This study aims to investigate the complications due to misoprostol administration for second-trimester termination of pregnancy among women with history of 2 or more cesarean scarring.
The cohort of this retrospective study included 678 subjects who required second-trimester pregnancy termination, from 2013 to 2015 and treated with vaginal misoprostol of 100 to 400 µg. The subjects were divided into 3 groups based on their history of cesarean sections: without a history of cesarean section, with a history of one cesarean section, and with a history of more than one cesarean section and uterine scaring.
The results showed that the success rate of misoprostol administration for pregnancy termination was 95.72%. The rate of bleeding as a complication was significantly higher in subjects with a history of more than one cesarean section than in other participants (risk ratio [RR], 2.24; 95% confidence interval [CI], 1.11–4.0). The incidence of uterine rupture was higher in the group with a history of more than one cesarean section than in other groups. However, no significant difference was observed between the groups (RR, 1.44; 95% CI, 0.27–7.6). There was a significant relationship between the need for other auxiliary treatments in the pregnancy termination and the history of uterine scarring (RR, 3.3; 95% CI, 1.23–9.1).
The present study showed that pregnancy termination using smaller divided dose of misoprostol in patients with previous history of cesarean scarring may be associated with lower incidence of uterine rupture.
Second-trimester termination of pregnancy is increasing due to the progress in early diagnosis of fetal abnormalities and maternal life-threatening conditions [
Considering the increase in the number of applicants for pregnancy termination, choosing the most appropriate method is one of the most important challenges in women's health science [
Misoprostol is a synthetic prostaglandin E1 analogue, indicated for the prevention of gastric ulcers, for the management of spontaneous abortion and also for inducing abortion [
Although uterine rupture is a serious complication with misoprostol use and is associated with high mortality and morbidity, there is a relative contraindication for the use of this drug in women with a history of cesarean section [
This retrospective cohort study was conducted among 678 subjects, referred to teaching hospitals of the Shahid Beheshti University of Medical Sciences, Tehran, Iran, during 2013–2015, who required a second-trimester termination of pregnancy through treatment with vaginal misoprostol.
The inclusion criteria were as follows: pregnant women in the second trimester with 14 to 24 weeks gestational age determined by ultrasound, and candidates for pregnancy termination due to major fetal abnormalities, fetal death, premature rupture of membranes, and other maternal indications for termination of pregnancy. The exclusion criteria were as follows: multiple pregnancy, women with classic cesarean scarring, known allergies to misoprostol, history of heart or liver disease, use of misoprostol by non-vaginal methods, and incomplete medical records.
The participants were divided into 3 groups based on their history of cesarean sections: without a history of cesarean section, with a history of one cesarean section and with a history of more than one cesarean sections and uterine scaring (any history of uterine surgery such as cesarean and myomectomy). The divided dose of misoprostol in all cases ranged from 100 to 400 µg, at intervals of 4 to 6 hours, via vaginal administration [
A checklist including patient's age, gestational age, divided dose of misoprostol, total dose of misoprostol, duration of induction per hour, number of previous cesarean sections and complications, was completed by the study subjects. The recorded complications included postpartum hemorrhage (>500 mL), need for uterine packing, and hysterectomy.
The primary aim of the current study was to investigate the major complications of using misoprostol (such as hemorrhage, uterine laceration, and hysterectomy) in women with a history of 2 or more cesarean sections and in the second place, to evaluate the success rate of misoprostol use in pregnancy termination.
If 48 hours after the administration of misoprostol at a total dosage of 2,000 µg, pregnancy termination was not completed and there was no response to misoprostol, other methods could be used, including high-dose oxytocin induction (50 units oxytocin in 500 mL of normal saline infused during 3 hours; then 1-hour diuresis; then sequentially escalating in a similar fashion to 150, 250, 200, 250, and finally 300 units oxytocin, each in 500 mL normal saline) [
Percentages were calculated for categorical variables, and mean and standard deviation were calculated for continuous variables. Differences between the 2 groups of participants were assessed using independent Student's
In this retrospective study, 678 subjects were studied. Out of them, 247 patients had no cesarean section (group 1), 218 patients had a history of one cesarean section (group 2), and 213 patients had a history of 2 or more cesarean sections (group 3). There was no case of placenta previa in this study. The mean age in the studied groups was 26.3±5.1, 28.8±3.8 and 28.5±4.3 years, respectively. There was no significant difference in gestational age (
Variables | Group 1 (n=247) | Group 2 (n=218) | Group 3 (n=213) | |
---|---|---|---|---|
Age (yr) | 26.3±5.1 | 28.8±3.8 | 28.4±4.3 | <0.001 |
Gestational age (wk) | 19.1±2.8 | 18.9±2.8 | 19.1±3.3 | NS |
Divided dose of misoprostol (µg) | 320.6±98.0 | 313.3±113.0 | 208.4±111.3 | <0.001 |
Total dose of misoprostol (µg) | 1,585.4±229.1 | 1,508.3±264.0 | 1,012.7±351.1 | <0.001 |
Induction time (hr) | 38.3±11.2 | 29.4±8.7 | 24.4±9.9 | <0.001 |
Divided dose of uterine rupture | 133.3±33.3 | 150.0±2.9 | 266.6±66.6 | 0.001 |
Total dose of uterine rupture | 1,533.3±176.4 | 1,000.0±216.0 | 1,266.7±290.6 | 0.001 |
Data are shown as mean±standard deviation.
NS, not significant.
The mean divided dose of the administered misoprostol in group 1 was 320.6±98.0 μg, in participants with one cesarean section was 313.3±113.0 μg and in participants with more than one cesarean section was 208.4±111.3 μg. There was a significant relationship between the total doses of misoprostol vaginal administration in the 3 groups. The total dose of misoprostol vaginal administration in the first group was significantly higher than other participants (
Variables | Group 1 (n=247) | Group 2 (n=218) | Group 3 (n=213) | ARRa) (95% CI) |
---|---|---|---|---|
Bleeding | 8 (3.2) | 7 (3.2) | 16 (7.5) | 2.24 (1.11–4) |
Blood transfusion | 8 (3.2) | 7 (3.2) | 8 (3.8) | 1.14 (0.91–2.1) |
Uterine rupture | 2 (0.8) | 3 (1.4) | 7 (3.3) | 1.44 (0.27–7.6) |
Hysterectomy | 1 (0.4) | 2 (0.9) | 2 (0.9) | 1.0 (0.8–1.1) |
Auxiliary method | 0 | 7 (3.2) | 22 (10.3) | 3.3 (1.23–9.1) |
Curettage | 58 (23.5) | 51 (23.4) | 48 (22.5) | 0.98 (0.87–3.26) |
Total | 77 (31.2) | 77 (35.3) | 87 (40.8) | - |
Values are presented as number (%).
ARR, adjusted relative risk; CI, confidence interval.
a)The reference group is comprised of women with history of one or without a history of cesarean section, adjusted for age, divided dose and total dose of Misoprostol, induction time, parity and maternal body mass index.
The mean induction period in the group, that did not have uterine rupture, was 31.05±11.60 hours. The mean induction period in the group with uterine rupture was 30.00±9.83 hours. The mean induction period was not significantly different in the 2 groups (
In addition, 95.7% of misoprostol cases did not require an auxiliary treatment and only 29 patients needed an auxiliary method, of whom 22 patients were participants with more than one cesarean section (
While surgical abortion is safe when done appropriately [
Various studies have explored the effects of misoprostol on the induction of spontaneous termination of pregnancy, which indicates the positive effects of this drug. However, the use of this drug is always accompanied by complications [
In this retrospective cohort study, we found that medical termination of pregnancy using vaginal misoprostol alone was 95.72% effective in women with 14–24 weeks gestational age. Zikopoulos et al. [
The results of current study showed that the mean divided dose of misoprostol in patients with more than once cesarean section was significantly lower than doses in the other 2 groups. Furthermore, the mean total dose of misoprostol was the highest in group 1 and was also the lowest in subjects group 3. In addition, the induction time in group 3 was lower than in the rest of the subjects. The results of our study showed that there is no significant relationship between uterine rupture and induction period.
Karaçor et al.'s findings [
The results also showed that 4.57% of the subjects of the study lost more than 500 mL of blood during the pregnancy termination and 3.4% of them needed blood transfusion. Statistical analysis showed that there is a significant relationship between hemorrhage complications and history of uterine scarring. The chance of hemorrhage was higher in women with history of more than one cesarean section.
Daskalakis et al.'s study [
Our results also showed that the rate of using auxiliary methods such as high dose oxytocin induction, mechanical methods, or hysterotomy for pregnancy termination was 4.28% and was significantly higher in group 3 than in other groups. It seems that uterine scarring reduces the response of uterine receptors to misoprostol and increases the need for additional approaches in pregnancy termination. In addition, 23.1% of the study subjects required curettage for the removal of fetal remains due to retained placenta or hemorrhage. The results showed that the need for curettage was significantly higher in participants without cesarean section than in those with a history of cesarean section. However, there was no significant difference between participants with one cesarean section and more than one cesarean section.
These contradictions in the results of different studies can be related to ethnic differences as well as differences in the study sample size. Therefore, further studies are required for establishing reliable results. However, it can be argued that drugs with such complications should be used with caution and careful monitoring.
The present study showed that misoprostol use in pregnancy termination did not increase the incidence of uterine rupture in patients with previous history of cesarean scarring. The major complication of misoprostol administration was hemorrhage in the groups with previous cesarean section. In addition, the rate of using auxiliary methods in the pregnancy termination was higher in groups with history of previous cesarean section.
The fact that we did not perform routine curettage or manual uterine vacuity verification after abortion, might be highlighted as a strength of our study. Indications were directed towards placental examination and blood loss evaluation. Moreover, the relatively large sample size of our study, allowed researchers to compare the different outcomes between the 3 groups (without a history of cesarean, with a history of one, and those with 2 or more cesarean sections).
The limitations of this study were related to the retrospective data gathering; therefore, the risk of information bias, such as measurement and misclassification, should be considered. It was assumed that the local regimens of Misoprostol were administered as recorded, but it is possible that some participants received additional medication, although this is unlikely. Uterine scar complications might have been missed if clinical manifestation were not found in the participants. Also, as the dosage of Misoprostol used in each group was different, it should be considered as a limitation of the current study.
The present study showed that termination of pregnancy by less divided dose of misoprostol in patients with previous history of cesarean scarring may be associated with lower uterine rupture. However, considering the incidence of uterine rupture in the group with a history of cesarean section, caution must be exercised.