doi:10.1111/jog.13193 J. Obstet. Gynaecol. Res.

2016

Vaginal misoprostol and cervical ripening balloon for

induction of labor in late-term pregnancies

Jorge Duro Gmez1, Mara Fernanda Garrido Oyarzn2, Ana Beln Rodrguez Marn1,
Antonio Jess de la Torre Gonzlez1, Jos Eduardo Arjona Berral1 and Camil Castelo-Branco3
1
Hospital Universitario Reina Sofa, Crdoba, 3Clinic Institute of Gynecology, Obstetrics and Neonatology, Hospital Clinic-Institut
dInvestigacions Biomdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain and 2Clnica Universidad de los Andes,
Santiago de Chile, Chile

Abstract
Aim: The aim of this study was to compare vaginal misoprostol with the Cook cervical ripening balloon (CCRB)
for induction of labor in late-term nulliparous women.
Methods: This open, quasi-experimental, prospective study included 109 nulliparous women with late-term
pregnancies and Bishop scores < 7. Fifty-ve women were allocated to receive vaginal misoprostol 25 mcg and
54 received the CCRB to induce labor. The primary outcome was the time until delivery. Secondary outcomes
included time to the onset of labor and obstetric and perinatal outcomes.
Results: Women in the misoprostol group experienced shorter time until delivery (25.41 h vs 31.26 h; P < 0.01)
and in a greater percentage gave birth within the rst 24 h. Time to active stage of labor was 19.5 h and 23.8 h
(P < 0.01) for misoprostol and the CCRB, respectively. There were no differences in the rates of cesarean section
or post-partum anemia. Additionally, there were no differences in rates of tachysystolia, intrapartum fever, or
meconium. Perinatal outcomes, post-partum pH, Apgar scores, and neonatal admissions were similar in the
two groups.
Conclusion: Misoprostol 25 mcg reduces labor induction time compared with the CCRB with similar safety in
late-term pregnancies.
Key words: balloon catheter, cervical ripening, labor induction, misoprostol, perinatal outcomes.

Introduction aspiration syndrome, dysmaturity, neonatal acidemia,

Post-term pregnancy is dened as a pregnancy that
extends to 42+0 weeks of gestation or 294 days from
the rst day of the last menstrual period.1 The majority
of post-term pregnancies have no known cause, but
women at highest risk are those with a previous post-
term pregnancy.2 Other causes, such as advanced
maternal age, nulliparity, previous cesarean section,
male fetuses, and obesity, have been involved.38
Post-term pregnancies are associated with increased
fetal and neonatal morbidity and mortality. These fetuses
are at higher risk of fetal macrosomia, meconium
umbilical cord compression due to oligohydramnios,
abnormal antepartum or intrapartum fetal heart rate
patterns, and stillbirth.914 Maternal morbidity is also
increased due to labor dystocia, severe perineal
lacerations related to macrosomia, operative vaginal
delivery, infection, post-partum hemorrhage, and higher
cesarean section rates.3 For these reasons, induction of
labor is recommended in late-term pregnancies, dened
as one that has reached 41+041+6 weeks of gestation,1,4
in order to reduce post-term pregnancies and to avoid
related adverse outcomes.4,1518 Present evidence
reveals that elective labor induction is associated with a

Received: June 4 2016.

Accepted: September 3 2016.
Correspondence: Dr Camil Castelo-Branco, Department of Gynecology & Obstetrics, Hospital Clinic i Provincial de Barcelona, c/Villarroel 170
08036, Barcelona, Spain. Email: castelobranco@ub.edu

2016 Japan Society of Obstetrics and Gynecology 1

J. Duro Gmez et al.
reduced risk of intrapartum meconium, low perinatal
morbidity/mortality rates, and higher satisfaction
expressed by women1620 without increasing the risk of
cesarean section.21
For pregnant women with unfavorable Bishop scores,
dened as <7, cervical ripening is necessary before
inducing labor. Prostaglandin E1 (PGE1) or E2 (PGE2),
misoprostol and dinoprostone, as well as mechanical
methods, such as the Cook cervical ripening balloon
(CCRB), are the most common options for cervical
ripening. Although prostaglandins are associated with
a shorter induction time,22 especially PG1, mechanical
methods have advantages, such as a decreased risk of
both uterine tachysystolia and systemic adverse effects
caused by prostaglandins.
The present study was designed to compare the
effectiveness and safety of vaginally administered
misoprostol with the CCRB for onset of labor in a
homogeneous group of nulliparous women with
late-term pregnancies.
Methods
This survey was conducted as an open prospective
quasi-experimental cohort study and was approved by
the institutional review board of the Reina Soa
Hospital, Crdoba, Spain (Reference 24323/07/2015).
All of the procedures were in accordance with the
Helsinki Declaration of 1975. Over the 6-month period
from July 2015 to January 2016, 109 women were
recruited to compare vaginally administered misopros-
tol 25 mcg (Misofar, Bial Laboratories) and the CCRB
(Cook, Inc.) as methods of induction of labor for late-
term pregnancy. Nulliparous pregnant women between
41+0 and 42+0 weeks of gestation according to last
menstrual period or rst trimester ultrasound, with
Bishop score < 7, were included. Exclusion criteria
included premature rupture of membranes, multiple
gestation, personal history of previous cesarean section,
major uterine surgery, absence of fetal well-being,
previous childbirths, chorioamnionitis or an active
infection in the birth canal, metrorrhagia, and
non-cephalic presentation.
After admission, women could choose misoprostol or
the CCRB as an induction method. Misoprostol 25 mcg
tablets were administered vaginally every 4 h up to a
maximum of four tablets. The CCRB was inserted
bimanually into the cervical canal; both the intrauterine
and intravaginal balloons were lled with 50 mL
glucosaline solution and left in place for up to 24 h.
2 2016 Japan Society of Obstetrics and Gynecology
Pregnancies with abnormal cardiotocography, onset of
the active stage of labor, and the presence of regular
uterine contractions (three to ve every 10 min) were
excluded. If labor did not initiate within 24 h of
beginning the protocol, oxytocin was administered at
increasing doses to stimulate regular contractions.
The following variables were recorded: maternal
age, gestational age, previous childbirths, body mass
index, Bishop score, misoprostol doses, type of
anesthesia, hours until the onset of active stage of
labor and delivery, presence of uterine tachysystolia,
intrapartum fever (>38C), maternal hemoglobin,
meconium, type of delivery and reasons for operative
delivery, oxytocin use, birthweight, pH, and Apgar
score at 5 min. Maternal and newborn complications,
including neonatal intensive care unit admissions,
were also recorded.
Statistical analysis
For the sample calculation, GRANMO 7.11 was used,
developed by the URLEC consortium. We used an risk
of 0.05 and a risk of 0.20 in a bilateral contrast, resulting
in a sample of 76 women for each group to detect a
difference 0.2 units, assuming a proportion of 0.5 and
a loss rate of 1%.
Data were analyzed using the G-Stat 2.0 free statistical
software (Glaxo Smith Kline). The Students t-test was
used for comparisons between quantitative variables
and the 2-test or Fishers test were used for qualitative
variables. A P-value < 0.05 was considered statistically
signicant.
Results
A total of 109 nulliparous pregnant women were
included. Of them, 54 chose the CCRB method for labor
induction while the other 55 opted for vaginal
misoprostol. No signicant differences in clinical
baseline parameters were observed between the two
groups (Table 1).
The main outcome, time until delivery, was shorter in
the misoprostol group. Women in the misoprostol group
experienced less time until delivery (25.4 h vs 31.3 h;
P = 0.006) and in a greater percentage gave birth within
the rst 24 h (Table 2). Also, women in the misoprostol
group started the active stage of labor faster than those
in the CCRB group (19.5 h vs 23.9 h, respectively; P < 0.01).
Women in the CCRB group required more oxytocin
than those in the misoprostol group (5.9 mUI vs 3.3
mUI, respectively; P = 0.007). No differences were
 Induction in late-term pregnancies

Table 1 Clinical and demographic characteristics of the entire sample at inclusion

Misoprostol (n = 55) CCRB (n = 54) P-value
Maternal age (years) 29.6 (3.6) 28.9 (4.4) 0.434
Gestational age (weeks) 41 (0) 41 (0)
Previous childbirths 0 (0) 0 (0)
Pre-induction Bishop score 2.2 (1.6) 2.4 (1.1) 0.591
Body mass index (kg/m2) 30.2 (5.1) 28.0 (4.7) 0.224
Obesity 22 (52%) 13 (36.1%) 0.142
Birthweight (g) 3600 (436) 3511 (414) 0.275
Misoprostol (25-mcg tablets) 2.7 (0.1)
Admission hemoglobin (g/dL) 11.4 (1) 11.7 (1) 0.091
Post-partum hemoglobin (g/dL) 10.1 (2) 10.34 (1.6) 0.510
Epidural anesthesia 52 (95%) 46 (85%) 0.086
Number of misoprostol tablets range = 1 to 3. No signicant differences were detected between the two groups. n = 109. Data are given as
means (standard deviation) or n (%). CCRB, Cook cervical ripening balloon.

Table 2 Studied outcomes in misoprostol and CCRB groups

Variable Misoprostol (n = 55) CCRB (n = 54) P-value
Hours until active stage of labor 19.5 (7.9) 23.9 (6.2) 0.002
Hours until delivery 25.4 (8.9) 31.3 (6.6) 0.006
Delivery after > 24 h, n (%) 29 (53%) 45 (85%) 0.000
Post-induction Bishop score 3.0 (1.7) 4.9 (1.7) 0.008
Mean change in Bishop score 1.2 (1.6) 2.5 (1.4) 0.015
Fetal scalp sampling (pH) 7.26 (0.08) 7.3 (0.08) 0.531
Apgar score at 5 min 9.8 (0.5) 9.7 (0.5) 0.828
Oxytocin (milliunits) 3.3 (4.6) 5.9 (5.1) 0.007
Tachysystolia, n (%) 2 (4%) 1 (2%) 0.562
Intrapartum fever, n (%) 4 (7%) 3 (6%) 0.710
Meconium, n (%) 8 (15%) 13 (24%) 0.201
Type of delivery, n (%)
Vaginal 30 (55%) 27 (5%)
Instrumental 7 (13%) 13 (24%) 0.129
Cesarean section 18 (33%) 14 (26%) 0.430
Hematic losses (Hb g/dL) 1.7 (1.2) 1.8 (1.2) 0.592
Admissions to NICU, n (%) 0 (0%) 1 (2%) 0.495
Complications (n)
Uterine atony 4 1
Perineal tear degree III 1 0
Data are given as mean (standard deviation) or n (%). CCRB, Cook cervical ripening balloon; NICU, neonatal intensive care unit.

observed in the rates of uterine tachysystolia,
intrapartum fever, or presence of meconium. There were
also no differences in perinatal outcomes (Table 2), type
of delivery, rates of cesarean section, or incidence of
anemia (Table 3). Outcomes of labor induction and oper-
ative rates and indications are given in Table 3.
Intrapartum complications included ve cases of uterine
atony requiring treatment, four in the misoprostol group
and one in the CCRB group.
Discussion
Labor induction refers to the articial initiation of labor
before its spontaneous onset using a set of techniques
to stimulating uterine contractions with the purpose of
a vaginal delivery.23 One of the most frequent indications
for labor induction is late-term pregnancy. There are two
types of labor-inducing agents: (i) pharmacological, such
as prostaglandins (PGE1 and PGE2); and (ii) mechanical,
such as Foleys catheter and the CCRB. Among
prostaglandins, vaginal misoprostol (PGE1) has proved
to be a better alternative than dinoprostone (PGE2)
regarding effectiveness, safety, and cost.24 Results from
the present study suggest that for late-term gestations,
misoprostol is very effective and it was not associated
with an increased rate of uterine hyperstimulation,
cesarean section, or neonatal admissions. These data
appear to be consistent with previous reports from other

2016 Japan Society of Obstetrics and Gynecology 3

J. Duro Gmez et al.
Table 3 Operative delivery (forceps and CS) in both study groups according to indication
Instrumental delivery due to risk of loss of fetal well-being
Instrumental delivery due to prolonged expulsive (> 1 h)
CS due to risk of loss of fetal well-being
CS due to failed induction
CS due to stagnant labor
CS due to cephalopelvic disproportion
Data are given as n (%). CCRB, Cook cervical ripening balloon; CS, cesarean section.
authors, including Lawani et al.,23 Hofmeyr et al.,25 and
Ozkan et al.26
In our study, we did not observe an increased
incidence of uterine tachysystolia or cardiotocography
abnormalities in the misoprostol group. However, some
reports suggest that the main adverse effect of
prostaglandins is an increased prevalence of uterine
tachysystolia, which may originate from abnormal fetal
heart rate, resulting in nonreassuring fetal status and
increased rate of cesarean sections and instrumental
deliveries. In this sense, a recent study by Jozwiak
et al.27 showed a decreased risk of uterine tachysystolia
and reduced maternal systemic effects with the CCRB
when compared with prostaglandins.
In accordance with a recent study by Mackeen et al.,28
the present series did not observe a higher incidence of
chorioamnionitis or intrapartum fever associated with
the use of mechanical methods; however, in a systematic
review by Mozurkewich et al.,29 an increased rate of
infection with mechanical methods was suggested.
In our study, misoprostol was associated with a
shorter time until delivery with an increased likelihood
of giving birth within the rst 24 h compared with the
CCRB and shorter elapsed time from administration un-
til the onset of the active stage of labor. In other reports,
misoprostol has also been related to a shorter induction
time and a higher frequency of vaginal deliveries within
the rst 12 h compared with dinoprostone and mechan-
ical methods.27,28
Controversy exists regarding the cost-effectiveness of
both mechanical and pharmacological methods to in-
duce labor. In this sense, misoprostol seems to be more
effective than the CCRB, taking into account the current
low cost of four tablets of misoprostol and those of the
CCRB (4.5-fold higher), as well as the lack of differences
observed regarding the type of delivery, complications,
duration of hospital stay, and the anesthesia required.
However, other reports are not consistent with our nd-
ings. Gelber and Sciscione suggested that mechanical
methods are an alternative just as effective as other
methods of labor induction with additional benets,
4 2016 Japan Society of Obstetrics and Gynecology
Misoprostol CCRB P-value
2 (28%) 2 (15%) 0.580
5 (72%) 11 (85%) 0.589
4 (22%) 3 (21%) 0.640
4 (22%) 5 (36%) 0.452
2 (11%) 4 (29%) 0.369
8 (44%) 2 (145) 0.126
such as low cost, very few adverse and systemic effects,
and low risk of uterine hyperstimulation.30
The limitations of this study include the limited num-
ber of patients included, the lack of randomization, and
the fact that, in this open study, the women could select
the method that they preferred, biasing the nal results.
In conclusion, although further studies solving the pres-
ent limitations are needed, it appears that 25-mcg miso-
prostol tablets administered vaginally every 4 h are
safe, effective, and reduce labor induction time in late-
term nulliparous pregnant women when compared with
the CCRB.
Disclosure
The authors report that they have no conicts of interest
either with the information included in this manuscript
or with the devices and drugs used in this study.
References
1. American College of Obstetricians and Gynecologists. ACOG
Committee opinion no. 579: Denition of term pregnancy.
Obstet Gynecol 2013; 122: 11391140.
2. Kistka ZA, Palomar L, Boslaugh SE, DeBaun MR, DeFranco
EA, Muglia LJ. Risk for postterm delivery after previous
postterm delivery. Am J Obstet Gynecol 2007; 196: 241.
3. Galal M, Symonds I, Murray H, Petraglia F, Smith R. Postterm
pregnancy. Facts Views Vis Obgyn 2012; 4: 175187.
4. American College of Obstetricians and Gynecologists. Practice
bulletin no. 146: Management of late-term and postterm preg-
nancies. Obstet Gynecol 2014; 124: 390396.
5. Divon MY, Ferber A, Nisell H, Westgren M. Male gender pre-
disposes to prolongation of pregnancy. Am J Obstet Gynecol
2002; 187: 10811083.
6. Stotland NE, Washington AE, Caughey AB. Prepregnancy
body mass index and the length of gestation at term. Am J
Obstet Gynecol 2007; 197: 378.
7. Caughey AB, Stotland NE, Washington AE, Escobar GJ. Who is
at risk for prolonged and postterm pregnancy? Am J Obstet
Gynecol 2009; 200: 683.

8. Denison FC, Price J, Graham C, Wild S, Liston WA. Maternal
obesity, length of gestation, risk of postdates pregnancy and
spontaneous onset of labour at term. BJOG 2008; 115: 720725.
9. Roos N, Sahlin L, Ekman-Ordeberg G, Kieler H, Stephansson O.
Maternal risk factors for postterm pregnancy and cesarean
delivery following labor induction. Acta Obstet Gynecol Scand
2010; 89: 10031010.
10. Bruckner TA, Cheng YW, Caughey AB. Increased neonatal
mortality among normal-weight births beyond 41 weeks of
gestation in California. Am J Obstet Gynecol 2008; 199: 421.
11. Spellacy WN, Miller S, Winegar A, Peterson PQ. Macrosomia
maternal characteristics and infant complications. Obstet
Gynecol 1985; 66: 158161.
12. Rosen MG, Dickinson JC. Management of post-term pregnancy.
N Engl J Med 1992; 326: 16281629.
13. Lu Y, Zhang J, Lu X, Xi W, Li Z. Secular trends of macrosomia in
southeast China, 1994-2005. BMC Public Health 2011; 11: 818.
14. Treger M, Hallak M, Silberstein T, Friger M, Katz M, Mazor M.
Postterm pregnancy: Should induction of labor be reconsidered
before 42 weeks? J Matern Fetal Neonatal Med 2002; 11: 5053.
15. Caughey AB, Sundaram V, Kaimal AJ et al. Systematic review:
Elective induction of labor versus expectant management of
pregnancy. Ann Intern Med 2009; 151: 252.
16. Alexander JM, McIntire DD, Leveno KJ. Forty weeks and
beyond: Pregnancy outcomes by week of gestation. Obstet
Gynecol 2000; 96: 291294.
17. Doherty L, Norwitz ER. Prolonged pregnancy: When
should we intervene? Curr Opin Obstet Gynecol 2008; 20:
519527.
18. Glmezoglu AM, Crowther CA, Middleton P, Heatley E. In-
duction of labour for improving birth outcomes for women
at or beyond term. Cochrane Database Syst Rev 2012; 6:
CD004945.
19. Divon MY, Ferber A, Sanderson M, Nisell H, Westgren M. A
functional denition of prolonged pregnancy based on daily
fetal and neonatal mortality rates. Ultrasound Obstet Gynecol
2004; 23: 423426.
2016 Japan Society of Obstetrics and Gynecology
Induction in late-term pregnancies
20. Hermus MA, Verhoeven CJ, Mol BW, de Wolf GS, Fiedeldeij
CA. Comparison of induction of labour and expectant
management in postterm pregnancy: A matched cohort study.
J Midwifery Womens Health 2009; 54: 351356.
21. Delaney M, Roggensack A, Leduc DC et al. Guidelines for the
management of pregnancy at 41 + 0 to 42 + 0 weeks. J Obstet
Gynaecol Can 2008; 30: 800823.
22. Heimstad R, Romundstad PR, Hyett J, Mattson LA, Salvesen
KA. Womens experiences and attitudes toward expectant
management and induction of labor for post-term pregnancy.
Acta Obstet Gynecol Scand 2007; 86: 950956.
23. Lawani OL, Onyebuchi AK, Iyoke CA, Okafo CN, Ajah LO.
Obstetric outcome and signicance of labour induction in a
health resource poor setting. Obstet Gynecol Int 2014; 2014:
419621. DOI:10.1155/2014/419621.
24. Shakya R, Shrestha J, Thapa P. Safety and efcacy of misopros-
tol and dinoprostone as cervical ripening agents. JNMA J Nepal
Med Assoc 2010; 49: 3337.
25. Hofmeyr GJ, Glmezoglu AM, Pileggi C. Vaginal misoprostol
for cervical ripening and induction of labour. Cochrane Database
Syst Rev 2010: (10)CD000941.
26. Ozkan S, Calikan E, Doer E, Ycesoy I, Ozeren S, Vural B.
Comparative efcacy and safety of vaginal misoprostol versus
dinoprostone vaginal insert in labor induction at term: A
randomized trial. Arch Gynecol Obstet 2009; 280: 1924.
27. Jozwiak M, Bloemenkamp KW, Kelly AJ, Mol BW, Irion O,
Boulvain M. Mechanical methods for induction of labour.
Cochrane Database Syst Rev 2012; 3: CD001233.
28. Mackeen AD, Walker L, Ruhstaller K, Schuster M, Sciscione A.
Foley catheter vs prostaglandin as ripening agent in pregnant
women with premature rupture of membranes. J Am Osteopath
Assoc 2014; 114: 686692.
29. Mozurkewich EL, Chilimigras JL, Berman DR et al. Methods of
induction of labour: A systematic review. BMC Pregnancy
Childbirth 2011; 11: 84.
30. Gelber S, Sciscione A. Mechanical methods of cervical ripening
and labor induction. Clin Obstet Gynecol 2006; 49: 642657.
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