Induction of Labor

For expecting mothers, the onset of labor is a highly-anticipated process; however, close to 25% of women will have their labor induced. In fact, the rate of induction of labor doubled between 1990 and 2006 and has continued to trend upwards. ^[1]  Regardless of whether labor is induced or spontaneously occurs, the goal is vaginal birth.  

Indications for labor induction include both maternal and fetal conditions and are listed in Table 1. ^[2] These medical indications are not absolute and factors such as gestational age, patient and provider preferences are important considerations.  

In addition to maternal and fetal conditions, non-medical or “elective” indications for labor induction also exist. In general, these indications are the exception rather than the rule.  For example, the patient may live far away from hospital and/or have transportation issues. There may be other psychosocial or logistical reasons such as prior history of rapid labor as well. In these situations, the gestational age should be greater than or equal to 39 weeks. ^{[1, 3]}  Additionally, particularly in nulliparous women, the cervix should be favorable (Bishop score 8 or greater). ^[3] Regardless of the indication, risks and benefits of labor induction must be weighed against the benefits of pregnancy prolongation. Furthermore, correct determination of gestational age is critical. Criteria for determining a term gestation include an early ultrasound prior to 20 weeks gestation that supports current gestational age at or above 39 weeks, fetal heart tones documented via Doppler for 30 weeks or 36 weeks since positive pregnancy test. ^[1]

The contraindications for induction are the same as the contraindications for a vaginal delivery. Examples include, vasa previa, placenta previa, myomectomy with entry into uterine cavity, previous classical hysterotomy, active genital herpes outbreak, umbilical cord prolapse, or transverse fetal lie. ^[1]  

Cervical ripening is an important first component to labor induction.  Prior to spontaneous labor, the cervix first begins to soften over time, and then before contractions ensue, the connective tissue components of the cervix are extensively remodeled, which is also known as cervical ripening.  In the setting of labor induction, mechanical or pharmacological agents can be used to cause cervical ripening. Ripening often stimulates labor. If not, further pharmacologic agents (i.e. oxytocin) can be used for induction. Generally, cervical ripening and induction of labor are on a continuum and not all women undergoing induction of labor need cervical ripening. The Bishop scoring system can be used to determine if the cervix is favorable or unfavorable. If the cervix is deemed unfavorable, usually defined as Bishop score less than or equal to 6, cervical ripening is indicated. There are 5 components to the Bishop scoring: dilation, position of cervix, effacement, station (based on -2 to +3 scale), and cervical consistency, which are then scored from 0 to 3 (Table 2). ^{[1, 4]}

Table 2. Bishop Scoring System. (Open Table in a new window)

Table 2. Bishop Scoring System

There are several mechanical methods for cervical ripening, including osmotic dilators, transcervical Foley and double balloon catheters. Mechanical methods work by directly causing cervical dilation and also by releasing endogenous prostaglandins and oxytocin. Notably, when placing a mechanical device for cervical ripening in the presence of a low-lying placenta (edge within 2cm of internal os), there is a risk for potential hemorrhage and disruption of the placenta; thus, mechanical methods should be carefully considered in the setting of a low-lying placenta. ^{[5, 6]}

Osmotic Dilators

Osmotic dilators include seaweed (Laminaria) and synthetic compounds (Lamicel and Dilapan). The dilators are hydrophilic such that they absorb water and enlarge, which in turn causes the cervix to dilate. Data regarding the efficacy of these dilators for induction of labor are mixed. Additionally, studies have shown an increased risk of infection with Laminaria use, resulting in chorioamnionitis, endometritis and neonatal sepsis. ^{[1, 5]}

Extraamniotic Saline Infusion

A catheter is used to infuse saline into the space between the uterine wall and the amnion. This results in additional prostaglandin release.  Rates are commonly 30-40 mL per hour. The Cochrane review on mechanical methods for induction of labor cited no evidence to support use of extraamniotic infusion. There was not a shorter time from induction to delivery. ^[6]

Transcervical Foley Catheter

A Foley catheter is placed just above the internal cervical os when used for mechanical cervical ripening. Most commonly, the catheter is inserted through the cervical canal with the aid of forceps during a sterile speculum exam. Other times, the Foley catheter can be placed during a digital exam. The catheter is then inflated and placed on traction such that it sits just above internal os, applying pressure. Some leave the Foley catheter in until it is spontaneously expelled, while others remove catheter after a specific time interval. In general, transcervical Foley catheters may safely remain in place for more than 24 hours. Following catheter removal, most women require further induction of labor with oxytocin and/or amniotomy.

Different size catheters (ranging from 14 to 26 French) and different amounts of balloon catheter inflation volume (25 to 80 mL of sterile saline or water) are used. ^[5] A randomized trial compared 30mL to 80mL balloon inflation volumes. There was no difference in multiparous women. However, in nulliparous women who received the 80mL balloon inflation volume, they had greater cervical dilation, faster labor, and decreased oxytocin augmentation requirement compared to nulliparous women who were ripened with 30mL balloon inflation volume. ^[7] In general, 30 to 50mL is most commonly used. ^[5]

A transcervical Foley catheter remains an option for women with premature rupture of membranes. Data does not indicate an increased risk of infection with this mechanical method. ^{[8, 9]} However, some providers chose other options in the setting of premature rupture of membranes, but this decision is at the discretion of the provider.

Generally, transcervical Foley catheter cervical ripening is done while the patient is hospitalized; however, there have been a few preliminary studies regarding outpatient regimens that have shown promising results. A randomized trial comparing transcervical Foley catheter ripening in an outpatient versus inpatient setting found the efficacy to be similar across settings with no adverse  maternal or neonatal outcomes. ^[10]

The transcervical Foley catheter cervical ripening method overall has a very safe profile. Premature rupture of membranes, bleeding, displacement of presenting part and chorioamnionitis/endometritis have been associated infrequently with this form of cervical ripening. ^[5]

The transcervical Foley catheter has been shown to be as effective as other methods of cervical ripening. The Bishop score changes on average between 3 and 5 points.  Furthermore, uterine tachysystole is uncommon with transcervical Foley catheter ripening, and if this method is poorly tolerated by patient and/or fetus, it can easily be removed. Because of these reasons as well as its low cost and room temperature stability, it is a strong option for cervical ripening, especially in low resource settings. ^{[5, 11]}

Double Balloon Catheter

The double balloon catheter is similar to the transcervical Foley catheter method but has an additional second balloon that sits just below the external os. Thus, the double balloon catheter is able to apply pressure to both the internal and external os. The double balloon catheter is significantly more expensive than the single Foley balloon catheter method. A randomized control trial comparing single to double balloon catheters showed equal efficacy for labor induction. ^[11]  

Prostaglandins

During spontaneous labor, prostaglandins produced in the myometrium and decidua result in uterine contractions. Synthetic prostaglandins can be given for cervical ripening and labor induction. ^[4]

Prostaglandins are associated with increased risk of uterine rupture with a scarred uterus and thus should not be used in patients desiring trial of labor after cesarean delivery. ^{[1, 12]}

When prostaglandins are given, fetal heart rate and uterine contractions should be monitored continuously initially and the patient should lie down for at least 30 minutes. ^[1]

PGE1 misoprostol (Cytotec)

The typical dose for intravaginal misoprostol is 25 micrograms every 3 to 6 hours. A randomized control trial comparing 25 and 50 mcg doses found the 50mcg dose was slightly more effective but was associated with a higher incidence of uterine tachysystole and neonatal cord pH less than 7.16. ^{[1, 13]} In addition to intravaginal, misoprostol can also be administered orally, bucally and sublingually. Sublingual misoprostol is as effective as oral misoprostol at the same dose, but larger research studies are needed before routine use of buccal or sublingual administration. ^[14] The typical corresponding oral dose of misoprostol is 100mcg. A randomized trial compared intravaginal 25 mcg of misoprostol to oral 100mcg and found similar efficacy for cervical ripening and labor induction. ^{[15, 16]} Misoprostol remains an appropriate option in women with premature rupture of membranes. ^[17] No studies have demonstrated long-term adverse fetal outcomes related to in-utero exposure to misoprostol in absence of fetal distress. ^[1]  

PGE₂ dinoprostone

Synthetic prostaglandin E₂, dinoprostone, comes in two forms: a gel in a 2.5mL syringe containing 0.5 mg or a vaginal insert containing 10mg. The insert releases prostaglandin more slowly than the gel. There is some data regarding outpatient use of dinoprostone, but additional studies are needed before this becomes routine practice. ^[1]

PGE₁ vs PGE₂

In a randomized trial, intravaginal misoprostol was compared to dinoprostone intracervical gel. The time from induction to vaginal delivery was shorter on average with misoprostol. There was not a difference in the delivery route between the two groups. The incidence of uterine tachysystole was similar between the two groups. ^[18] Additionally, misoprostol is significantly less expensive than dinoprostone.

Oxytocin

Synthetic oxytocin is the most common method for labor induction. It mimics natural endogenous oxytocin produced during spontaneous labor and similarly stimulates uterine contractions. Contractions begin after 3 to 5 minutes, and oxytocin reaches a steady level in plasma by 40 minutes. Oxytocin side effects include uterine tachysystole and fetal heart rate abnormalities. ^[1] Fetal heart rate and contractions should be monitored during oxytocin administration. ^[4]

Most commonly Oxytocin is administered intravenously and can be titrated based on contraction frequency and strength. There are various regimens for oxytocin administration. A Cochrane review compared the effectiveness of low versus high-dose oxytocin for induction of labor. There was no difference in time to delivery or cesarean delivery rate between the two groups. There was a significant increase in uterine tachysystole in the high-dose group, but the consequences of this were not clearly identified. The review was unable to recommend either a low or high-dose protocol over the other. ^[19] An oxytocin checklist was developed for oxytocin administration focusing on uterine contractions and fetal heart rate rather than specific infusion rates or dosing. Outcomes were compared before and after initiation of the checklist protocol. The maximum infusion rate of oxytocin was lower in the checklist protocol group. There was no difference in time in labor between groups. Furthermore, the cesarean delivery rate was lower and newborn outcomes  improved in the checklist protocol group. ^[20]

Non-pharmacologic methods for cervical ripening and induction of labor exist and offer an alternate and inexpensive approach for patients.

Nipple Stimulation

Breast stimulation stimulates uterine contractions, likely by increasing oxytocin levels. A Cochrane review found that when compared to no intervention, more women entered labor by 72 hours with nipple stimulation; however, this was only significant for women who had a favorable cervix initially. Additionally, there was a decrease in post-partum hemorrhage among women who performed nipple stimulation. There were no cases of uterine tachysystole. However, a trend towards an increase in perinatal death amongst women who used nipple stimulation was noted. More information is needed regarding the safety of this method  before recommendations about its use can be endorsed. ^[21]

Membrane Stripping

Membrane stripping releases endogenous prostaglandins, which can induce labor, and by doing so, eliminate the need for formal induction. To perform membrane stripping, the clinician performs a vaginal exam and places a finger into cervical os in a circular movement to separate the inferior portion of membranes from the lower uterine segment. A Cochrane review found that membrane stripping results in an increased number of women entering spontaneous labor within 48 hours and decreases the need for induction. There was no difference in risk of maternal or neonatal infection. Potential side effects include patient discomfort during the procedure, vaginal bleeding, rupture of membranes and contractions following the procedure. ^[22]

Amniotomy

The amniotic membranes can be ruptured artificially to induce labor. It is difficult to know the time interval from amniotomy to delivery, and with increasing time from amniotomy to delivery, there is an increasing risk for infection. A Cochrane review found that there was not sufficient data regarding amniotomy as a method for labor induction to draw a conclusion on its safety and efficacy. ^[23]  

There is no clear consensus on what method is the best for cervical ripening and induction of labor. There have been multiple studies comparing individual methods as well as combinations of various methods. A few will be reviewed below.

Of note, the obstetric care consensus on the safe prevention of the primary cesarean delivery made the recommendation for cervical ripening methods to be implemented in women undergoing induction of labor with an unfavorable cervix. The obstetric care consensus is a joint statement from both the American College of Obstetricians and Gynecologist and the Society for Maternal Fetal Medicine. ^[24]

Misoprostol versus Transcervical Foley Catheter

A randomized controlled trial compared induction of labor with misoprostol to transcervical Foley catheter. There was no difference in cesarean delivery rate or time from induction to delivery between groups. Additionally, there was no difference in maternal or neonatal infections. ^[9]

A Cochrane review comparing prostaglandins with mechanical methods found no difference in cesarean delivery rate. Additionally, it was noted that there was less uterine tachysystole with fetal heart rate changes with mechanical methods compared to prostaglandins. ^[6]

Misoprostol versus Oxytocin

A randomized controlled trial compared induction of labor with misoprostol to oxytocin. All women included started with an unfavorable cervix. There was no difference in cesarean delivery rates, maternal complications or neonatal outcomes between groups. However, the time from induction to delivery was shorter in the oxytocin group. ^[25]

Transcervical Foley Catheter versus Oxytocin

A Cochrane review found reduction in cesarean delivery rate when transcervical Foley catheter was used versus oxytocin. Uterine tachysystole with fetal heart rate changes was not reported. There was no difference in maternal complications but neonatal morbidity was not reported. ^[6]

Transcervical Foley Catheter with Oxytocin versus Misoprostol

A randomized control trial compared induction of labor in nulliparous women with an unfavorable cervix using transcervical Foley catheter with oxytocin versus misoprostol. There was no difference in cesarean delivery rates, maternal complications or neonatal outcomes between groups. The time from induction to delivery was shorter in the transcervical Foley catheter and oxytocin group. ^[26]

 Transcervical Foley Catheter with Misoprostol versus Misoprostol

A randomized control trial compared induction of labor with transcervical Foley catheter plus misoprostol to misoprostol alone. There was no difference in cesarean delivery rates nor maternal complications or neonatal outcomes between groups. The time from induction to delivery was shorter in the transcervical Foley catheter with misoprostol group. ^[27]

Transcervical Foley Catheter with Oxytocin versus Transcervical Foley Catheter

A randomized control trial compared induction of labor with transcervical Foley catheter with oxytocin to transcervical Foley catheter alone. There was no difference in cesarean delivery rates or time from induction to delivery between the two groups. ^[28]

Induction of labor for nulliparous women with an unfavorable cervix has a two-fold increased risk of cesarean delivery¹. Thus, first ensuring the induction of labor is indicated is very important. ^{[3, 24]}

 A prospective study examined induction outcomes after institution of a standardized protocol for the diagnosis of a failed induction of labor. A cesarean delivery could not be performed for a failed induction of labor before reaching the active phase of labor until after at least 12 hours of oxytocin administration after membrane rupture. Active phase of labor was defined as 4cm dilated and 90% effaced or 5cm dilated. If fetal heart rate tracing was not reassuring, then a cesarean delivery was performed for fetal indication rather than a failed induction of labor. No multiparous women underwent a cesarean delivery for failed induction of labor, and many nulliparous women were able to have a vaginal delivery after allowance of additional time in the latent phase of labor induction rather than proceeding to cesarean delivery earlier. ^[29]

A subsequent observational study investigated induction of labor outcomes for nulliparous patients only. Active labor was similarly defined. The study found that allowing even up to 18 hours of induction prior to reaching active labor in nulliparous women allowed more women to have a vaginal delivery without increasing maternal or neonatal morbidity. ^[30]

The obstetric care consensus on the safe prevention of the primary cesarean delivery recommends that before proceeding with cesarean delivery for a failed induction of labor prior to reaching active phase of labor, oxytocin should be given for a least 12 to 18 hours after membrane rupture, as long as maternal and fetal status are reassuring. ^{[1, 24]} The latent phase of labor may last longer than 24 hours. A prolonged latent phase in itself is not an indication for cesarean delivery. The active phase was defined at 6cm dilated. ^[24]

The workshop summary on preventing the first cesarean delivery defined failed induction of labor as: “failure to generate regular (e.g. every 3 minutes) contractions and cervical change after at least 24 hours of oxytocin administration, with artificial rupture of membranes if feasible.” The workshop was a collaboration between the Society for Maternal Fetal Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the American College of Obstetricians and Gynecologists. ^[3]  

Women who are candidates for a trial of labor after cesarean delivery (TOLAC) should be offered one. It is necessary to have an extensive discussion between provider and patient regarding risks and benefits of TOLAC versus repeat cesarean. Contraindications to TOLAC include any contraindication for a vaginal delivery, prior classical or T-incision of the uterus, and previous uterine rupture. Women with one or two previous cesarean deliveries are candidates for TOLAC, but data regarding TOLAC risk in women with more than two previous cesareans deliveries are limited. ^[31]

A vaginal birth after cesarean delivery (VBAC) offers a faster recovery, avoidance of abdominal surgery, and lower risk for complications such as infection and hemorrhage than a cesarean delivery. There is however the unlikely but potentially catastrophic event of uterine rupture. With a prior low transverse hysterotomy, the risk of uterine rupture is 0.5 to 0.9%. When uterine rupture occurs, there is an increased risk for maternal and neonatal morbidity and mortality. ^[31]

A repeat cesarean delivery avoids the risk of uterine rupture during TOLAC. However, every cesarean delivery has the increased risk of hemorrhage, infection, thromboembolism, bowel or bladder injury as well as a longer recovery compared to a vaginal delivery. It is imperative to consider future reproductive plans as well. Additional repeat cesareans carry more risk for intra-operative complications as a result of adhesions and furthermore the very morbid risk of abnormal placentation requiring cesarean hysterectomy. ^{[3, 31]}

In summary, a successful VBAC has less risk for maternal morbidity and mortality than scheduled repeat cesarean delivery, which has less risk than cesarean delivery after a failed TOLAC. ^{[24, 31]} Similarly, neonatal morbidity is lower with VBAC than failed TOLAC. The trouble is it is not possible to know who will have a successful VBAC ahead of time. The overall likelihood of successful VBAC is 60-80%. There is a calculator that was developed to help to provide an estimated likelihood of successful VBAC (https://mfmu.bsc.gwu.edu/). If a woman had a cesarean delivery for a recurring issue (such as arrest of labor or descent), she has a lower likelihood than a woman who had a cesarean delivery for a non-recurring issue such as fetal intolerance or breech presentation. Factors that increase likelihood of successful VBAC include previous vaginal delivery and spontaneous labor. Factors that decrease likelihood of successful VBAC include older maternal age, obesity, non-white ethnicity, pre-eclampsia, short interpregnancy interval, late-term or postterm gestation, and increased birth weight. ^[31]

 An induction of labor for women desiring TOLAC is not contraindicated. The likelihood of successful VBAC with induction of labor is slightly decreased and risk of uterine rupture is slightly increased when compared to VBAC with spontaneous labor. ^[31] A transcervical Foley catheter is a great option for cervical ripening in women with prior cesarean delivery. Misoprostol is contraindicated for induction of labor in the third trimester in women with a prior uterine scar. ^{[1, 12, 31]}  Lastly, when performing a TOLAC, a physician capable of performing a cesarean delivery must be readily available. ^[31]  

A critical aspect of prenatal care and ultimately successful labor induction is patient education with appropriate management of expectations.  Important discussion points include reasons for labor induction, when and how labor is induced, as well as potential risks of an induced labor. The American College of Obstetricians and Gynecologists has put forth various patient education materials that are useful for patient preparation. Additionally, utilization of a patient safety checklist tool is highly recommended in order to facilitate standardization of the induction process (https://www.acog.org/Resources-And-Publications/Patient-Safety-Checklists/Scheduling-Induction-of-Labor and https://www.acog.org/Resources-And-Publications/Patient-Safety-Checklists/Inpatient-Induction-of-Labor).

Labor is a natural process by which uterine contractions results in cervical change and subsequent delivery of an infant.  Whether spontaneous or induced, the hope is that labor will result in a vaginal delivery. Generally speaking, induction of labor is a viable therapeutic option for appropriately selected patients; however, the benefits of continuing a pregnancy must be outweighed by the potential maternal and fetal risks associated with the procedure.