Termination of mid-trimester pregnancies: misoprostol versus concurrent weighted Foley catheter and misoprostol

Introduction

The universal prenatal screening programs have lead to an increase in the diagnosis of congenital malformations with subsequent gradual increase in second trimester termination of pregnancy (TOP)¹. This represents 10–15% of total abortions performed worldwide².

Termination in the second trimester is more risky than during the first trimester³ and therefore; the pharmacologic management seems to be an appealing alternative to surgical evacuation. Misoprostol has been widely used in different dosages and routes for second-trimester pregnancy terminations. Doses ranging from 200 to 800 µg at intervals ranging from 3 to 12 hours have been described^4–8. High doses at short intervals have been linked to higher percentage of side effects.

Several studies have described the Foley’s catheter as an effective method in ripening the cervix. Obed and Adewole (1994)⁹ showed that it increased the Bishop’s score in women with unripe cervices. Sciscione et al.¹⁰ stated that the Foley’s catheter appears to be superior to prostaglandins for pre-induction cervical ripening. Its use is common in poor countries because it is safe, inexpensive and have low incidence of contractile abnormalities¹¹.

This study was designed to investigate whether the insertion of a weighted fluid filled trans-cervical Foley’s catheter would further improve the effectiveness of 400 µg vaginal misoprostol in terminating mid trimester pregnancies.

Material and methods

This study was carried out at the department of Obstetrics and Gynecology, Menofyia University Hospital, Egypt. Women were recruited and enrolled in the study from July 2011 till the end of April 2012. The institutional review board approved the protocol of the study and an informed consent was obtained from all participants. (see Supplementary Material).

Women enrolled were primigravidae with a singleton pregnancy at a gestational age ranging between 13–23 weeks with a fetal anomaly that is incompatible with life or a fetal demise within one week. We chose to enroll just primigravidae, because we believe that the induction to expulsion time should be considered separately for multiparous and nulliparous women. Furthermore, for multiparas, if a woman had 10 previous vaginal deliveries, she cannot be compared to a woman who had only one vaginal delivery even though both are considered as multipara. A separate analysis would be needed for primiparous women, and both low order and high order multiparous women. Gestational age was calculated from the date of the first day of last menstrual period and confirmed by a vaginal ultrasound scan. Women with any of the following were excluded from the study: 1) Previous uterine scar; 2) Contraindication to misoprostol; 3) Low lying placenta; 4) Operation on the cervix; 5) Chorioamnionitis.

In our institution, women with a planned a mid-trimester termination of pregnancy can have a varied and unpredictable response to the method of termination selected. The population of patients at the hospital we conducted the study is mainly illiterate. So, if a patient is assigned to a specific group, you must then to ask for that individual to sign a consent form. For the most, the perception is that their signature provides permission to perform a harmful procedure or a procedure with an unknown outcome. This apprehension leads to asking members of their family who are present what to do, and more often than not they change their mind about the specific line of management offered to them. Due to this uncertainty we were unable to ensure that the participants would accept the method they would receive under randomized conditions. Our expectation was that we would probably have too many withdrawals, and so we refrained from randomizing the participants to maintain our chosen cohort for the completion of the study. We assumed that a significant difference in the induction to abortion interval between both groups would be 3 hours. With an alpha of 0.05, 80% power and a 2 sided significance level of 0.05, we predicted a sample size of 50 women would be needed. Initially we planned to recruit 50 women divided equally between two groups. However, after starting enrollment, we were confronted with the fact that many women preferred to be enrolled in the combined group rather than the misoprostol only group. When patient number 50 was enrolled, there were 20 women assigned to group I and 30 women to group II.

All participants were subjected to complete history taking and thorough clinical examination. Induction of abortion was carried out in group I by inserting two tablets; each contains 200 microgram misoprostol (Segma pharmaceuticals, Egypt), in the posterior vaginal fornix every four hours. In group II, with the patient in the lithotomy position, the cervix was visualized using a Cusco’s speculum and then sterilized with povidone iodine. The anterior lip of the cervix was grasped with a ring forceps and another ring forceps was then used to push the catheter through the cervix under direct visualization. The balloon was then inflated with 30 ml saline and the catheter was pulled back snugly against the internal os and taped to the inner aspect of thigh. A bag filled with saline was applied to the distal end of the catheter to provide moderate traction. Different filling volumes were used at different gestational ages. We used 250 ml. at 13–17 weeks, 300 ml. with ages at 18–20 weeks and 500 ml at gestational ages more than 20 weeks. The filled bag was approximately equivalent to 250, 300 and 500 grams in weight respectively. A 400 ug misoprostol vaginal dose “two tablets” was then inserted in the posterior vaginal fornix/4 hours as in group I. A maximum of 4 misoprostol doses was used in both groups. Each patient received 1 gram Ampicillin/6 hours as a prophylactic antibiotic. As soon as the catheter was expelled, re-assessment of the dilatation and effacement of the cervix was carried out. Oxytocin infusion was started 4 hours after the last dose of misoprostol in both groups according to the standard protocol in our department.

The patient was assessed every 4 hours for vital signs, cervical dilatation, expulsion of fetus and occurrence of complications such as nausea, vomiting, abdominal pain and infection. All patients received intravenous oxytocin 20 IU after expulsion of the fetus to help placental separation and delivery. Retained placenta was considered if no manifestations for placental separation appeared 30 minutes after fetal expulsion. The patient was anesthetized and manual separation of the placenta was carried out. Surgical evacuation was performed if any remnant of conception such as missed placental lobe or piece of membranes was suspected to be retained inside the uterus.

After placental expulsion, mothers were observed for the presence of uterine atony and post abortive bleeding. This was assessed by counting the number and change in the weight of the sanitary pads used by the patient. Bleeding was considered average if less than 200 cc and excessive if more than 200 cc.

The measured primary outcome parameter was the induction to abortion interval. Secondary parameters were: 1) Occurrence of side effects; 2) Need for manual separation of the placenta; 3) The need for surgical evacuation; and 4) Occurrence of post-abortive bleeding.

For the purpose of statistical analysis, women enrolled were categorized into 3 groups according to gestational age (Table 1). Early mid trimester group between 13 to 17 weeks, mid mid-trimester group 18–20 weeks and late mid trimester group 21 to 23 weeks.

Results were tabulated and analyzed on an IBM personal computer using Epi Info, version 6, a word-processing database and statistics program. Descriptive statistics was expressed as mean and standard deviation. The student t test was used to evaluate independent variables that are normally distributed. The Chi square test was used to compare 2 rates unless the number in the contingency table was < 6 where Fisher’s exact test was used. A significant statistical level was considered if P was < 0.05.

Results

The groups were equal at the baseline characteristics. Age of mothers was not significantly different between both groups (27.93 ± 6.48 years in group I versus 27.19 ± 5.23 years in group II; P > 0.05). There was no significant difference in gestational age at enrollment (18.0 ± 2.41 weeks in group I versus 17.9 ± 2.88 weeks in group II; P > 0.05). We subdivided participants into 3 groups according to gestational age and we had a separate statistical analysis for each group. Women enrolled were categorized into 3 groups as shown in Table 1.

Table 3 shows that the secondary outcome parameters are not statistically different between both groups. Table 4 reports the side effects in both groups.

Discussion

This study showed that the combination of Foley’s catheter and misoprostol resulted in a significantly shorter induction to abortion interval compared to misoprostol alone. Because we used similar misoprostol dose in both groups, this decrease in duration was attributed to the use of weighted Foley’s catheter with moderate traction applied over its distal end. Early studies comparing the Foley catheter with PGE2 tablets found no difference in the termination time between both methods^12,13. No traction was applied in either of these studies. Bani-Irshaid et al.¹⁴ compared the efficacy and safety of Foley catheter (with and without traction) and prostaglandin E2 vaginal tablets in terminating second and early third trimester pregnancies in 258 women. They concluded that the efficacy of the Foley’s catheter can be enhanced with the use of traction to give similar results to prostaglandin E2. No studies have compared the use of prostaglandin E1 vaginal tablets alone versus its combined use with Foley’s catheter in terminating mid trimester gestations. The catheter exerts its effect by disrupting the integrity of amnion–chorion and myometrium in addition to cervical collagen increasing prostaglandin and cytokines release rendering the uterus susceptible^15–17.

The induction to delivery interval increased with increasing gestational age in both groups. We also had rates of fetal expulsion of 100% in both groups at a gestational age between 13–17 weeks which decreased with advancement of gestational age. This is in agreement with other investigators’ findings. Gómez et al. in 2009¹⁸ found that the mean induction-to-abortion interval increases by 4 hours after 20 weeks GA. Ashok. et al., 2003¹⁹ in another study on mid-trimester medical termination of pregnancy concluded that the induction to abortion interval was significantly longer in the higher gestational age pregnancies. Similar finding were reported by Dilbaz et al.²⁰ in pregnancies between 13–20 weeks. We used a misoprostol dose of 400 microgram administered every 4 hours. Doses of 600 and 800 µg have shown comparable successful abortion rates but were associated with high rates of side effects^21,22. Wong and colleagues compared the efficacy and side effects of 400 microgram misoprostol administered every 3 and every 6 hours. They concluded that the three-hour regime was more effective in terms of a significantly shorter drug administration to abortion interval on the expense of more side effects. We had no significant difference in the incidence of side effects between both groups. Side effects are less common with the vaginal route compared to other routes of administration²³.

In the present study, there was no significant difference in the need for post abortive manual separation of the placenta. Surgical evacuation should only be considered if there is clinical evidence that the abortion is incomplete²⁴. In the current study an incidence of 20% was reported in the misoprostol group while only 10% required surgical evacuation in the combined group. Ashok et al. 2003¹⁹ studied midtrimester medical termination of pregnancy using misoprostol and concluded that surgical evacuation of the uterus under general anesthesia was required to complete the abortion in 8.1% of women. In 2005 report from the Scottish group estimated the rate of surgical evacuation as low as 2.5%²⁵. The high incidence of surgical evacuation in this study may reflect the inadequate experience dealing with second trimester abortions. Cases of induced abortion in our society are few because they are considered illegal unless performed to save a maternal life. Our findings showed that the majority of cases who required surgical evacuation in both groups were between 13–17 weeks (5/7). This is in agreement with the results of other investigators²⁶. It is probably wise to inform women undergoing pregnancy termination early in the second trimester of possible higher chance of incomplete abortion. There was no statistically significant difference in the amount of blood loss between both groups.

To conclude, the use of a weighted trans-cervical Foley’s catheter filled with 30 ml saline improve the effectiveness of 400 µg vaginal misoprostol in terminating mid trimester pregnancies as reflected by a shorter induction to delivery interval with no significant increase in the incidence of side effects.