CERVICAL RIPENING WITH INTRACERVICAL PROSTAGLANDIN-E2GEL I. Clinical Results and Effect on Plasma Levels of Oxytocin and 13,14-Dihydro, 15-Ketoprostaglandin-F2a

Tylose gel containing 400 jug prostaglandin E2 in 3 ml gel was injected into the cervical canal of 20 patients with high-risk pregnancy and indication for induction of labor, but with unfavorable cervix. Ten were studied after the first gel application, five during repeat injection, and five after application of gel without PGE2. Blood samples were drawn serially during the first 8 hours for determination of oxytocin and 13,14-dihydro,15-ketoprostaglandin-F2a (PGFM). The PGE2 gel increased the Bishop score within 8 hours in all patients; in half of them, artificial rupture of the membranes could be performed and labor induced without further gel application; in the others, it was repeated every 8 hours until a Bishop score of > 8 was achieved. Fourteen of the 15 PGE2-induced patients delivered vaginally. Mean PGFM levels did not increase significantly during the 8 hours of observation, but in patients who responded with rapid progression, an increase was seen after cervical dilation was 6 cm or more. The mean oxytocin levels increased within 60 minutes after PGE2 application and were increased for the remaining observation period. Application of inactive gel had no effect on cervical ripening nor on oxytocin or PGFM levels. Cervical ripening is an important factor in the process of human birth. Several methods have been used to accelerate cervical ripening in patients in whom induction of labor is necessary before the physiologic softening process has taken place. These methods include the insertion of mechanical devices such as laminaria tents or weighted balloons inflated inside the internal os. Induction of labor with oxytocin or PGF2a, whether successful, often has a softening effect on the cervix, which facilitates subsequent induction when necessary. These methods are not always effective and are often associated with side effects that reduce their usefulness in high-risk pregnancies. More recently, it has been shown that PGE9 applied extra-amniotically for induction of labor has a market softening effect on the unripe cervix. The use of viscous gel as the vehicle for the active compound has greatly increased the usefulness of local PGE2 application for cervical ripening, because it provides a relatively slow and steady release of the PGE2 from the gel. 6 Little is known about the mechanism by which cervical PGE2 application brings about the desired effect. The purpose of the present study was to determine whether cervical ripening with PGE2 is associated with increased production of PGF9a, and to investigate whether there is a release of oxytocin which in turn might contribute to the observed cervical changes by stimulating the uterus to contract. We have therefore measured plasma levels of oxytocin and (54 *Department of Obstetrics and Gynecology, Cornell University Medical College, New York, New York institute of Perinatal Medicine, The Free University of Berlin, and the Department of Obstetrics, BerlinNeukolln, Germany Reprint requests: Dr. A.-R. Fuchs, Department of Obstetrics and Gynecology, Cornell Univerisity Medical College, 1300 York Avenue, New York, NY 10021 Publisher: Thieme-Stratton Inc., 381 Park Avenue South, New York, NY 10016 INTRACERVICAL PGE2 AND PLASMA PGFM AND OT/Fuchs et al the major metabolite of PGF2a, 13,14-dihydro, 15-keto-PGF2a (PGFM), in the peripheral blood of women in whom induction of labor and cervical ripening were indicated. The clinical studies were carried out in Berlin and the assays of oxytocin and prostaglandin in New York. MATERIALS AND METHODS Twenty patients with high risk pregnancy participated in this study. The indications for induction were placental insufficiency, premature rupture of the membranes (PROM), prolonged pregnancy, pre-eclampsia, diabetes mellitus, and previous cesarean section. All had an unfavorable cervix with a Bishop score below 7, mean 5.4 ±1.06 (SD). Ten patients were given 400 jug PGE in 3 ml Tylose gel (Group A); five patients were given 400 fig PGE in 3 ml gel for a second time, 8 hours after first application (Group B); and five women were given 3 ml gel without PGE2 (Group C). The gel was injected with a blunt cannula attached to a 5 ml disposable syringe. The PGE2 gel was prepared by mixing one ampoule containing 10 mg PGE (Minprostin E2®, Upjohn Co., Kalamazoo, MI) with 75 ml of sterile Tylose gel (Lederle) in a mechanical shaker. Aliquots of 3 ml were drawn into sterile syringes which were kept frozen until needed. The clinical characteristics of the patients are given in Table 1. They were randomly assigned to the experimental groups. The same investigator performed all cervical examinations to determine the Bishop score. Blood samples were collected before, and . 5, 1, 2, 4, 6, and 8 hours after application of the gel. The examinations were always done after the blood samples were drawn. If the Bishop score increased to > 8, the patient was taken into the labor room, artificial rupture of membranes was performed in all patients with intact membranes, and an oxytocin infusion was initiated if necessary to stimulate uterine contractions. If the Bishop score had not reached 8 points, the PGE2 gel application was repeated 8 hours after the first application. All women in the control group had PGE gel applied 8 hours after administration of the inactive gel. Fetal heart rate and uterine activity were monitored by external cardiotocography for 30 minutes before and 2 hours after gel application, and Table 1. Clinical Characteristics of Twenty Participants