Abstract
Objective:
To compare, in a pilot study, combined dinoprostone vaginal insert and Foley catheter (DVI+Foley) with Foley alone (Foley) for cervical ripening and labor induction at term.
Study Design:
In this open-label pilot randomized controlled trial, women not in labor, with intact membranes, no prior uterine incision, an unfavorable cervix, gestational age ≥37 weeks, and a live, non-anomalous singleton fetus in cephalic presentation were randomly assigned, stratified by parity, to DVI+Foley or Foley. Oxytocin was used in both groups after cervical ripening. Primary outcome was time to vaginal delivery.
Results:
From April 2017 to January 2018, 100 women were randomized. Median (25th–75th percentile) time to vaginal delivery for nulliparous women was 21.2 (16.6–38.0) hours with DVI+Foley (n=26) compared to 31.3 (23.3–46.9) hours with Foley (n=24) (Wilcoxon p=0.05). Median time to vaginal delivery for parous women was 17.1 (13.6–21.9) hours with DVI+Foley (n=25) compared to 14.8 (12.7–19.5) hours with Foley (n=25) (Wilcoxon p=0.21). Results were also analyzed to consider the competing risk of cesarean using cumulative incidence functions.
Conclusion:
Compared to Foley alone, combined use of the dinoprostone vaginal insert and Foley for cervical ripening may shorten time to vaginal delivery for nulliparous but not parous women.
Keywords: Cervical ripening, cumulative incidence function, labor, labor induction, multiparae, nulliparae, nulliparous women, parous women
INTRODUCTION
Almost one-fourth of pregnant women in the United States currently undergo labor induction.1 The rate has more than doubled in recent years, having been less than 10% in 1990.2 Furthermore, due to the recently published ARRIVE trial—showing lower cesarean rates, lower maternal morbidity rates, and lower rates of neonatal respiratory morbidity with induction in low-risk nulliparous women at 39 weeks (compared to expectant management until 41 weeks)3—the rate of labor induction almost certainly will increase further in the near future.
Cervical ripening agents are used to start labor inductions in the setting of an unfavorable cervix. The reason for this fact is that oxytocin administration alone, in the setting of an unfavorable cervix, is less successful in achieving vaginal delivery.4 Options for cervical ripening include mechanical agents, such as Foley catheter, and pharmacologic methods, primarily synthetic prostaglandins. Due to a lower cesarean delivery rate and less oxytocin use, a systematic review and meta-analysis concluded that the controlled release dinoprostone vaginal insert (Cervidil®; Ferring Pharmaceuticals, Saint-Prex, Switzerland) was superior to repeated prostaglandin administration (either dinoprostone or misoprostol).5 Compared to the dinoprostone vaginal insert, starting labor inductions for women with unfavorable cervices with the Foley catheter leads to shorter times to delivery.6
There has been recent interest in combined use of cervical ripening methods. Combined use of misoprostol and Foley has been shown to result in shorter times to delivery than with Foley alone.7 However, not all authors have found a decreased time to delivery with this combination, and some have seen more uterine tachysystole with the addition of misoprostol.8 This unwanted effect with misoprostol is what causes many to favor agents besides misoprostol, despite that drug’s low cost. The combination of the dinoprostone vaginal insert and Foley catheter for cervical ripening and labor induction had not been studied when we designed this trial (PubMed and ClinicalTrials.gov searches using the terms “dinoprostone” AND “Foley” on July 23, 2016). We hypothesized that this combination might be superior to Foley alone. Therefore, we designed a pilot study to estimate the parameters necessary to guide the development of a multicenter randomized controlled trial to compare the combined use of the dinoprostone vaginal insert and Foley catheter with Foley catheter alone for cervical ripening and labor induction in term pregnant women.
MATERIALS AND METHODS
We conducted an open-label pilot randomized controlled trial enrolling mother-infant pairs at The Children’s Hospital at the University of Oklahoma Medical Center. Our labor and delivery unit is staffed by academic faculty of the Department of Obstetrics and Gynecology, at least one of whom in in the hospital at all times. Our practice, for labor and other clinical topics/problems, is based both on local and national guidelines, and labor management decisions are based on the current recommendations from the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine.9 Women were eligible for the study if they were to undergo labor induction with an unfavorable cervix (defined as ≤2 cm dilated and if 2 cm, <80% effaced) at a gestational age ≥37 weeks and were carrying a live, singleton fetus in cephalic presentation. Exclusion criteria were age younger than 18 or older than 50 years; labor or contractions more frequent than every five minutes; ruptured membranes; prior uterine incision; temperature ≥38 degrees Celsius; placenta previa, suspected placental abruption or undiagnosed bleeding more than spotting, or any other contraindication to vaginal delivery; HIV infection or any other condition that adversely affects the immune system; allergy to dinoprostone; inability to undergo informed consent in English or Spanish; known fetal anomaly; or fetal heart rate tracing prior to enrollment that had less than minimal variability, one or more late decelerations, or more than two variable decelerations. The institutional review board of the University of Oklahoma approved the study, and it was registered with ClinicalTrials.gov (NCT03111316).
Women who were to undergo labor inductions starting with cervical ripening with a Foley catheter (the most frequent approach at our center) were approached about participation. After a non-latex transcervical Foley catheter with a 30-mL balloon was placed according to standard clinical practice, the balloon was inflated with 30 mL of sterile water, pulled back against the internal os, and the Foley catheter was taped to the inner maternal thigh under minimal tension. Then, those women who agreed to participate were randomized 1:1 within parity strata (nulliparous or parous) to also have either a dinoprostone vaginal insert placed in the posterior vaginal fornix according to package insert instructions or to have no additional agent used. In both groups, women remained recumbent for 30 minutes after agent placement and, except for trips to the restroom, underwent continuous monitoring of uterine contractions and fetal heart rate. Oxytocin, according to standard intravenous protocol, was allowed only after removal of cervical ripening agent(s). The oxytocin protocol at our institution is to start at two milliunits/minute and increase by two milliunits/minute every 30 minutes until three contractions per 10 minutes or Montevideo units of 200–300, with a maximum infusion rate of 36 milliunits/minute. For women undergoing labor inductions, amniotomy is performed as soon as it is deemed feasible.
In both groups, the Foley catheter was to be removed if any of the following occurred: expulsion, fetal heart rate tracing mandating evaluation for membrane rupture and placement of internal monitors, spontaneous membrane rupture, or if 12 hours had elapsed since placement. The dinoprostone vaginal insert was to be removed if: fetal heart rate tracing mandated evaluation for membrane rupture and placement of internal monitors, tachysystole developed (more than five contractions per 10 minutes averaged over 30 minutes), spontaneous membrane rupture, or 12 hours had elapsed since placement. These criteria for removal were provided to patients’ healthcare team. However, in keeping with the pragmatic design of the trial, decisions regarding removal of ripening agent(s), labor management after removal and decision for cesarean delivery were left to the discretion of the attending obstetrician.
The primary outcome of interest was time from placement of the transcervical Foley catheter to vaginal delivery. Secondary outcomes included delivery by 12 and 24 hours and vaginal delivery by 12 and 24 hours. Other outcomes examined included cesarean delivery, chorioamnionitis (temperature ≥38 degrees Celsius prior to delivery and one or more of: maternal heart rate >100, baseline fetal heart rate >160, uterine tenderness, and/or purulent or foul-smelling cervical discharge), endometritis (temperature ≥38 degrees Celsius after delivery on two or more occasions and no other source of fever apparent), wound infection (cesarean wound disruption and treatment with antibiotics for that indication; specifically excludes antibiotic treatment for “wound cellulitis” not associated with spontaneous or iatrogenic wound disruption), puerperal infection (chorioamnionitis, endometritis, and/or wound infection), uterine tachysystole (more than five contractions per 10 minutes, averaged over 30 minutes), and neonatal characteristics at delivery and discharge (birth weight, Apgar scores, neonatal intensive care unit admission, other complications, and neonatal death). We also evaluated reason(s) for cesarean delivery including fetal heart rate abnormality, failed induction (poor labor progress and cervical dilation <6 cm), active phase abnormality (poor labor progress and cervix at least 6 cm dilated but not completely dilated), second stage abnormality (poor labor progress and cervix completely dilated).
Using an intent-to-treat approach, patient characteristics and outcomes were compared between study groups. Continuous measures were analyzed using the two-sample t-test or Wilcoxon two-sample test, as appropriate for the distribution. Categorical measures were analyzed using the chi-square test of association or Fisher’s exact test. Consistent with methods that have customarily been reported for comparisons of cervical ripening and labor induction agents, Kaplan Meier survival curves were generated separately for nulliparous and parous women to display time to vaginal delivery for each treatment group, censoring cesarean deliveries. The survival functions for the two treatment groups were compared using the generalized Wilcoxon test. However, because patients who experience a cesarean delivery do not remain at risk of vaginal delivery, cesarean delivery could be considered a competing event in the time-to-event analyses, which, if ignored, can lead to overestimation of the benefits of the intervention.10,11 Thus, we also analyzed the data using methods appropriate for competing events, comparing the cumulative incidence function (CIF) for vaginal delivery by treatment group using the Gray’s test.10
The randomization scheme was produced by JDP using a computer generated random number sequence in randomly varying blocks of 4 and 6. Allocation assignments were managed using the randomization module in the web-based Research Electronic Data Capture (REDCap) system.12 Other authors and research nurses were unaware of the sequence. This was a pilot study aimed at estimating the outcomes to be evaluated in a planned next-step multicenter trial, so it is not surprising that we had less than 50% power to detect a 4-hour difference between groups.
RESULTS
From April 2017 to January 2018, we enrolled 100 women. Though the recruitment goal was to have 25 women in each of the 4 groups defined by the combination of parity and treatment status, after correction of one patient randomized to the wrong parity stratum there were 26 women in the nulliparous dinoprostone insert and Foley group, 24 women in the nulliparous Foley only group, and 25 women in each of the parous treatment and control groups. Otherwise, there was 100% adherence to the assigned group. See Figure 1 for patient distribution. Demographic data and baseline obstetric characteristics of the study patients are presented in Table 1. There was a higher proportion of gestational hypertension in parous women randomized to the dinoprostone insert and Foley combined than in parous women randomized to Foley alone. Otherwise, there were no statistically significant differences between groups.
Figure 1.
Flow diagram showing details of patient allocation as enrolled and randomized
Table 1.
Study patient demographic data and baseline characteristics
| Dinoprostone Insert and Foley | Foley Alone | |
|---|---|---|
| Nulliparous Women | n=26 | n=24 |
| Age (y) | 24.4 ± 5.8 | 26.4 ± 5.6 |
| Gestational age (w) | 38.5 ± 1.5 | 38.9 ± 1.2 |
| BMI | 33.0 ± 1.5 | 35.0 ± 0.27 |
| Race or ethnicity | ||
| Chronic hypertension | 3 (12%) | 4 (17%) |
| Diabetes | ||
| Preeclampsia | 5 (19%) | 0 (0%) |
| Gestational hypertension | 5 (19%) | 9 (38%) |
| Fetal growth restriction | 1 (4%) | 0 (0%) |
| Parous Women | n=25 | n=25 |
| Age (y) | 29.7 ± 5.9 | 32.2 ± 6.3 |
| Gestational age (w) | 38.8 ± 1.3 | 38.9 ± 1.2 |
| BMI | 33.9 ± 6.8 | 34.8 ± 5.6 |
| Race or ethnicity | ||
| Chronic hypertension | 2 (8%) | 3 (12%) |
| Diabetes | ||
| Preeclampsia | 1 (4%) | 0 (0%) |
| Gestational hypertension | 8 (32%) | 1 (4%) |
| Fetal growth restriction | 1 (4%) | 1 (4%) |
Data are presented as mean ± standard deviation or n (%). Abbreviations used in the table: y=years; w=weeks; BMI=body mass index—measured as weight in kilograms divided by the square of height in meters. Data were analyzed using Wilcoxon two-sample test, two-sample t-test, Fisher’s exact test, or chi-square test, as appropriate.
Using Kaplan-Meier estimation, the median (25th–75th percentile) time from Foley placement to vaginal delivery for nulliparous women in the combined dinoprostone insert and Foley group was 21.2 (16.6–38.0) compared to 31.3 (23.3–46.9) hours for those in the Foley only group (generalized Wilcoxon p=0.05, Figure 2A). The median time from Foley placement to vaginal delivery for parous women in the combined dinoprostone insert and Foley group was 17.1 (13.6–21.9) compared to 14.8 (12.7–19.5) hours for those in the Foley only group (generalized Wilcoxon p=0.21, Figure 2B). These differences did not achieve statistical significance.
Figure 2.
Kaplan Meier survival curves for time to vaginal delivery among patients randomized to the dinoprostone insert and Foley (blue line) or Foley alone (red line). Nulliparous women are shown in panel A, and parous women are shown in panel B.
When taking the competing risk of cesarean delivery into account and estimating the cumulative incidence function for vaginal delivery, nulliparous women in the combined dinoprostone insert and Foley group exhibited a greater incidence of vaginal delivery across most time points compared to the Foley only group, but the observed differences did not achieve statistical significance in this sample (Gray’s test p=0.34, Figure 3A). Among parous women, differences by treatment group were more modest and reversed, with slightly increased vaginal deliveries at all time points among the Foley only group, but did not reach statistical significance (Gray’s test, p=0.20, Figure 3B).
Figure 3.
Cumulative incidence function curves for vaginal delivery accounting for competing events among patients randomized to the dinoprostone insert and Foley (blue line) or Foley alone (red line). Nulliparous women are shown in panel A, and parous women are shown in panel B.
Secondary and other outcomes are shown in Table 2. Nulliparous women randomized to the dinoprostone insert and Foley group were statistically significantly more likely to be delivered within 24 hours (p=0.002) and to be delivered vaginally within 24 hours (p=0.02) without an increase in the rate of cesarean delivery. No such differences between treatment groups were noted among parous women.
Table 2.
Secondary and other outcomes among women randomized to the dinoprostone insert and Foley or Foley alone, stratified by parity
| Dinoprostone Insert and Foley | Foley Alone | p | |
|---|---|---|---|
| Nulliparous Women | n=26 | n=24 | |
| Cesarean delivery | 8 (31%) | 7 (29%) | 0.90 |
| Delivered by 12 h | 2 (8%) | 1 (4%) | 1.00 |
| Delivered by 24 h | 19 (73%) | 7 (29%) | 0.002 |
| Delivered vaginally by 12 h | 2 (8%) | 1 (4%) | 1.00 |
| Delivered vaginally by 24 h | 15 (58%) | 6 (25%) | 0.02 |
| Chorioamnionitis | 2 (8%) | 4 (17%) | 0.41 |
| Endometritis | 1 (4%) | 1 (4%) | 1.00 |
| Wound infection | 0 | 0 | - |
| Tachysystole | 2 (8%) | 0 | 0.49 |
| Birth weight (g) | 3077 ± 435 | 3248 ± 500 | 0.20 |
| 5-minute Apgar | 9 (8–9) | 9 (9–9) | 0.18 |
| Neonatal ICU admission | 3 (12%) | 1 (4%) | 0.61 |
| Neonatal death | 0 | 0 | - |
| Parous Women | n=25 | n=25 | |
| Cesarean delivery | 4 (16%) | 1 (4%) | 0.35 |
| Delivered by 12 h | 5 (20%) | 7 (28%) | 0.51 |
| Delivered by 24 h | 22 (88%) | 22 (88%) | 1.00 |
| Delivered vaginally by 12 h | 3 (12%) | 6 (24%) | 0.46 |
| Delivered vaginally by 24 h | 19 (76%) | 21 (84%) | 0.48 |
| Chorioamnionitis | 0 | 0 | - |
| Endometritis | 0 | 0 | - |
| Wound infection | 0 | 0 | - |
| Tachysystole | 0 | 1 (4%) | 1.00 |
| Birth weight (g) | 3314 ± 474 | 3312 ± 541 | 0.99 |
| 5-minute Apgar | 9 (9–9) | 9 (9–9) | 0.76 |
| Neonatal ICU admission | 3 (12%) | 4 (16%) | 1.00 |
| Neonatal death | 0 | 0 | - |
Data are presented as n (%), mean ± standard deviation or median (25th–75th percentile). Abbreviations used in the table: min=minutes; mL=milliliters; g=grams; C=degrees Celsius. Data were analyzed using chi-square test of independence, Fisher’s exact test, two-sample t-test, or Wilcoxon rank-sum test, as appropriate.
Of the eight nulliparous women who received the dinoprostone insert and Foley and underwent cesarean delivery, the indications were fetal heart rate tracing (2), failed induction (2), active phase abnormality (1), both second stage abnormality and fetal heart rate tracing (2), and both active phase abnormality and fetal heart rate tracing (1). Of the seven nulliparous women who received Foley alone and underwent cesarean delivery, the indications were failed induction (3), active phase abnormality (3), and fetal heart rate tracing (1). Of the four parous women who received the dinoprostone insert and Foley and underwent cesarean delivery, the indications were breech presentation (presentation changed during labor) (1), cord prolapse (1), active phase abnormality (1), and second stage abnormality (1). The indication for cesarean delivery in the parous woman who received Foley alone was failed induction.
DISCUSSION
This pilot randomized controlled trial demonstrated that starting cervical ripening and labor induction with the combination of the dinoprostone vaginal insert and Foley catheter, compared to Foley alone, results in a 10-hour reduction in median time to vaginal delivery for nulliparous women. The p value of 0.05 indicates this difference approaches, but did not strictly meet the criterion for, statistical significance. Also noted was a significantly higher proportion of nulliparous women delivered (via any route) by 24 hours and a significantly higher proportion delivered vaginally by 24 hours. When accounting for cesarean deliveries as competing events, the cumulative incidence of vaginal delivery in nulliparous women was shifted toward reduced time to delivery for those who underwent cervical ripening with both the dinoprostone insert and Foley catheter, although a statistical difference by treatment group was not detected in this small sample. Interestingly, there did not appear to be similar differences by treatment group for parous women.
As would be expected in a small pilot study, we did not find a significant difference between groups in terms of adverse maternal or neonatal outcomes. The overall rate of neonatal intensive care unit admission of 11% (Table 2) may seem high for infants delivered to women undergoing term labor inductions. However, it is similar to but slightly lower than that reported in either arm of the ARRIVE trial—11.7% and 13.0% in the induction and expectant management groups, respectively.3
There is a precedent for using multiple agents for cervical ripening. Vaginally-administered misoprostol and Foley combined have been shown to result in shorter times to delivery than with misoprostol alone7,13–16 and with Foley alone.7,16 However, not all authors have found a decreased time to delivery with this combination, and more uterine tachysystole occurs with the addition of misoprostol to Foley.8
When our trial began, cervical ripening with Foley catheter alone was thought to be equivalent to Foley catheter with concurrent intravenous oxytocin in terms of time to delivery.17 However, additional trials have been published since then that demonstrate shorter times to delivery with combined Foley and oxytocin compared to Foley alone and then oxytocin only after Foley expulsion from the cervix.18,19 This difference in time to vaginal delivery in nulliparous patients seems to be somewhere between two and five hours.16,17,19
Our study has some limitations. Since this was a pilot trial, we did not employ a placebo dinoprostone vaginal insert, so unmeasured bias could have been introduced by lack of blinding. In addition, the study was performed at a single center, potentially limiting the generalizability of our results. Finally, owing to the fact that this study was a pilot trial, the sample size is relatively small, statistical power is limited and point estimates may lack precision. Despite these limitations, our study has certain strengths that are worth mentioning. These include the randomized nature of the trial, complete follow-up and 100% compliance (making a per protocol not applicable), the use of methods that account for competing events and the diversity of our study population in terms of race/ethnicity, low- and high-risk pregnancies, and an average body mass index reflective of many delivery services in the United States today.
We are uncertain why we found such a difference in results between nulliparous and parous women, but our findings underscore the need to consider these two groups separately in studies comparing methods of labor induction. We think that the results of the current study are intriguing and suggest that the finding of a shorter time to vaginal delivery in nulliparous women with the combined use of Foley and the dinoprostone vaginal insert compared to Foley alone should be evaluated in a large multicenter trial. Given the findings of the recent trials described above,16–19 we consider the standard of care with cervical ripening with Foley to now include concurrent use of oxytocin. Therefore, we think that the appropriate comparison groups in a next-step trial are the concurrent combinations of 1) the dinoprostone vaginal insert and Foley and 2) Foley and intravenous oxytocin. Furthermore, we think that, rather than powering the study to a specified difference in median time to vaginal delivery censoring cesarean deliveries, that study (and all labor trials) should be powered to detect differences in time to vaginal delivery when accounting for cesarean deliveries as competing events.
ACKNOWLEDGMENTS
The study was funded by an investigator-initiated grant from Ferring Pharmaceuticals (IIT-2016-100752). Partial funding provided by National Institutes of Health, National Institute of General Medical Sciences, grant 1 U54GM104938. All work was performed by the listed authors. Ferring had no role in the study design; collection, analysis, and interpretation of data; writing of the report; or the decision to submit the report for publication.
Footnotes
Prior Presentation: This study was presented at the 39th annual meeting of the Society for Maternal-Fetal Medicine in Las Vegas, Nevada held February 11–16, 2019.
Registration: ClinicalTrials.gov Identifier: NCT03111316; first submitted March 13, 2017; initial participant enrolled April 9, 2017
Disclosure: Unrelated to this study, RKE has received remuneration from Ferring Pharmaceuticals for work as a consultant and for serving on medical advisory boards. CZ has received remuneration from Ferring Pharmaceuticals for serving on an advisory board. None of the other authors have any potential conflicts of interest. The authors alone are responsible for the content and writing of this article.
REFERENCES
- 1.Martin JA, Hamilton BE, Ventura SJ, Osterman MJ, Wilson EC, Mathews TJ. Births: final data for 2010. Natl Vital Stat Rep 2012; 61:1–72 [PubMed] [Google Scholar]
- 2.Ventura SJ, Martin JA, Curtin SC, Menacker F, Hamilton BE. Births: final data for 1999. Natl Vital Stat Rep 2001; 49:1–100 [PubMed] [Google Scholar]
- 3.Grobman WA, Rice MM, Reddy UM, et al. Labor induction versus expectant management in low-risk nulliparous women. N Engl J Med 2018; 379:513–23 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Alfirevic Z, Kelly AJ, Dowswell T. Intravenous oxytocin alone for cervical ripening and induction of labour. Cochrane Database of Systematic Reviews 2009, Issue 4. Art No: CD003246. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Faccinetti F, Fontanesi F, Del Giovane C. Pre-induction of labour: comparing dinoprostone vaginal insert to repeated prostaglandin administration: a systematic review and meta-analysis. J Matern Fetal Neonatal Med 2012; 25:1965–9 [DOI] [PubMed] [Google Scholar]
- 6.Edwards RK, Szychowski JM, Berger JL, et al. Foley catheter compared with the controlled release dinoprostone insert: a randomized controlled trial. Obstet Gynecol 2014; 123:1280–7 [DOI] [PubMed] [Google Scholar]
- 7.Aduloju OP, Akintayo AA, Adanikin AI, Ade-Ojo IP. Combined Foley’s catheter with vaginal misoprostol for pre-induction cervical ripening: A randomised controlled trial. Aust N Z J Obstet Gynaecol 2016; 56:578–84 [DOI] [PubMed] [Google Scholar]
- 8.Lanka S, Surapaneni T, Nirmalan PK. Concurrent use of Foley catheter and misoprostol for induction of labor: a randomized clinical trial of efficacy and safety. J Obstet Gynaecol Res 2014; 40:1527–33 [DOI] [PubMed] [Google Scholar]
- 9.American College of Obstetricians and Gynecologists; Society for Maternal-Fetal Medicine. Obstetric care consensus no. 1: safe prevention of the primary cesarean delivery. Obstet Gynecol 2014; 123:693–711. [DOI] [PubMed] [Google Scholar]
- 10.Varadhan R, Weiss CO, Segal JB, Wu AW, Scharfstein D, Boyd C. Evaluating health outcomes in the presence of competing risks: a review of statistical methods and clinical applications. Med Care 2010; 48:S96–105 [DOI] [PubMed] [Google Scholar]
- 11.Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 1999; 18:695–706 [DOI] [PubMed] [Google Scholar]
- 12.Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)–a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42:377–81 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Carbone JF, Tuuli MG, Fogertey PJ, Roehl KA, Macones GA. Combination of Foley bulb and vaginal misoprostol compared with vaginal misoprostol alone for cervical ripening and labor induction: a randomized controlled trial. Obstet Gynecol 2013; 121:247–52 [DOI] [PubMed] [Google Scholar]
- 14.Chen W, Xue J, Gaudet L, Walker M, Wen SW. Meta-analysis of Foley catheter plus misoprostol versus misoprostol alone for cervical ripening. Int J Gynaecol Obstet 2015; 129:193–8 [DOI] [PubMed] [Google Scholar]
- 15.Al-Ibraheemi Z, Brustman L, Bimson BE, Porat N, Rosenn B. Misoprostol with Foley bulb compared with misoprostol alone for cervical ripening: a randomized controlled trial. Obstet Gynecol 2018; 131:23–29 [DOI] [PubMed] [Google Scholar]
- 16.Levine LD, Downes KL, Elovitz MA, Parry S, Sammel MD, Srinivas SK. Mechanical and pharmacologic methods of labor induction: a randomized controlled trial. Obstet Gynecol 2016; 128:1357–64 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Pettker CM, Pocock SB, Smok DP, Lee SM, Devine PC. Transcervical Foley catheter with and without oxytocin for cervical ripening. Obstet Gynecol 2008; 111:1320–6 [DOI] [PubMed] [Google Scholar]
- 18.Bauer AM, Lappen JR, Gecsi KS, Hackney DN. Cervical ripening balloon with and without oxytocin in multiparas: a randomized controlled trial. Am J Obstet Gynecol 2018; 219:294.e1–6 [DOI] [PubMed] [Google Scholar]
- 19.Schoen CN, Grant G, Berghella V, Hoffman MK, Sciscione A. Intracervical Foley catheter with and without oxytocin for labor induction: a randomized controlled trial. Obstet Gynecol 2017; 129:1046–53 [DOI] [PubMed] [Google Scholar]