Abstract

Background: In the context of a rising trend in labor induction cases, limited research has explored the efficacy of the simultaneous use of misoprostol and Foley catheter methods. This clinical trial investigates the efficacy and safety of combining these labor induction techniques compared to the use of oral misoprostol alone.

Methods: This randomized, open-label clinical trial was conducted on pregnant women candidates for induction of labor due to various medical indications referred to Shariati Hospital, Tehran. The oral misoprostol plus Foley catheter group received 50 mg of oral misoprostol every 4 hours, along with the insertion of a Foley catheter into the cervix under sterile conditions. The comparison group received only oral misoprostol. The Bishop scores in this study were measured prior to induction, and at 6 hours and 12 hours after the initiation of the intervention by a single specialist. Statistical comparisons included the number of deliveries within 24 hours, Bishop score, oxytocin dosage, and maternal and fetal complications.

Results: The two groups were homogeneous in regard to age (27.11 ± 3.88 vs. 26.46 ± 4.95, P=0.26), gestational week (P = 0.44), and BMI (P = 0.88). The combination of the Foley catheter and oral misoprostol group showed significantly higher Bishop scores at 6 hours (P < 0.001) and 12 hours (P = 0.02). The oral misoprostol alone group exhibited a significantly higher rate of cases failing to deliver within 24 hours of induction compared to the combination treatment group (73.4% vs. 11.6%, P < 0.001). Furthermore, the oral misoprostol alone group demonstrated significantly higher incidences of adverse outcomes, including uterine tachysystole (17.6% vs. 3.85%, P < 0.001), NICU hospitalization (8% vs. 1.54%, P = 0.015), abnormal Apgar score at five minutes (4.8% vs. 0%, P=0.01), and meconium presence (7.2% vs. 1.54%, P = 0.03).

Conclusion: This study suggests that the combined method for labor induction is more appropriate due to its quicker and more impactful results, along with lower complication rates.

Introduction

Induction of labor involves the initiation of uterine contractions to facilitate the completion of labor before spontaneous contractions begin. In recent years, there has been a significant surge in the frequency of induced labor, with rates in the United States escalating from 9.5% in 1990 to 27.1% in 20181. Indications for induction include post-term pregnancy, premature rupture of membranes (PROM), conditions associated with high blood pressure like pre-eclampsia and eclampsia, diabetes, chorioamnionitis, and pregnancies involving twins, with post-term pregnancy being one of the most common indications2.

Despite its widespread use, induction of labor carries certain risks, including an elevated risk of infection, hyperstimulation, fetal distress, uterine rupture, and an increased risk of cesarean section3, 4, 5. For women with an unfavorable cervix, the induction process often begins with cervical ripening. Various methods exist for inducing labor and ripening, categorized into non-drug methods such as amniotomy and Foley catheter, and drug methods such as the use of prostaglandins. Prostaglandins stand out as one of the most extensively employed pharmaceuticals for labor induction, particularly in regions with favorable conditions. They can be administered orally, intravenously, or topically in the vagina or cervix6. Previous studies have demonstrated that misoprostol (PGE1) is more effective than prostaglandins E2 (PGE2) and oxytocin7.

Due to the lower incidence of uterine hyperstimulation and fetal complications, prescribing misoprostol in oral form is preferred over vaginal administration. Its availability and cost-effectiveness are among other significant advantages of misoprostol8. The incidence of side effects with misoprostol varies depending on the method of administration, ranging from 8% (vaginal method) to 22% (oral method) and 34% (sublingual method). It proves effective in regions with more limited resources. The purpose of using the Foley catheter is to prepare the cervix (ripening) through mechanical dilation of the cervical canal and an increase in the endogenous secretion of prostaglandins9. Previous studies have consistently reported equal efficacy and fewer occurrences of hyperstimulation, uterine, and fetal complications following the use of the Foley catheter compared to other methods of labor induction10, 11. It appears that the use of the Foley catheter does not elevate the risk of infection12.

The optimal method for inducing labor is currently a topic lacking consensus. Considering the distinct mechanisms of action for each of the pharmacological and mechanical methods of labor induction, there is potential for a synergistic effect when these methods are used in combination. However, concerns exist regarding potential adverse effects on both the mother and the neonate13, 14. Due to limited treatment options and relatively few studies addressing the efficacy and safety of simultaneous use, especially with the oral form of misoprostol, there is a need for further investigation13. Therefore, we have decided to conduct a clinical trial study to assess the effectiveness and side effects of combining these two labor induction methods. This study aims to compare the outcomes with the use of oral misoprostol alone in a group of Iranian women with different indications.

Methods

The present study is a clinical trial conducted on pregnant women with a gestational age of 37 weeks or more who were candidates for induction of labor due to various medical indications. The trial compared the effectiveness and safety of two methods of labor induction: the combination of mechanical (Foley catheter) and pharmacological (misoprostol) methods versus the use of misoprostol alone. The study was conducted in the Obstetrics and Gynecology Department of Shariati Hospital in Tehran during the first three months of 2022.

Sample size determination was based on the results of a study by Hossein et al. 13, where the rates of failed induction within the first 24 hours were 11.8% for the combination of oral misoprostol plus Foley catheter group and 28.7% for the oral misoprostol group. Considering an 85% power of the test, a type I error level of 0.05, and an estimated attrition rate of 15%, the sample size for each study arm was calculated to be 132 participants.

The inclusion criteria were as follows: the need for labor induction as determined by a physician, maternal age of 18 years or older, gestational age of 37 weeks or more, singleton pregnancy, and a Bishop score of less than 6. Women with contraindications to labor induction, such as cephalopelvic disproportion, placenta previa, previous uterine surgery, multiple pregnancies, and medical conditions contraindicating vaginal delivery, were excluded from the study.

In this study, eligible women were randomly allocated to two groups: one receiving oral misoprostol and the other receiving a combination of oral misoprostol and a Foley catheter, following detailed explanations about the study procedures and obtaining written consent from the participants. It's important to note that blinding was not implemented due to the nature of the study design.

Upon entry into the study, eligible participants underwent a comprehensive clinical examination conducted by a gynecologist and their assistant. All relevant demographic information, medical history, details of the pregnancy, and cervical scores were thoroughly documented in specialized forms.

The pregnant women in the combination of oral misoprostol with Foley catheter group were administered oral misoprostol tablets at a dosage of 50 mg every 4 hours, with a maximum of three doses a day. Prior to each dose, the fetal and uterine conditions were assessed, and upon confirmation, the specialist doctor would prescribe the next dose. Subsequently, a sterile Foley catheter of suitable size was inserted into the cervix and secured after evaluating the condition of the cervix and the fetus. The Foley catheter balloon was filled with 30 ml of distilled water or normal saline and fixed to the patient's thigh. In the control group, patients received only the prescribed misoprostol pill, following the same procedure. The Bishop scores in this study were measured prior to induction, and 6 and 12 hours after the initiation of the intervention by a single specialist, which helps to maintain consistency and reduce variability in the scoring process.

If labor did not commence within 24 hours after the intervention in both groups, the induction process was deemed unsuccessful. The decision to continue the treatment process depended on the specialist doctor's opinion. Various parameters, including the number of childbirths within 24 hours after the intervention, the time interval from the beginning of the intervention to delivery, the frequency of cesarean sections, cases of no change in the cervix in the first 24 hours, the dose of oxytocin received, and maternal and fetal complications (such as uterine systolic tachycardia, hypertonic uterine contractions, uterine rupture, postpartum hemorrhage, infection, asphyxia, Apgar score less than 7), and NICU hospitalization, were statistically compared between both groups.

In the statistical analysis, a t-test was employed to compare the time interval between induction and delivery across the two groups. Additionally, a chi-square test was utilized to compare the outcomes after delivery between the two groups. The significance level for establishing relationships was set at less than 0.05. Data analysis was performed using SPSS version 24 software.

× Figure 1 . The process of selecting and allocating the patients in the investigated treatment groups . Figure 1 . The process of selecting and allocating the patients in the investigated treatment groups .

Table 1.

Comparison of the baseline characteristics of patients in the two investigated groups

Variable Foley's catheter and oral misoprostol Oral misoprostol alone P-Value Age (year) 27.11 ± 3.88 26.46 ± 4.95 0.26 Gestational age at delivery (week) 40.03 ± 4.12 39.63 ± 3.77 0.44 BMI (kg/m 2 ) 65 (50) 62 (49.6) 0.88 25 - 30 44 (33.85) 40 (32.0) > 30 21(16.15) 23 (18.4) Labor induction cause Post term 31 (23.85) 30 (24.0) 0.99 High BP 22 (16.92) 23 (18.4) LP 22 (16.92) 21 (16.8) Preeclampsia 17 (13.08) 15 (12.0) GDM 15 (11.54) 14 (11.2) Vaginal bleeding 11 (8.46) 11 (8.8) Decreased fetal movement 12 (9.23) 11 (8.8)

Table 2.

Comparison of the primary outcome between two investigated group

Variable Foley's catheter and oral misoprostol Oral misoprostol alone P.Value Time from the intervention to delivery (h) 18.01 ± 7.66 26 ±6.93