Induction of labor
Author
Deborah A Wing, MD
Section Editor
Charles J Lockwood, MD
Deputy Editor
Vanessa A Barss, MD
Disclosures
Last literature review version 19.3: Fri Sep 30 00:00:00 GMT 2011 | This topic
last updated: Fri Sep 23 00:00:00 GMT 2011 (More)
INTRODUCTION — Induction of labor refers to iatrogenic stimulation of uterine
contractions to accomplish delivery prior to the onset of spontaneous labor. It is one of
the most commonly performed obstetrical procedures in the United States. Between
1990 and 2006, the overall frequency of labor induction approximately doubled, rising
from 9.5 to 22.5 percent [1], and early term (in the 37th and 38th week) inductions
quadrupled, rising from 2 to 8 percent [2]. Reasons for this increase include the
availability of better cervical ripening agents, patient and clinicians desire to arrange a
convenient time of delivery, and more relaxed attitudes toward marginal indications for
induction [3]. Patient or provider concerns about the risk of fetal demise with
expectant management near term or postterm also have contributed to the increased
rate of induction.
Induction of labor in women with an unscarred uterus will be discussed here. Issues
regarding induction of labor in women who have had a previous cesarean delivery are
reviewed separately. (See "Cervical ripening and induction of labor in women with a
prior cesarean delivery".)
INDICATIONS AND CONTRAINDICATIONS
Indications — Labor may be induced for either maternal or fetal indications. Induction
of labor is undertaken when both of the following criteria are met [4]:
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Continuing the pregnancy is believed to be associated with greater maternal or
fetal risk than intervention to deliver the pregnancy, and
There is no contraindication to vaginal birth
The magnitude of risk is influenced by factors such as gestational age,
presence/absence of fetal lung maturity, severity of the clinical condition, and cervical
status. Some examples of common medical and obstetrical conditions for which
induction may be indicated include postterm pregnancy, prelabor (premature) rupture
of membranes, intrauterine fetal growth restriction, preeclampsia/eclampsia, and fetal
demise (see individual topic reviews). Appropriately timed induction of women with
these pregnancy complications can improve maternal-fetal outcome [5]. However,
there is only limited high quality evidence establishing any benefits for specific medical
and obstetrical indications for induction [6].
The risks of iatrogenic late preterm birth appear to outweigh any theoretical benefits
when the indication for delivery is “soft,” such as suspected macrosomia without
maternal diabetes, uncomplicated gestational or chronic hypertension, or history of
fetal, maternal, or obstetric complication in a previous pregnancy [7,8]. These risks
are discussed in detail separately. (See "Late preterm infants".)
Contraindications — Most obstetricians consider induction of labor contraindicated in
the following settings. For each of these conditions, the maternal or fetal risk
associated with labor or vaginal delivery is believed to be greater than the risk
associated with cesarean delivery.

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Prior classical uterine incision
Prior transmural uterine incision entering the uterine cavity
Active genital herpes infection
Placenta or vasa previa
Umbilical cord prolapse
Transverse fetal lie
Other clinical scenarios (eg, previous low transverse cesarean delivery, multifetal
pregnancy, nonreactive nonstress test) may be associated with an increased risk of
maternal or fetal morbidity during induction. These pregnancies warrant close
monitoring during the procedure, with a low threshold for intervention if labor is not
progressing or there are no reassuring signs of fetal well-being.
Elective induction at term — As discussed above, the prevalence of labor induction
has doubled over the past two decades. Some of this increase is related to a rise in the
number of medically and obstetrically indicated inductions; however, it appears that
marginally indicated and elective inductions account for a large proportion of the
increase [9].
The major concerns associated with elective induction of labor at term are the potential
for increased rates of cesarean delivery, iatrogenic prematurity, and cost. Another
concern is that maternal-fetal medical benefits, such as reduction in stillbirth, have not
been proven. Nevertheless, there are potential advantages to scheduled induction of
labor, such as avoiding the risk of delivery en route to the hospital if labor is rapid or
the patient lives far away and avoiding sudden disruption of the patient's (and
provider's) work and nonwork related responsibilities.
There are insufficient data to support a policy of routine elective induction of labor at
term. Large, randomized trials with emphasis on maternal and neonatal safety,
determination of neonatal benefit as a reflection of reduced unexplained fetal death,
and cost-effectiveness/cost-benefit analyses are needed.
The increased risk of cesarean delivery with elective induction was illustrated in one of
the largest observational studies of elective induction in low risk women, which
included 1847 women undergoing elective induction and 35,597 spontaneously
laboring women [10]. In this study, the WHO Global Survey on Maternal and Perinatal
Health in Latin America Study Group observed cesarean delivery rates of 11.7 percent
with elective induction and 8.6 percent after spontaneous labor (crude RR 1.36, 95%
CI 1.19-1.55).
If successful elective induction is defined as achieving a vaginal birth while avoiding
excessive costs and admission to a special care nursery, then the best candidates are
women (nulliparous or multiparous) with well-dated pregnancies of at least 39 weeks
of gestation (table 1) and favorable cervices. The excess neonatal morbidity of earlier
intervention was illustrated in a prospective observational study that compared the
outcome of 790 planned elective inductions at 37 to 38 weeks of gestation with the
outcome of 2004 planned elective inductions at ≥39 weeks of gestation [11]. Earlier
induction was associated with a significantly higher risk of neonatal intensive care unit
admission (7.7 versus 3.0 percent).
Cesarean delivery rate by parity

Nulliparas — Elective induction of nulliparous women appears to double the
risk of operative delivery compared to the risk in women who undergo
spontaneous labor. This is best illustrated by a matched cohort study that
compared the fetomaternal outcome of 7683 women who underwent electively
induced labor to 7683 women who experienced spontaneous labor [12]. All of
the women were nulliparous with singleton pregnancies in cephalic
presentation, gestational age 266 to 287 days, and birth weight 3000 to 4000
grams. Information on cervical status and use of cervical ripening agents was
not available. Elective induction led to statistically significant higher rates of
cesarean delivery (10 versus 7 percent), instrumental delivery (32 versus 29
percent), and use of epidural anesthesia (80 versus 58 percent). The higher
cesarean delivery rate was attributed to an increased frequency of intervention
for failure to progress in the first stage of labor.
Similar findings have been reported in multiple cohort studies of nulliparous
women with vertex, singleton term pregnancies delivering in the United States
[13-19]. These studies consistently showed that the rate of cesarean delivery
was increased approximately two-fold in women who underwent elective or
medical induction of labor compared to those who experienced spontaneous
labor.
The increased risk of cesarean delivery appears to be related primarily to an
unfavorable cervix (ie, Bishop score ≤5) at admission. Most studies, including
one small randomized trial [20], have reported that women with favorable
cervices were not at increased risk of cesarean birth.
Women in spontaneous labor are not an appropriate control group for these
studies. Using them as controls biases differences in cesarean rates to favor the
control group because many patients managed expectantly would have gone on
to have an indicated cesarean delivery rather than spontaneous labor. When
cesarean delivery rates have been compared for induced labors versus
expectant management at the same gestational age, the differences in
cesarean delivery rates were small [21,22].

Multiparas — By comparison, most studies in multiparous women have not
shown an increased risk of cesarean delivery with induction of labor [9]. Almost
all of these reports were retrospective, but one small randomized trial
confirmed these findings [20].
One of the largest series was a population-based cohort study that compared
the risk of cesarean delivery in 1775 healthy, low risk multiparous women at
term who underwent induction without an identifiable indication to 5785 similar
women who entered labor spontaneously [23]. Cervical ripening agents were
used in women with unfavorable cervices. The overall cesarean delivery rate
was similar for induced and spontaneous labors, 3.8 and 3.6 percent,
respectively (RR 1.07, 95% CI 0.91-1.39). Although the cesarean delivery rate
was higher in women with a previous cesarean delivery, the rate did not differ
significantly for induced and spontaneous labors (30.5 and 30.7 percent,
respectively).
Even when inductions for medical indications are included, multiparas have a
relatively low rate of cesarean delivery. In one retrospective cohort study, the
rates of cesarean delivery in multiparas in spontaneous labor (n = 7208),
induced with oxytocin (n = 2190), and induced with cervical ripening agents (n
= 239) were 4.2, 6.3, and 14.2 percent, respectively [24]. Oxytocin-induced
multiparas were 37 percent more likely to require cesarean than those with
spontaneous labor (OR, 1.37; 95% CI, 1.10-1.71) and nearly three times more
likely to undergo cesarean when cervical ripening agents were used (OR, 2.82;
95% CI, 1.84-4.53).
Pediatric issues — Neonatal respiratory problems are the major pediatric concerns
with elective delivery. Respiratory problems can result from inadvertent delivery of a
premature infant or transient tachypnea related to cesarean delivery after failed
induction. Guidelines to help ensure that gestational age is at least 39 weeks before
elective delivery are listed below (see 'Preinduction assessment' below). However,
several, primarily retrospective, studies have not shown a marked impairment in
neonatal outcome when elective induction of labor was undertaken at term in welldated pregnancies [25-29]. There may, in fact, be a slight benefit as fewer electively
induced infants have meconium passage when compared to spontaneously labored
infants. Macrosomia also may be reduced.
The risk of respiratory morbidity was illustrated in a retrospective review of the infants
with respiratory distress or transient tachypnea of the newborn admitted to the
neonatal intensive care unit following elective delivery at term [30]. The data were
stratified by gestational age and route of delivery:
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Baseline incidence of respiratory distress syndrome and transient tachypnea at
term were 2.2/1000 deliveries (95% CI 1.7-2.7/1000) and 5.7/1000 deliveries
(95% CI 4.9-6.5/1000), respectively.
The frequencies of respiratory morbidity following vaginal delivery were:
week 37+0 to 37+6: 12.6 (7.6-19.6)/1000 deliveries with OR 2.5 (95% CI 1.54.2)
week 38+0 to 38+6: 7.0 (4.6-10.2)/1000 deliveries with OR 1.4 (95% CI 0.82.2)

week 39+0 to 39+6: 3.2 (1.8-4.5)/1000 deliveries with OR 0.6 (95% CI 0.41.0).

The frequencies of respiratory morbidity with cesarean delivery following labor
(as would occur following an induction attempt) were:

week 37+0 to 37+6: 57.7 (26.7-107.1)/1000 deliveries with OR 11.2 (95%CI
5.4-13.1)
week 38+0 to 38+6: 9.4 (1.9-27.2)/1000 deliveries with OR 1.8 (95% CI 0.65.9)
week 39+0 to 39+6: 16.2 (5.9-35.50)/1000 deliveries with OR 3.2 (95% CI
1.4-7.4).
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Delivery by cesarean without preceding labor increased the frequencies of respiratory
morbidities even higher across all gestational ages. These data provide support for
delaying elective delivery until 39 weeks of gestation.
Health care cost estimates — A study using decision analysis analyzed the economic
consequences of elective induction of labor at term in a cohort of 100,000 women for
whom an initial decision was made to either (1) induce labor at 39 weeks of gestation
or (2) to follow expectantly through the remainder of pregnancy [31]. All patients in
this model underwent elective induction at 42 weeks. Using baseline estimates, the
major findings were:
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A policy of elective induction would result in over 12,000 excess cesarean
deliveries and impose a cost to the United States medical system of nearly $100
million per year.
A policy of induction at any gestational age, regardless of parity or cervical
ripeness, required additional economic expenditures. Although never costsaving, inductions were less expensive at later gestational ages, for multiparous
patients, and for women with favorable cervices.
The inductions most costly to the health care system were those performed in
nulliparas with unfavorable cervices at 39 weeks. When nulliparous women with
favorable cervices underwent labor induction, the estimated cost was
approximately halved compared to nulliparas with unfavorable cervices;
however, it still resulted in an overall added expenditure and additional
cesarean deliveries.
Active Management Of Risk In Pregnancy At Term (AMOR-IPAT) — An approach
called the Active Management Of Risk In Pregnancy At Term (AMOR-IPAT) is a
promising method to reduce the risk of cesarean following induction of labor [32-34].
Using a retrospective cohort design, delivery outcomes of over 200 women with a
tailored approach to prenatal care and individualization of risk of cesarean birth were
compared to over 600 control women [33,34]. Consideration was given to the most
common indications for nonelective cesarean: cephalopelvic disproportion and
uteroplacental insufficiency. A hypothetical ceiling for gestational age at delivery,
always ≤41 weeks and ≥38 weeks of gestation, was set for each subject. Cervical
ripening was used for all women with Bishop scores less than 5. Despite a significant
increase in the labor induction rate in the women managed by AMOR-IPAT (nulliparas
47 versus 24 percent; multiparas 61 versus 16 percent), there was a significant
reduction in cesarean births in the actively managed group (nulliparas 9 versus 26
percent; multiparas 1 versus 10 percent).
In a similar retrospective cohort study, a protocol of risk-guided prostaglandin-assisted
preventive labor induction with differing intensity was applied [35]. Compared with
nonexposed subjects, the exposed group (n = 794) had a significantly higher rate of
labor induction (31.4 versus 20.4 percent), and use of prostaglandin E2 (23.3 versus
15.7 percent), and a significantly lower cesarean delivery rate (5.3 versus 11.8
percent).
A small prospective trial of AMOR-IPAT failed to confirm these promising results. Lack
of difference in the cesarean delivery rates (10.3 percent in the AMOR-IPAT group
versus 14.9 percent in the conventional management group; P = .25) may have been
because the sample size was too small to reveal a true difference between treatment
groups [5]. Larger, randomized, controlled, multi-center investigations are planned. In
addition, neonatal outcomes need to be thoroughly evaluated since delivery before 39
weeks of gestation without assessment of fetal pulmonary maturity may result in
higher neonatal respiratory morbidity. This risk may outweigh any benefit from
reduction of the cesarean delivery rate.
PREINDUCTION ASSESSMENT — A thorough evaluation of the maternal and fetal
condition is important prior to undertaking labor induction to make sure there are no
contraindications to labor or vaginal delivery and to assess the likelihood of successful
induction. At a minimum, this includes assessing the gestational age and fetal size,
determining presentation, performing a cervical examination, and reviewing the
patient's pregnancy and medical history. The indications for and alternatives to the
procedure, techniques for cervical ripening and labor induction, and the possibility of
cesarean delivery or induction over several days should be reviewed with the patient.
The probability of fetal maturity should be determined. Clinical criteria presumptive of
fetal maturity include [36]:
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Fetal heart tones have been documented for 20 weeks by nonelectronic
fetoscope or for 30 weeks by Doppler.
Thirty-six weeks have elapsed since a serum or urine human chorionic
gonadotropin (hCG) based pregnancy test was reported to be positive.
Ultrasound measurement of the crown-rump length at 6 to 11 weeks of
gestation or other ultrasound measurements (eg, biparietal diameter, femur
length) at 12 to 20 weeks of gestation support a clinically determined
gestational age equal to or greater than 39 weeks.
Amniocentesis to assess fetal lung maturity is suggested prior to initiation of induction
if none of these clinical criteria are met and the potential risk of neonatal respiratory
problems exceeds the risk associated with not delivering the pregnancy. In preterm
gestations, administration of steroids is indicated if time permits. (See "Assessment of
fetal lung maturity" and "Antenatal use of corticosteroids in women at risk for preterm
delivery".)
PREDICTING A SUCCESSFUL INDUCTION — Cervical status is one of the most
important factors for predicting the likelihood of successfully inducing labor. For this
reason, a cervical examination should be performed before initiating attempts at
induction. There are several cervical scoring systems available for this purpose (eg,
Bishop system; Fields system; Burnett, Caldor, and Friedman modifications of the
Bishop system [37]).
In observational studies, other characteristics associated with successful induction
include multiparity, tall stature (over 5 feet 5 inches), increasing gestational age,
nonobese maternal weight or body mass index, and infant birthweight less than 3.5 kg
[38,39]. However, these characteristics are predictive of success even in spontaneous
labors, which suggests they are more predictive of the route of delivery than the
likelihood the patient will reach the active phase of labor.
Bishop score — The modified Bishop score is the system most commonly used in
clinical practice in the United States [40]. This system tabulates a score based upon
the station of the presenting part and four characteristics of the cervix: dilatation,
effacement, consistency, and position (table 2).
If the Bishop score is high (variously defined as ≥5 or ≥8), the likelihood of vaginal
delivery is similar whether labor is spontaneous or induced (table 3) [15,40]. In
contrast, a low Bishop score is predictive that induction will fail to result in vaginal
delivery. These relationships are particularly strong in nulliparous women who undergo
induction, although Bishop scoring was originally described in multiparous women
[13,15]. As an example, a study of 4635 spontaneous and 2647 induced labors in
nulliparous women at term reported the cesarean birth rate was twice as high with
induced labor, 24 versus 12 percent, and the cesarean delivery rates for women with
Bishop scores <5 versus ≥5 were 32 and 18 percent, respectively [41].
The relationship between a low Bishop score and failed induction, prolonged labor, and
a high cesarean birth rate was first described prior to widespread use of cervical
ripening agents [42]. However, this relationship has persisted even after the
introduction of these agents (table 4) [43]. (See "Techniques for cervical ripening prior
to labor induction".)
Fetal fibronectin — The presence of an elevated fetal fibronectin (fFN) concentration
in cervicovaginal secretions has also been used to predict uterine readiness for
induction. In several studies, women with a positive fFN result had a significantly
shorter interval until delivery than those with a negative fFN result [44-49] and there
was reduction in the frequency of cesarean delivery [49]. Positive fFN results were
predictive of a shorter interval to delivery, even in nulliparas with low (<5) Bishop
scores [45]. However, others have not confirmed these findings [50,51]. Thus, the role
of fFN as a tool for selecting women likely to have a successful induction remains
uncertain. More data, including cost-benefit analysis, are needed before this test can
be recommended for choosing candidates for semi-elective induction.
Sonographically measured cervical length — In pregnant women, the risk of
preterm birth increases as cervical length decreases. (See "Prediction of prematurity
by transvaginal ultrasound assessment of the cervix".) Cervical length is also predictive
of the likelihood of spontaneous onset of labor postterm [52].
Sonographic assessment of cervical length for predicting the outcome of labor
induction has been evaluated in numerous studies. A systematic review of 20
prospective studies found that cervical length was predictive of successful induction
(likelihood ratio of a positive test, 1.66; 95% CI 1.20-2.31) and failed induction
(likelihood ratio of a negative test, 0.51; 95% CI, 0.39-0.67) [53]. However,
sonographic cervical length performed poorly for predicting vaginal delivery within 24
hours (sensitivity 59 percent, specificity 65 percent), vaginal delivery (sensitivity 67
percent, specificity 58 percent), achieving active labor (sensitivity 57 percent,
specificity 60 percent), and delivery within 24 hours (sensitivity 56 percent, specificity
47 percent), and did not perform significantly better than Bishop score for predicting a
successful induction. These data are limited by substantial heterogeneity among the
studies.
As with fFN, the role of ultrasound examination as a tool for selecting women likely to
have a successful induction is uncertain. More data, including cost-benefit analysis, is
needed before this test can be recommended in choosing candidates for semi-elective
induction.
Discussion — The Bishop score appears to be the best available tool for predicting the
likelihood that induction will result in vaginal delivery. This conclusion is based on
systematic reviews of controlled studies that found the Bishop score was as, or more,
predictive of the outcome of labor induction than fFN [38] or sonographic
measurement of cervical length [38,53,54], and that dilatation was the most important
element of the Bishop score [38].
METHODS FOR INDUCTION OF LABOR — Major societies have published guidelines
for labor induction [4,55].
Membrane stripping — Stripping or sweeping of the membranes is widely utilized. It
involves inserting the examiner's finger beyond the internal cervical os and then
rotating the finger circumferentially along the lower uterine segment to detach the
fetal membranes. Membrane stripping is typically performed during an office visit in
women with a partially dilated cervix who wish to hasten the onset of spontaneous
labor.
The efficacy of membrane sweeping was demonstrated in a meta-analysis of 22 trials
in which 20 compared sweeping of membranes to no treatment, three compared
sweeping to prostaglandin administration, and one compared sweeping
to oxytocin administration before formal induction of labor [56]. Compared to no
intervention, membrane sweeping was associated with reduced frequency of
pregnancy continuing beyond 41 weeks (RR 0.59, 95% CI 0.46-0.74) and 42 weeks of
gestation (RR 0.28, 95% CI 0.15-0.50), and reduced frequency of formal induction (RR
0.72, 95% CI 0.52-1.00). The cesarean delivery rate was not altered; the change in
Bishop score was not assessed. Overall, eight women would need to undergo
membrane sweeping to avoid one formal induction of labor. There was no increased
risk of maternal or neonatal infection, but minor maternal discomforts were common.
We do not recommend routine membrane stripping, given there is no evidence that
this practice results in an improvement in maternal or neonatal outcome. However,
compared to no intervention, weekly membrane stripping at term shortens the interval
of time to onset of spontaneous labor and reduces the need for formal induction. For
this reason, we offer membrane stripping to term patients who wish to hasten the
onset of spontaneous labor. This may be initiated at 39 weeks of gestation.
While the existing meta-analysis on the use of membrane stripping [56] was not
associated with an increase in neonatal infection, it is unclear if the included studies
involved carriers of Group B streptococcus (GBS). There are no studies currently in the
literature specifically designed to address the safety of membrane stripping in known
carriers of GBS. Given a paucity of safety data regarding membrane stripping in known
GBS carriers, caution should be exercised when considering the procedure for women
known to be carriers of GBS.
Oxytocin — Oxytocin is a polypeptide hormone produced in the hypothalamus and
secreted from the posterior lobe of the pituitary gland in a pulsatile fashion. It is
identical to its synthetic analog, which is among the most potent uterotonic agents
known.
Exogenous oxytocin administration produces periodic uterine contractions first
demonstrable at approximately 20 weeks of gestation, with increasing responsiveness
with advancing gestational age. There is little change in myometrial sensitivity to
oxytocin from 34 weeks to term; however, once spontaneous labor begins, the uterine
sensitivity to oxytocin increases rapidly [57]. The gestational increase in uterine
sensitivity is due primarily to an increase in myometrial oxytocin binding sites [58].
Progress during spontaneous labor is not related to increasing oxytocin concentration,
uterine contractions are not associated with changes in plasma oxytocin concentration,
and hypocontractile labor does not appear to be the result of a deficit of oxytocin [59].
Synthetic oxytocin administration is a proven method of labor induction [60].
Regimen — Oxytocin is most commonly given intravenously. It cannot be
administered orally because the polypeptide is degraded into small, inactive forms by
gastrointestinal enzymes. The plasma half-life is short, estimated at three to six
minutes [61]. Steady state concentrations are reached within 40 minutes of initiation
or dose change [62].
Historically, synthetic oxytocin was diluted by placing 10 units in 1000 mL of an
isotonic solution, such as normal saline, yielding an oxytocin concentration of 10
mU/mL. A common practice is to make a solution of 60 units in 1000 mL crystalloid to
allow the infusion pump setting to match the dose administered, eg, 1 mU per minute
equals a pump infusion rate of 1 mL per hour. This practice is becoming more common
in an attempt to improve safety by avoidance of simple arithmetical errors in dosing.
Infusion pumps are used to allow continuous, precise control of the dose administered.
The optimum regimen for oxytocin administration is controversial. Several experts
have suggested that implementation of a standardized protocol is desirable to
minimize errors in oxytocin administration [63-65]. However, no protocol has been
subjected to the scientific scrutiny necessary to demonstrate its superiority in both
efficacy and safety over another.
Protocols differ as to initial dose (0.5-6 mU/min), time period between dose increments
(10-60 minutes), and maximum dose (16-64 mU/minute) (table 5) [63], but success
rates for varying protocols are strikingly similar [4]. A literature review of randomized
clinical trials of high versus low dose oxytocin regimens for augmentation or induction
of labor concluded high-dose oxytocin decreased the time from admission to vaginal
delivery, but did not decrease the incidence of cesarean delivery compared with lowdose therapy [66]. Only one double-blinded randomized trial has been published, and
had the same findings [67]. High dose regimens are associated with a higher rate of
tachysystole than low dose regimes, and in some studies this has resulted in a higher
rate of cesarean delivery for fetal distress [68], but no significant difference in
neonatal outcomes [69].
The dose is typically increased until there is normal progression of labor, or strong
contractions occurring at two to three minute intervals, or uterine activity reaches 150
to 350 Montevideo units (ie, the peak strength of contractions in mmHg measured by
an internal monitor multiplied by their frequency per 10 minutes). There is no benefit
to increasing the dose after one of these endpoints has been achieved. In addition, two
randomized trials found there was no significant benefit in continuing oxytocin infusion
after the onset of active labor [70,71]. Continuing oxytocin may result in a higher rate
of cesarean delivery.
When uterotonic drugs are administered, continuous monitoring of uterine activity and
fetal heart rate are important so the dose can be adjusted if excessive or inadequate
uterine activity is noted.
Some examples of oxytocin regimens are described below:

Low dose — Low-dose protocols attempt to mimic a physiologic approach [4].
The dose of oxytocin is initiated at 0.5 to 1 mU per minute and increased by 1
mU per minute at 40 to 60 minute intervals. This interval was based upon
studies showing approximately 40 minutes were required for any particular
dose of oxytocin to reach a steady-state concentration and maximal uterine
contractile response [62].
Slightly higher doses (begin at 1 to 2 mU/min and increase by 1 to 2 mU/min)
and shorter incremental time intervals (15 to 30 minutes) have also been
recommended [72,73].


High dose — Active management of labor regimens, and others, use a highdose oxytocin infusion with short incremental time intervals. One example of a
high-dose regimen is shown in the table (table 6) [74,75]. A maximum oxytocin
dose has not been established; however, most labor units do not go above 40
mU/min. The most common complication of the high dose regimen is uterine
tachysystole (see 'Tachysystole' below).
Pulsatile — Pulsatile administration of intravenous oxytocin at 8 to 10 minute
intervals may better simulate normal labor and offers the advantage of lower
total doses of oxytocin [76]. The total dose administered is 20 to 50 percent
less than that using standard nonpulsatile infusion regimens [77].
Amniotomy — Amniotomy appears to be an effective method of labor induction, but
can only be performed in women with partially dilated and effaced cervices. To reduce
the risk of prolapse, the clinician should ensure that the fetal vertex is well-applied to
the cervix and the umbilical cord or other fetal part is not presenting. We document
the fetal heart rate before and after the procedure, and also note the color of the
amniotic fluid.
A Cochrane review of randomized trials found the combination of amniotomy plus
intravenous oxytocin administration was more effective than amniotomy alone [78].
With the combined regimen, fewer women were undelivered at 24 hours than with
amniotomy alone (RR 0.13, 95% CI 0.04-0.41). To achieve the greatest impact on
duration of labor, amniotomy should be performed as early as possible and oxytocin
should be initiated immediately thereafter [79].
There are inadequate data for assessing the efficacy of the combination of amniotomy
plus intravenous oxytocin administration compared to intravenous oxytocin alone [80].
There are limited data suggesting the efficacy of amniotomy plus oxytocin is similar to
that of prostaglandins alone [78].
In contrast, there is evidence from randomized trials that amniotomy does not shorten
the duration of spontaneous labor. (See "Management of normal labor and delivery",
section on 'Amniotomy'.)
Prostaglandins — Randomized trials have established that prostaglandins (E2, F2alpha, and E1) are effective for both cervical ripening and labor induction [81-84].
However, the distinction between formal induction and cervical ripening has not always
been clearly made in these studies.
In the United States, prostaglandin E2 or E1 is typically administered intravaginally for
cervical ripening as the first step in labor induction. This alone initiates labor in many
women [85]. If labor does not ensue or is not progressing adequately, oxytocin is
administered. Alternatively, repeated doses of prostaglandins can be given. In
randomized trials, prostaglandins have been found to be as good or better than
oxytocin for labor induction [85-88].
The optimal type and dose of prostaglandin for induction of labor has not been
determined. One option is a dinoprostone vaginal insert (Cervidil) containing 10 mg of
prostaglandin E2 in a timed-release formulation (the medication is released at 0.3
mg/h). The suppository is left in place until active labor begins or for 12 hours.
Another option is misoprostol 25 mcg intravaginally with redosing at three- to six-hour
intervals.
Oxytocin may be initiated, if necessary, 30 to 60 minutes after removal of
the dinoprostone insert or four hours after the final misoprostol dose.
Use of prostaglandins for cervical ripening prior to labor induction is discussed in detail
separately. (See "Techniques for cervical ripening prior to labor induction", section on
'Prostaglandins'.)
Breast stimulation — Breast stimulation causes uterine contractions and has been
used to induce labor. A Cochrane meta-analysis did not find this technique to be useful
in women with an unfavorable cervix or to be more effective than oxytocin; however, it
appeared to be effective for initiating labor within 72 hours in women with favorable
cervices [89]. The authors cautioned that neither the efficacy nor safety of breast
stimulation has been adequately evaluated.
Other methods — There is a paucity of data regarding the efficacy of glucocorticoids,
castor oil, hyaluronidase, or sexual intercourse for labor induction [90-94]. A
randomized trial showed that isosorbide mononitrate was associated with significantly
longer time from first treatment to delivery than prostaglandin E2 gel (39.7 versus
26.9 hours); cesarean delivery rates were similar [95]. Similarly, the combination of
isosorbide mononitrate and misoprostol was no more effective and caused more
headaches than misoprostol alone [96].
A large randomized trial (n = 364 women) compared use of acupuncture versus sham
acupuncture for induction of labor in postterm pregnancy and found acupuncture was
not effective [96]. Both the acupuncture and sham groups had similar times from the
intervention to delivery and similar needs for pharmacologic or mechanical
interventions to induce labor. These results are discordant with those from smaller
trials; however, the control group in the smaller trials received only usual care [97,98].
The lack of blinding to the intervention received could have biased the results; it is also
possible that even sham acupuncture has favorable physiological effects, and thus is
advantageous to no acupuncture.
Interestingly, a survey distributed to postpartum women who had delivered in a
Midwestern hospital revealed that some women attempted to induce their labor by
walking, intercourse, ingesting of spicy food, or nipple stimulation [99]. Very few used
laxatives, heavy exercise, masturbation, acupuncture, or herbal preparations.
CERVICAL RIPENING TO ENHANCE THE SUCCESS OF INDUCTION — Oxytocin is
less successful for labor induction when used in women with uneffaced and undilated
cervices. Therefore, a ripening process should be used prior to oxytocin induction when
the cervix is unfavorable. The two major methods are: (1) mechanical (physical)
interventions, such as disruption of the fetal membranes or insertion of dilators or a
balloon catheter, and (2) application of cervical ripening agents, such as prostaglandin
compounds. Techniques for cervical ripening and enhancing the likelihood of a
successful induction are discussed in detail separately. (See "Techniques for cervical
ripening prior to labor induction".)
COMPLICATIONS — All methods of labor induction carry risks.
Tachysystole — Abnormal or excessive uterine contractions can occur with the use of
prostaglandin compounds or oxytocin. There are no uniform worldwide definitions for
such terms as tachysystole, hyperstimulation, and hypertonus. The American College
of Obstetricians and Gynecologists suggests use of the term tachysystole, which is
defined as more than five contractions in 10 minutes, averaged over a 30-minute
window; the presence or absence of associated fetal heart rate changes should always
be stated [100].
Other authorities have used alternative terminology. The term "uterine
hyperstimulation without fetal heart rate changes" has been used to describe uterine
tachysystole (>5 contractions in 10 minutes for at least 30 minutes) or uterine
hypersystole/hypertonus (a contraction lasting at least two minutes) with a normal
fetal heart rate. The term "uterine hyperstimulation with fetal heart rate changes" has
been used to denote uterine hyperstimulation with fetal heart rate changes such as
persistent decelerations, tachycardia, or decreased short term variability. The reader
should be mindful of these semantic differences.
Since uterine activity causes intermittent interruption of blood flow to the intervillous
space, excessive uterine activity that exceeds the critical level for an individual fetus
will result in fetal hypoxemia. This, in turn, leads to nonreassuring fetal heart rate
patterns and umbilical artery pH ≤7.11 [101-104]. Rarely, tachysystole may cause
uterine rupture; this is more common in multigravidas than primigravida [105,106].
The various PGE2 preparations have up to a 5 percent rate of uterine tachysystole,
which is usually well tolerated and not associated with an adverse outcome. The
reported risk of tachysystole with oxytocin varies widely. Tachysystole occurs more
frequently when higher doses of oxytocin, prostaglandin E2, or misoprostol are used
[69,105,107].
Concurrent administration of oxytocin and a prostaglandin is believed to increase the
risk of tachysystole since both drugs carry a risk of this complication. Additionally, data
from human and animal studies show that prostaglandin administration increases
uterine sensitivity to oxytocin [108-112]. Although some studies have not observed a
statistically significant increase in excessive uterine activity with concurrent use, this is
likely due to the small numbers of patients in these studies, differences in methodology
(eg, uterine activity was not continuously monitored), and the relatively low frequency
of adverse events [113-117]. In one such trial, the frequency of uterine tachysystole
with concurrent dinoprostone and oxytocin administration was 14 percent versus 5
percent with oxytocin alone (p = 0.20) [113].
Management — Removing the PGE2 vaginal insert (eg, Cervidil) will usually help
reverse the effects of tachysystole. If prostaglandin gel was applied locally,
cervical/vaginal lavage is not helpful for removing the drug or reversing adverse
effects.
If oxytocin is being infused, it should be discontinued or the dose decreased to quickly
restore a reassuring fetal heart rate pattern. Placing the woman in the left lateral
position, administering oxygen (10 L/min of oxygen via nonrebreather mask), and
increasing intravenous fluids (eg, fluid bolus of 500 mL of lactated Ringer's solution or
more) also appear to be of benefit [103,118]. If there is no prompt response to these
measures, we suggest administering a tocolytic, such as terbutaline 250 mcg
subcutaneously or intravenously or atosiban 6.75 mg intravenously over one minute
for fetal resuscitation. Nitroglycerin (60 to 90 mcg intravenously) is usually successful
in recalcitrant cases [119,120]. (See "Management of intrapartum category I, II, and
III fetal heart rate tracings", section on 'Recurrent late decelerations'.)
Hyponatremia — Oxytocin has a similar structure to vasopressin (antidiuretic
hormone) and can cross-react with the renal vasopressin receptor. If high doses (eg,
40 mU/minute) of oxytocin are administered in large quantities (eg, over 3 liters) of
hypotonic solutions (eg, dextrose in water, D5W) for prolonged periods of time,
excessive water retention can occur and result in severe, symptomatic hyponatremia
(similar to the syndrome of inappropriate antidiuretic hormone secretion) [121,122].
Symptoms of severe acute hyponatremia include headache, anorexia, nausea,
vomiting, abdominal pain, lethargy, drowsiness, unconsciousness, grand mal type
seizures, and potentially irreversible neurologic injury. (See "Manifestations of
hyponatremia and hypernatremia".)
If water intoxication occurs, oxytocin and any hypotonic solutions should be stopped.
Correction of hyponatremia must be performed carefully and consists of restricting
water intake, and careful administration of hypertonic saline if the patient is
symptomatic. (See "Overview of the treatment of hyponatremia".)
Hypotension — Hypotension can result from rapid intravenous injection of oxytocin;
however, studies demonstrating this effect were performed in men, nonpregnant
women, and first trimester women under general anesthesia. A randomized trial of
oxytocin bolus versus slow infusion in women at delivery of the anterior shoulder did
not find clinically significant differences in hemodynamic responses [123].
Nevertheless, it is prudent to administer oxytocin by infusion pump or slow drip to
avoid tachysystole, as well as possible hypotension.
Failed induction — Induction of labor usually culminates in vaginal delivery, but, as
discussed above, this occurs less often than when women enter labor spontaneously. A
low Bishop score, before or after administration of prostaglandins, is a poor prognostic
factor for successful induction. Women whose induction of labor does not lead to
delivery are typically offered cesarean birth.
There are no standards for what constitutes a failed induction. It is important to allow
adequate time for cervical ripening and development of an active labor pattern before
determining that an induction has failed. One group proposed that failed induction be
defined as the inability to achieve cervical dilatation of 4 cm and 80 percent
effacement or 5 cm (regardless of effacement) after a minimum of 12 to 18 hours of
both oxytocin administration and membrane rupture [124]. They also specified that
uterine contractile activity should reach 5 contractions/10 minutes or 250 Montevideo
units, which is the minimum level achieved by most women whose labor is progressing
normally. The goal is to minimize the number of cesarean deliveries performed for
failed induction in patients who are progressing slowly because they are still in the
latent phase of labor [43,125,126]. Once induced women enter active labor,
progression should be comparable to progression in women with spontaneous active
labor, or faster [127]. Several studies have shown that the duration of the second
stage is similar in induced and spontaneous labors [16,27,127,128].
The utility of administering oxytocin for at least 10 to 12 hours after membrane
rupture is illustrated by the following examples:

An Australian researcher evaluated a group of 978 nulliparous women after
either artificial or spontaneous rupture of membranes to determine factors that
could predict failed induction [129]. There was a direct correlation between
increasing duration of the latent phase and the probability of cesarean birth.
After 10 hours of oxytocin administration, the 8 percent of women not in the
active phase of labor had an approximately 75 percent chance of being
delivered by cesarean for failed induction; after 12 hours of oxytocin
administration, the chance of cesarean was almost 90 percent. (See "Latent

phase of labor" and "Abnormal labor: Protraction and arrest disorders", section
on 'Normal uterine activity'.)
Two large studies that required a minimum of 12 hours
of oxytocin administration after membrane rupture before diagnosing failed
labor induction reported [125,130]:


Vaginal delivery occurred in 75 percent of all nulliparas [125].
For nulliparous women with an unfavorable cervix, the overall rate of vaginal
delivery was 63 percent [130]. Most of the 95 percent of women who exited the
latent phase delivered vaginally, and approximately 40 percent of the remaining
5 percent of women, went on to deliver vaginally.
 For parous women, failed labor induction was eliminated as an indication for
cesarean birth [125].
Other — Risks associated with amniotomy include introducing infection, disruption of
an occult placenta previa, rupture of a vasa previa, and umbilical cord prolapse. Many
of these same risks, and inadvertent amniotomy, also apply to membrane stripping.
A drawback of hygroscopic dilator and laminaria usage is the potential for a higher
incidence of postpartum maternal and fetal infections as compared to prostaglandin
administration [131,132].
Meconium passage is more common in women who were given misoprostol than in
those given dinoprostone [105,107]. Although studies using misoprostol have not
shown differences in perinatal outcome, these reports have been of insufficient size to
exclude the possibility of uncommon serious side effects, such as uterine rupture
[107].
Induction of labor has been consistently found to be a risk factor for uterine rupture,
although the incidence of rupture is low and most cases occur in women with a scarred
uterus. Uterine rupture in the unscarred uterus has been reported with the use
of oxytocin, misoprostol (prostaglandin E1), and prostaglandin E2 preparations. In a
series of 41 true uterine ruptures occurring in a hospital system in 2006, 27 occurred
in women with prior uterine surgery (cesarean delivery or other uterine surgery) and
12 of the remaining 14 ruptures occurred in patients who received uterotonic drugs
(two of these women were nulliparous) [133].
Oxytocin should always be administered in the lowest dose within a low dose or high
dose regimen that produces regular contractions and cervical change. Prostaglandins
should be given according to the manufacturer's recommendations or established
protocols. Misoprostol should not be used in a woman in the third trimester with
scarred uterus [4,134]. (See "Cervical ripening and induction of labor in women with a
prior cesarean delivery".)
Oxytocin use has been associated with hyperbilirubinemia in the neonate in some
studies, but not others. The hyperbilirubinemia may be related more to factors related
to induction (eg, preterm pregnancy) than to a direct effect of oxytocin.
A population based retrospective cohort study including 3 million deliveries reported
that medical induction of labor was associated with an increased risk of amniotic fluid
embolism (adjusted OR 1.8, 95% CI 1.2-2.7) [135]. However, the absolute risk was
small 10.3 per 100,000 births with medical induction versus 5.2 per 100,000 births
without medical induction. Moreover, given that these women were induced for medical
indications, not inducing labor could potentially result in greater maternal-fetal
morbidity/mortality than inducing labor. These findings should be confirmed by others
before changes in management of induction are considered.
SUMMARY AND RECOMMENDATIONS









Induction of labor is best undertaken when continuing the pregnancy is thought
to be associated with greater maternal or fetal risk than intervention to deliver
the pregnancy, and there is no contraindication to vaginal birth.
(See 'Indications and contraindications' above.)
We suggest avoiding elective induction of labor at term if there is no
medical/obstetrical indication for delivery (Grade 2C). Elective induction has
the potential for increased rates of cesarean delivery, iatrogenic prematurity,
and higher health care costs, without proven medical/obstetrical benefits. If
elective induction is undertaken for nonmedical reasons, optimal candidates are
women with favorable cervices and well-dated pregnancies over 39 weeks as
these women are not at increased risk of cesarean delivery or iatrogenic
prematurity. (See 'Elective induction at term' above.)
The probability of fetal lung maturity should be estimated prior to induction at
term. If fetal lung maturity cannot be established by clinical criteria, then
amniocentesis should be performed if the need for delivery is not urgent.
(See 'Preinduction assessment' above.)
The Bishop score is the best available tool for predicting the likelihood that
induction will result in vaginal delivery. (See 'Predicting a successful
induction' above.)
We suggest administration of oxytocin with or without amniotomy for women
with favorable cervices (Grade 2B). (See 'Oxytocin' above.)
High-dose oxytocin regimens decrease the time from admission to vaginal
delivery, but do not appear to decrease the incidence of cesarean delivery
compared to low-dose therapy. High dose regimens are associated with a
higher rate of tachysystole than low dose regimes, but no significant difference
in neonatal outcomes. (See 'Oxytocin' above.)
When the cervix is unfavorable, we suggest cervical ripening prior
to oxytocin induction (Grade 2B). We use dinoprostone or misoprostol for
preinduction cervical ripening. (See 'Cervical ripening to enhance the success of
induction' above and 'Prostaglandins' above.)
In women who wish to avoid potential drug-related side effects, we suggest
amniotomy for induction of labor as long as the cervix is partially dilated and
the vertex is well-applied (Grade 2B). Weekly membrane stripping at term
shortens the interval of time to onset of spontaneous labor and reduces the
need for formal induction. (See 'Amniotomy' above and 'Membrane
stripping' above.)
There are no standards for what constitutes a failed induction. It is important to
allow adequate time for cervical ripening and development of an active labor
pattern before determining that an induction has failed. (See 'Failed
induction' above.)

High doses of oxytocin should not be administered in hypotonic solutions as this
can lead to excessive water retention and dilutional hyponatremia.
(See'Hyponatremia' above.)
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