Combination of Foley Bulb and Vaginal
Misoprostol Compared With Vaginal
Misoprostol Alone for Cervical Ripening and
Labor Induction
A Randomized Controlled Trial
Jeanine F. Carbone, MD, Methodius G. Tuuli, MD, MPH, Patricia J. Fogertey,
Kimberly A. Roehl, MPH, and George A. Macones, MD, MSCE
OBJECTIVE: To test the hypothesis that use of the Foley
bulb plus vaginal misoprostol will result in shorter
induction-to-delivery time compared with vaginal miso-
prostol alone.
METHODS: We randomized 123 women undergoing
induction of labor with singleton pregnancies at 24 weeks
of gestation or greater with an unfavorable cervix (Bishop
score 6 or lower) to Foley bulb plus vaginal misoprostol
(n556) or vaginal misoprostol alone (n561). Women with
fetal malpresentation, multifetal gestation, spontaneous
labor, contraindication to prostaglandins, nonreassuring
fetal heart rate tracing, intrauterine growth restriction,
anomalous fetus, fetal demise, or previous cesarean deliv-
ery or other significant uterine surgery were excluded. The
primary outcome measure was induction-to-delivery
time. Secondary outcomes were mode of delivery, tachy-
systole with fetal decelerations, terbutaline use, postpar-
tum hemorrhage, chorioamnionitis, neonatal Apgar
scores, and neonatal intensive care unit admission. Anal-
ysis followed the intention-to-treat principle.
RESULTS: The mean induction-to-delivery time was
shorter with the combination of the Foley bulb and
vaginal misoprostol when compared with vaginal miso-
prostol alone (15.366.5 compared with 18.368.7 hours,
difference 23.1 hours, 95% confidence interval [CI] 25.9
From the Washington University in St. Louis School of Medicine, St. Louis,
Missouri.
Corresponding author: Jeanine F. Carbone, MD, 4911 Barnes-Jewish Hospital
Plaza, Campus Box 8064, St. Louis, MO 63110; e-mail: jfcarbone@hotmail.com.
Financial Disclosure
The authors did not report any potential conflicts of interest.
2013 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins.
ISSN: 0029-7844/13
VOL. 121, NO. 2, PART 1, FEBRUARY 2013
RN, MSN,
to 20.30). The combination also resulted in shorter induc-
tion to complete cervical dilation time (13.765.9 com-
pared with 17.168.7 hours, difference 23.5 hours, 95%
CI 26.7 to 20.4). There were no differences in labor com-
plications or adverse neonatal and maternal outcomes.
CONCLUSION: A combination of the Foley bulb and
vaginal misoprostol resulted in a shorter induction-to-
delivery time when compared with vaginal misoprostol
alone without increasing labor complications.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
www.clinicaltrials.gov, NCT01279343.
(Obstet Gynecol 2013;121:24752)
DOI: http://10.1097/AOG.0b013e31827e5dca
LEVEL OF EVIDENCE: I
T
he rate of induction of labor in the United States has
more than doubled over the last 20 years. In 2009,
23.2% of all gravid women underwent induction of
labor for various indications.1 The goal of induction
of labor is to achieve vaginal delivery in a safe and
timely manner. It is estimated that currently the rate
of labor induction in the United States is even higher.
There are many proposed methods for induction of
labor including mechanical (supracervical Foley bulb,
laminaria tents) and chemical methods (synthetic pros-
taglandins, oxytocin). These methods can be used alone
but are most often used in combination with each other.
A number of randomized trials have compared
the use of the Foley bulb, oxytocin, and misoprostol
in different combinations for induction of labor and
their results are contradictory with regard to induction
to delivery time, successful vaginal delivery, and labor
complications.25 Two randomized trials compared
vaginal misoprostol with the Foley bulb compared
OBSTETRICS & GYNECOLOGY 247
with vaginal misoprostol plus the Foley bulb. Both
trials found no difference in the induction-to-delivery
time.6,7 Thus, although the best agent and method for
induction of labor remains uncertain, it is biologically
plausible that a combination of a mechanical device
(Foley bulb) and chemical agent (synthetic prostaglan-
din) may have an additive or synergistic effect, result-
ing in a greater degree of cervical ripening and shorter
induction-to-delivery time. The addition of a synthetic
prostaglandin to the Foley bulb may also overcome
the frequent observation of cervical dilation with the
Foley bulb without significant effacement.
The objective of this study was to compare the
efficacy of a combination of the Foley bulb and vaginal
misoprostol with vaginal misoprostol alone for labor
induction. We hypothesized that use of the Foley bulb
plus vaginal misoprostol will result in shorter induc-
tion-to-delivery time.
MATERIALS AND METHODS
This was a randomized clinical trial comparing the
efficacy of vaginal misoprostol plus a Foley bulb with
vaginal misoprostol alone for induction of labor. The
study was approved by the Washington University
Human Research Protection Office and was registered
with the clinical trials registry (ClinicalTrials.gov
#NCT01279343). Women with a singleton, viable ges-
tation (24 weeks of gestation or greater), cephalic pre-
senting fetus, intact membranes, and an unfavorable
cervix (Bishops score 6 or less) presenting to our labor
and delivery unit for labor induction from January 6,
2011, to April 30, 2012, were evaluated for participa-
tion. Women were excluded if any of the following
criteria were encountered: fetal malpresentation, multi-
fetal gestation, spontaneous labor (regular uterine con-
tractions with cervical change), more than five uterine
contractions in 10 minutes, contraindication to prosta-
glandins, a Category II or greater fetal heart rate trac-
ing, fetal growth restriction (defined as estimated fetal
weight less than the 10th percentile for gestational age
on the Hadlock growth standard), anomalous fetus, fetal
demise, or previous cesarean delivery or other uterine
surgery (myomectomy, cornual wedge resection). Eligi-
ble patients were approached by a research nurse or
other members of the research team for consent to par-
ticipate in the study if inclusion criteria had been met.
Randomization was achieved by computer-gen-
erated random sequences. On enrollment, an opaque
envelope was opened containing the participants
enrollment number and assignment to either the
Foley plus vaginal misoprostol or vaginal misoprostol
alone. Women in the misoprostol-only group received
25 micrograms of misoprostol per vagina every
248 Carbone et al Foley Bulb and Misoprostol for Labor Induction
4 hours. Once the cervix became favorable (Bishops
score greater than 6) or the patient was in active labor,
misoprostol administration was discontinued. Further
management of labor was at the discretion of the labor
team with expectant management, amniotomy, or
intravenous (IV) oxytocin per protocol. If indicated,
IV oxytocin was started per standard protocol after
4 hours from the last misoprostol dose. Oxytocin
was administered per standard protocol starting at
2 milliunits/min increasing by 2 milliunits every
20 minutes until regular uterine contractions occur.
Women in the combination group received vaginal
misoprostol per standard protocol at 25 micrograms
every 4 hours. In addition, a Foley bulb was inserted
digitally or by direct visualization with the aid of
a sterile speculum. The Foley was inserted through
the internal cervical os, filled with 60 mL of normal
saline, and then pulled snugly against the internal os.
The catheter of the Foley bulb was taped to the
patients inner thigh under gentle traction. If the Foley
bulb was unable to be placed, the patient was examined
every 4 hours and Foley bulb placement was reattemp-
ted if Bishops score was still 6 or less. When the Foley
bulb had fallen out, further management of labor was at
the discretion of the labor team and included expectant
management, amniotomy, or IV oxytocin. If indicated,
IV oxytocin was started per standard protocol after 4
hours from the last misoprostol dose. Oxytocin was
administered per standard protocol starting at 2 milli-
units/min increasing by 2 milliunits every 20 minutes
until regular uterine contractions occur. Other aspects
of labor management were similar for both groups,
including continuous electronic fetal monitoring with
either external Doppler device or fetal scalp electrode.
Uterine contraction assessment was performed with
either an external tocodynamometer or an internal
pressure catheter. Amniotomy was performed when
feasible at the discretion of the health care provider.
Participant data including demographic charac-
teristics, medical and pregnancy history, labor course,
and outcomes were collected by a dedicated research
nurse. Each indication for labor induction was docu-
mented. Postdate induction was defined as a preg-
nancy being induced for being past the estimated date
of confinement (greater than 40 weeks of gestation).
After each delivery, the fetal heart rate tracing was
carefully reviewed for the presence of tachysystole
(greater than five uterine contractions in 10 minutes)
with subsequent decelerations requiring terbutaline or
cessation of oxytocin infusion.
An independent three-member data safety and
monitoring board conducted one planned interim
analysis after half of the patients were enrolled with
OBSTETRICS & GYNECOLOGY
 Assessed for eligibility
N=393 Excluded: n=270
Not meeting inclusion criteria: 229
Declined to participate: 32
Randomized Other reasons: 9
n=123

Foley bulb and Misoprostol

misoprostol n=64
n=59

Did not receive Did not receive

allocated intervention allocated intervention
n=2 n=6

Received allocated Received allocated

intervention intervention
n=57 n=58
Not analyzed Not analyzed
(met exclusion criteria) (met exclusion criteria)
Fig. 1. Flow chart of study partic- n=3 n=3
ipants.
Carbone. Foley Bulb and Misoprostol for Analyzed Analyzed
Labor Induction. Obstet Gynecol 2013. n=56 n=61

induction-to-delivery time as the primary outcome of
interest. None of the investigators were involved in
the interim analysis. The significance level for the
interim analysis was calculated using the Haybittle-
Peto stopping boundaries.8
The primary outcome measure was induction-to-
delivery time. Secondary outcomes were mode of
delivery, tachysystole (defined as greater than five
uterine contractions in 5 minutes) with fetal heart rate
decelerations requiring terbutaline use, postpartum

Table 1. Baseline Demographics

Characteristic Foley+Misoprostol (n556) Misoprostol (n561)

Maternal age (y) 25.767.2 24.265.5

Maternal weight (kg) 89.6620.3 90.6624.9
Maternal BMI (kg/m2) 33.666.8 33.868.2
Gestational age (wk) 39.561.4 (3541) 39.861.4 (3641)
Parity
Nulliparous 37 (67.3) 40 (65.6)
Race
White 13 (24.1) 11 (18.6)
Black 34 (63.0) 40 (67.8)
Asian 0 (0.0) 2 (3.4)
Other 7 (13.0) 6 (10.2)
Admission Bishops score 3 (06) 3 (06)
Indication for labor inductions
Postdates 24 (42.9) 26 (42.6)
Preeclampsia 7 (12.5) 8 (13.1)
Chronic hypertension 4 (7.1) 4 (6.6)
Pregnancy-induced hypertension 2 (3.6) 2 (3.3)
Pregestational diabetes 2 (3.6) 4 (6.6)
Gestational diabetes 3 (5.4) 2 (3.3)
Oligohydramnios 2 (3.6) 1 (1.6)
Elective 6 (10.7) 8 (13.1)
Other* 6 (10.7) 6 (9.8)
BMI, body mass index.
Data are mean6standard deviation, mean6deviation (range), n (%), or median (range).
* Sickle cell disease, cholestasis of pregnancy, alloimmunization with suspected fetal anemia at term, fetal macrosomia, thrombophilia, and
abnormal antenatal testing.

VOL. 121, NO. 2, PART 1, FEBRUARY 2013 Carbone et al Foley Bulb and Misoprostol for Labor Induction 249
Table 2. Maternal Outcomes
Duration
Foley+Misoprostol Misoprostol Difference
(n556) (n561) (95% CI) P

Primary outcome
Induction to delivery (h) 15.3 66.5 18.368.7 23.1 (25.9 to 20.3) .03
Secondary outcomes
Induction to complete dilation (h) 13.765.9 17.168.7 23.5 (26.7 to 20.4) .03
Delivery within 24 h 49 (89.1) 46 (75.4) 1.18 (1.001.40)* .09
Vaginal delivery 41 (73.2) 45 (73.8) 0.99 (0.801.23)* .96
Cesarean delivery 15 (27.3) 16 (26.2) 1.03 (0.571.90)* .90
CI, confidence interval.
Data are mean6standard deviation or n (%) unless otherwise specified.
* Relative risk (95% CI).

hemorrhage (defined as estimated blood loss greater
than 500 mL for vaginal delivery or greater than 1,000
mL for cesarean delivery), chorioamnionitis, neonatal
Apgar scores, and neonatal intensive care unit
admission.
The sample size was estimated a priori based on
the primary outcome. We assumed a mean induction-
to-delivery time of 17.067.8 hours with vaginal miso-
prostol based on previously published data.9 We
estimated that 122 women would be needed for 80%
to detect a 4-hour difference in mean induction-to-
delivery time between the two groups using a two-
tailed t test and a of 0.05.
Analysis was based on the intent-to-treat principle;
participants were analyzed in the groups to which they
were randomized whether or not they received the
assigned intervention. Selected baseline characteristics
and outcome measures were compared using the
independent t test for continuous variables and the x2
test or Fishers exact test for categorical variables as
appropriate. The mean induction-to-delivery times in
the two groups were compared using the independent
1.00
Foley and misoprostol
Undelivered (proportion)
t test. Induction-to-delivery time was also analyzed using
Kaplan-Meier survival analysis. Survival functions of the
two groups were compared using the log-rank test. Anal-
yses were performed using STATA 10.0. Tests with
P,.05 were considered significant.
RESULTS
A total of 123 women were enrolled from February
2011 to April 2012 (Fig. 1). Of these, 59 women were
assigned to vaginal misoprostol plus Foley bulb,
whereas 64 were assigned to the vaginal misoprostol-
only group. Fifty-seven of the 59 assigned to the com-
bination group received the allocated intervention,
whereas two did not. Among the 64 patients assigned
to vaginal misoprostol only, 58 received the allocated
intervention, whereas six did not. Three women in each
group were excluded after enrollment for meeting one
or more exclusion criteria: four were excluded as a result
of an indication for induction being fetal growth restric-
tion and two were excluded as a result of Category III
fetal heart rate tracings on admission. This yielded 56
patients in the combination group and 61 patients in the
vaginal misoprostol-alone group for analysis.
The two groups were comparable with regard to
baseline characteristics including indications for induc-
Misoprostol
tion of labor (Table 1). Most of the women were at term,

0.75 nulliparous, and of black race. The most common indi-

Logrank P=.03 cation for induction of labor was postdate induction.
0.50 The median Bishops score was similar in the two
groups (3 [range 06]).
Induction-to-delivery time was shorter by a mean
0.25
of 3 hours among women induced with a combination
of the Foley bulb plus misoprostol when compared
0.00
0 10 20 30 40 50
with those induced with vaginal misoprostol alone
Time to delivery (hours) (mean time 15.366.5 compared with 18.368.7 hours,
Fig. 2. KaplanMeier time curve for induction to delivery. mean difference 23.1 hours, 95% confidence interval
Carbone. Foley Bulb and Misoprostol for Labor Induction. Obstet [CI] 25.9 to 20.3). The time from induction to
Gynecol 2013. complete cervical dilation was also shorter in the

250 Carbone et al Foley Bulb and Misoprostol for Labor Induction OBSTETRICS & GYNECOLOGY
Table 3. Neonatal Outcomes
Foley+Misoprostol Misoprostol Relative Risk
(n556) (n561) (95% CI) P

Birth weight (g) 3,2896494 3,2616504 .76

1-min Apgar score 8 (2, 9) 8 (2, 9) .55
5-min Apgar score 9 (1, 9) 9 (7, 9) .86
Admission to NICU 0 (0.0) 2 (3.3) .50
Admission to NICU or special care nursery 8 (14.3) 11 (18.0) 0.79 (0.341.83) .62
CI, confidence interval; NICU, neonatal intensive care unit.
Data are mean6standard deviation, median (range), or n (%) unless otherwise specified.

combination group compared with the vaginal miso- DISCUSSION

prostol-only group (mean time 13.765.9 compared
with 17.168.7 hours, mean difference 23.5 hours,
95% CI 26.7 to 20.4). There was a higher rate of
delivery within 24 hours in the combination group,
but the difference was not statistically significant (49
[89.1%] compared with 46 [75.4%]), relative risk 1.18,
95% CI 1.001.40, P5.09). There were no differences
in mode of delivery (Table 2). The KaplanMeier sur-
vival curve showed a more rapid decline in the Foley
bulb plus misoprostol group of the proportion of pa-
tients remaining undelivered with time (log-rank
P5.03) (Fig. 2).
Neonatal outcomes are shown in Table 3. There
were no differences in birth weight, Apgar scores, or
neonatal intensive care unit admissions. Umbilical cord
gases were not significantly different in the two groups.
Labor characteristics and complications are shown in
Table 4. There were no differences in oxytocin augmen-
tation or epidural anesthesia use. The combination
group used fewer doses of misoprostol when compared
with the vaginal misoprostol-alone group. There were
no differences in the incidence of tachysystole with
decelerations, use of terbutaline, or meconium passage
in the two groups. The risks of chorioamnionitis,
endometritis, and postpartum hemorrhage were also
not significantly different in the two groups.
We found that use of a combination of the Foley bulb
and vaginal misoprostol for induction of labor short-
ened induction-to-delivery time by an average of 3
hours compared with vaginal misoprostol alone. No
differences were observed in labor complications or
adverse neonatal and maternal outcomes.
One randomized trial examining a combination of
the Foley bulb plus vaginal misoprostol compared with
vaginal misoprostol alone for induction of labor found
no differences in the total induction-to-delivery time.
The study was small and appears to be underpowered.10
The authors did not report a primary outcome or a priori
power calculation. Two other randomized trials using
three arms compared vaginal misoprostol alone with
Foley bulb alone compared with the combination of
Foley bulb plus vaginal misoprostol. Whereas Kashian
et al found vaginal misoprostol alone to be faster than
the combination of the Foley bulb and vaginal misopros-
tol, Chung et al reported no difference in induction-to-
delivery time between the three groups.6,7 Contrary to
our study, there was a statistically significant increase in
tachysystole, terbutaline use, and chorioamnionitis with
misoprostol alone when compared with the combina-
tion group. The differences between our results and
these studies may be attributable to differences in study
populations, doses of misoprostol used, and sample
sizes.

Table 4. Labor Characteristics and Complications

Foley+Misoprostol Misoprostol Relative Risk (95% CI) P

No. of doses of misoprostol (25 micrograms each) used 1 (02) 1 (15) ,.01
Oxytocin augmentation 46 (82.1) 54 (88.5) 0.93 (90.801.08) .43
Labor epidural 50 (89.3) 52 (85.3) 1.05 (0.911.20) .59
Tachysystole with decelerations 10 (17.9) 12 (19.7) 0.91 (0.431.93) .82
Use of terbutaline 1 (1.8) 5 (8.2) 0.22 (0.031.81) .21
Meconium 8 (14.3) 15 (24.6) 0.58 (0.271.26) .17
Chorioamnionitis 5 (8.9) 7 (11.5) 0.78 (0.262.31) .77
Endometritis 1 (1.8) 2 (3.3) 0.54 (0.055.84) ..99
Postpartum hemorrhage 2 (3.6) 5 (8.2) 0.44 (0.092.16) .44
CI, confidence interval.
Data are median (range) or n (%) unless otherwise specified.

VOL. 121, NO. 2, PART 1, FEBRUARY 2013 Carbone et al Foley Bulb and Misoprostol for Labor Induction 251
 Our study was a relatively large randomized
clinical trial comparing the combination of Foley bulb
with vaginal misoprostol with vaginal misoprostol
alone for induction of labor. The major strength is
in the randomized design. Randomization was effec-
tive, resulting in comparable groups with regard to
known and presumably unknown confounders. We
included both nulliparous and multiparous women,
making our results more generalizable.
Despite the strengths, there are limitations that
should be considered when interpreting our results.
The nature of the intervention did not permit blinding
of health care providers. The absence of blinding may
have influenced how patients were managed. Six
participants were dropped because they met exclusion
criteria after enrollment. This number is small and
balanced in the two groups. There were six participants
in the misoprostol-alone group who did not receive
their allocated intervention; each received a Foley bulb
in addition to misoprostol. In addition, two participants
in the Foley bulb plus misoprostol group did not
receive misoprostol. However, this crossover would
tend to bias our results toward the null hypothesis of no
difference. Although we did not find any differences in
mode of delivery, neonatal complications, or labor
complications, our study was only sufficiently powered
to assess the primary outcome.
In conclusion, results of this randomized trial
show that use of the Foley bulb combined with
vaginal misoprostol results in a shorter induction-to-
delivery time compared with vaginal misoprostol
alone. These results suggest that the combination
may be used to achieve timely and safe delivery in
the presence of an unfavorable cervix. Although not
directly evaluated in this study, shortening of induc-
tion time by 3 hours would be significant for patients,
health care providers, and hospitals. Future studies
should be of sufficient power to assess significant labor
complications and adverse neonatal and maternal
252 Carbone et al Foley Bulb and Misoprostol for Labor Induction
complications. In addition, studies comparing a com-
bination of the Foley bulb plus misoprostol with the
Foley bulb alone will be informative as to whether the
combination is superior to the Foley bulb alone.
REFERENCES
1. Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Menacker F,
Kirmeyer S. Births: final data for 2006. Natl Vital Stat Rep
2009;57:1101.
2. Hill JB, Thigpen BD, Bofill JA, Magann E, Moore LE,
Martin JN. A randomized clinical trial comparing vaginal mi-
soprostol versus cervical Foley plus oral misoprostol for cervi-
cal ripening and labor induction. Am J Perinatol 2009;26:338.
3. Culver J, Strauss RA, Brody S, Dorman K, Timlin S,
McMahon MJ. A randomized trial comparing vaginal misopros-
tol versus Foley catheter with concurrent oxytocin for labor
induction in nulliparous women. Am J Perinatol 2004;21:13946.
4. Kehl S, Ehard A, Berlit S, Spaich S, Sutterlin M, Siemer J.
Combination of misoprostol and mechanical dilation for induc-
tion of labour: a randomized controlled trial. Eur J Obstet
Gynecol Reprod Biol 2011;159:3159.
5. Sciscione AC, Nguyen L, Manley J, Pollock M, Mass B,
Colmorgen G. A randomized comparison of transcervical Foley
catheter to intravaginal misoprostol for preinduction cervical
ripening. Obstet Gynecol 2001;97:6037.
6. Kashanian M, Akbarian AR, Fekrat M. Cervical ripening and
induction of labor with intravaginal misoprostol and Foley cath-
eter cervical traction. Int J Gynaecol Obstet 2006;92:7980.
7. Chung JH, Huang WH, Rumney PJ, Garite TJ, Nageotte MP. A
prospective randomized controlled trial that compared miso-
prostol, Foley catheter and combination miosprostol-Foley
catheter for labor induction. Am J Obstet Gynecol 2003;189:
10315.
8. Montori VM, Devereaux PJ, Adhikari NK, Burns KEA,
Eggert CH, Briel M, et al. Randomized trials stopped early
for benet: a systematic review. JAMA 2005;294:22039.
9. Moraes Filho OB, Albuquerque RM, Cecatti JG. A randomized
controlled trial comparing vaginal misoprostol versus Foley
catheter plus oxytocin for labor induction. Acta Obstet Gynecol
Scand 2010;89:104552.
10. Rust OA, Greybush M, Atlas RO, Jones KJ, Balducci J. Prein-
duction cervical ripening. A randomized trial of intravaginal mi-
soprostol alone vs. a combination of transcervical Foley balloon
and intravaginal misoprostol. J Reprod Med 2001;46:899904.
OBSTETRICS & GYNECOLOGY