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.     

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.     

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.     

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.     

A randomised comparison of oral and vaginal misoprostol for cervical priming before suction termination of pregnancy

Objective To assess the effectiveness and acceptability of oral misoprostol, self-administered 12 h before surgery, as a cervical priming agent prior to day case suction termination of pregnancy.
Design Randomised trial comparing oral misoprostol with the local standard regimen of vaginal misoprostol.
Subjects Sixty consecutive women scheduled for day case suction termination in one gynaecology unit.
Interventions Cervical priming with misoprostol 400 mg orally, 12 h prior to surgery or 800 mg vaginally, two to four hours prior to surgery.
Main outcome measures Basal cervical dilatation, cumulative force required to dilate the cervix to 9 mm, operative blood loss and side effects (nausea, vomiting, diarrhoea, abdominal pain and vaginal bleeding).
Results There were no significant differences between the oral and vaginal treatment groups in relation to basal dilatation, cumulative force to achieve 9 mm dilatation or gastrointestinal side effects. However, those in the oral group experienced more severe pain and heavier pre-operative bleeding. Two patients in the oral group experienced incomplete abortion at home after taking misoprostol and a further patient required early admission because of heavy bleeding.
Conclusions Because of the unpredictability of action of oral misoprostol, with incomplete abortion or heavy bleeding occurring prior to admission in three patients, we cannot recommend the dosage schedule evaluated here for routine clinical use.     

The psychosocial sequelae of a second-trimester termination of pregnancy for fetal abnormality.

A retrospective study to investigate the psychosocial sequelae of a second-trimester termination of pregnancy (TOP) for fetal abnormality (FA) is described. After appropriate consent was obtained, 84 women and 68 spouses were visited 2 years after the event and asked to complete an extensive questionnaire. Most couples reported a state of emotional turmoil after the TOP. There were differences in the way couples coped with this confusion of feelings. After 2 years about 20 per cent of the women still complained of regular bouts of crying, sadness, and irritability. Husbands reported increased listlessness, loss of concentration, and irritability for up to 12 months after the TOP. In the same period, there was increased marital disharmony in which 12 per cent of the couples separated for a while and one couple obtained a divorce. These problems could be attributed to a lack of synchrony in the grieving process. Confusing and conflicting feelings led to social isolation and lack of communication. Difficulties in coming to terms with the fetal loss were not found to be linked to the type of fetal abnormality or religious beliefs but were related to parental immaturity, inability to communicate needs, a deep-rooted lack of self-esteem before the pregnancy, lack of supporting relationships, and secondary infertility. Suggestions for improved management are given.     

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.     

A randomised trial of oral versus vaginal administration of misoprostol for the purpose of mid-trimester termination of pregnancy

A prospective randomised controlled trial was undertaken to compare the efficacy of two routes of administration, oral versus vaginal, of the prostaglandin E1 analogue misoprostol (Cytotec) to effect termination of pregnancy in the mid-trimester. Fifty-five women were recruited into the trial; 26 to receive all doses orally and 29 via the vaginal route. The dosing regimen was 400 microg as the initial dose followed by a second dose of 200 microg two hours later and then four-hourly 200 microg doses until delivery or 32 hours from commencement of treatment. If delivery had not been effected by the last dose of misoprostol, a Syntocinon infusion was started synchronously Misoprostol administered vaginally was significantly more effective than when administered orally as judged by induction-to-delivery interval and also the need or otherwise to augment therapy with a Syntocinon infusion. The average induction-to-delivery interval was 17.5 hours in the vaginal group compared to 33 hours in the oral group (p = 0.0003). The percentages of women who delivered at 24 and 48 hours were 93% and 100% in the vaginal administration group and 19% and 70% in the oral administration group (p < 0.05). No significant differences in complication rates or side effects were noted between the two groups     

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.     

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.     

Low-dose vaginal misoprostol with or without Foley catheter for late second-trimester pregnancy termination in women with previous multiple cesarean sections

Purpose: To compare between low dose vaginal misoprostol with and without Foley catheter for late second trimester pregnancy termination in women with previous multiple cesarean sections.

Materials and methods: A prospective randomized controlled clinical trial, patients were randomly allocated to either low dose vaginal misoprostol group (n?=?40) or combined low dose vaginal misoprostol plus Foley catheter group (n?=?38). The primary outcome was complete abortion. Secondary outcomes were induction-to-abortion interval, the number of misoprostol doses and occurrence of complications.

Results: Incomplete abortion rate was significantly lower in combined group than misoprostol only group (2.6%versus 15% respectively, p?=?.03). Induction-to-expulsion interval with the combined vaginal misoprostol plus Foley catheter was significantly shorter (p?=?.01) and the number of misoprostol doses in the combined group was significantly lower (p?=?.04). No statistically significant difference in the frequency of complications between both groups.

Conclusions: The combination of low dose vaginal misoprostol and Foley catheter is an effective and safe method for termination of second trimester pregnancy in women with previous multiple cesarean sections.     

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 prospective randomised comparison of sublingual and vaginal misoprostol in second trimester termination of pregnancy

OBJECTIVE: To compare the efficacy, side effects and acceptability of sublingual and vaginal misoprostol for second trimester medical abortion. DESIGN: Prospective randomised controlled trial. SETTING: Tertiary referral unit and a teaching hospital. POPULATION: Two hundred and twenty-four women at 12 to 20 weeks of gestation. METHODS: The women were randomised to receive either sublingual or vaginal misoprostol 400 microg every 3 hours for a maximum of five doses. The course of misoprostol was repeated if the woman did not abort within 24 hours. MAIN OUTCOME MEASURES: The success rate at 48 hours, induction-to-abortion interval and the side effects. RESULTS: There was no significant difference in the success rate at 48 hours (sublingual: 91%; vaginal: 95%). However, the success rate at 24 hours was significantly higher in the vaginal group (85%) compared with the sublingual group (64%). There was no difference in the median induction-to-abortion interval (sublingual: 13.8 hours; vaginal: 12.0 hours). Significantly more women in the sublingual group preferred the route to which they were assigned when compared with the vaginal group. The incidence of fever was also less in the sublingual group. CONCLUSION: The use of vaginal misoprostol for second trimester medical abortion resulted in a higher success rate than sublingual misoprostol at 24 hours but the abortion rate was similar at 48 hours. Vaginal misoprostol should be the regimen of choice but sublingual misoprostol is also an effective alternative.     

The optimization of intravaginal misoprostol dosing schedules in second-trimester pregnancy termination

OBJECTIVE: The purpose of this study was to compare the clinical efficacy and side effects of 3 doses of intravaginal misoprostol for second-trimester pregnancy termination. STUDY DESIGN: This was a prospective randomized, double-blind controlled clinical trial of 150 women who underwent pregnancy termination between 14 and 30 weeks of gestation. Three intravaginal misoprostol regimens were compared: 200 microg misoprostol at 6-hour intervals (group 1), 400 microg misoprostol at 6-hour intervals (group 2), and a loading dose of 600 microg misoprostol followed by 200 microg at 6-hour intervals (group 3). RESULTS: There was a significant difference in the median time to achieve delivery among the 3 groups: group 1 (18.2 hours [IQ, 13.3-32.5 hours]) vs group 2 (15.1 hours [IQ, 10.9-23.7 hours]) vs group 3 (13.2 hours [IQ, 11.2-21.7 hours]; P =.035). Fifty-nine percent of the women in group 1, 76% of the women in group 2, and 80% of the women in group 3 delivered within 24 hours (P =.013). There were 7.8% of the women in group 1, 0% of the women in group 2, and 2% of the women in group 3 who were undelivered at 48 hours (P =.02). There was an increase in the incidence of fever in the first 12 hours (P =.038) and in the incidence of vomiting within 3 hours of the initial dose (P =.048) in group 3 compared with the other groups. CONCLUSION: Intravaginal misoprostol 400 microg at 6-hour intervals appears to be the preferred regimen for second-trimester pregnancy termination, with a shorter commencement to delivery interval than the 200 microg regimen and fewer maternal side-effects than the 600 microg loading dose regimen.