One- and two-day mifepristone-misoprostol intervals for second trimester termination of pregnancy between 13 and 16 weeks of gestation

Objective

To compare the efficacy of 1-day and 2-day mifepristone and misoprostol intervals for second trimester termination of pregnancy between 13 and 16 weeks.

Methods

A prospective randomized cohort study of 100 women who underwent voluntary termination between 13 and 16 weeks of gestation. Patients were randomly assigned to receive 200 mg of oral mifepristone, followed 1 day (group 1) or 2 days (group 2) later by 600 μg of vaginal misoprostol. All patients received 400 μg of oral misoprostol every 6 hours for a maximum of 2 doses. Main outcome measure was successful abortion rate at 24 hours after the start of misoprostol treatment. Secondary outcome measures were induction-to-abortion interval and frequency of adverse events.

Results

The 24-hour successful abortion rate was similar between groups 1 and 2 (47 [94%] vs 50 [100%]; P = 0.241). The mean misoprostol-to-abortion interval was also similar (7.0 ± 3.0 vs 6.8 ± 4.3 hours; P = 0.744). Among the 86 patients for whom histological examination of the products of conception was performed, retained chorionic villi rates were higher in the 1-day regimen group compared with the 2-day regimen group (46.2% [18/39] vs 29.8% [14/47]; P < 0.001).

Conclusion

A 2-day mifepristone-misoprostol interval resulted in fewer incomplete abortions than a 1-day interval for second trimester termination of pregnancy between 13 and 16 weeks.     

Dilation and evacuation for second-trimester genetic pregnancy termination

Dilation and evacuation (D&E) is the most common procedure for second-trimester pregnancy termination currently used by United States obstetrician-gynecologists. Although this method carries morbidity and mortality rates significantly lower than methods requiring labor induction, the procedure most commonly used for second-trimester genetic terminations seems to be labor induction (eg, vaginal prostaglandin suppositories). Many geneticists appear reluctant to recommend D&E over induction methods of pregnancy termination because they perceive that fetal abnormalities cannot be consistently confirmed by evaluation of the products of conception obtained by D&E. We report here 60 consecutive patients who underwent D&E (14-22 weeks' gestation) after detection of fetal abnormalities. The prenatal diagnoses were confirmed in all cases. Our experience thus indicates that D&E is reliable in confirming most prenatal diagnoses and should be the procedure of choice when second-trimester pregnancy termination is chosen because of fetal abnormalities.     

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.     

Intravaginal gemeprost and second-trimester pregnancy termination in the scarred uterus.

OBJECTIVE: To investigate the effectiveness and complication rate of intravaginal gemeprost, a prostaglandin E(1) analogue, for second-trimester pregnancy termination in women with a scarred uterus. METHODS: Of 439 women undergoing induced abortion between the 13th and the 23rd week of pregnancy, 67 had a scarred uterus because of 1 or more cesarean sections or myomectomy. All women received a 1 mg dose of gemeprost intravaginally every 3 h, up to 5 times over 24 h. Those who did not respond received further cycles of gemeprost treatment. RESULTS: The rate of successful abortions among women with uterine scars was not different from that observed in the nulliparous controls, but previously vaginal delivery was associated with a shorter induction to abortion interval. The rate of severe complications did not differ between the groups, and was about 1%. CONCLUSION: The rate of complications following intravaginal administration of a PGE(1) analogue for second-trimester pregnancy termination was similar in women with a scarred or unscarred uterus.     

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.     

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.     

Misoprostol for second-trimester pregnancy termination in women with a prior cesarean delivery

OBJECTIVE: To evaluate the use of misoprostol in second-trimester abortion in women with prior cesarean deliveries. METHODS: A review of women with prior cesarean deliveries undergoing abortion at 14-28 weeks of gestation for a fetal anomaly over a 7.5-year period. Outcome data were compared with a contemporaneous cohort of women with unscarred uteri undergoing the same procedure. Misoprostol was used to induce abortion in all cases, and a variety of dosage regimens were used, the most frequent being 400 mug vaginally every 6 hours (71.3%). RESULTS: During the study period, 720 consecutive women underwent a second-trimester abortion for a fetal anomaly using misoprostol. One hundred one women (14%) had at least 1 prior cesarean delivery: 78 women had 1, 19 women had 2, and 4 women had 3 prior cesarean deliveries. Women with a prior cesarean birth were significantly older (30 years [interquartile range 26-35] versus 33 years [29-37], no cesarean delivery versus cesarean delivery, P = < .001) and of increased parity. The median gestational age at delivery was 19.4 weeks (interquartile range 18-20.7) versus 19.3 weeks (17.7-21), no cesarean delivery versus cesarean delivery, P = .48. The presence of a prior uterine scar did not impact upon abortion duration (16.6 hours [12.1-23.8] versus 14.5 hours [11.4-21.4], no cesarean delivery versus cesarean delivery, P = .07). No differences in blood loss, major hemorrhage, or blood transfusion occurred. There was no case of uterine rupture or hysterectomy. CONCLUSION: In second-trimester abortion, the use of misoprostol in women with prior cesarean delivery was not associated with an excess of complications compared with women with unscarred uteri. LEVEL OF EVIDENCE: II-2.     

Bacteriologic studies in second-trimester pregnancy termination: a comparison of intra- and extra-amniotic methods

Vaginal and cervical cultures were obtained in 20 women undergoing intra-amniotic saline infusion and 20 women having extraamniotic saline infusion for second-trimester abortion. Following expulsion intrauterine cultures were taken and the patients were followed for signs of clinical infection. Sixty percent of the patients had pathogenic bacteria cultured intrauterine cultures after abortion and 7.5% had clinical infection. There was a positive correlation between infection-abortion time and pathogenic intrauterine cultures. No significant differences in the incidence of positive intrauterine cultures or clinical infection between the two groups were found. Of those patients with positive preabortion cultures 70% had identical pathogens cultured from the uterus after expulsion suggesting that most postabortal pathogens arise from endogenous vaginal and cervical sites rather than from exogenous sources.     

Efficacy of mifepristone for cervical priming for second-trimester surgical termination of pregnancy

Objective

To determine whether mifepristone plus misoprostol was as effective as misoprostol with or without laminaria (depending on gestational age) for cervical preparation for second-trimester termination of pregnancy.

Methods

A retrospective cohort study was carried out among women who underwent surgical termination between 14 and 19 + 6 weeks of pregnancy. Those who received preoperative mifepristone were compared with those who did not. The study group received mifepristone plus misoprostol before dilation and evacuation of the uterus between May 2008 and September 2011. The comparison (non-mifepristone) group received misoprostol with or without laminaria between January 2005 and April 2008.

Results

There was no difference between the groups in terms of difficulty of cervical dilation, with an overall relative risk for moderate–difficult dilation in the mifepristone group of 0.91 (95% confidence interval, 0.49–1.68). There was no difference between the groups with regard to complications arising from the procedure.

Conclusion

Mifepristone is effective for cervical priming prior to second-trimester dilation and evacuation in both multiparous and primiparous women, without an increase in complication rates.     

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.     

Modern techniques of medical pregnancy termination

Dilatation and curettage, hysterotomy, vacuum aspiration, hypertonic solutions and prostaglandins are reviewed briefly as abortion techniques. Dilatation, especially beyond Hegar dilator No. 13, can lead to cervical incompetence; the curettage the curettage can result in perforations or adhesions. Hysterotomy is now recommended when tubal ligation is also indicated. Vacuum aspiration entails dilatation under local or regional anesthesia to 2 Hegar numbers beyond the number of postmenstrual weeks of pregnancy. A vacuum source more powerful than usual in surgery and apparatus for resuscitation are required. Vacuum aspiration can be performed up to 12 weeks of amenorrhea; Karman or "miniaspiration" up to 8 weeks. The Karman method requires operative skill to dilate the cervix 5 mm without causing too much pain or leaving retained products. Intraamniotic saline, glucose, or urea used after 16 weeks results in few long-term complications because the delivery resembles natural labor, but it does require up to 5 days' hospitalization. Intraamniotic prostaglandin administration is preferred over the intravenous or intrauterine routes. A self-administered method for bringing on menses has been unsuccessful in women.