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.
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.
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.]