ACOG

PRACTICE
BULLETIN
CLINICAL MANAGEMENT GUIDELINES FOR OBSTETRICIAN–GYNECOLOGISTS
NUMBER 107, AUGUST 2009
Replaces Practice Bulletin Number 10, November 1999; Committee Opinion Number 228, November
1999; Committee Opinion Number 248, December 2000; Committee Opinion Number 283, May 2003

Induction of Labor
This Practice Bulletin was devel- More than 22% of all gravid women undergo induction of labor in the United
oped by the ACOG Committee on States, and the overall rate of induction of labor in the United States has more
Practice Bulletins—Obstetrics with than doubled since 1990 to 225 per 1,000 live births in 2006 (1). The goal of
the assistance of Mildred Ramirez, induction of labor is to achieve vaginal delivery by stimulating uterine con-
MD, and Susan Ramin, MD. The tractions before the spontaneous onset of labor. Generally, induction of labor
information is designed to aid prac-
has merit as a therapeutic option when the benefits of expeditious delivery out-
titioners in making decisions about
weigh the risks of continuing the pregnancy. The benefits of labor induction
appropriate obstetric and gyneco-
logic care. These guidelines should must be weighed against the potential maternal and fetal risks associated with
not be construed as dictating an this procedure (2). The purpose of this document is to review current methods
exclusive course of treatment or for cervical ripening and induction of labor and to summarize the effectiveness
procedure. Variations in practice of these approaches based on appropriately conducted outcomes-based
may be warranted based on the research. These practice guidelines classify the indications for and contraindi-
needs of the individual patient, cations to induction of labor, describe the various agents used for cervical
resources, and limitations unique to ripening, cite methods used to induce labor, and outline the requirements for the
the institution or type of practice. safe clinical use of the various methods of inducing labor.

Background
In 1948, Theobald and associates described their use of the posterior pituitary
extract, oxytocin, by intravenous drip for labor induction (3). Five years later,
oxytocin was the first polypeptide hormone synthesized by du Vigneaud and
associates (4). This synthetic polypeptide hormone has since been used to stim-
ulate uterine contractions. Other methods used for induction of labor include
membrane stripping, amniotomy, nipple stimulation, and administration of
prostaglandin E analogues.
THE AMERICAN COLLEGE OF
OBSTETRICIANS AND Cervical Ripening
GYNECOLOGISTS The goal of cervical ripening is to facilitate the process of cervical softening,
WOMEN’S HEALTH CARE PHYSICIANS thinning, and dilating with resultant reduction in the rate of failed induction and

386 VOL. 114, NO. 2, PART 1, AUGUST 2009 OBSTETRICS & GYNECOLOGY
induction to delivery time. Cervical remodeling is a crit- currently is available in a 100-mcg (unscored) or a 200-
ical component of normal parturition. Observed changes mcg tablet, and can be broken to provide 25-mcg or 50-
not only include collagen breakdown and rearrangement mcg doses. There is extensive clinical experience with
but also changes in the glycosaminoglycans, increased this agent and a large body of published reports support-
production of cytokines, and white blood cell infiltration ing its safety and efficacy when used appropriately. No
(5). If induction is indicated and the status of the cervix studies indicate that intrapartum exposure to misoprostol
is unfavorable, agents for cervical ripening may be used. (or other prostaglandin cervical ripening agents) has any
The status of the cervix can be determined by the Bishop long-term adverse health consequences to the fetus in the
pelvic scoring system (Table 1) (6). An unfavorable cer- absence of fetal distress, nor is there a plausible biologic
vix generally has been defined as a Bishop score of 6 or basis for such a concern. Although misoprostol currently
less in most randomized trials. If the total score is more is approved by the U.S. Food and Drug Administration
than 8, the probability of vaginal delivery after labor (FDA) for the prevention of peptic ulcers, the FDA in
induction is similar to that after spontaneous labor. 2002 approved a new label on the use of misoprostol
Effective methods for cervical ripening include the during pregnancy for cervical ripening and for the induc-
use of mechanical cervical dilators and administration of tion of labor. This labeling does not contain claims
synthetic prostaglandin E1 (PGE1) and prostaglandin E2 regarding the efficacy or safety of misoprostol, nor does
(PGE2) (7–10). Mechanical dilation methods are effec- it stipulate doses or dose intervals. The majority of ad-
tive in ripening the cervix and include hygroscopic dila- verse maternal and fetal outcomes associated with miso-
tors, osmotic dilators (Laminaria japonicum), Foley prostol therapy resulted from the use of doses greater than
catheters (14–26 F) with inflation volume of 30–80 mL, 25 mcg.
double balloon devices (Atad Ripener Device), and Two PGE2 preparations are commercially available:
extraamniotic saline infusion using infusion rates of a gel available in a 2.5-mL syringe containing 0.5 mg of
30–40 mL/h (11–19). Laminaria japonicum ripens the dinoprostone and a vaginal insert containing 10 mg of
cervix but may be associated with increased peripartum dinoprostone. Both are approved by the FDA for cervi-
infections (7, 20). In women undergoing induction with cal ripening in women at or near term. The vaginal insert
an unfavorable cervix, mechanical methods, except releases prostaglandins at a slower rate (0.3 mg/h) than
extraamniotic saline infusion, are associated with a the gel. Compared with placebo or oxytocin alone, vagi-
decreased cesarean delivery rate when compared with nal prostaglandins used for cervical ripening increase the
oxytocin alone (18). Multiple studies have demonstrated likelihood of delivery within 24 hours, do not reduce the
the efficacy of mechanical cervical dilators. There is rate of cesarean delivery, and increase the risk of uterine
insufficient evidence to assess how effective (vaginal tachysystole with associated FHR changes (22).
delivery within 24 hours) mechanical methods are com-
pared with prostaglandins (18). Advantages of the Foley Methods of Labor Induction
catheter include low cost when compared with
prostaglandins, stability at room temperature, and Oxytocin
reduced risk of uterine tachysystole with or without fetal Oxytocin is one of the most commonly used drugs in the
heart rate (FHR) changes (18, 21). United States. The physiology of oxytocin-stimulated
Misoprostol, a synthetic PGE1 analogue, can be labor is similar to that of spontaneous labor, although
administered intravaginally, orally, or sublingually and is individual patients vary in sensitivity and response to
used for both cervical ripening and induction of labor. It oxytocin. Based on pharmacokinetic studies of synthetic

Table 1. Bishop Scoring System

Factor

Score Dilation (cm) Position of Cervix Effacement (%) Station* Cervical Consistency
0 Closed Posterior 0–30 –3 Firm
1 1–2 Midposition 40–50 –2 Medium
2 3–4 Anterior 60–70 –1, 0 Soft
3 5–6 — 80 +1, +2 —
*Station reflects a –3 to +3 scale.
Modified from Bishop EH. Pelvic scoring for elective induction. Obstet Gynecol 1964;24:267.

VOL. 114, NO. 2, PART 1, AUGUST 2009 ACOG Practice Bulletin Induction of Labor 387
oxytocin, uterine response ensues after 3–5 minutes of only in women with favorable cervices (31). None of the
infusion, and a steady level of oxytocin in plasma is women had uterine tachysystole with or without FHR
achieved by 40 minutes (23). The uterine response to changes, and there were no differences in meconium-
oxytocin depends on the duration of the pregnancy; there stained amniotic fluid or cesarean delivery rates (31).
is a gradual increase in response from 20 to 30 weeks of Breast stimulation was associated with a decrease in
gestation, followed by a plateau from 34 weeks of gesta- postpartum hemorrhage (31). This method has only been
tion until term, when sensitivity increases (24). Lower studied in low-risk pregnancies.
body mass index and greater cervical dilation, parity, or
gestational age are predictors of successful response to Labor Induction Terminology
oxytocin for induction (25). At a 2008 workshop sponsored by the American College
of Obstetricians and Gynecologists, the Eunice Kennedy
Membrane Stripping
Shriver National Institute of Child Health and Human
Stripping or sweeping the amniotic membranes is com- Development, and the Society for Maternal–Fetal Med-
monly practiced to induce labor. Significant increases in icine on intrapartum electronic FHR monitoring, the defi-
phospholipase A2 activity and prostaglandin F2α (PGF2α) nitions for FHR pattern categorization were reviewed and
levels occur from membrane stripping (26). Stripping updated. The existing classification systems for FHR pat-
membranes increases the likelihood of spontaneous terns were assessed and new recommendations for use in
labor within 48 hours and reduces the incidence of induc- the United States were made (32). In particular, it was
tion with other methods (27). Although membrane sweep- determined that the terms hyperstimulation and hypercon-
ing has been associated with increased risk of prelabor tractility should be abandoned. It was recommended that
rupture of membranes (28), other published systematic the term tachysystole, with or without corresponding FHR
reviews, including one with 1,525 women, have not cor- decelerations, be used instead.
roborated this finding (27). Women who undergo mem-
brane stripping may experience discomfort from the Uterine Contractions
procedure as well as vaginal bleeding and irregular uter-
Uterine contractions are quantified as the number of con-
ine contractions within the ensuing 24 hours (27). There
tractions present in a 10-minute window, averaged over
are insufficient data to guide clinical practice for mem-
30 minutes. Contraction frequency alone is a partial assess-
brane stripping in women whose group B streptococcus
ment of uterine activity. Other factors such as duration,
culture is positive.
intensity, and relaxation time between contractions are
Amniotomy equally important in clinical practice. The following rep-
resents terminology to describe uterine activity:
Artificial rupture of the membranes may be used as a
method of labor induction, especially if the condition of • Normal: Five contractions or less in 10 minutes,
the cervix is favorable. Used alone for inducing labor, averaged over a 30-minute window
amniotomy can be associated with unpredictable and • Tachysystole: More than five contractions in 10 min-
sometimes long intervals before the onset of contrac- utes, averaged over a 30-minute window
tions. There is insufficient evidence on the efficacy and
safety of amniotomy alone for labor induction (29). In a Listed are characteristics of uterine contractions:
trial of amniotomy combined with early oxytocin infusion • Tachysystole should always be qualified as to the
compared with amniotomy alone, the induction-to-deliv- presence or absence of associated FHR decelera-
ery interval was shorter with the amniotomy-plus-oxy- tions.
tocin method (30). There are insufficient data to guide the
• The term tachysystole applies to both spontaneous
timing of amniotomy in patients who are receiving intra-
and stimulated labor. The clinical response to tachy-
partum prophylaxis for group B streptococcal infection.
systole may differ depending on whether contrac-
tions are spontaneous or stimulated.
Nipple Stimulation
Nipple stimulation or unilateral breast stimulation has The majority of literature cited in this Practice
been used as a natural and inexpensive nonmedical Bulletin was published prior to the 2008 NICHD defini-
method for inducing labor. In a systematic review of 6 tions and interpretations of FHR tracings. Consequently,
trials including 719 women that compared breast stimu- it is difficult to generalize the results of the cited litera-
lation with no intervention, a significant decrease in the ture, which used nonstandardized and ambiguous defini-
number of women not in labor at 72 hours was noted, but tions for FHR patterns.

388 ACOG Practice Bulletin Induction of Labor OBSTETRICS & GYNECOLOGY

Clinical Considerations and
Confirmation of Term Gestation
Recommendations • Ultrasound measurement at less than 20 weeks of
What are the indications and contraindica- gestation supports gestational age of 39 weeks or
tions to induction of labor? greater.
• Fetal heart tones have been documented as present
Indications for induction of labor are not absolute but for 30 weeks by Doppler ultrasonography.
should take into account maternal and fetal conditions,
• It has been 36 weeks since a positive serum or urine
gestational age, cervical status, and other factors.
human chorionic gonadotropin pregnancy test result.
Following are examples of maternal or fetal conditions
that may be indications for induction of labor:
• Abruptio placentae
importance for appropriate evaluation and counseling
• Chorioamnionitis before initiating cervical ripening or labor induction. The
• Fetal demise patient should be counseled regarding the indications for
• Gestational hypertension induction, the agents and methods of labor stimulation,
• Preeclampsia, eclampsia and the possible need for repeat induction or cesarean
delivery. Although prospective studies are limited in
• Premature rupture of membranes
evaluating the benefits of elective induction of labor, nul-
• Postterm pregnancy liparous women undergoing induction of labor with
• Maternal medical conditions (eg, diabetes mellitus, unfavorable cervices should be counseled about a two-
renal disease, chronic pulmonary disease, chronic fold increased risk of cesarean delivery (33, 34, 35). In
hypertension, antiphospholipid syndrome) addition, labor progression differs significantly for
• Fetal compromise (eg, severe fetal growth restric- women with an elective induction of labor compared
tion, isoimmunization, oligohydramnios) with women who have spontaneous onset of labor (36).
Allowing at least 12–18 hours of latent labor before
Labor also may be induced for logistic reasons, for diagnosing a failed induction may reduce the risk of
example, risk of rapid labor, distance from hospital, or cesarean delivery (37, 38).
psychosocial indications. In such circumstances, at least Additional requirements for cervical ripening and
one of the gestational age criteria in the box should be induction of labor include assessment of the cervix,
met, or fetal lung maturity should be established. A pelvis, fetal size, and presentation. Monitoring FHR and
mature fetal lung test result before 39 weeks of gestation, uterine contractions is recommended as for any high-risk
in the absence of appropriate clinical circumstances, is patient in active labor. Although trained nursing person-
not an indication for delivery. nel can monitor labor induction, a physician capable
The individual patient and clinical situation should of performing a cesarean delivery should be readily
be considered in determining when induction of labor is
available.
contraindicated. Generally, the contraindications to labor
induction are the same as those for spontaneous labor What is the relative effectiveness of available
and vaginal delivery. They include, but are not limited to,
methods for cervical ripening in reducing the
the following situations:
duration of labor?
• Vasa previa or complete placenta previa
A systematic review found that in patients with an unfa-
• Transverse fetal lie vorable cervix, Foley catheter placement before oxytocin
• Umbilical cord prolapse induction significantly reduced the duration of labor
• Previous classical cesarean delivery (21). This review also concluded that catheter placement
• Active genital herpes infection resulted in a reduced risk of cesarean delivery. When the
Foley catheter was compared with PGE2 gel, the majority
• Previous myomectomy entering the endometrial cavity
of the studies have found no difference in duration of
What criteria should be met before the cervix induction to delivery or cesarean delivery rate. The use
of prostaglandins is associated with an increased risk of
is ripened or labor is induced?
tachysystole with or without FHR changes when com-
Assessment of gestational age and consideration of any pared with the Foley catheter (21). The use of different
potential risks to the mother or fetus are of paramount size Foley catheters, insufflation volumes, as well as dif-

VOL. 114, NO. 2, PART 1, AUGUST 2009 ACOG Practice Bulletin Induction of Labor 389
ferent misoprostol protocols, yields inconsistent results of 1.5 mg of dinoprostone (three doses or 7.5 mL of gel)
to determine induction to delivery times, cesarean deliv- within a 24-hour period. A minimum safe time interval
ery rate, and risk of meconium passage (18, 21). The between prostaglandin administration and initiation of
addition of oxytocin along with the use of the Foley oxytocin has not been determined. According to the
catheter does not appear to shorten the time of delivery manufacturers’ guidelines, after use of 1.5 mg of dino-
in a randomized controlled trial (39). prostone in the cervix or 2.5 mg in the vagina, oxytocin
Studies examining extraamniotic saline infused induction should be delayed for 6–12 hours because the
through the Foley catheter compared with use of the effect of prostaglandins may be heightened with oxy-
Foley catheter with concurrent oxytocin administration tocin. After use of dinoprostone in sustained-release
report conflicting results on the time from induction to form, delaying oxytocin induction for 30–60 minutes
delivery (19, 40, 41). Differences in methodology could after removal is sufficient. Limited data are available on
explain the opposing findings. The Foley catheter is a the use of buccal or sublingual misoprostol for cervical
reasonable and effective alternative for cervical ripening ripening or induction of labor, and these methods are not
and inducing labor. recommended for clinical use until further studies sup-
Intracervical or intravaginal PGE2 (dinoprostone) port their safety (53).
commonly is used and is superior to placebo or no therapy
in promoting cervical ripening (42). Several prospective What are the potential complications with
randomized clinical trials and two meta-analyses have each method of cervical ripening, and how
demonstrated that PGE1 (misoprostol) is an effective are they managed?
method for cervical ripening (43–48). Misoprostol admin-
istered intravaginally has been reported to be either supe- Tachysystole with or without FHR changes is more com-
rior to or as efficacious as dinoprostone gel (48–51). mon with vaginal misoprostol compared with vaginal
Vaginal misoprostol has been associated with less use of prostaglandin E2, intracervical prostaglandin E2, and oxy-
epidural analgesia, more vaginal deliveries within 24 tocin (48). Tachysystole (defined in some studies as greater
hours, and more uterine tachysystole with or without FHR than 5 uterine contractions in 10 minutes in consecutive
changes compared with dinoprostone and oxytocin (48). 10-minute intervals) and tachysystole with associated
In contrast, misoprostol compared with oxytocin for cer- FHR decelerations are increased with a 50-mcg or greater
vical ripening resulted in longer intervals to active labor dose of misoprostol (43, 47, 48, 54). There seems to be
and delivery in a randomized controlled trial (52). It is dif- a trend toward lower rates of uterine tachysystole with
ficult, however, to compare the results of studies on miso- FHR changes with lower dosages of misoprostol (25
prostol because of differences in endpoints, including mcg every 6 hours versus every 3 hours) (48).
Bishop score, duration of labor, total oxytocin use, suc- The use of misoprostol in women with prior cesare-
cessful induction, and cesarean delivery rate. Pharma- an delivery or major uterine surgery has been associated
cologic methods for cervical ripening do not decrease the with an increase in uterine rupture and, therefore, should
likelihood of cesarean delivery. be avoided in the third trimester (55, 56). An increase in
meconium-stained amniotic fluid also has been reported
How should prostaglandins be administered? with misoprostol use (47, 48). Although misoprostol appears
to be safe and effective in inducing labor in women with
One quarter of an unscored 100-mcg tablet (ie, approxi- unfavorable cervices, further studies are needed to deter-
mately 25 mcg) of misoprostol should be considered as mine the optimal route, dosage, timing interval, and phar-
the initial dose for cervical ripening and labor induction. macokinetics of misoprostol. Moreover, data are needed on
The frequency of administration should not be more than the management of complications related to misoprostol
every 3–6 hours. In addition, oxytocin should not be use and when it should be discontinued. If uterine tachy-
administered less than 4 hours after the last misoprostol systole and a Category III FHR tracing (defined as either
dose. Misoprostol in higher doses (50 mcg every 6 a sinusoidal pattern or an absent baseline FHR variability
hours) may be appropriate in some situations, although and any of the following: recurrent late decelerations, recur-
higher doses are associated with an increased risk of rent variable decelerations, or bradycardia) occurs with
complications, including uterine tachysystole with FHR misoprostol use and there is no response to routine cor-
decelerations. rective measures (maternal repositioning and supplemen-
If there is inadequate cervical change with minimal tal oxygen administration), cesarean delivery should be
uterine activity after one dose of intracervical dinopros- considered (32). Subcutaneous terbutaline also can be used
tone, a second dose may be given 6–12 hours later. The in an attempt to correct the Category III FHR tracing or
manufacturers recommend a maximum cumulative dose uterine tachysystole.

390 ACOG Practice Bulletin Induction of Labor OBSTETRICS & GYNECOLOGY

 The intracervical PGE2 gel (0.5 mg) has a 1% rate of an outpatient procedure, it was noted that PGE2 gel was
uterine tachysystole with associated FHR changes while effective and safe for initiation of labor in women at term
the intravaginal PGE2 gel (2–5 mg) or vaginal insert is with a Bishop score of 6 or less (64). No significant dif-
associated with a 5% rate (42, 57, 58). Uterine tachysys- ferences in adverse outcomes were noted in another ran-
tole typically begins within 1 hour after the gel or insert domized trial of 300 women at term comparing the use
is placed but may occur up to 9 1/2 hours after the vagi- of controlled-release PGE2 in an outpatient versus inpa-
nal insert has been placed (57–59). tient setting (65). Larger controlled studies are needed to
Removing the PGE2 vaginal insert usually will help establish an effective and safe dose and vehicle for PGE2
reverse the effect of uterine tachysystole. Irrigation of the before use on an outpatient basis can be recommended.
cervix and vagina is not beneficial. Maternal side effects However, outpatient use may be appropriate in carefully
from the use of low-dose PGE2 (fever, vomiting, and diar- selected patients. Mechanical methods may be particu-
rhea) are quite uncommon (60). Prophylactic antiemetics, larly appropriate in the outpatient setting. A randomized
antipyretics, and antidiarrheal agents usually are not trial comparing the Foley catheter in an outpatient versus
needed. The manufacturers recommend that caution be inpatient setting for preinduction cervical ripening
exercised when using PGE2 in patients with glaucoma, demonstrated similar efficacy and safety with a reduc-
severe hepatic or renal dysfunction, or asthma. However, tion of hospital stay of 9.6 hours (66).
PGE2 is a bronchodilator, and there are no reports of bron-
choconstriction or significant blood pressure changes after What are the potential complications of
the administration of the low-dose gel. various methods of induction?
Increased maternal and neonatal infections have been
The side effects of oxytocin use are principally dose
reported in connection with the use of Laminaria japon-
related; uterine tachysystole and Category II or III FHR
icum and hygroscopic dilators when compared with the
tracings are the most common side effects. Uterine tachy-
PGE2 analogues (7, 13, 20). The Foley catheter can cause
systole may result in abruptio placentae or uterine rupture.
significant vaginal bleeding in women with a low-lying
Uterine rupture secondary to oxytocin use is rare even in
placenta (21). Other reported complications include rup-
parous women (67). Water intoxication can occur with
ture of membranes, febrile morbidity, and displacement of
high concentrations of oxytocin infused with large quanti-
the presenting part (61).
ties of hypotonic solutions, but is rare in doses used for
labor induction.
What are the recommended guidelines for
Misoprostol appears to be safe and beneficial for
fetal surveillance after prostaglandin use? inducing labor in a woman with an unfavorable cervix.
The prostaglandin preparations should be administered Although the exact incidence of uterine tachysystole
where uterine activity and the FHR can be monitored with or without FHR changes is unknown and the crite-
continuously for an initial observation period. Further ria used to define this complication are not always clear
monitoring can be governed by individual indications for in the various reports, there are reports of uterine
induction and fetal status. tachysystole with or without FHR changes occurring
The patient should remain recumbent for at least 30 more frequently in women given misoprostol compared
minutes. The FHR and uterine activity should be moni- with women given PGE2 (43, 45, 48, 68). There does not
tored continuously for a period of 30 minutes to 2 hours appear to be a significant increase in adverse fetal out-
after administration of the PGE2 gel (62). Uterine con- comes from tachysystole without associated FHR decel-
tractions usually are evident in the first hour and exhibit erations (68, 69). The occurrence of complications does
peak activity in the first 4 hours (62, 63). The FHR mon- appear to be dose-dependent (10, 48). Clinical trials have
itoring should be continued if regular uterine contrac- shown that at an equivalent dosage, the vaginal route
tions persist; maternal vital signs also should be produces greater clinical efficacy than the oral route
recorded. (53). Oral misoprostol administration is associated with
fewer abnormal FHR patterns and episodes of uterine
Are cervical ripening methods appropriate in tachy-systole with associated FHR changes when com-
an outpatient setting? pared with vaginal administration (70, 71).
The potential risks associated with amniotomy
Limited information is available on the safety of outpa- include prolapse of the umbilical cord, chorioamnionitis,
tient management of induction of labor. In a randomized, significant umbilical cord compression, and rupture of
double-blind, controlled trial comparing 2 mg of intrav- vasa previa. The physician should palpate for an umbili-
aginal PGE2 gel with placebo for 5 consecutive days as cal cord and avoid dislodging the fetal head. The FHR

VOL. 114, NO. 2, PART 1, AUGUST 2009 ACOG Practice Bulletin Induction of Labor 391
should be assessed before and immediately after amni- is diluted 10 units in 1,000 mL of an isotonic solution for
otomy. Amniotomy for induction of labor may be con- an oxytocin concentration of 10 mU/mL. Oxytocin should
traindicated in women known to have HIV infection be administered by infusion using a pump that allows
because duration of ruptured membranes has been iden- precise control of the flow rate and permits accurate
tified as an independent risk factor for vertical transmis- minute-to-minute control. Bolus administration of oxy-
sion of HIV infection (29). tocin can be avoided by piggybacking the infusion into
Stripping the amniotic membranes is associated with the main intravenous line near the venipuncture site.
bleeding from undiagnosed placenta previa or low-lying A numeric value for the maximum dose of oxytocin
placenta, and accidental amniotomy. Bilateral breast stim- has not been established. The FHR and uterine contrac-
ulation has been associated with uterine tachysystole with tions should be monitored closely. Oxytocin should be
associated FHR decelerations. In a systematic review, administered by trained personnel who are familiar with
breast stimulation was associated with an increased trend its effects.
in perinatal death (31). Until safety issues are studied fur-
ther, this practice is not recommended in an unmonitored How should complications associated with
setting. oxytocin use be managed?

When oxytocin is used for induction of labor, If uterine tachysystole with Category III FHR tracings
what dosage should be used and what pre- occur, prompt evaluation is required and intravenous
infusion of oxytocin should be decreased or discontin-
cautions should be taken?
ued to correct the pattern (32). Additional measures may
Any of the low- or high-dose oxytocin regimens outlined include turning the woman on her side and administer-
in Table 2 are appropriate for labor induction (72–78). ing oxygen or more intravenous fluid. If uterine
Low-dose regimens and less frequent increases in dose tachysystole persists, use of terbutaline or other tocolyt-
are associated with decreased uterine tachysystole with ics may be considered. Hypotension may occur follow-
associated FHR changes (70). High-dose regimens and ing a rapid intravenous injection of oxytocin; therefore,
more frequent dose increases are associated with shorter it is imperative that a dilute oxytocin infusion be used
labor and less frequent cases of chorioamnionitis and even in the immediate puerperium.
cesarean delivery for dystocia, but increased rates of uter-
ine tachysystole with associated FHR changes (74, 79). Are there special considerations that apply
Each hospital’s obstetrics and gynecology depart- for induction in a woman with ruptured
ment should develop guidelines for the preparation and membranes?
administration of oxytocin. Synthetic oxytocin generally
The largest randomized study to date found that oxy-
Table 2. Labor Stimulation with Oxytocin: Examples of Low- tocin induction reduced the time interval between pre-
and High-Dose Oxytocin mature rupture of membranes and delivery as well as the
frequencies of chorioamnionitis, postpartum febrile mor-
Starting Incremental Dosage bidity, and neonatal antibiotic treatments, without increas-
Regimen Dose Increase (mU/min) Interval (min) ing cesarean deliveries or neonatal infections (80). These
Low-Dose 0.5–2 1–2 15–40 data suggest that for women with premature rupture of
High-Dose 6 3–6* 15–40 membranes at term, labor should be induced at the time of
presentation, generally with oxytocin infusion, to reduce
*The incremental increase is reduced to 3 mU/min in presence of hyperstimula-
tion and reduced to 1 mU/min with recurrent hyperstimulation. the risk of chorioamnionitis. An adequate time for the
Data from Hauth JC, Hankins GD, Gilstrap LC 3rd, Strickland DM, Vance P.
latent phase of labor to progress should be allowed.
Uterine contraction pressures with oxytocin induction/augmentation. Obstet The same precautions should be exercised when
Gynecol 1986;68:305–9; Satin AJ, Leveno KJ, Sherman ML, Brewster DS, prostaglandins are used for induction of labor with rup-
Cunningham FG. High- versus low-dose oxytocin for labor stimulation. Obstet
Gynecol 1992;80:111–6; Crane JM, Young DC. Meta-analysis of low-dose versus
tured membranes as for intact membranes. Intravaginal
high-dose oxytocin for labour induction. J SOGC 1998;20:1215–23; Cummiskey PGE2 for induction of labor in women with premature
KC, Dawood MY. Induction of labor with pulsatile oxytocin. Am J Obstet Gynecol rupture of membranes appears to be safe and effective
1990;163:1868–74; Blakemore KJ, Qin NG, Petrie RH, Paine LL. A prospective
comparison of hourly and quarter-hourly oxytocin dose increase intervals for the (81). In a randomized study of labor induction in women
induction of labor at term. Obstet Gynecol 1990;75:757–61; Mercer B, Pilgrim with premature rupture of membranes at term, only one
P, Sibai B. Labor induction with continuous low-dose oxytocin infusion: a ran- dose of intravaginal misoprostol was necessary for suc-
domized trial. Obstet Gynecol 1991;77:659–63; and Muller PR, Stubbs TM,
Laurent SL. A prospective randomized clinical trial comparing two oxytocin cessful labor induction in 86% of the patients (67).
induction protocols. Am J Obstet Gynecol 1992;167:373–80; discussion 380–1. There is no evidence that use of either of these prostag-

392 ACOG Practice Bulletin Induction of Labor OBSTETRICS & GYNECOLOGY

landins increases the risk of infection in women with Several studies have evaluated the use of misopros-
ruptured membranes (67, 81). There is insufficient evi- tol at a dosage of 400 mcg every 6 hours in women with
dence to guide the physician on use of mechanical dila- a stillbirth up to 28 weeks of gestation and a prior uter-
tors in women with ruptured membranes. ine scar (85, 89). There does not appear to be an increase
A meta-analysis that included 6,814 women with pre- in complications in those women. Further research is
mature rupture of membranes at term compared induction required to assess effectiveness and safety, optimal route
of labor with prostaglandins or oxytocin to expectant of administration, and dose.
management (82). A significant reduction in the risk of In patients after 28 weeks of gestation, cervical ripen-
women developing chorioamnionitis or endometritis and a ing with a transcervical Foley catheter has been associated
reduced number of neonates requiring admission to the with uterine rupture rates comparable to spontaneous
neonatal intensive care unit was noted in the women who labor (90) and this may be a helpful adjunct in patients
underwent induction of labor compared with expectant with an unfavorable cervical assessment. Therefore, in
management (82). patients with a prior low transverse cesarean delivery, trial
of labor remains a favorable option. There are limited data
What methods can be used for induction of to guide clinical practice in a patient with a prior classical
labor with intrauterine fetal demise in the cesarean delivery, and the delivery plan should be individ-
late second or third trimester? ualized.

The method and timing of delivery after a fetal death

depends on the gestational age at which the death occur-
red, on the maternal history of a previous uterine scar, and
Summary of
maternal preference. Although most patients will desire Recommendations and
prompt delivery, the timing of delivery is not critical; Conclusions
coagulopathies are associated with prolonged fetal reten-
tion and are uncommon. In the second trimester, dilation The following recommendations and conclusions
and evacuation can be offered if an experienced health are based on good and consistent scientific evi-
care provider is available, although patients should be dence (Level A):
counseled that dilation and evacuation may limit efficacy
of autopsy for the detection of macroscopic fetal abnor- Prostaglandin E analogues are effective for cervical
malities. ripening and inducing labor.
Labor induction is appropriate at later gestational Low- or high-dose oxytocin regimens are appropri-
ages, if second-trimester dilation and evacuation is un- ate for women in whom induction of labor is indi-
available, or based on patient preference. Much of the cated (Table 2).
data for management of fetal demise has been extrapo-
lated from randomized trials of management of second Before 28 weeks of gestation, vaginal misoprostol
trimester pregnancy termination. Available evidence from appears to be the most efficient method of labor
randomized trials supports the use of vaginal misopros- induction regardless of Bishop score, although high-
tol as a medical treatment to terminate nonviable preg- dose oxytocin infusion also is an acceptable choice.
nancies before 24 weeks of gestation (83). Based on Approximately 25 mcg of misoprostol should be
limited data, the use of misoprostol between 24 to 28 considered as the initial dose for cervical ripening
weeks of gestation also appears to be safe and effective and labor induction. The frequency of administra-
(84, 85). Before 28 weeks of gestation, vaginal miso- tion should not be more than every 3–6 hours.
prostol appears to be the most efficient method of labor Intravaginal PGE2 for induction of labor in women
induction, regardless of cervical Bishop score (84, 86), with premature rupture of membranes appears to be
although high-dose oxytocin infusion also is an accept- safe and effective.
able choice (87, 88). Typical dosages for misoprostol use
are 200–400 mcg vaginally every 4–12 hours. After 28 The use of misoprostol in women with prior cesarean
weeks of gestation, induction of labor should be managed delivery or major uterine surgery has been associated
according to usual obstetric protocols. Cesarean delivery with an increase in uterine rupture and, therefore,
for fetal demise should be reserved for unusual circum- should be avoided in the third trimester.
stances because it is associated with potential maternal The Foley catheter is a reasonable and effective
morbidity without any fetal benefit. alternative for cervical ripening and inducing labor.

VOL. 114, NO. 2, PART 1, AUGUST 2009 ACOG Practice Bulletin Induction of Labor 393
The following recommendation is based on evi- 12. Blumenthal PD, Ramanauskas R. Randomized trial of
Dilapan and Laminaria as cervical ripening agents before
dence that may be limited or inconsistent (Level B) induction of labor. Obstet Gynecol 1990;75:365–8. (Level I)
Misoprostol (50 mcg every 6 hours) to induce labor 13. Chua S, Arulkumaran S, Vanaja K, Ratnam SS. Preinduc-
may be appropriate in some situations, although tion cervical ripening: prostaglandin E2 gel vs hygroscopic
higher doses are associated with an increased risk of mechanical dilator. J Obstet Gynaecol Res 1997;23:
171–7. (Level I)
complications, including uterine tachysystole with
FHR decelerations. 14. Gilson GJ, Russell DJ, Izquierdo LA, Qualls CR, Curet
LB. A prospective randomized evaluation of a hygroscopic
cervical dilator, Dilapan, in the preinduction ripening of
patients undergoing induction of labor. Am J Obstet
Proposed Performance Gynecol 1996;175:145–9. (Level I)
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Measure extra-amniotic saline infusion versus laminaria for cervi-
Percentage of patients in whom gestational age is estab- cal ripening. Obstet Gynecol 1995;86:545–9. (Level I)
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otic saline infusion (BCEAS): a randomised comparison
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64. O’Brien JM, Mercer BM, Cleary NT, Sibai BM. Efficacy 79. Hannah ME, Ohlsson A, Farine D, Hewson SA, Hodnett ED,
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prostaglandin E2: a randomized, double-blind, placebo- tant management for prelabor rupture of the membranes at
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65. Biem SR, Turnell RW, Olatunbosun O, Tauh M, Biem HJ. 80. Merrill DC, Zlatnik FJ. Randomized, double-masked
A randomized controlled trial of outpatient versus inpa- comparison of oxytocin dosage in induction and augmen-
tient labour induction with vaginal controlled-release tation of labor. Obstet Gynecol 1999;94:455–63. (Level I)
prostaglandin-E2: effectiveness and satisfaction. J Obstet 81. Ray DA, Garite TJ. Prostaglandin E2 for induction of
Gynaecol Can 2003;25:23–31. (Level I) labor in patients with premature rupture of membranes at
66. Sciscione AC, Muench M, Pollock M, Jenkins TM, term. Am J Obstet Gynecol 1992;166:836–43. (Level I)
Tildon-Burton J, Colmorgen GH. Transcervical Foley 82. Dare MR, Middleton P, Crowther CA, Flenady VJ,
catheter for preinduction cervical ripening in an outpatient Varatharaju B. Planned early birth versus expectant man-
versus inpatient setting. Obstet Gynecol 2001;98:751–6. agement (waiting) for prelabour rupture of membranes
(Level I) at term (37 weeks or more). Cochrane Database of
67. Flannelly GM, Turner MJ, Rassmussen MJ, Stronge JM. Systematic Reviews 2006, Issue 1. Art. No.: CD005302.
Rupture of the uterus in Dublin; an update. J Obstet DOI: 10.1002/14651858.CD005302.pub2. (Level III)
Gynaecol 1993;13:440–3. (Level II-3) 83. Neilson JP, Hickey M, Vazquez J. Medical treatment for
68. Sanchez-Ramos L, Chen AH, Kaunitz AM, Gaudier FL, early fetal death (less than 24 weeks). Cochrane Database
Delke I. Labor induction with intravaginal misoprostol in of Systematic Reviews 2006, Issue 3. Art. No.: CD002253.
term premature rupture of membranes: a randomized DOI: 10.1002/14651858.CD002253.pub3. (Level I)
study. Obstet Gynecol 1997;89:909–12. (Level I) 84. Dickinson JE, Evans SF. The optimization of intravaginal
69. Wing DA, Ortiz-Omphroy G, Paul RH. A comparison of misoprostol dosing schedules in second-trimester preg-
intermittent vaginal administration of misoprostol with nancy termination [published erratum appears in Am J
continuous dinoprostone for cervical ripening and labor Obstet Gynecol 2005;193:597]. Am J Obstet Gynecol
induction. Am J Obstet Gynecol 1997;177:612–8. (Level I) 2002;186:470–4. (Level I)

396 ACOG Practice Bulletin Induction of Labor OBSTETRICS & GYNECOLOGY

85. Dickinson JE. Misoprostol for second-trimester pregnancy
termination in women with a prior cesarean delivery. The MEDLINE database, the Cochrane Library, and
Obstet Gynecol 2005;105:352–6. (Level II-2) ACOG’s own internal resources and documents were used
to conduct a literature search to locate relevant articles pub-
86. Tang OS, Lau WN, Chan CC, Ho PC. A prospective ran- lished between January 1985 and January 2009. The search
domised comparison of sublingual and vaginal misopros- was restricted to articles published in the English language.
tol in second trimester termination of pregnancy. BJOG Priority was given to articles reporting results of original re-
2004;111:1001–5. (Level I) search, although review articles and commentaries also
87. Toaff R, Ayalon D, Gogol G. Clinical use of high concen- were consulted. Abstracts of research presented at symposia
tration oxytocin drip. Obstet Gynecol 1971;37:112–20. and scientific conferences were not considered adequate for
(Level II-3) inclusion in this document. Guidelines published by organi-
zations or institutions such as the National Institutes of
88. Winkler CL, Gray SE, Hauth JC, Owen J, Tucker JM. Health and the American College of Obstetricians and
Mid-second-trimester labor induction: concentrated oxy- Gynecologists were reviewed, and additional studies were
tocin compared with prostaglandin E2 vaginal supposito- located by reviewing bibliographies of identified articles.
ries. Obstet Gynecol 1991;77:297–300. (Level II-3) When reliable research was not available, expert opinions
89. Daskalakis GJ, Mesogitis SA, Papantoniou NE, from obstetrician–gynecologists were used.
Moulopoulos GG, Papapanagiotou AA, Antsaklis AJ. Studies were reviewed and evaluated for quality according
Misoprostol for second trimester pregnancy termination to the method outlined by the U.S. Preventive Services
in women with prior caesarean section. BJOG 2005;112: Task Force:
97–9. (Level II-2)
I Evidence obtained from at least one properly
90. Bujold E, Blackwell SC, Gauthier RJ. Cervical ripening designed randomized controlled trial.
with transcervical Foley catheter and the risk of uterine II-1 Evidence obtained from well-designed controlled
rupture. Obstet Gynecol 2004;103:18–23. (Level II-2) trials without randomization.
II-2 Evidence obtained from well-designed cohort or
case–control analytic studies, preferably from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
without the intervention. Dramatic results in uncon-
trolled experiments also could be regarded as this
type of evidence.
III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
following categories:
Level A—Recommendations are based on good and con-
sistent scientific evidence.
Level B—Recommendations are based on limited or incon-
sistent scientific evidence.
Level C—Recommendations are based primarily on con-
sensus and expert opinion.

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VOL. 114, NO. 2, PART 1, AUGUST 2009 ACOG Practice Bulletin Induction of Labor 397