Ripening of the human cervix and induction of labor with intracervical purified porcine relaxin. Ripening of the human cervix and induction of labour with purified porcine relaxin. Recombinant human relaxin as a cervical ripening agent. A randomized, double-blind, placebo-controlled trial of the safety of vaginal recombinant human relaxin for cervical ripening. Multisite, double-blind, placebo-controlled trial of porcine secretin in autism. Effect of preinduction cervical softening with dinoprostone gel on outcome of oxytocin-induced labor. A randomized, double-blind, placebo-controlled trial of porcine versus synthetic secretin for reducing symptoms of autism. A double-blind, randomized, placebo-controlled trial of prilocaine and felypressin (Citanest and Octapressin) for the relief of pain associated with cervical biopsy and treatment with the Semm coagulator. A comparison of three preinduction cervical priming methods: prostaglandin E2 gel, Dilapan S rods and Estradiol gel.
In a randomized double-blind placebo-controlled trial involving 71 patients, a viscous gel containing distilled water or 1 or 2 mg pure porcine relaxin was instilled in the cervical canal on the evening before the surgical induction of labor. Eleven of 48 patients receiving relaxin labored overnight, whereas only one of 23 patients went into labor. Only the 2-mg dose significantly improved the mean cervical score compared with the placebo treatment; the effect was greatest in primigravid patients with unripe cervixes. Intracervical application appeared to confer no benefit over vaginal application in effecting cervical ripening or inducing labor. Systemic absorption of the porcine relaxin after its intracervical application was confirmed by the measurement of immunoreactive relaxin in a homologous porcine relaxin radioimmunoassay. Thus, the cervical ripening effect of exogenous relaxin may be mediated either systemically or by direct action at the site of local application. This trial confirms the responsiveness of the human term cervix to exogenous relaxin and supports the suggestion that endogenous relaxin may play a similar role at term in facilitating cervical ripening and parturition. In a randomised double-blind trial 10 of 30 patients given 2 mg of intravaginal purified porcine relaxin on the evening before surgical induction of labour went into labour before the proposed induction. Of 30 control patients, none went into labour. Of the 30 patients treated with relaxin, 25 had improved cervical scores after treatment and significantly fewer required augmentation in labour with intravenous oxytocin than the control group. Administration of relaxin was associated with very little increase in uterine activity and no side-effects. The trial shows that exogenous relaxin causes cervical ripening and can initiate parturition. Endogenous relaxin may have a similar role. The aim of this study was to investigate the efficacy and safety of recombinant human relaxin (rhRIx) as a cervical ripening agent in women with an unfavourable cervix before induction of labour at term.
                A multi-centre, double-blind, placebo-controlled trial performed in Edinburgh, Glasgow and Oxford. Women were treated with 0, 1, 2 or 4 mg of rhRIx in a gel vehicle administered intravaginally. Analysis of variance tests were performed on all continuous variables, and Cochran Mantel-Haenszel tests employed for all discrete variables.
                Ninety-six women at 37 to 42 weeks of gestation with a singleton pregnancy and a modified Bishop score of < or = 4 were recruited.
                There was no significant difference in the change in modified Bishop score between the four treatment groups. The lengths of the first and second stages of labour were similar in all 4 groups. PGE2 and oxytocin requirements were similar in all groups, as was the mode of delivery. There was no evidence that relaxin was absorbed systemically when given in this way.
                Recombinant human relaxin 1 to 4 mg, administered as an intravaginal gel, has no effect as a cervical ripening agent before induction of labour at term. To assess the safety of vaginal recombinant human relaxin in pregnant women treated before the induction of labor and to collect preliminary data on the efficacy of recombinant human relaxin in promoting cervical ripening.
                In a multi-center, randomized, double-blind placebo-controlled trial, 40 women were studied before induction of labor because of post-dates. The women were randomized to receive either 1.5 mg recombinant human relaxin in 3% methylcellulose gel or gel only, placed into the posterior vaginal fornix after a cervical assessment on the evening before scheduled induction. If a subject did not go into spontaneous labor overnight, another cervical assessment was performed 15 hours following treatment, immediately before the standard induction regimen of the hospital.
                No important maternal or fetal-neonatal complications could be attributed to the drug. The differences between the recombinant human relaxin group and the placebo group for all the outcome measures of efficacy did not achieve statistical significance. Placebo patients were more likely to report moderate or strong uterine contractions in the first 4 hours following treatment than were the recombinant human relaxin-treated patients.
                The use of recombinant human relaxin at a dose of 1.5 mg was not associated with any significant maternal or fetal-neonatal complications. The relatively small number of subjects in this study was chosen deliberately because this was the first use of the drug in pregnant subjects. Assessment of efficacy will require studies that include more patients and a range of relaxin doses. To examine the efficacy of intravenous porcine secretin for the treatment of autistic disorder.
                Randomized, double-blind, placebo-controlled, crossover design. Fifty-six subjects with autistic disorder received either a secretin or placebo infusion at baseline and the other substance at week 4. Subjects were given the Autism Diagnostic Observation Schedule (ADOS) and other pertinent developmental measures at baseline and at weeks 4 and 8 to assess drug effects.
                For the primary efficacy analysis, change of ADOS social-communication total score from week 0 to week 4, no statistically significant difference was obtained between placebo (-0.8 +/- 2.9) and secretin groups (-0.6 +/- 1.4; t54 = 0.346, p < .73). The other measures showed no treatment effect for secretin compared with placebo.
                There was no evidence for efficacy of secretin in this randomized, placebo-controlled, double-blind trial. Five hundred fourteen pregnant women at or near term with medically indicated inductions and unfavorable cervical induction features (Bishop score 0-4) were enrolled in an open-label randomized multicenter clinical trial to study the effect of endocervical administration of 0.5 mg of dinoprostone cervical gel as a preinduction cervical ripening agent. Patients in the treatment group (n = 265) received dinoprostone cervical gel 12 hours prior to oxytocin induction; patients in the control group (n = 249) were observed during this period. Thirteen patients in each group were excluded from efficacy evaluations. All patients were included in safety analysis. A mean Bishop score increase of 2.9 points was achieved in the treatment group, as compared with 0.6 point in the control group (P < 0.001). During the observation period, spontaneous labor occurred in a significantly greater percentage of patients in the treatment group (27%) than in the control group (2%). The percentage of patients who achieved labor either during the observation period or during the initial induction attempt was significantly larger in the dinoprostone cervical gel group (71.8%) than in the control group (54.2%). In addition, there was a statistically significant (P < 0.001) difference in median induction-to-vaginal delivery time for the treatment group (10.6 hr) and the control group (13.0 hr). Side effects were reported for 42% and 35% of patients in the treatment and control groups, respectively, with fetal heart rate abnormalities reported for approximately 27% of patients in each group.(ABSTRACT TRUNCATED AT 250 WORDS) To compare the effects of a single dose of biologic and synthetic porcine secretin to placebo on a variety of autism symptoms.
                Eighty-five children with autism without other medical conditions and not taking other psychotropic medications participated (ages between 3 and 12 years, mean IQ = 55). Children were grouped into trios matched by age and communication level and then randomly assigned to one of three treatment groups: biologic secretin (2 CU/kg), synthetic secretin (0.4 microg/kg), and placebo. Measures collected 1 week before and 4 weeks after infusion included autism symptoms, language skills, and problem behaviors, gathered from parents, teachers, and investigators, who were all blind to treatment. Two-factor, repeated-measures analyses of variance (3 treatment levels by 2 repeated measures, pre- and postinfusion) were used to examine efficacy.
                Direct observation measures did not show change over time related to secretin. Parent reports showed an overall reduction of symptom severity for all treatment groups, including the placebo group. One teacher-report measure showed decreases in autism symptoms in the placebo and synthetic secretin groups.
                No evidence that either biologic or synthetic secretin provided amelioration of symptoms beyond placebo was observed. This held true when children with and without gastrointestinal problems were examined separately. To quantify the anticipated and actual pain experienced in association with preliminary cervical punch biopsies and subsequent ablative treatment with the Semm coagulator, and to test the hypothesis that the intracervical injection of prilocaine with felypressin reduces the intensity of the pain experienced.
                One hundred consecutive women referred with abnormal cervical smears for colposcopic assessment and considered suitable for treatment with the Semm coagulator were recruited to a double-blind, randomized, prospective, placebo-controlled trial conducted in a colposcopy clinic in a university teaching hospital. Personal particulars were taken and anticipated pain scored. The patients were injected with randomized externally identical vials of prilocaine and felypressin (Citanest and Octapressin) or placebo. After biopsy and treatment, patients scored their actual pain experienced. Pain scores were compared as the main outcome measure. Relative risks with 95% CIs were calculated and compared using the CI Analysis computer programme (Professor Martin J Gardner and the British Medical Journal Version 1.1, copyright 1991).
                Anticipated pain was greater than the actual pain experienced in both groups. Women receiving the local anesthesia experienced a significantly greater reduction in pain (p < .05) with only 4.3% and 6.7% experiencing moderate pain during biopsy and treatment, respectively. The active drug abolished severe pain. In the placebo group, 44.7% felt mild pain at the most.
                Intracervical injection of prilocaine and felypressin reduces the intensity of pain experienced in women undergoing cervical biopsy and treatment with the Semm coagulator. Its use is commendable but is not absolutely necessary in all cases. The aim of the study was to evaluate the efficacy of three cervical priming methods. From January 1, 1994 to December 31, 1996 247 patients presenting an indication for induction of labor with an unripe cervix were randomly assigned to one of the following preinduction protocols: 0.5 mg of Prostaglandin E2 gel administered intracervically (n = 83), four hygroscopic Dilapan S rods applied intracervically (n = 82), and 150 mg of Estradiol gel administered intravaginally (n = 82). The inclusion criteria were the patient's informed consent, singleton pregnancy of more than 36 weeks, cephalic presentation, Bishop score < 5 points and reactive non-stress test. If the cervical maturation (Bishop score > or = 5, and/or Bishop score augmentation by 2 points) did not occur after 14 hours of priming, the case was considered a failure. In the opposite case the patient was induced by means of extraamniotic PGE2 administration. The mean gain in the Bishop score was 3.7 points in the PGE2 group 3.9 points in the Dilapan S group, and 2.8 points in the Estradiol group. 71 patients (85.5%) were successfully preinduced in the PGE2 group, 73 (89.0%) in the Dilapan S group, and 63 (76.8%) in the Estradiol group. Labor was induced by preinduction only in 23 patients (31.3%) of the PGE2 group in 17 (20.7%) of the Dilapan S group, and in 14 (17.1%) of the Estradiol group. The mean induction to delivery interval was 7 h 27 min in PGE2 group, 7 h 49 min in the Dilapan S group and 9 h 15 min in the Estradiol group. The Caesarean section rate was 24.4% in the PGE2 group, 10.5% in the Dilapan S group, and 24.4% in the Estradiol group. PGE2 gel and Dilapan S rods proved higher efficacy than Estradiol gel. The highest frequency of labor induced by preinduction only was in the PGE2 group. There were shorter induction to delivery intervals in the PGE2, and Dilapan S groups. The lowest Caesarean section rate was in the Dilapan S group. Neither serious side effects nor negative neonatal outcome were noted in either group.
The place of relaxin, either purified porcine or recombinant human, as an induction or cervical priming agent is unclear. Further trials are needed to estimate the true effect of relaxin within current clinical practice.
[Note: The three citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]