A comparison of two dosing regimens of intravaginal misoprostol for second-trimester pregnancy termination

OBJECTIVE: To compare the effectiveness of misoprostol administered intravaginally every 6 versus every 12 hours for termination of second-trimester pregnancies. METHODS: One hundred pregnant women at 12-22 weeks' gestation were randomized to receive 200 microg of misoprostol intravaginally either every 6 or every 12 hours for up to 48 hours. RESULTS: The incidences of abortion within 48 hours after initial drug administration were 87.2 and 89.2%, the complete abortion rates 43.9 and 33.3%, and the mean abortion intervals 13.8 and 14.0 hours in the 6- and 12-hour groups, respectively. Side effects were similar between groups. CONCLUSION: Misoprostol administered vaginally is effective for terminating second-trimester pregnancies. Shortening the dosing interval from 12 to 6 hours produced no significant benefit.     

The use of misoprostol in termination of second-trimester pregnancy

Misoprostol, a synthetic prostaglandin E1 analog, is initially used to prevent peptic ulcer. The initial US Food and Drug Administration-approved indication in the product labeling is the treatment and prevention of intestinal ulcer disease resulting from nonsteroidal anti-inflammatory drugs use. In recent two decades, misoprostol has approved to be an effective agent for termination of pregnancy in various gestation, cervical ripening, labor induction in term pregnancy, and possible management of postpartum hemorrhage. For the termination of second-trimester pregnancy using the combination of mifepristone and misoprostol seems to have the highest efficacy and the shortest time interval of abortion. When mifepristone is not available, misoprostol alone is a good alternative. Misoprostol, 400 μg given vaginally every 3-6 hours, is probably the optimal regimen for second-trimester abortion. More than 800 μg of misoprostol is likely to have more side effects, especially diarrhea. Although misoprostol can be used in women with scarred uterus for termination of second-trimester pregnancy, it is recommended that women with a scarred uterus should receive lower doses and do not double the dose if there is no initial response. It is also important for us to recognize the associated teratogenic effects of misoprostol and thorough consultation before prescribing this medication to patients regarding these risks, especially when failure of abortion occurs, is needed.     

Frequent low-dose misoprostol for termination of second-trimester pregnancy

Objectives?To determine the efficacy of an application regimen of low-dose frequent misoprostol for second-trimester pregnancy termination.

Methods?A total of 250 women between 12 and 20 weeks of gestation who were scheduled for second-trimester pregnancy termination received 200?μg vaginal misoprostol followed by 100?μg oral misoprostol every 2?h until expulsion of the fetus. Mechanical cervical dilatation with a 16-French Foley balloon catheter was performed if no cervical dilatation was observed after 24?h. The main outcome measures were the delivery rate within 24?h and the factors influencing the interval between the onset of induction and abortion. Secondary outcome measures were the side-effects of the regimen and the total misoprostol dose required.

Results?With application of this protocol, 245 women (98%) delivered within 24?h of induction. The mean (± standard deviation) misoprostol dose used was 728?±?297?μg (200–2100?μg). Cox regression analysis revealed that vaginal spotting or nulliparity do not effect the induction–abortion time. On the other hand, using this regimen induction to abortion time tends to be longer in the presence of live fetuses (odds ratio (OR)?=?0.45; confidence interval (CI)?=?0.2–0.8; p?=?0.008) and pregnancies with gestational age >?16 weeks (OR?=?0.59; CI?=?0.4–0.8; p?=?0.003) when compared with cases of in utero death and pregnancies with a gestational age of 12–13 weeks, respectively. Twenty-seven women (10.8%) experienced one or more side-effects attributable to misoprostol.

Conclusion?The 100-μg oral misoprostol every 2?h following 200?μg vaginal misoprostol is a highly effective protocol for inducing abortion at 12–20 weeks of pregnancy. Cases with live fetuses or pregnancies with older gestational age (>?16 weeks) deliver in a longer time period.     

Frequent low-dose misoprostol for termination of second-trimester pregnancy.

OBJECTIVES: To determine the efficacy of an application regimen of low-dose frequent misoprostol for second-trimester pregnancy termination. METHODS: A total of 250 women between 12 and 20 weeks of gestation who were scheduled for second-trimester pregnancy termination received 200 microg vaginal misoprostol followed by 100 microg oral misoprostol every 2 h until expulsion of the fetus. Mechanical cervical dilatation with a 16-French Foley balloon catheter was performed if no cervical dilatation was observed after 24 h. The main outcome measures were the delivery rate within 24 h and the factors influencing the interval between the onset of induction and abortion. Secondary outcome measures were the side-effects of the regimen and the total misoprostol dose required. RESULTS: With application of this protocol, 245 women (98%) delivered within 24 h of induction. The mean (+/-standard deviation) misoprostol dose used was 728+/-297 microg (200-2100 microg). Cox regression analysis revealed that vaginal spotting or nulliparity do not effect the induction-abortion time. On the other hand, using this regimen induction to abortion time tends to be longer in the presence of live fetuses (odds ratio (OR) = 0.45; confidence interval (CI) =0.2-0.8; p=0.008) and pregnancies with gestational age > 16 weeks (OR= 0.59; CI = 0.4-0.8; p= 0.003) when compared with cases of in utero death and pregnancies with a gestational age of 12-13 weeks, respectively. Twenty-seven women (10.8%) experienced one or more side-effects attributable to misoprostol. CONCLUSION: The 100-microg oral misoprostol every 2 h following 200 microg vaginal misoprostol is a highly effective protocol for inducing abortion at 12-20 weeks of pregnancy. Cases with live fetuses or pregnancies with older gestational age (> 16 weeks) deliver in a longer time period.     

Efficacy of two regimens of misoprostol for early second-trimester pregnancy termination

OBJECTIVE: To compare the efficacy of a combined regimen of misoprostol with vaginal misoprostol for early 2nd-trimester pregnancy termination. METHODS: This is a prospective study that includes 79 pregnant women who requested legal termination of 2nd-trimester pregnancy between 13 and 22 weeks. Two regimens of misoprostol were used. Group 1: 400 microg of oral plus 400 microg vaginal misoprostol every 8 h (combined regimen) and group 2: 400 microg of vaginal misoprostol every 3 h up to a maximum of five doses (vaginal regimen). RESULTS: The induction-to-abortion interval was significantly longer in group 1 (25.5 +/- 24.45 h) than in group 2 (15 +/- 7.14 h) (p = 0.016). The abortion rate within 24 h in group 1 was of 56.8 vs. 85.7% in group 2 (p = 0.006). The hazard rate for vaginal delivery within 24 h was found to be 2.277-fold greater in the group with the combined therapy once controlled for plausible confounders. CONCLUSIONS: Our study suggests that oral misoprostol combined with vaginal misoprostol does not reduce the induction-to-abortion interval compared to an exclusively vaginal route when used for early 2nd-trimester pregnancy termination.     

Vaginal misoprostol for second-trimester pregnancy termination after one previous cesarean delivery

Objective

To determine the safety and efficacy of using misoprostol vaginally for second-trimester abortion in women with a single previous cesarean delivery.

Method

This prospective observational study was carried out at a university hospital in Egypt with 50 pregnant women with 1 previous cesarean delivery; a gestation of at least 16 weeks but less than 20 weeks (group 1) or 20 or more weeks (group 2); and a need to terminate the pregnancy. The regimen was 4 doses of 200 μg of misoprostol applied vaginally every 4 hours daily, with a 12-hour nightly rest from misoprostol applications, until contractions appeared but not for more than 72 hours. The primary outcome was the induction-to-abortion interval.

Results

There were no cases of uterine rupture. Abortion within the study protocol occurred in 45 of the 50 women, for a 90% success rate. There was no significant difference in the induction-to-abortion interval between the 2 groups.

Conclusion

Inducing abortion with lower misoprostol doses appear to be safe and effective throughout the second trimester in women with a single previous cesarean delivery. Larger randomized trials are needed to validate these results.     

A randomized comparison of two regimens of misoprostol for second-trimester pregnancy termination

OBJECTIVE: The purpose of this study was to compare the efficacy and side effects of two different misoprostol regimens for second-trimester pregnancy termination. STUDY DESIGN: We performed a randomized clinical trial in patients who were at 14 to 23 weeks of gestation and who were admitted for medical termination of pregnancy. All patients received 800 microg of vaginal misoprostol and were assigned randomly to 400 microg of oral misoprostol or 400 microg of vaginal misoprostol every 8 hours. Efficacy and side effects were compared. The mean induction time of the study group was compared with that of an historic control group that had received 400 microg vaginally every 12 hours. RESULTS: Forty-three women were assigned randomly, 22 women to vaginal misoprostol and 21 women to oral misoprostol. Induction time and hospital stay were slightly shorter for the oral group; however, the differences were not significant. Side effects were similar for both groups. CONCLUSION: After an initial 800 microg dose of vaginal misoprostol, a regimen of 400 microg of oral misoprostol every 8 hours is as effective as the same dose of vaginal misoprostol with no additional side effects, which provides a convenient alternative for midtrimester pregnancy termination.     

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.     

Randomized controlled trial of misoprostol for second-trimester pregnancy termination associated with fetal malformation

OBJECTIVE: Our purpose was to compare the effectiveness, women's views of the termination procedure, and success of umbilical cord culture for vaginal and oral misoprostol versus intra-amniotic prostaglandin PGF(2alpha) for second-trimester pregnancy termination (STPT). STUDY DESIGN: We randomized 217 women, 15 to 24 weeks' gestation, into 3 groups. Oral (OM) and vaginal (VM) misoprostol groups received 400 microg of misoprostol every 4 hours for 24 hours. The intra-amniotic PGF(2alpha) (IAPG) group received 40 mg of PGF(2alpha) followed by oxytocin infusion. Women completed self-administered questionnaires 3 weeks after the termination procedure. Umbilical cord samples were collected at delivery for karyotype analysis. The primary outcome was the time from start of the procedure to placental delivery. Secondary outcomes were maternal complications, women's acceptance of the termination procedure, and success rates of umbilical cord culture. RESULTS: The time was longer for the OM group (30.5+/-14.4 hours) compared with the VM group (18.3+/-8.2 hours) and the IAPG group (21.1+/-10.2 hours), P<.001 for both comparisons. Women in the VM group reported being more willing to repeat the termination method in the future and reported fewer side effects than those in the other groups, P<.001. Failure rates for umbilical cord cultures were 9.6%, 17.0%, and 45.6% for the VM, OM, and IAPG groups, respectively. CONCLUSION: Oral misoprostol is less effective than intra-amniotic PGF(2alpha) or vaginal misoprostol for STPT. Women report vaginal misoprostol more acceptable than other methods. Umbilical cord culture failure rate is highest in the IAPG group.     

Second trimester pregnancy termination: a comparison of 600 and 800 micrograms of intravaginal misoprostol

OBJECTIVE: To compare the effectiveness of 600 and 800 microg of misoprostol administered intravaginally every 12 hours for termination of second trimester pregnancies. METHODS: One hundred and forty-three pregnant women at 14-26 weeks' gestation were randomized in 2 groups to receive either 600 microg (N = 67), or 800 microg (N = 76) of intravaginal misoprostol every 12 hours until abortion was induced. RESULTS: The incidences of abortion within 24 hours after initial drug administration were 82.1% (n = 55) and 78.9% (n = 60), within 48 hours 92.5% (n = 62) and 92.1% (n = 70), the mean abortion intervals were 15.2 (10.5, 20.8) hours and 15.3 (10.2, 21.8) hours, the complete abortion rates 77.6% (n = 52) and 72.4% (n = 55), and body temperature of more than 38 degrees C were 26.9% (n = 18) and 71.1% (n = 54, p = < 0.001) in the 600 and 800 microg group, respectively. All other side-effects were similar between the 2 groups. CONCLUSION: In consideration of effectiveness and febrile complication, we suggest that 600 microg applied every 12 hours is the most appropriate dose to use for second trimester termination     

Comparison of intravaginal misoprostol and intracervical Foley catheter alone or in combination for termination of second trimester pregnancy

Objectives: To examine the effectiveness, safety and acceptability of intravaginal misoprostol and intracervical Foley catheter alone or in combination for termination of second trimester pregnancy.

Methods: This clinical study was conducted on 90 pregnant patients intended for termination of pregnancy between 13 and 24 gestational weeks for any indication. Enrolled women are equally allocated into three groups:

??Group I (Misoprostol group): a standard regimen of moistened misoprostol (400?μg) 4 hourly inserted vaginally.

??Group II (Catheter group): intracervical Foley catheter inserted, inflated and placed on traction.

??Group III (Combined group): intracervical Foley catheter inserted with a standard regimen of moistened misoprostol (400?μg) 4 hourly intravaginally was used.

Procedure efficacy (defined as complete abortion performed on site), safety and acceptability were assessed.

Results: The induction to abortion interval was 7.5?±?1.25?h in the combined group, compared to 11.76?±?1.63?h in the misoprostol group and 19.76?±?1.52?h in the catheter group (p value?Conclusions: The present results confirmed the high success rate with the shortest induction to abortion interval with a combined use of intracervical Foley catheter and misoprostol for termination of second trimester pregnancy.     

Randomized study on the effect of adding oxytocin to ethacridine lactate or misoprostol for second-trimester termination of pregnancy

OBJECTIVE: To compare effectiveness of misoprostol and ethacridine lactate with or without oxytocin in second-trimester medical abortions. SUBJECTS AND METHODS: A randomized prospective study. A total of 388 women with genetic indications for termination of pregnancy at 13-24 weeks of gestation were recruited. Group I (n=85) were treated with extra-amniotic ethacridine lactate, 10 ml instilled per gestational week, to a maximum of 200 ml. Group II (n=93) were treated with misoprostol administered intravaginally (200 microg), followed by 100 microg of oral misoprostol 4 hourly for 24 h. Group III (n=102) were treated with a combination of ethacrine lactate and oxytocin. An initial dose of 6 mU/min oxytocin was given, followed by additional 6 mU/min doses every 20 min. Group IV (n=96) were treated with a combination of misoprostol and oxytocin administered in a similar way as in group III. The main outcome measures were time to induce abortion, side effects, and failure/success rates. RESULTS: The mean time to induce abortion was 14.2+/-3.6, 13.2+/-3.4, 10.8+/-2.6, and 9.9+/-2.4 h in groups I, II, III, and IV, respectively (p<0.001). Addition of oxytocin to ethacridine lactate did not decrease the risk of prolongation of induction beyond 24 h but use of oxytocin with misoprostol did reduce the risk of induction beyond 24 h (OR: 0.46, 95%CI: 0.21-1, p<0.05). The occurrence of minor side effects was similar in all groups. CONCLUSION: Addition of oxytocin to ethacridine lactate or misoprostol significantly decreases the length of time to induce abortion without supplementary side effects.     

Vaginal misoprostol in termination of second trimester pregnancy

OBJECTIVE: To study the effectiveness and complications of 600 micrograms of intravaginal misoprostol for terminating second trimester pregnancies. STUDY DESIGN: One hundred and seventy-two patients undergoing termination of pregnancy between March 1997 and April 1999 were studied. Each patient received 600 micrograms of intravaginal misoprostol every 12 hours until abortion occurred. RESULTS: The mean induction to abortion time was 24.1 +/- 21.6 hours. The percentage of women aborting within 24 and 48 hours was 68.6 and 89.5 respectively. There was no significant difference in the mean induction to abortion time and the percentage of women aborted within 48 hours between nulliparous and multiparous women. The mean amount of misoprostol used was 1405.5 +/- 1084.6 micrograms. Incomplete abortion occurred in 23.3% of women. The most common complication was temperature of more than 38 degrees C occurred in 41% followed by diarrhoea (20%), nausea and vomiting (15%). CONCLUSION: Six hundred micrograms of vaginal misoprostol is effective, but whether the 48 hours abortion rate can be improved with a large dose or shortened the time interval between doses, requires further study.     

Manual vacuum aspiration for second-trimester pregnancy termination.

OBJECTIVES: To compare manual and electric vacuum aspiration for surgical abortions between 14 and 18 weeks of pregnancy. METHODS: A consecutive case series of pregnant women presenting to Johns Hopkins Bayview Medical Center for abortion. There were 73 women in the manual vacuum aspiration group and 37 women in the electric vacuum aspiration group. Dilatation and evacuation was performed using manual or electric vacuum aspiration according to protocol. Procedure time was assessed with the t-test. RESULTS: In all cases, abortion was performed with initial vacuum. Group sizes were sufficient to detect a 20% difference in mean procedure time with 80% power (calculated with two separate S.D.s for procedure time). There was no significant difference in procedure time between the two groups. CONCLUSIONS: Manual vacuum aspiration can be safely and effectively used in second-trimester abortion procedures and should be more widely investigated for this purpose.