INTRODUCTION — When labor is induced, cervical status has an impact on the duration of induction and the likelihood of vaginal delivery. If the cervical status is unfavorable, a ripening process is generally employed prior to induction to shorten the duration of induction and maximize the possibility of vaginal delivery. Although cervical status at induction provides insight into the chance of cesarean delivery, it does not predict whether avoiding labor induction and managing the patient expectantly will result in a higher chance of vaginal delivery [1,2].
The two major techniques for cervical ripening are (1) mechanical interventions, such as insertion of balloon catheters or, less commonly, hygroscopic cervical dilators, and (2) application of pharmacologic agents, such as prostaglandins. These techniques will be reviewed in this topic. General issues regarding induction of labor and use of oxytocin are discussed separately. (See "Induction of labor with oxytocin".)
CANDIDATES FOR CERVICAL RIPENING — There is no universally accepted definition of favorable or unfavorable cervix. Many clinicians consider a Bishop score <6 (table 1) indicative of an unfavorable cervix and the need for a ripening agent, while others use a lower threshold (eg, ≤3 or 4) .
INPATIENT VERSUS OUTPATIENT CERVICAL RIPENING — Most patients undergo cervical ripening in the hospital. Outpatient approaches to cervical ripening for indications for which maternal and/or fetal monitoring are not otherwise necessary during the ripening phase could be useful in reducing the duration of hospitalization and costs of medical care. Investigators have used both prostaglandins and mechanical means for outpatient ripening; in the United States, there has been a tendency to prefer the latter given the greater chance of tachysystole with prostaglandin agents. Nevertheless, the available body of evidence is insufficient to support a recommendation for the most effective and safest approach, but it does suggest that outpatient approaches are feasible [4-6].
If institutions decide to proceed with outpatient ripening, they should follow clear protocols that describe preprocedure patient evaluation (eg, nonstress test or biophysical profile, ultrasound for fetal presentation); list contraindications for outpatient ripening, which are broader than those for inpatient ripening where continuous maternal and fetal monitoring is possible; and include a period of transient monitoring after initiating ripening (eg, after placement of a mechanical device) to assess for conditions (eg, rupture of membranes) that would preclude discharging the patient to home.
A survey of United Kingdom obstetric providers indicated that more than 17 percent of units were currently or soon-to-be providing outpatient induction of labor. The vast majority began the procedures in the hospital, used the time-released prostaglandin E2 insert, and monitored women with cardiotocodynamometry after insertion . Only 40 percent, however, had clear procedures for management once the woman had gone home. The authors stated that there is a need for robust comparative research to establish the safety and cost-effectiveness of outpatient labor induction.
Investigators in the United States have reported that outpatient preinduction cervical ripening using a balloon catheter can be safely performed in properly selected patients [8-11]. The procedure generally has been limited to low-risk women with a singleton, live, vertex fetus at ≥37 weeks of gestation; exclusion criteria have included previous cesarean delivery, gestational hypertension or preeclampsia, pregestational diabetes, fetal growth restriction, rupture of membranes, and factors that could preclude prompt return to the hospital in the event of a problem.
The cost-effectiveness of outpatient cervical ripening compared with an inpatient approach has not been established. In an Australian cost-effectiveness analysis run in parallel with a small randomized trial of inpatient prostaglandin gel administration versus outpatient catheter placement, the outpatient arm was not more cost-effective . Although outpatient balloon catheter treatment resulted in fewer inpatient hours and costs prior to birth, it did not reduce overall inpatient hours and failed to achieve comparable rates of vaginal delivery within 12 hours of birthing unit admission. In a randomized trial in the United States comparing the inpatient versus outpatient setting in nulliparas who underwent cervical ripening with a balloon catheter, outcomes were similar, but the outpatient group had a shorter time (4.3 hours) between admission to the hospital and delivery .
CHOICE OF RIPENING AGENT — There is no single, clear best practice with respect to the choice of agent used for cervical ripening: both mechanical and pharmacologic agents are acceptable options, in general. The choice should be based on provider or patient preference, unless there is a contraindication for use of a specific agent or technique [13-15]. In the United States, mechanical methods are preferred for outpatient cervical ripening. (See 'Contraindications' below and 'Contraindications' below.)
In general, balloon catheters have no or minimal side effects but necessitate a potentially uncomfortable vaginal procedure for catheter insertion. They have convenient storage requirements (eg, no refrigeration), which is an issue for some prostaglandin agents. Compared with balloon catheters, a theoretical advantage of using prostaglandins is a reduction in the need for oxytocin for augmentation or induction of labor since prostaglandins promote myometrial contractility [13,16]. Conversely, a theoretical disadvantage of using prostaglandins is the potential for excessive uterine activity, leading to fetal heart rate (FHR) abnormalities. However, in clinical trials, neither the theoretical advantage nor disadvantage has resulted in differences in clinically important outcomes (eg, cesarean delivery, neonatal morbidity).
A 2016 network meta-analysis comparing the use of misoprostol (oral, vaginal), dinoprostone, and the balloon catheter for cervical ripening concluded that no method was clearly superior when the rates of failure to achieve vaginal delivery within 24 hours, uterine tachysystole with adverse FHR changes, and cesarean delivery were all taken into account :
●Use of vaginal misoprostol or vaginal dinoprostone reduced the risk of failure to achieve vaginal delivery within 24 hours compared with use of a balloon catheter, oral misoprostol, or intracervical dinoprostone, but increased the risk of uterine hyperstimulation with adverse FHR changes compared with other agents.
●Use of a balloon catheter for cervical ripening resulted in the lowest risk of uterine hyperstimulation with adverse FHR changes.
●Use of oral misoprostol resulted in the lowest risk of cesarean delivery.
This analysis did not consider combined methods (balloon catheter and concurrent prostaglandin or oxytocin), which in some studies have been shown to shorten the time to vaginal delivery and are becoming increasingly common. (See 'Balloon catheter combined with a prostaglandin or oxytocin' below.)
Limitations of available data — Interpretation of available data on cervical ripening is hindered by several factors, which make it difficult to identify the methods of cervical ripening and labor induction, either used alone or in combination, that are most effective. These factors include:
●A basic lack of understanding of the physiologic events that initiate and sustain labor.
●Wide biologic variation in the progress of normal labor.
●Failure of studies to distinguish between cervical ripening and labor induction.
●Use of different clinical endpoints in research studies (eg, change in cervical status versus length of labor versus route of delivery).
●Few trials comparing multiple methods.
●Inadequate data on patient-reported outcomes, such as satisfaction.
WHEN TO DISCONTINUE THE CERVICAL RIPENING AGENT — Once a ripening agent is initiated, it is typically continued until the cervix is favorable. There is no evidence-based time cutoff that prohibits continued efforts at cervical ripening when the cervix remains unfavorable. However, when using a balloon catheter, many clinicians will not continue efforts at cervical ripening if it falls out or if membranes spontaneously rupture.
Overview of use
Mechanism of action — Prostaglandins promote a number of biochemical and biophysical changes that lead to cervical ripening and an increase in myometrial contractility. The mechanisms involved in prostaglandin-induced cervical ripening are beyond the scope of this topic but have been reviewed elsewhere [17,18].
●Prostaglandins are contraindicated for cervical ripening or labor induction in term pregnancies with a prior cesarean birth or other prior major uterine surgery (eg, intramyometrial myomectomy that was likely to have significantly compromised the myometrium, repair of major congenital uterine anomalies) because of the association with an increased risk for uterine rupture . (See "Cervical ripening and induction of labor in women with a prior cesarean birth", section on 'Use of prostaglandins'.)
●Preexisting regular uterine activity is a relative contraindication to use of prostaglandins, given that the addition of an exogenous uterotonic agent could prompt excessive uterine activity.
When administering prostaglandins for cervical ripening, clinicians should be mindful of baseline uterine activity and consider delaying or avoiding administration if the patient is having ≥2 painful contractions/10 minutes. This is most important in patients who have already received at least one dose of prostaglandin as there appears to be a cumulative uterotonic effect. However, good evidence as to the best threshold of uterine activity for avoiding prostaglandins is not available. Clinicians should use their clinical judgment in making this decision, taking into account patient-specific factors such as grand multiparity, fetal status, the degree of discomfort/pain that the patient has experienced with previous doses, and the total number of doses of prostaglandins administered.
Administration and use of oxytocin and amniotomy
●Uterine contraction frequency and intensity should be checked before administration. As discussed above, delaying or avoiding administration if the patient is having ≥2 painful contractions/10 minutes may reduce the risk of tachysystole. (See 'Contraindications' above.)
●Uterine activity and fetal heart rate (FHR) should be monitored continuously for at least 30 minutes after administration, and monitoring should be maintained as long as regular uterine activity is present .
●If labor does not ensue and the cervix remains unfavorable after administration, repeated doses can be given (timing depends on the specific agent) or oxytocin can be initiated (timing depends on the specific agent) . (See 'Specific agents' below and "Induction of labor with oxytocin", section on 'Oxytocin administration'.)
●Amniotomy soon after the last dose of misoprostol or removal of a dinoprostone insert shortens the time interval from induction to delivery compared with waiting until spontaneous rupture of membranes [21,22].
Side effects — Side effects of prostaglandins include tachysystole, fever, chills, vomiting, and diarrhea. The frequency of these side effects depends upon the type of prostaglandin, dose, and route of administration. Uterine contractile abnormalities occur in up to 30 percent of cases, depending upon the vehicle and route of administration; other systemic effects occur in up to 5 percent of cases.
●Treatment of maternal discomfort is supportive (eg, acetaminophen, warm blanket, antiemetic).
●If tachysystole with an abnormal FHR occurs after placement of a prostaglandin vaginal insert, removal of the insert usually reduces uterine contractility, normalizes the FHR, and does not appear to prolong the time to delivery . However, if prostaglandin gel was applied, removal of remaining gel is not possible. Cervicovaginal lavage is not helpful for removing the drug or reversing adverse effects. Theoretically, remnants of a misoprostol tablet can be removed from the vagina if necessary. A tocolytic drug (eg, terbutaline 250 mcg subcutaneously) can be administered if in utero resuscitation is indicated.
Efficacy — Multiple meta-analyses of randomized trials have established the efficacy of these agents for cervical ripening (change in Bishop score) and improving the chance of delivering vaginally within 12 or 24 hours, but a clear reduction in overall cesarean delivery rate has not been demonstrated consistently [16,24-30].
Specific agents — The optimal type, route, frequency, and dose of prostaglandins for cervical ripening has not been determined despite many studies of their use. Meta-analyses have reported the following relative findings, but reliable absolute rates of vaginal delivery within 24 hours are difficult to cite because of variability in patients and procedures among the underlying trials:
●Local administration of prostaglandins via the vagina or endocervix is associated with a lower frequency of side effects than oral administration, while maintaining an acceptable clinical response .
●Intravaginal prostaglandin E2 (PGE2) is more likely to result in vaginal delivery within 24 hours than endocervical PGE2, but both preparations are associated with similar rates of cesarean delivery and tachysystole .
Prostaglandin E1 (misoprostol) — Misoprostol (Cytotec) is a prostaglandin E1 analog available as 100 and 200 mcg tablets, which can be broken to provide 25 or 50 mcg doses. It is rapidly absorbed from both the oral and vaginal routes . Either route is reasonable; available data do not indicate that one route of administration is clearly better than another in terms of important health outcomes.
The approved indication for misoprostol is treatment and prevention of gastric ulcer disease related to chronic nonsteroidal anti-inflammatory drug use. Administration of this drug for cervical ripening and labor induction is considered an off-label use in the United States. However, there is good evidence that it is an effective alternative to PGE2 preparations for cervical ripening and labor induction [16,28-30,32]. The American College of Obstetricians and Gynecologists (ACOG) has stated that use of misoprostol appears as safe and efficacious as other prostaglandin agents when used as a cervical ripening and/or labor induction agent as described below .
Vaginal administration — In most patients, a dose such as 25 mcg should be used initially, with redosing intervals of three to six hours [28,33-35]. Oxytocin may be initiated, if necessary, four hours after the final misoprostol dose.
The optimal dose and timing interval of intravaginally applied misoprostol are unknown [28,36-39]. A meta-analysis reported that the 50 mcg dose was more effective than the 25 mcg dose (eg, resulted in a higher chance of delivery after a single dose and of delivery within 24 hours, and a lower chance of oxytocin use), but the 25 mcg dose resulted in lower rates of tachysystole, cesarean delivery for nonreassuring FHR, neonatal intensive care units admission, and meconium passage .
Misoprostol 50 mcg at six-hour intervals may be appropriate in some situations, such as inadequate uterine activity at lower doses; however, this dose has been associated with a higher risk of tachysystole .
A misoprostol vaginal insert consisting of a controlled-release, retrievable polymer chip for gradual delivery of 200 mcg over 24 hours is available in some countries, but is not available in the United States. In a large randomized trial comparing women who received the misoprostol vaginal insert with those receiving a dinoprostone vaginal insert, use of the misoprostol vaginal insert resulted in a significantly shorter median time to vaginal delivery (21.5 versus 32.8 hours) but also resulted in a higher chance of uterine tachysystole requiring intervention (13.3 versus 4 percent) and did not change the chance of cesarean delivery .
Oral administration — When administered orally, the concentration peaks sooner and declines more rapidly than with vaginal administration (figure 1) . Oxytocin may be initiated, if necessary, four hours after the final misoprostol dose.
Despite the large number of trials of oral misoprostol for cervical ripening, there is no clear consensus as to the optimum oral dose, dosing interval, or maximum number of doses. There is also no consensus regarding having the patient swallow a tablet versus a titrated oral misoprostol solution. A 2021 meta-analysis supported the use of low-dose oral misoprostol for induction of labor, and suggested that a starting dose of 25 mcg may offer a good balance of efficacy and safety . It should be noted, however, that the authors considered the recommendation to have only moderate-to-low certainty given imprecision, inconsistency, and study limitations. Included trials compared oral misoprostol protocols of one‐ to two‐hourly versus four‐ to six‐hourly dosing; doses of 20 to 25 mcg versus 50 mcg; and 20 mcg hourly titrated versus 25 mcg two‐hourly static.
Buccal or sublingual administration — Other approaches to use of misoprostol, including buccal and sublingual administration, have been described, but are less well studied and should be considered investigational [42-45]. These routes of administration may avoid first-pass hepatic metabolism associated with oral ingestion and thus increase bioavailability similar to that achieved with vaginal administration. Pharmacokinetic data support the hypothesis that buccal and sublingual routes of administration are associated with more rapid onset of action and greater bioavailability than other routes . Additionally, it is hypothesized that administration using these routes may reduce the risk of tachysystole by avoiding direct uterine effects.
However, a meta-analysis of five small trials (n = 740 women) of sublingual versus vaginal administration found no significant differences in rate of vaginal delivery not achieved within 24 hours (odds ratio [OR] 1.27, 95% CI 0.87-1.84), uterine hyperstimulation syndrome (OR 1.20, 95% CI 0.61-2.33), or cesarean delivery (OR 1.33, 95% CI 0.96-1.85), but uterine tachysystole was increased in the sublingual misoprostol group (OR 1.70, 95% CI 1.02-2.83) . A subsequent well-designed trial (IMPROVE) including 300 women suggested vaginal misoprostol may be superior to the buccal route: time to vaginal delivery was reduced by eight hours, and fewer emergency cesareans were performed for FHR abnormalities .
Prostaglandin E2 — Prepidil and Cervidil are two PGE2 preparations commercially available for cervical ripening in the United States. Other formulations are available worldwide (eg, Prostin E2 gel containing 1 mg or 2 mg dinoprostone for vaginal insertion, Prostin E2 0.5 mg tablet for oral administration). These drugs are more costly than misoprostol.
Prepidil — Prepidil contains 0.5 mg of dinoprostone in 2.5 mL of gel for endocervical administration. The dose can be repeated in 6 to 12 hours if cervical change is inadequate and uterine activity is minimal following the first dose. The manufacturer recommends that the maximum cumulative dose of dinoprostone not exceed 1.5 mg (ie, three doses) within a 24-hour period.
The time interval between the final dose and initiation of oxytocin should be 6 to 12 hours because of the potential for uterine tachysystole with concurrent oxytocin and PGE2 prostaglandin administration. (See "Induction of labor with oxytocin", section on 'Complications'.)
Cervidil — Cervidil is a vaginal insert containing 10 mg of dinoprostone in a timed-release formulation (the medication is released at 0.3 mg/hour). The insert is left in place until active labor begins or for 12 hours. Oxytocin may be initiated anytime beyond 30 minutes after removal of the insert unless there is a contraction or FHR pattern that is a contraindication to oxytocin use.
A theoretical advantage of the vaginal insert over the gel formulation is that the vaginal insert can be removed in cases of uterine tachysystole or abnormalities of the FHR tracing [48,49], although this possibility has not translated into better clinical outcomes than other ripening methods.
Overview of use
Types — Insertion of a balloon catheter (eg, Foley bladder catheter) through the endocervical canal and into the extraamniotic space is the most common mechanical method currently in use. Placement of hygroscopic dilators into the endocervical canal and extending through the internal cervical os is an alternative mechanical method.
Mechanism of action — Mechanical methods of cervical ripening have been theorized to work both by direct physical pressure on the internal cervical os and by causing the release of prostaglandins from the decidua, adjacent membranes, and/or cervix. These effects combine to promote a number of biochemical and biophysical changes that lead to cervical ripening and an increase in myometrial contractility.
Contraindications — There are no absolute contraindications to mechanical methods of cervical ripening in women who are candidates for labor and vaginal delivery. Group B Streptococcus (GBS) colonization is not a contraindication to use of mechanical methods of cervical ripening, and standard chemoprophylaxis should be used when labor begins or at rupture of membranes, whichever occurs first. (See "Early-onset neonatal group B streptococcal disease: Prevention", section on 'Patients undergoing obstetric procedures'.)
Although polyhydramnios is stated as a contraindication to use of a balloon catheter in the Cook Cervical Ripening Balloon package insert, this is not an absolute contraindication to use if induction is indicated, as long as there are no other contraindications to labor induction and vaginal birth (eg, malpresentation, which is more likely in the setting of hydramnios). The author has not seen any evidence that the balloon catheter is more likely to lead to prelabor rupture of membranes, cord prolapse, or adverse perinatal outcomes compared with use of prostaglandins for cervical ripening.
A low-lying placenta is a relative contraindication since the edge of the placenta may be disrupted by manipulation during placement of the device.
Some practitioners do not place mechanical devices for cervical ripening in women with ruptured membranes, some remove the device if membranes rupture at any time after placement, and others limit the duration of cervical ripening to 12 hours if membranes rupture after placement. While there is not total consensus on optimal management in this setting, the package insert for the Cook Cervical Ripening Balloon lists ruptured membranes as a contraindication to placement and an indication for deflation and removal. This author typically does not place a balloon catheter if membranes have ruptured and removes the catheter if rupture of membranes occurs while it is in place, given concerns about increasing the risk of clinical chorioamnionitis. Available data are reviewed separately. (See "Prelabor rupture of the fetal membranes at term: Management", section on 'Active management'.)
In patients with intact membranes who are undergoing cervical ripening for labor induction, the use of a balloon catheter is not absolutely contraindicated in the uncommon scenario of intraamniotic infection.
Side effects — Mechanical methods of cervical ripening do not cause systemic side effects and are associated with a lower rate of tachysystole than prostaglandins [13,16]. Meta-analyses of randomized trials have not found convincing evidence of an increased risk of infectious morbidity in mothers or neonates exposed to mechanical methods of cervical ripening compared with those exposed to prostaglandins [15,50]. Importantly, these trials typically have excluded women with ruptured membranes.
Device selection — A double-balloon catheter specifically designed for cervical ripening is commercially available (figure 2); alternatively, a single-balloon catheter (eg, Foley bladder catheter) can be used. In meta-analyses of comparative trials, there were no clinically important differences in outcomes with use of a double- versus a single-balloon catheter [51,52]. However, the single-balloon catheter is less expensive and more readily available.
Procedure — The balloon catheter is placed using aseptic technique. Although continuous uterine activity and fetal heart rate (FHR) monitoring are often used while it is in place, investigators also have assessed and safely used only transient monitoring (eg, 30 minutes) after placement [8-10].
●Ring forceps can be used to pass a deflated single-balloon catheter (30 to 80 mL) through the internal cervical os and into the extraamniotic space [53,54]. Alternatively, the catheter can be inserted manually, similar to an intrauterine pressure catheter. This is usually possible even if the cervix is not dilated since the pregnant cervix is soft and distensible and rarely tightly closed. If it is difficult to pass the catheter, a urologic sound or other rigid device can be inserted into the catheter to facilitate placement.
In a meta-analysis of randomized trials comparing use of larger (60 to 80 mL) versus smaller (30 mL) volumes during cervical ripening, larger balloon volumes resulted in a shorter time from induction to delivery (mean difference 1.97 hours, 95% CI -3.88 to -0.06) but had a similar cesarean delivery rate, time to vaginal delivery, time to catheter expulsion, and maternal and fetal complication rates . These data suggest that either a large or small balloon volume is a reasonable choice.
●The balloon is distended with saline. If a sound or other rigid device was used, it is removed before or while beginning instillation of saline. The dilated balloon is then gently retracted so that it rests against the internal os without extending into the endocervical canal.
●Many clinicians tape the end of the catheter to the inner thigh, placing it on tension, with readjustment to maintain tension at occasional intervals. A randomized trial noted a decrease in time to balloon expulsion when traction was used but no effect on the time to delivery . Some clinicians attach a weight (eg, 1 L of fluid) to the end of the catheter and suspend it from the end of the bed. Weighted traction may shorten the time to spontaneous expulsion but did not shorten the time to delivery in two randomized trials [56,57].
●The catheter is typically left in place until it is extruded; if not extruded, it is removed by 12 hours after insertion. A randomized trial found that removing nonextruded catheters after 12 hours and beginning oxytocin resulted in significantly more vaginal deliveries within 24 hours than waiting 24 hours before removal and oxytocin induction (60 versus 21 percent) and did not lead to an increased risk of cesarean delivery . That said, there is no absolute contraindication to leaving the catheter in place for more than 12 hours.
Double-balloon catheter — The procedure for inserting a double-balloon catheter is similar to that described for the single-balloon catheter (see 'Single-balloon catheter' above), with the following modifications:
●The catheter is inserted until the proximal balloon is in the cervical canal, at which point the distal balloon should be intrauterine and in the extraamniotic space.
●The intrauterine balloon is inflated with 40 mL saline and gently retracted so that it rests against the internal os.
●The proximal balloon should now be outside the external os and is inflated with 20 mL saline.
●If the balloons are correctly situated on either end of the cervix, the balloons can now be inflated with up to 80 mL saline per balloon.
Alternatively, oxytocin can be initiated concurrently with the catheter in place. (See 'Balloon catheter combined with a prostaglandin or oxytocin' below.)
Efficacy — Use of balloon catheters has been associated with a mean change in Bishop score of 3.3 to 5.3 . A meta-analysis of mechanical methods for induction of labor reported an unfavorable cervix was still present after 12 hours in only 6 percent of women treated with a balloon catheter compared with 86 percent of women in the no treatment group (relative risk [RR] 0.07, 95% CI 0.03-0.19) .
A subsequent meta-analysis compared outcomes using the balloon catheter with outcomes using prostaglandin E2 (PGE2) as well as with oral or vaginal misoprostol (n = 113 trials, >22,000 women) . Major findings were:
●The balloon catheter and PGE2 were similarly effective:
•Vaginal delivery not achieved in 24 hours – RR 1.01, 95% CI 0.82-1.26
•Cesarean delivery – RR 1.00, 95% CI 0.92-1.09
●The balloon catheter may be slightly less effective than low-dose vaginal misoprostol:
•Vaginal delivery not achieved in 24 hours – RR 1.09, 95% CI 0.85-1.39
•Cesarean delivery – RR 1.28, 95% CI 1.02-1.60
●The balloon catheter may be slightly less effective than low-dose oral misoprostol:
•Vaginal delivery not achieved in 24 hours – RR 1.28, 95% CI 1.13-1.46
•Cesarean delivery – RR 1.17, 95% CI 1.04-1.32
●The balloon catheter resulted in a lower risk of uterine tachysystole with FHR changes compared with PGE2, vaginal misoprostol, and oral misoprostol (RR 0.35, 95% CI 0.18-0.67; RR 0.39, 95% CI 0.18-0.85; and RR 0.81, 95% CI 0.48-1.38, respectively).
●The balloon catheter resulted in less serious neonatal morbidity or perinatal death compared with PGE2 (RR 0.48, 95% CI 0.25-0.93).
It should be noted, however, that much of the evidence in this meta-analysis was classified as "low quality."
Balloon catheter combined with a prostaglandin or oxytocin — The combination of mechanical and pharmacologic ripening methods does not appear to increase adverse obstetric or perinatal outcomes and may have modest benefits over the use of a single method alone. If a provider chooses to give oxytocin concurrently, either a fixed low dose or standard incremental dose regimen is acceptable (table 2) .
●In a network meta-analysis (30 randomized trials, 6465 pregnancies), the combination of a balloon catheter plus a prostaglandin (cBC/P) or a balloon catheter plus oxytocin (cBC/O) compared with a balloon catheter alone :
•Hastened the time to vaginal delivery (cBC/P: -2.9 hours, 95% CI -5.7 to 0; cBC/O: -4.2 hours, 95% CI -6.5 to -1.9).
•Increased the chance of delivery within 24 hours (cBC/P: odds ratio [OR] 1.80, 95% CI 1.02-3.20; cBC/O: OR 2.04, 95% CI 1.29-3.24).
•Did not significantly affect the chance of cesarean delivery (cBC/P: OR 0.89, 95% CI 0.65-1.20; cBC/O: OR 0.99, 95% CI 0.74-1.33) or adverse events (chorioamnionitis, endometritis, tachysystole, meconium, neonatal intensive care unit admission, postpartum hemorrhage).
●In a previous meta-analysis of randomized trials, compared with using a prostaglandin alone, cBC/P reduced the chances of not achieving a vaginal delivery within 24 hours (RR 0.45, 95% CI 0.28-0.71, three trials, 698 women) but did not significantly impact the chance of cesarean delivery (RR 0.92, 95% CI 0.79-1.08, eight trials, 1295 women) . Surprisingly, cBC/P reduced the risk of uterine tachysystole with adverse FHR changes (RR 0.53, 95% CI 0.35-0.78).
Two randomized trials addressing this issue were subsequently published. In one (491 participants), women who received cBC/vaginal misoprostol delivered more quickly than those who received either vaginal misoprostol alone (hazard ratio [HR] 1.92, 95% CI 1.42-2.59) or a balloon catheter alone (HR 1.87, 95% CI 1.39-2.52); there were no significant differences between groups in the frequency of cesarean delivery or adverse maternal or neonatal health outcomes .
In the other trial, 1117 women at term were assigned to receive cBC/oral misoprostol and 1110 were assigned to oral misoprostol alone . As in previous trials, the two groups had similar rates of vaginal delivery. In contrast to other trials, however, the groups had similar time to delivery, and those in the cBC/oral misoprostol arm had a higher risk of clinical chorioamnionitis compared with oral misoprostol alone (18 versus 14 percent). The trial design was cluster randomization: randomization was not performed at the individual level. Instead, all individuals induced during a given week were assigned to an unblinded method randomly determined at the start of the week. Also, the investigators used a misoprostol dose higher than that in many other studies (100 mcg), had a notable proportion (15 percent) of individuals in whom the balloon catheter was not placed after randomization to the combined arm, and utilized 12 to 24 hours of rest for some individuals after the induction had started based on judgment regarding progress of the induction. Given these aspects, the applicability of these results to other settings is uncertain.
Hygroscopic dilators — There are two types of hygroscopic dilators: One is made from natural seaweed (laminaria tents), and the other is a synthetic product (eg, Dilapan-S). Hygroscopic dilators are designed to absorb moisture and thus gradually expand within the cervical canal. In addition, disruption of the interface between the fetal membranes and decidua can lead to prostaglandin release, with consequent changes in cervical tissue beyond the passive mechanical stretching provided by the tent itself.
Hygroscopic dilators are as safe and effective as other cervical ripening agents [67,68], although they are more commonly used during pregnancy termination than for preinduction cervical ripening of term pregnancies. (See "Overview of pregnancy termination", section on 'Cervical dilation and preparation'.)
Some clinicians prefer to use hygroscopic dilators rather than balloon catheters in patients with a prior cesarean delivery who are scheduled for induction of labor. However, there is no strong evidence on which to base a recommendation favoring one approach over the other.
Procedure — After prepping the cervix and vagina with an antiseptic, the cervix is held with a nontraumatic clamp, if necessary, and the maximum number of dilators that the endocervical canal can accommodate are inserted without using excessive force; some cramping is common. Dipping the laminaria in a sterile lubricant before insertion may facilitate placement. The dilators can be packed in place with two 4 by 4 inch gauze sponges tucked into the fornices; the number of dilators and gauze sponges that were inserted should be recorded in the patient's chart at insertion and at removal.
Laminaria typically are removed 12 to 24 hours after placement, whereas synthetic dilators can be removed sooner, after 6 to 8 hours.
Efficacy — In a meta-analysis of randomized trials, the risk of tachysystole with adverse FHR changes was lower in women who received laminaria compared with those who received prostaglandins (RR 0.13, 95% CI 0.04-0.48, five studies, 538 women). The cesarean delivery rate was similar for women receiving laminaria and those receiving any prostaglandin (vaginal PGE2, intracervical PGE2, or misoprostol) or balloon catheters . Addition of either prostaglandins or oxytocin to laminaria during cervical ripening did not appear to improve outcomes.
Other cervical ripening drugs and techniques — Relaxin [69-71], nitric oxide donors , hyaluronidase , corticosteroids , castor oil , sexual intercourse [76,77], breast stimulation , and herbal preparations  have been used for cervical ripening, although we recommend not using these approaches because of limited data regarding safety and/or efficacy and the availability of proven alternatives.
Extraamniotic saline infusion is a procedure in which sterile saline is infused continuously via a balloon catheter placed in the extraamniotic space [80-83]. However, it has not been shown to have clear advantage over other methods (balloon catheter alone, prostaglandins) [62,84-86].
Fetal demise — (See "Stillbirth: Maternal care", section on 'Birth'.)
Previous cesarean delivery — (See "Cervical ripening and induction of labor in women with a prior cesarean birth".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cervical ripening and labor induction".)
SUMMARY AND RECOMMENDATIONS
Choice of cervical ripening agent — The ideal methods for cervical ripening and labor induction have yet to be identified. Clinical studies of human parturition are hindered by a lack of understanding of the physiologic events that initiate and sustain labor. There is wide biologic variation among pregnant women in the progress of normal labor and iatrogenic variation in the management of labor and labor induction; this makes the investigation of new uterotonic agents difficult. Although data from randomized trials comparing different cervical ripening approaches are available, there are insufficient comparative data to determine which of several methods (type, dose, inpatient/outpatient) is the most effective and offers the best safety profile. Variation in indications for induction, parity, and gestational age at induction, as well as other demographic features, undoubtedly affects clinical results.
●For women who are scheduled for labor induction and have an unfavorable cervix (eg, Bishop score <6), clinical outcomes are similar whether prostaglandins (E2 or E1) or transcervical balloon catheter placement is used for cervical ripening. (See 'Choice of ripening agent' above.)
●Prostaglandins are contraindicated for cervical ripening or labor induction in term pregnancies with a prior cesarean birth or other prior major uterine surgery. Preexisting regular uterine activity is a relative contraindication. (See 'Contraindications' above.)
●After administration of a prostaglandin, if labor does not ensue and the cervix remains unfavorable, then repeated doses of prostaglandin can be given (timing depends on the specific agent) or oxytocin can be initiated (timing after the last prostaglandin dose depends upon the specific agent), respectively. (See 'Administration and use of oxytocin and amniotomy' above.)
●Side effects of prostaglandins include tachysystole, fever, chills, vomiting, and diarrhea. The frequency of these complications depends upon the type of prostaglandin, dose, and route of administration. Uterine contractile abnormalities are encountered in up to 30 percent of cases, depending upon the vehicle and route of administration; other systemic effects occur in up to 5 percent of cases. (See 'Side effects' above.)
•Treatment of maternal discomfort is supportive (eg, acetaminophen, blanket, antiemetic).
•If tachysystole with fetal heart rate (FHR) changes occurs after placement of a prostaglandin vaginal insert, removal of the insert usually reduces uterine contractility and normalizes FHR abnormalities. It may be possible to remove the remaining portion of a misoprostol pill, but prostaglandin gel cannot be removed. A tocolytic drug (eg, terbutaline 250 mcg subcutaneously) can be administered if in utero resuscitation is indicated.
●There are no absolute contraindications to mechanical methods of cervical ripening in women who are candidates for labor and vaginal delivery. A low-lying placenta is a relative contraindication since the edge of the placenta may be disrupted by manipulation during placement of the device. (See 'Contraindications' above.)
●Some practitioners do not place mechanical devices for cervical ripening in women with ruptured membranes, some remove the device if membranes rupture at any time after placement, and others limit the duration of cervical ripening to 12 hours if membranes rupture after placement. While there is not total consensus on optimal management in this setting, the package insert for the Cook Cervical Ripening Balloon lists ruptured membranes as a contraindication to placement and an indication for deflation and removal. (See 'Contraindications' above.)
●Mechanical methods of cervical ripening do not cause systemic side effects and are associated with a lower rate of tachysystole than prostaglandins. (See 'Side effects' above.)
Combined use of a balloon catheter and a prostaglandin or oxytocin
●The combination of mechanical and pharmacologic ripening methods does not appear to increase adverse obstetric or perinatal outcomes and may have modest benefits over the use of a single method alone. Combination therapy appears to hasten the time to vaginal delivery and increases the chance of delivery within 24 hours, but does not appear to affect cesarean delivery rates or risk of adverse events, such as chorioamnionitis, endometritis, tachysystole, meconium, neonatal intensive care unit admission, or postpartum hemorrhage. (See 'Balloon catheter combined with a prostaglandin or oxytocin' above.)
ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Deborah A Wing, MD, MBA, who contributed to an earlier version of this topic review.