ToP remains one of the most common procedures in obstetrics and gynaecology. ToP is generally performed by surgical evacuation. Modern induced abortion methods typically include the use of one or a combination of the following: prostaglandin analogues (such as misoprostol, gemeprost, dinoprostone), mifepristone, osmotic cervical dilators, Foley catheters, and oxytocin. In 1994, Jain JK et al., first described the use of the prostaglandins for second trimester ToP [1]. Misoprostol has been widely used, both orally and vaginally, for ToP owing to its low cost and high effectiveness [2]. However, using prostaglandins provides the opportunity to perform a post-mortem autopsy on the foetus, when further information is required. Using prostaglandins also has lower maternal morbidity rates than those using surgical evacuation. Although prostaglandins have shown remarkably good results, serious complications have been reported during ToP procedures in the second trimester. These complications include: blood loss requiring transfusion, infections, uterine rupture, cervical lacerations, obstetric fistulas and major unintended surgery [3,4].
The number of CDs has increased worldwide. CD rates reached 51.9% (42.9% in the public and 87.9% in the private health sector) of all births in Brazil [5]. Due to the increasing rate of CDs, the number of women with a history of CD who is offered ToP has increased. Several guidelines are available on the safety of misoprostol in women with one previous CD [6,7].
The aim of this study was to compare the safety and efficacy of two different vaginal misoprostol regimens in the second trimester ToP in women who had one prior CD against controls.
Materials and Methods
This retrospective study was conducted at the Department of Obstetrics and Hacettepe University Faculty of Medicine from January 2005 to December 2014. The study was approved by the Local Ethical Committee (approval number: GO 14-595), Hacettepe University, Faculty of Medicine, Ankara, Turkey.
The demographic and clinical characteristics of the patients were obtained from patient files and electronic records of the hospital. Patient demographics (age, parity, gravida, etc.,), Body Mass Index (BMI), indication of ToP, gestational age at ToP (weeks), duration between induction to abortion (hours), total misoprostol dose (μg), foetal weight (gram), post-abortion hospitalisation time (days), and complications were recorded. The duration between induction to abortion was defined as the interval between the placement of the first dose of misoprostol and the expulsion of the products of conception.
Patient records with the following characteristics were excluded from the study: first or third trimester ToP, twin pregnancy, history of myomectomy, cervical incompetence, presence of large uterine leiomyoma, or congenital uterine anomaly.
The study cohort comprised 519 women, including 85 with previous CD (Group I) and 434 with no known uterine scar (Group II). The method used for ToP was chosen based on history of CD. Group I included data records of patients with the following procedure done on them as per the hospital protocol; a 50 μg misoprostol tablet (Cytotec®, Ali Raif Pharm. Co, Turkey) inserted vaginally every six hours until regular uterine contraction. Group II consisted data of patients that underwent the following procedure; a 200 μg misoprostol tablet inserted vaginally every six hours for the first 24 hours; subsequently, 800 μg/day misoprostol applied vaginally until regular uterine contractions.
Statistical Analysis
The Chi-square or Fisher’s-Exact test was used for qualitative data, and the Student’s t-test or Mann-Whitney U-test was used for quantitative data. The p<0.05 was considered statistically significant. Statistical analysis was performed using SPSS version 17 (SPSS, Chicago, Illinois, USA).
Results
A total of 519 patient’s data were enrolled in this study and were divided into two groups. The study group consisted of patients/data with a history of caesarean section (Group I, n: 85). The control group consisted of patients/data with no uterine scar or CD (Group II, n: 434). Forty-six patient records were excluded because of several reasons, such as incomplete data, history of myomectomy, and protocol corruption. Most common indications for ToP in both groups were linked to foetal causes, including chromosomal abnormalities, non-chromosomal malformations, single gene disorders, and congenital infections. There were no statistically significant differences in maternal demographics such as age (years), gravida, parity, BMI (kg/m2) [Table/Fig-1].
Demographic and clinical features of the groups.
| Group I (n: 85) | Group II (n: 434) | p-value |
|---|
| Maternal age (years) | 32.55±4.50 | 32.17±4.59 | 0.136 |
| Gravida | 3.08±1.29 | 2.98±1.50 | 0.398 |
| Parity | 1.49±0.82 | 1.39±1.37 | 0.076 |
| BMI (kg/m2) | 25.71±3.04 | 25.40±3.59 | 0.192 |
BMI: Body mass index
Data are given as mean±standard deviation
The mean dose of misoprostol required to induce labour was 579.41±411.90 μg in Group I and 1091.60±515.60 μg in Group II (p<0.001). There were no statistically significant differences detected in foetal weight and the induction to abortion interval (p=0.319 and p=0.371, respectively). [Table/Fig-2] summarises the characteristics of procedures in the two groups.
Clinical characteristics of termination of pregnancy procedures in the both groups.
| Group I (n:85) | Group II (n: 434) | p-value |
|---|
| Gestational age at time of ToP (weeks) | 19.19±2.63 | 19.6±305 | 0.380 |
| Total doses (μg) | 579.41±411.90 | 1091.60±515.60 | <0.001 |
| Induction to abortion interval (hours) | 54.08±42.85 | 47.19±31.39 | 0.371 |
| Fetal weight (g) | 280.7±167.9 | 317.2±213.5 | 0.319 |
| Post-abortion hospitalisation (days) | 3.34±2.89 | 2.58±2.27 | 0.003 |
ToP: Termination of pregnancy
There were no serious adverse effects of misoprostol in this series of patients. However, the procedure was terminated in two patients owing to fever and sepsis, respectively. Three patients (3.6%) in the Group I and 48 (11.1%) patients in the Group II developed fever during labour (p=0.019). There was no statistically significant difference between these two groups in terms of chills and diarrhoea for the period of hospitalisation for termination and for 48 hours post-termination.
Successful rates of procedures were 91.8% and 99.1% in Group I and II, respectively (p<0.001). Cases of haemorrhages requiring transfusion were higher in Group I than in Group II (5.9% vs. 1.6%, p=0.032). Rates of other complications such as placenta retention, uterine rupture, and sepsis were similar in both groups [Table/Fig-3].
Side effects of misoprostol and complication of both procedures.
| Group I (n: 85) | Group II (n: 434) | p-value |
|---|
| Side effects |
| Fever | 3 (3.6%) | 48 (11.1%) | 0.019 |
| Chills | 3 (3.6%) | 36 (8.3%) | 0.178 |
| Diarrhoea | 1 (1.2%) | 18 (4.1%) | 0.338 |
| Complications |
| Procedure failure | 7 (8.2%) | 4 (0.9%) | <0.001 |
| Haemorrhage | 5 (5.9%) | 7 (1.6%) | 0.032 |
| Placenta retention | 1 (1.2%) | 6 (1.4%) | 1.000 |
| Uterine rupture | 1 (1.2%) | 0 (0%) | 0.164 |
| Sepsis | 0 (0%) | 1 (0.2%) | 1.000 |
Fisher’s Exact Test were used for statistical analysis
Discussion
This study is one of the largest series reported to date in women with one prior CD undergoing ToP using only intravaginal misoprostol. Different ToP protocols were used such as 4 doses of 50 μg misoprostol and 4 doses of 200 μg misoprostol applied vaginally until regular uterine contractions, in the previous CD group and control group, respectively. In our series, unresponsiveness to intravaginal misoprostol was more common in patients with history of CD compared to controls (8.2% vs. 0.9%, p<0.001). The lower success rate in our study may be attributed to the lower dose used in the protocol for Group I. However, the overall success rates in this study (97.88%) are consistent with those reported in the previous literature [4,8,9].
Several studies revealed that there were no statistically significant differences in induction to abortion time when using same dosage in the two groups [4]. Although we used lower doses in the previous CD group than in the control group, induction to abortion intervals in the two groups were also similar (p=0.371). We found that a lower dose of misoprostol used in the group with previous CD did not impact the delay to abortion significantly. However, when we compared the results of previous studies, the lower induction to abortion time (hours) in present study may be attributed to the lower dose used in the protocols.
Another important finding of this study was that a history of CD appears to increase the frequency of haemorrhage, with the need for a blood transfusion in women who performed a second trimester ToP (5.9% vs. 1.6%, p: 0.032). Present results do not comply with the existing literature. Fawzy M et al., found no significant difference between CD and control groups in the incidence of severe haemorrhage requiring a blood transfusion [3]. Similarly, other studies in the literature reported no evidence that a previous CD affects the incidence of complications including severe haemorrhage [4,9,10].
For labour induction, the risk of uterine rupture is increased with the use of misoprostol in women with CD compared with women without previous CD [11,12]. Recently, a study showed that use of misoprostol for second trimester abortion in women with a history of CD, risk of uterine rupture is similar when compared with the controls [11]. Present data suggest that a CD history cannot be a risk factor for uterine rupture in women scheduled for a second trimester ToP (p=0.164).
Limitation
Limitation of the study is the usage of different doses on the study groups.
Conclusion
History of a CD does not abolish the possibility of using misoprostol for second trimester ToP. However, patients who undergo misoprostol induction must be closely observed for possible side effects and complications.
BMI: Body mass indexData are given as mean±standard deviationToP: Termination of pregnancyFisher’s Exact Test were used for statistical analysis