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From Contemporary OB/GYN............

Cervical ripening and labor induction

By Deborah A. Wing, MD, and Richard H. Paul, MD

Labor should be induced when benefits to mother or fetus outweigh the risks of continuing the pregnancy, but the approach chosen depends on the cervical condition. In the first of two articles, experts discuss the many acceptable methods of cervical ripening and labor induction, as well as the indications and contraindications.

The obstetrician-gynecologist induces labor in order to stimulate uterine contractions prior to the onset of spontaneous labor for the purpose of accomplishing delivery, most commonly for post-term pregnancies. In the United States, an estimated 15% of pregnant women undergo labor augmentation, and another 15% require aid in labor augmentation.¹ While no ideal method of labor induction is known, many acceptable methods of cervical ripening and labor induction are effective and safe. In the first of two related articles, we will address the indications and contraindications for inducing labor, along with the requirements and risks. Part I discusses oxytocin combined with amniotomy as the current method of choice for those women in labor who have a favorable cervix. It also looks at other medications used for cervical ripening of the unfavor-able cervix: the prostaglandin compounds, as well as mifepristone, relaxin, and estrogens. Mechanical approaches will complete our review. A more narrowly focused article next month will guide the clinician in successful cervical ripening and labor induction with misoprostol.

Indications and contraindications

Induction of labor should be undertaken when the benefits to either the mother or fetus outweigh the risks of continuing the pregnancy. The several acceptable medical and obstetrical indications for labor induction include pregnancy-induced hypertension, premature rupture of membranes, chorioamnionitis, fetal growth retardation, isoimmunization, maternal diabetes mellitus, and fetal demise. The most frequent indication for labor induction in this country is prolonged, or postdates, pregnancy (Table 1). Although inductions commonly occur for convenience and because of geographic and other social factors, substantive data are lacking to support this practice. These are considered elective inductions and, as such, are questionable.

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Contraindications to labor induction include prior classical uterine incision, active genital herpes infection, placenta or vasa previa, fetal malpresentation, and prolapsed umbilical cord (Table 2 - only available in printed version). Certain other conditions, while not necessarily contraindications, dictate that the obstetrician exercise caution and judgment in management. These include multiple gestation, maternal cardiac disease, grand multiparity, breech presentation, abnormal fetal heart rate (FHR) patterns that do not require immediate delivery, history of prior cesarean section, and severe hypertension.

Requirements for induction

Before undertaking labor induction, carefully examine the maternal and fetal condition and review the indications and contraindications. Obtain informed consent for the planned procedure and method. Fetal maturity should also be evaluated, and when appropriate, amniocentesis may be indicated to assess fetal lung maturity prior to initiating induction.

Labor induction carries risks, notably uterine hyperstimulation and the possibility of an induction failure leading to C/S delivery.²Close monitoring of uterine activity is essential, and FHR monitoring must be used in the care of a high-risk pregnancy.

Clearly, the condition of the cervix influences the success of labor induction. For this reason, a cervical examination should be performed in close temporal proximity to the initiation of the labor attempt. Of the several available cervical scoring systems, the modified Bishop scoring system is used most routinely in clinical practice.³ This system tabulates a score based on four characteristics of the cervix--dilatation, effacement, consistency, and position--and the station of the presenting part. A low cervical score has been associated with failed induction, prolonged labor, and a high C/S birth rate.^2,4

Induction of labor with oxytocin

Oxytocin is a polypeptide hormone approved by the Food and Drug Administration for induction of labor in a viable pregnancy. Produced in the hypothalamus and secreted from the posterior lobe of the pituitary gland in a pulsatile fashion, it is among the most potent uterotonic agents.

The uterine response to exogenous oxytocin administration--periodic uterine contractions--is demonstrable after about 20 weeks' gestation. From 34 weeks' gestation to term, there is little change in the sensitivity of the myometrium to oxytocin. Once spontaneous labor begins, however, the uterine sensitivity to oxytocin increases rapidly.⁵

Oxytocin, as a polypeptide, cannot be administered orally; therefore, it is most commonly given intravenously. The plasma half-life of oxytocin is short, an estimated 3 to 6 minutes.⁶ Complications of oxytocin use include uterine hyperstimulation, and with excessive doses, hypotension, water intoxication, and neonatal hyperbilirubinemia.

Success rates for oxytocin in inducing labor are diminished when it is given to women with uneffaced and undilated cervices. Therefore, when confronted by unfavorable cervical findings or an unlabored cervix, the obstetrician-gynecologist should consider a ripening process before administering oxytocin.

The parameters for oxytocin administration are the subject of debate, even though success rates for varying protocols are strikingly similar. Protocols differ in initial dose, incremental time period, and steady-state dose. The protocols cited in Technical Bulletin No. 217 by the American College of Obstetricians and Gynecologists exemplify physiologic approaches.⁷ The incremental interval of 40 to 60 minutes suggested by Seitchik and colleagues, which was based on studies of low-dose oxytocin administration, is supported by pharmacokinetic studies.⁸ Others have suggested shorter incremental time intervals.^9,10 Manual pulsatile administration of oxytocin provides the advantage of lower total doses of oxytocin.¹¹ At Women's and Children's Hospital, a continuous infusion is started at a dose of 1 mU/min of oxytocin, and increased linearly by 1 mU/min every 30 minutes to a maximum of 22 mU/min. In addition, when no contraindications exist, early amniotomy is used to shorten the duration of labor and enhance the chances of a successful induction.

Cervical ripening

Cervical ripening is a complex process that culminates in the physical softening and distensibility of the cervix. The process involves action of the enzymatic dissolution of collagen fibrils within the cervix, an increase in water content of the cervix, and chemical changes that contribute to the clinical finding of cervical effacement and early dilatation. Methods for promoting cervical ripening have attracted widespread interest because cervical dilatation and effacement are reasonable predictors of the likelihood of vaginal delivery after labor induction. The various methods include extra-amniotic catheters, hygroscopic dilators, prostaglandin compounds, and local application of hormones such as relaxin and estrogen (Table 3).

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Prostaglandins

The histologic changes in the cervix after administration of prostaglandin E₂ (PGE₂) include dissolution of collagen bundles and an increase in the submucosal water content. Numerous prospective studies have shown the efficacy of cervical ripening with prostaglandins; the optimal route, frequency, and dosage have yet to be determined. Prostaglandin analogues were originally given by IV and oral routes. The administration of prostaglandins locally to the vagina or endocervix, first studied in the early 1980s, is currently the approach of choice because of fewer adverse effects and acceptable clinical response.^12,13

There are two FDA-approved PGE₂ preparations for cervical ripening. One of these contains 0.5 mg of dinoprostone in a gel preparation for intracervical administration. The other is a prostaglandin vaginal insert containing 10 mg of dinoprostone in a timed-released formulation. The manufacturer recommends a 12-hour exposure to the prostaglandin when administered in the vaginal-insert form, which releases the medication at a rate of 0.3 mg/hour. The vaginal insert's advantage over the gel formulation is its ease of removal if uterine hyperstimulation or an abnormal FHR tracing should occur.^14,15

These two approved preparations are costly.¹⁶ There is growing interest, therefore, in the accumulating evidence that a prostaglandin E₁ analogue, misoprostol, when administered intravaginally, is an effective alternative to endocervically or vaginally administered PGE₂ preparations.^17-19 The FDA-approved indication for misoprostol is the treatment and prevention of gastric ulcer disease related to chronic nonsteroidal anti-inflammatory use. Multiple studies now indicate that misoprostol is as effective as the dinoprostone vaginal insert for cervical ripening and labor induction.^20,21 When used off-label for cervical ripening and labor induction, it is usually given by the transvaginal route after minor modifications in the tablet. To prevent dosing errors, we recommend that the pharmacist use a pill-cutter to quarter the 100-mg tablet into the recommended 25-mg dose.

In addition to the cost-savings of this prostaglandin compound, it also offers the benefit of stability at room temperature. We will explore the use of misoprostol--including caveats for the physician who decides to prescribe its off-label use--in greater depth in a companion article next month, "Misoprostol for cervical ripening and labor induction: The clinician's perspective and guide to success."

Other medical methods

Various other drugs have been used to induce labor with varying degrees of success. Relaxin, a polypeptide hormone produced by the ovaries, affects connective tissue remodeling. Clinical trials that compared porcine relaxin with prostaglandin compounds demonstrated efficacy similar to that of cervical ripening, but trials that compared recombinant human relaxin showed no effect on cervical ripening.²² Mifepristone, also known as RU-486, an antiprogestational steroid, has emerged as a potential oral alternative for cervical ripening and induction of labor in early pregnancy termination. There are few trials describing the use of mifepristone in term pregnancies, however.^23,24

Mechanical methods

Mechanical methods are among the oldest approaches to promoting cervical ripening (Table 4). They include stripping of membranes, amniotomy, insertion of balloon catheters above the cervical os, extra-amniotic saline infusion, and introduction of hygroscopic dilators into the endocervix. The latter two methodologies cause a gradual cervical dilation with minimal discomfort to the patient.

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Stripping of the membranes. This widely used--but often undocumented--technique appears inconsistently efficacious and is difficult to test objectively.²⁵ It is believed to cause release of prostaglandin F_2a from the decidua and the adjacent membranes, or PGE₂ from the cervix.

Amniotomy. This approach is an effective method of labor induction when performed in women with partially dilated and effaced cervices. Exercise caution, however, to ensure that the fetal vertex is well applied to the cervix and that the umbilical cord or other fetal part is not presenting. Risks associated with amniotomy include the introduction of infection, disruption of an occult placenta previa, and cord prolapse. Amniotomy shortens the duration of labor, reduces the incidence of dystocia, and lessens the need for oxytocin augmentation.^26,27 Its use does not appear to reduce the rate of C/S births, however.

Catheters. Use of the Foley catheter technique alone, in which catheters are passed through an undilated cervix before inflation, was shown to be as effective as use of PGE₂ gel.²⁸ The successful use of extra-amniotic saline infusion with a balloon catheter has also been reported.^29,30

Dilators and tents. Hygroscopic dilators, although used primarily for pregnancy termination, have proved safe and effective in term pregnancies.^31,32 Laminaria tents, made from natural seaweed, are commercially available as Lamicel (Cabot Medical Corporation, Langhorne, Pa.). These synthetic devices, which are designed to expand within the cervical canal, probably function by disrupting the chorioamniotic decidual interface, causing lysosomal destruction and prostaglandin release. This cascade of events also brings about active stretching of the cervix beyond the passive mechanical stretching effected by the tent itself. Clinical trials that compared hygroscopic dilators to PGE₂ gel demonstrate the similarity of both methods in terms of cervical change. PGE₂, however, is associated with a higher success rate for induction.^31,32 A drawback of dilator use is the potential for a higher incidence of postpartum maternal and fetal infections.

Conclusion

The ideal method of labor induction has yet to be identified. Clinical studies of human parturition are hindered by the basic lack of understanding of the physiologic events that initiate and sustain labor. In addition, the wide biologic variation among patients in the progress of normal labor impedes the investigation of new uterotonic agents.

Oxytocin in combination with amniotomy currently remains the method of choice for inducing labor in women whose cervical examinations yield favorable findings. Women with less favorable cervices appear to benefit from
a "ripening" process promoted by the use of prostaglandins or hygroscopic tents when evaluating induction success.

Dr. Wing is Assistant Professor, University of Southern California School of Medicine, Los Angeles, Calif,
and with the Division of Maternal-Fetal Medicine, Department of Ob-Gyn, Women's and Children's Hospital, Los Angeles, Calif.
Dr. Wing is also a paid consultant to and a member of the speaker's program at Forest Pharmaceuticals, Inc.

Dr. Paul is Professor, University of Southern California School of Medicine, Los Angeles, Calif.,
and Former Chief, Division of Maternal-Fetal Medicine, Department of Ob-Gyn, Women's and Children's Hospital, Los Angeles, Calif.

 

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