group (p?=?.0001).

Conclusions: In settings like rural area or home delivery in which oxytocin is not available, alternative oral TA plus buccal misoprostol may be considered as an effective line in prevention of PPH.     

A randomised trial of two regimens of vaginal misoprostol to manage termination of pregnancy of up to 16 weeks

OBJECTIVE: The purpose of this study was to compare the efficacy and side-effects of two regimens of vaginal misoprostol for pregnancy termination of up to 16 weeks. METHODS: A randomised clinical trial of medical pregnancy termination of up to 16 weeks was conducted. A hundred pregnant women requesting legal termination of pregnancy were randomised into two groups to receive either 200 microg (50 women) or 400 microg (50 women)--vaginal misoprostol every six hours up to four doses. Outcome of abortion and side-effects were assessed. RESULTS: The groups were similar in maternal age, gestational age, parity and indication for pregnancy termination. There were no statistically significant differences between the two groups in abortion (P = 0.084) and mean induction to abortion time (P = 0.35). However, the side-effects in the 400 microg group were significantly higher than in the 200 microg group (P = 0.000). Conclusion: In pregnancy termination of up to 16 weeks, 200 microg vaginal misoprostol every six hours up to four doses was as effective as 400 microg, but side-effects were more common in 400 microg regimen.     

Comparison of oral and vaginal misoprostol for induction of labor at term: a randomized controlled trial

OBJECTIVE: To compare the efficacy of oral with vaginal misoprostol for induction of labor at term. METHODS: One hundred and fifty-three pregnant women at term with indications for induction of labor and Bishop score < or = 6 were randomly assigned to receive misoprostol either 100 microg orally or 50 microg vaginally every 6 h for 48 h. Repeated doses were given until Bishop score > or = 8 was achieved or spontaneous rupture of membranes occurred. Those who were not in labor after 48 h had labor induced with amniotomy and oxytocin. The main outcome measure was induction to delivery time. RESULTS: The median induction to vaginal delivery time in the oral group (14.3 h) was not significantly different from that of the vaginal group (15.8 h). The median number of doses was also not significantly different in the oral group compared with the vaginal group. There was a significant higher incidence of uterine tachysystole in the vaginal group compared to the oral group (17.1% vs 5.3%, P = 0.032). There was no hyperstimulation in either group. There were no significant differences between the groups with respect to oxytocin augmentation, cesarean section rate, analgesic requirement, and neonatal outcomes. CONCLUSION: Oral administration of 100 microg misoprostol has similar efficacy to intravaginal administration of 50 microg misoprostol for labor induction with less frequent abnormal uterine contractility. 100 microg of misoprostol orally can be used as an alternative to the vaginal route for labor induction.     

A randomized controlled trial of vaginal misoprostol for cervical priming before hysteroscopy.

OBJECTIVE: To evaluate the effectiveness and side effects of vaginal misoprostol for cervical dilation in nonpregnant women before hysteroscopy. METHODS: Ninety-one women scheduled to have hysteroscopy were randomized to receive either vaginal misoprostol or placebo. Cervical response, outcome of hysteroscopy, and side effects of vaginal misoprostol were assessed. RESULTS: The mean cervical dilatation estimated by Hegar dilator and the mean duration of hysteroscopy were significantly different between the treated group (7.0+/-1.0 mm [range 6-8.5] and 90.0+/-38.4 seconds [range 60-240], respectively) and the control group (3.8+/-1.2 mm [range 2-5.5] and 142.0+/-38.7 seconds [range 60-270]). In the misoprostol group, only three women (6.5%) needed cervical dilation before hysteroscopy, compared with 14 (31.1%) in the placebo group (P = .006). Cervical tears during hysteroscopy occurred in two patients (4.4%) in the control group and none in the misoprostol group. The two most common side effects of vaginal misoprostol were mild lower abdominal pain in 15 women (32.6%) and slight vaginal bleeding in 12 (26.1%). Both side effects were significantly different when compared with placebo (P<.001). CONCLUSION: Vaginal misoprostol lessens the cervical resistance in women undergoing hysteroscopy and facilitates the procedure, with only mild side effects.     

A randomized comparison of mifepristone and self-administered oral or vaginal misoprostol for early abortion

In France, mifepristone in association with orally administered misoprostol is widely used for the early termination of pregnancy (up to 49 days' gestation). In other centers, mifepristone in association with vaginally administered misoprostol has also been used. The aim of the present study was to compare the efficacy and tolerance of mifepristone in association with misoprostol administered orally or vaginally for the termination of pregnancy of up to 49 days' gestation.

A total of 237 women were enrolled in the study. All women received 600 mg mifepristone administered orally and 400 μg misoprostol administered either orally (n = 119) or vaginally (n = 118). A second dose of 400 μg misoprostol was administered if women had not expelled the pregnancy within 3 h. Women were randomized into treatment groups according to the day of their admission.

The overall success rate was 98.7% and there was no significant difference in efficacy between the two groups. There was one treatment failure in the group in which misoprostol was administered orally. Of those women who aborted within 3 h of administration of the first dose of misoprostol, the route of administration of misoprostol did not influence the time to abortion. Of the women who received a second dose of misoprostol, the time to abortion was shorter in those who received misoprostol orally (52 min versus 77 min).

Tolerance was assessed by visual analog scales and was similar for both groups. In both groups, women preferred the oral route of administration.     

A randomized comparison of mifepristone and self-administered oral or vaginal misoprostol for early abortion.

In France, mifepristone in association with orally administered misoprostol is widely used for the early termination of pregnancy (up to 49 days' gestation). In other centers, mifepristone in association with vaginally administered misoprostol has also been used. The aim of the present study was to compare the efficacy and tolerance of mifepristone in association with misoprostol administered orally or vaginally for the termination of pregnancy of up to 49 days' gestation. A total of 237 women were enrolled in the study. All women received 600 mg mifepristone administered orally and 400 microg misoprostol administered either orally (n = 119) or vaginally (n = 118). A second dose of 400 microg misoprostol was administered if women had not expelled the pregnancy within 3 h. Women were randomized into treatment groups according to the day of their admission. The overall success rate was 98.7% and there was no significant difference in efficacy between the two groups. There was one treatment failure in the group in which misoprostol was administered orally. Of those women who aborted within 3 h of administration of the first dose ofmisoprostol, the route of administration ofmisoprostol did not influence the time to abortion. Of the women who received a second dose ofmisoprostol, the time to abortion was shorter in those who received misoprostol orally (52 min versus 77 min). Tolerance was assessed by visual analog scales and was similar for both groups. In both groups, women preferred the oral route of administration.     

A randomized controlled trial comparing low dose vaginal misoprostol and dinoprostone gel for labor induction

Objectives

To compare the safety and efficacy of low dose misoprostol and dinoprostone for cervical ripening and labor induction

Methods

It was an open label randomized controlled trial conducted at department of Obstetrics & Gynecology, Dr TMA Pai Rotary Hospital, Karkala. The main outcome measure was induction-to-vaginal delivery interval. Secondary outcome measures were the labor characteristics, maternal complications and neonatal outcomes.

Results

Out of 320 eligible women included for final analysis, 159 received misoprostol and 161 dinoprostone. There was no significant difference between the two groups in induction-to-vaginal delivery interval, mode of delivery, number of women delivering within 24 hours and neonatal outcomes. The efficacies of the two prostaglandins were similar.

Conclusion

Low dose misoprostol is as efficient as dinoprostone in achieving active labor and delivering with in 24 hours. The maternal and neonatal outcomes associated with each group were similar. It is a cheaper alternative for labor induction.     

Cervical ripening using vaginal misoprostol before hysteroscopy: a double-blind randomized trial

Study ObjectiveThe aim of this study was to evaluate the use of vaginal misoprostol to decrease both the force required to dilate the cervix and the pain experienced during a hysteroscopy.DesignRandomized clinical trial (RCT) (Canadian Task Force classification I).SettingUniversity hospital gynecology clinic.PatientsA total of 101 patients needing a diagnostic hysteroscopy. Fifty patients were randomized to the misoprostol group and 51 to the placebo group. Patient characteristics were similar in the 2 groups.InterventionsSelf-administration of 400 μg of vaginal misoprostol or vaginal placebo 12 to 24 hours before a hysteroscopy.Measurements and Main ResultsThe force needed to dilate the cervix was assessed by a tonometer, and pain was measured by a visual analog scale. The force to dilate the cervix to 6 mm was significantly less in the misoprostol group (5.0 vs 7.5 N, p = .02). Pain-related measurements after dilatation of the cervix to 6 mm were significantly reduced in the misoprostol group (42.1 vs 57.2, p = .004). The main side effect reported with the use of the drug was pelvic cramping.ConclusionThe use of 400 μg of vaginal misoprostol 12 to 24 hours before hysteroscopy reduces the pain and the force needed to dilate the cervix, with only mild side effects.     

A randomized controlled trial comparing powdery sublingual misoprostol and sublingual misoprostol tablet for management of embryonic death or anembryonic pregnancy

Objectives  To compare complete abortion rate, duration of abortion, and side effects between 600 μg powdery sublingual misoprostol and 600 μg sublingual misoprostol tablet for management of embryonic death or anembryonic pregnancy. Materials and methods  Fifty-four pregnant women up to 13 weeks of gestation diagnosed with embryonic death or anembryonic pregnancy were randomized to receive 600 μg powdery sublingual misoprostol or 600 μg sublingual misoprostol tablet. Complete abortion was evaluated by transvaginal ultrasound at 48 h. Results  Twenty-six patients received 600 μg powdery sublingual misoprostol and 28 patients received 600 μg sublingual misoprostol tablet. Complete abortion rate was 34.6% in powdery sublingual misoprostol group and 32.1% in sublingual misoprostol tablet group (P = 0.847). Duration of abortion in powdery sublingual misoprostol group and sublingual misoprostol tablet group was similar (34.7 ± 18.8 vs. 36.9 ± 17.8 h, respectively, P = 0.656). There was no significant difference in the side effects between both groups. Conclusions  Single dose of 600 μg of powdery sublingual misoprostol does not improve its efficacy for management of embryonic death or anembryonic pregnancy when compared to sublingual misoprostol tablet.     

Oral versus vaginal misoprostol for cervical priming in first-trimester abortion: a randomized trial

The objective of this study was to compare the oral and vaginal administration of misoprostol for cervical priming before surgical abortion up to 63 days' gestation. A total of 900 pregnant women, with ages ranging from 18 to 42 years, who asked for pregnancy termination, were included in this study. Women were randomly allocated to one of the following groups: oral administration of 400 μg misoprostol, 8 h before aspiration; and vaginal self-administration of 400 μg misoprostol, 4 h before aspiration. During admission, all subjects were checked on a 15-min basis. The preoperative cervical dilatation achieved was the main outcome assessed. The cervix was dilated (Hegar ≥ 8) in 348 (78%) subjects from the oral treatment group and in 391 (87%) women from the vaginal treatment group; this difference was statistically significant (p = 0.0004). The mean dilatation achieved in the oral treatment group was 8.1 mm (SD 1.6 mm) and it was 8.5 mm (SD 1.5 mm) in the vaginal treatment group; this difference was statistically significant (p = 0.0001). The frequencies of side-effects such as nausea, vomiting, diarrhea and chills reported by women from the vaginal misoprostol group were 10, 8, 18 and 4 times lower, respectively, than those reported by subjects from the oral misoprostol group. In conclusion, vaginal self-administration of misoprostol was the best administration route, as it obtained the same or greater priming effectiveness of the cervix in half the time with a much lower frequency of side-effects.