Vaginal application of the nitric oxide donor isosorbide mononitrate for preinduction cervical ripening: a randomized controlled trial to determine effects on maternal and fetal hemodynamics. Evaluation of glyceryl trinitrate, misoprostol, and prostaglandin E2 gel for preinduction cervical ripening in term pregnancy. Randomised placebo-controlled trial of outpatient (at home) cervical ripening with isosorbide mononitrate (IMN) prior to induction of labour--clinical trial with analyses of efficacy and acceptability. The IMOP study. Randomized comparison of glyceryl trinitrate and prostaglandin E2 for cervical ripening at term. Randomized trial of isosorbide mononitrate versus misoprostol for cervical ripening at term. Nitric oxide donor isosorbide mononitrate for pre-induction cervical ripening at 41 weeks' gestation: A randomized controlled trial. The "PRIM" study: a randomized comparison of prostaglandin E2 gel with the nitric oxide donor isosorbide mononitrate for cervical ripening before the induction of labor at term.
Our aim was to assess the effects of vaginally administered isosorbide mononitrate (a nitric oxide donor) on maternal and fetal hemodynamics in pregnant women at term.
                We conducted a randomized controlled trial. Women were randomly selected to receive vaginally administered isosorbide mononitrate, 20 mg (n = 13) or 40 mg (n = 11), or to undergo a vaginal examination only (n = 12). Maternal pulse, blood pressure, and fetal heart rate were recorded at baseline and then every 30 minutes until 360 minutes. Umbilical artery resistance index and pulsatility index measurements were performed at 0, 180, and 330 minutes.
                Maternal pulse rate was greater after the administration of isosorbide mononitrate, 20 or 40 mg, compared with the pulse rate in the vaginal examination-only group (greatest difference in means, 21 beats/min; P <.01). Maternal systolic and diastolic blood pressures were greater in the 20-mg and 40-mg isosorbide mononitrate groups than in the vaginal examination-only group (greatest difference in mean systolic and diastolic blood pressure, 15 and 16 mm Hg, respectively; P <.02 and P <.001, respectively). Fetal heart rate was greater in the 40-mg isosorbide mononitrate group than in either the 20-mg isosorbide mononitrate group or the vaginal examination-only group (difference in mean, 15 beats/min; P <.05). No woman required treatment for maternal or fetal tachycardia or maternal hypotension. Neither dose of isosorbide mononitrate had a significant effect on umbilical artery resistance or pulsatility index.
                Vaginal administration of 20 or 40 mg isosorbide mononitrate to pregnant women at term has an effect on both maternal and fetal hemodynamics, but this effect is not clinically significant. To compare the efficacy of glyceryl trinitrate (GTN), dinoprostone and misoprostol for preinduction cervical ripening in primigravida at term.
                Sixty-five term primigravida, each with an unfavorable cervix (Bishop score </=5), were randomized to receive GTN (0.5 mg perivaginally, n = 21), dinoprostone gel (0.5 mg intracervically, n = 21) and misoprostol (50 microg perivaginally, n = 23) for a maximum of two doses, 6 h apart. Statistical analysis included paired t-tests to compare pre- and post-treatment Bishop scores, one-way analysis of variance (anova) tests to compare quantitative variables and chi-squared tests to compare the proportion of subjects achieving favorable Bishop scores.
                Baseline Bishop scores were similar in the GTN (3.4 +/- 0.9), dinoprostone (3.4 +/- 1.0) and misoprostol groups (3.2 +/- 1.2). The final outcome was favorable (Bishop score >6) in a greater proportion of subjects in the misoprostol (n = 18, 81.8%) and dinoprostone (n = 14, 66.7%) groups compared with the GTN group (n = 11, 55%). In subjects with a severely unfavorable cervix (Bishop score </=3), treatment with misoprostol led to a favorable response in 61.6% of patients compared with 45.6% in the misoprostol group and 33.3% in the GTN group. A significant improvement was noted in the Bishop score of all three groups (P < 0.001) but the increase in Bishop score was greater in misoprostol (3.5 +/- 2.1) and dinoprostone groups (2.8 +/- 1.5), compared with the GTN group (2.0 +/- 1.0, ANOVA F = 4.8, P = 0.01). Hyperstimulation and tachysystole were observed only in the misoprostol (9% and 4.3%) and dinoprostone groups (4.7% and 16.2%). The most common adverse effect in the GTN group was headache, which was observed in 47.6% of this group's subjects.
                The findings of the present study suggest that GTN is safer, but less efficacious, compared with prostaglandins for preinduction cervical ripening at term. To determine whether isosorbide mononitrate (IMN), self-administered vaginally by women at home, improves the process of induction of labour.
                Randomised double blind placebo-controlled trial.
                Large UK maternity hospital.
                Nulliparous women with a singleton pregnancy, cephalic presentation > or = 37 weeks gestation, requiring cervical ripening prior to induction of labour.
                IMN (n = 177) or placebo (n = 173) self-administered vaginally at home at 48, 32 and 16 hours prior to the scheduled time of admission for induction.
                Admission to delivery interval and women's experience of induction of labour.
                IMN did not shorten the admission to delivery interval as compared with placebo [mean difference of -1.6 hours (95% CI -5.1,1.9, P = 0.37)], despite being more effective than placebo in inducing a change in Bishop score [mean difference of 0.65 (95% CI 0.14,1.17, P = 0.013)]. While both groups found the overall experience of home treatment to be positive, (mean score of 3.8/10 +/- 2.3/10 for the IMN group, where 1 = extremely good and 10 = not at all good) women in the placebo group found it marginally more positive than those in the IMN group (just over half a unit on a 10-point scale, P = 0.043). There were no differences between the groups in the pain or anxiety experienced or willingness to take the treatment in a subsequent pregnancy.
                IMN self-administered vaginally at home does not shorten admission to delivery interval despite a significant effect on cervical ripeness assessed using the Bishop score. However, women report positive views on cervical ripening at home, and the setting deserves further investigation. To estimate the adverse effects of glyceryl trinitrate compared with prostaglandin (PG) E2 vaginal tablet for cervical ripening in term pregnancy.
                One hundred ten women with term pregnancies referred for induction of labor with Bishop scores of 6 or less were randomly assigned to receive a 500-microg glyceryl trinitrate tablet vaginally (n = 54) or a 3-mg PGE2 tablet vaginally (n = 56), every 6 hours for maximum of two doses. Subjects were sent to the labor ward for amniotomy or oxytocin if their Bishop scores were more than 6 or their cervices were not ripe 24 hours after treatment. Adverse effects, changes in the Bishop scores, progress, and outcomes of labor were assessed.
                Glyceryl trinitrate was associated with fewer episodes of uterine tachysystole (0% versus 9%; P =.02). The median Bishop score after 12 hours was lower in women given glyceryl trinitrate compared with those given PGE2. Adverse effects, including headache and palpitations, were more frequent with glyceryl trinitrate than with PGE2. The cesarean rate was not significantly different between groups.
                Cervical ripening with glyceryl trinitrate resulted in fewer episodes of tachysystole, but there were significantly more minor side effects. It can be used for cervical ripening at term, but it was not as effective as PGE2. To assess the adverse effects of isosorbide mononitrate (IMN) compared with misoprostol for cervical ripening at term.
                One hundred and seven women with term pregnancies referred for induction of labor with Bishop scores of 6 or less were randomly allocated to receive either a 40-mg IMN tablet vaginally (n = 55) or 50 microg misoprostol vaginally (n = 52) every 6 h for a maximum of three doses. They were sent to the labor ward for amniotomy or oxytocin if either their Bishop scores were more than 6 or their cervices were not ripe 24 h after the treatment. Adverse effects, progress, and outcomes of labor were assessed.
                Isosorbide mononitrate was associated with fewer adverse effects especially uterine tachysystole (0 vs. 19.2%, P < 0.01) and hyperstimulation (0 vs. 15.4%, P < 0.01). The time from start of medication to vaginal delivery in IMN group was significantly longer (25.6 +/- 6.1 vs. 14 +/- 6.9 h, P < 0.01). Oxytocin was needed in 51 women (92%) of the isosorbide mononitrate group and six women (11%) of the misoprostol group (P < 0.001). The cesarean rate was not significantly different between the groups, but the major indications were different: dystocia (45%) in the IMN group vs. persistent non-reassuring fetal heart rate pattern (56%) in the misoprostol group.
                Cervical ripening with IMN resulted in fewer adverse effects, but was less effective than misoprostol. Nitric oxide donors have been shown to cause cervical ripening. The aim of this study was to determine whether sustained release isosorbide mononitrate (ISMN-SR) 60 mg administered vaginally is effective for pre induction cervical ripening at 41 weeks' gestation.
                A double-blind randomised controlled trial was carried out at the University Obstetric Unit, Galle, Sri Lanka for a period of 9 months, commencing 1st August 2003. One hundred and fifty-six consecutive women with uncomplicated singleton pregnancies at 41 weeks' gestation with a modified Bishop Score <5 were allocated by stratified (primip/multip) block randomization to receive either ISMN-SR 60 mg (n = 78) or vitamin C 100 mg (n = 78) vaginally. Modified Bishop Score at 41 weeks + 2 days' gestation and the proportions establishing spontaneous labor or becoming favorable for induction of labor (IOL) by 41 weeks + 2 days' gestation were evaluated in each group.
                At the commencement of the study there were no differences between the mean age, parity or modified Bishop Score of the two groups. In the ISMN-SR group, there was a marked increase in the proportion establishing spontaneous labor (28% vs 7.5%, P < 0.01) and being favorable for IOL (40% vs 9% P < 0.001), 2 days after therapy. In the ISMN-SR group, there was a significantly higher increase in the mean modified Bishop Score (3.8, 95% CI 2.3-5.3 vs 1.3, 95% CI 0.3-2.2, P < 0.01) and a marked decrease in the proportion of subjects requiring further ripening of the cervix with a Foley catheter. (32% vs 79%, P < 0.001). The cesarean section rates were similar in both groups.
                Sustained release ISMN administered vaginally is effective for preinduction cervical ripening. The purpose of this study was to compare the efficacy and safety profile of prostaglandin E2 with isosorbide mononitrate for cervical ripening before the induction of labor at term.
                Primigravid women were assigned randomly to receive either 40 mg of isosorbide mononitrate or 2 mg of prostaglandin E2. Efficacy outcomes were the cervical ripening effect of each agent and the time from treatment initiation to delivery. Safety outcomes were the incidence and frequency of maternal side effects and events that would be potentially hazardous for mother and baby during outpatient cervical ripening.
                Prostaglandin E2 was more effective than isosorbide mononitrate in inducing a change in modified Bishop score. Mean duration from treatment initiation to delivery was greater for isosorbide mononitrate than prostaglandin E2. There were no adverse events in the isosorbide mononitrate group that would contraindicate outpatient treatment. However, in the prostaglandin E2 group, 7% of the pregnancies had abnormal fetal heart rate patterns (P = .0002). Maternal satisfaction was significantly higher in the isosorbide mononitrate group.
                Although isosorbide mononitrate was less effective, maternal satisfaction was significantly greater. The safety profile of each agent was such that it would be reasonable to give isosorbide mononitrate, but not prostaglandin E2, on an outpatient basis.
NO donors do not appear currently to be a useful tool in the process of induction of labour. More studies are required to examine how NO donors may work alongside established induction of labour protocols, especially those based in outpatient settings.