Outpatient cervical ripening before first-trimester surgical abortion: a comparison between misoprostol and isosorbide mononitrate. Nitric oxide donors induce ripening of the human uterine cervix: a randomised controlled trial. Second-trimester pregnancy termination: comparison of three different methods. Intracervical application of the nitric oxide donor isosorbide dinitrate for induction of cervical ripening: a randomised controlled trial to determine clinical efficacy and safety prior to first trimester surgical evacuation of retained products of conception. 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. A comparison of isosorbide mononitrate, misoprostol and combination therapy for first trimester pre-operative cervical ripening: a randomised controlled trial. Comparative study of various intracervically administered PG gel preparations for termination of first trimester pregnancies. Outpatient cervical ripening with nitric oxide donor isosorbide mononitrate prior to induction of labor.
Vaginal administration of prostaglandin analogues as well as nitric oxide donors before first-trimester surgical abortion has been shown to induce effective cervical ripening. In addition, nitric oxide donors, such as isosorbide mononitrate and nitroglycerin, have been associated with a patient-friendly side-effect profile when administered 3 h before the surgical procedure. We wanted to compare the cervical ripening effect and possible side effects of isosorbide mononitrate and the prostaglandin analogue misoprostol when self-administered at bedtime the evening before surgical abortion.
                One hundred and twenty nulliparous women scheduled for suction termination of pregnancy in the first trimester were randomly assigned to receive per vaginam either 40 mg of isosorbide mononitrate or 200 microg of misoprostol. Sixty of the women were included for assessment of cervical ripening as well as evaluation of side effects. The other 60 women were recruited for assessment of side effects only. Cervical ripening was evaluated by measuring baseline cervical dilation and the cumulative force to dilate the cervix to 9 mm by means of a cervical tonometer. For assessment of side effects, the women were asked to complete a symptom questionnaire.
                Cervical resistance was significantly higher in women treated with isosorbide mononitrate compared to misoprostol (median cumulative force 73 versus 15 N). Common side effects of misoprostol were abdominal pain (69%), nausea (44%), and vaginal bleeding (66%), while in the isosorbide mononitrate group headache was frequently experienced (79%). In both treatment groups, the frequency and intensity of side effects gradually increased during the treatment interval.
                Misoprostol induced a more pronounced cervical ripening than isosorbide mononitrate, but both regimens were associated with a high frequency of side effects. To determine whether nitric oxide donors can induce cervical ripening before surgical termination of pregnancy in the first trimester.
                Prospective, randomised controlled trial.
                Department of Obstetrics and Gynaecology, Royal Infirmary, Glasgow.
                Forty-eight primigravid women undergoing surgical termination of pregnancy before 12 weeks of gestation.
                The women were randomised to receive per vaginam before surgery either the nitric oxide donor isosorbide mononitrate, the nitric oxide donor glyceryl trinitrate, the prostaglandin analogue gemeprost, or no treatment.
                The cumulative force required to dilate the cervix to 8 mm was measured objectively and the cervical diameter before surgical dilatation was recorded.
                Following isosorbide mononitrate or gemeprost, a lower cumulative force was required to dilate the cervix to 8 mm and a higher cervical diameter before dilatation was recorded. Pretreatment with glyceryl trinitrate reduced the cumulative force required to dilate the cervix but had no effect on cervical diameter.
                Like the prostaglandin analogue gemeprost, the nitric oxide donors isosorbide mononitrate and glyceryl trinitrate can effect cervical ripening. Nitric oxide donors may provide an alternative to prostaglandins for cervical ripening before surgical procedures in the first trimester. The object of this study was to compare intravaginal misoprostol and dinoprostone (prostaglandin E2) for second-trimester pregnancy termination, and to examine the role of the nitric oxide donor, glyceryl trinitrate, as a possible alternative to prostaglandins to induce cervical ripening in second-trimester pregnancy termination. This was a randomised clinical trial. The trial involved pregnant women between 13 and 28 weeks' gestation admitted with clear medical or obstetric indications for pregnancy termination, and was carried out in the department of obstetrics and gynecology, Assiut University Hospital, Egypt. Patients were classified into Group A, where pregnancy termination was induced by vaginal misoprostol 100 micrograms every 4 hours with a maximum dose of 500 micrograms; Group B, where induction was by vaginal dinoprostone 6 mg every 6 hours with a maximum dose of 24 mg; and Group C, where induction involved vaginal glyceryl trinitrate 500 micrograms every 6 hours with a maximum dose of 2.5 mg. Twenty-four hours after the start of induction, the rate of complete abortion in the three groups was 100%, 66.67% and 0%, respectively. The rate of complete abortion was 100% in the nitric oxide (glyceryl trinitrate)-induced group after introducing a complementary procedure. The induction-abortion interval was significantly shorter, the number of doses needed was less and the maximum Bishop score reached was greater with misoprostol than with dinoprostone. A higher rate of side effects occurred with the misoprostol-induced group (74%) compared with the other two groups (46.6% and 0%). Misoprostol is a cheap, effective drug for second-trimester pregnancy termination with short induction abortion intervals but a higher rate of side effects. Prostin E2 is also effective in termination of second-trimester pregnancy but is expensive and may require high doses to be administered. Glyceryl trinitrate is an effective drug for cervical ripening (softening) but it has no role in the stimulation of uterine contractions. To determine the therapeutic efficacy and safety of a nitric oxide (NO) isosorbide dinitrate donor to induce cervical ripening of women with missed abortions before surgical evacuation of the uterus.
                A prospective, randomised, double-blind controlled trial.
                Tertiary referral maternity teaching hospital. Population Sixty women with missed abortions and no cervical dilation.
                Women requesting surgical evacuation of the uterus were randomly selected to receive endocervical 80 mg/1.5 mL isosorbide dinitrate gel solution (n= 30) or 400 mug/1.5 mL misoprostol gel solution (n= 30) every 3 hours to a maximum of four doses or until reaching cervical ripening. Vital signs and symptoms were recorded at baseline and then every 3 hours until finishing therapy. Adverse events, such as headache, abdominal pain, pelvic pain, backache, nausea and vomiting, were evaluated.
                Probability of reaching cervical ripening >8 mm Hegar dilator; evaluated at 3, 6, 9 and 12 hours after application of isosorbide dinitrate or misoprostol.
                The probabilities of induction of cervical ripening by isosorbide dinitrate and misoprostol after four repeated doses at 3-hour intervals were significantly different (P<0.001). Efficacy of therapy after 12 hours was 97% for the isosorbide dinitrate group and 70% for the misoprostol group. Systolic and diastolic blood pressures were lower after administration of isosorbide dinitrate than prostaglandin analogues. The difference in the mean systolic and diastolic blood pressure between treatment groups was greatest at 3 hours, with a difference of 7.7 mmHg (P<0.001) and 5.9 mmHg (P<0.003), respectively. The most frequent side effect associated with isosorbide dinitrate administration was headache, which occurred in 18 out of 30 patients, compared with only 5 out of 30 women in the misoprostol group [relative risk (RR) 2.41, 95% confidence interval (CI) 1.45-4.03, P<0.001). Women treated with misoprostol reported mainly pelvic pain (RR 3.24, 95% CI 1.99-5.27, P<0.001).
                Intracervical administration of 80 mg isosorbide dinitrate in women with missed abortions appears to be effective for cervical ripening prior to surgical evacuation of the uterus. Differences in the incidence of non-serious adverse events are not likely to be clinically significant. 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. To determine whether a combined therapy with isosorbide mononitrate (40mg) and misoprostol (400 microg) for pre-operative cervical ripening in the first trimester would result in improved clinical effectiveness, and fewer side effects compared with each agent used alone.
                Randomised controlled trial.
                Glasgow Royal Infirmary.
                Sixty-six primigravid women scheduled for suction termination of pregnancy.
                Women were randomly assigned to receive before surgery, per vaginam, isosorbide mononitrate 40 mg (n = 22), misoprostol 400 microg (n = 22) or both agents together [isosorbide mononitrate 40 mg and misoprostol 400 microg] (n = 22).
                1. To assess the cumulative force required to dilate the cervix to 8 mm; 2. the onset of new symptoms before termination of pregnancy.
                The cervical resistance following combination therapy with isosorbide mononitrate and misoprostol was not significantly different than following misoprostol alone [24.5N vs 18.5N; median difference (95% CI) 19N (-22 to 49)]. Pre-treatment with misoprostol used alone resulted in a lower cervical resistance than isosorbide mononitrate alone (18.5N vs 39N, P = 0.04, Mann-Whitney U test). There was no difference in the number of women remaining asymptomatic following either isosorbide mononitrate or misoprostol or combination therapy [14/22 (64%) vs 11/21 (52%) vs 11/22 (50%), Fisher's exact test].
                We have not shown any advantage of combining misoprostol with the nitric oxide donor isosorbide mononitrate compared with misoprostol alone for pre-operative cervical ripening in the first trimester. In a randomized, double-blind study, 30 healthy, nulliparous women of similar gestational age were given intracervical applications of 0.5mg PGE2, 0.05mg Sulprostone or 0.1mg Sulprostone gel in order to soften the cervix prior to curettage for first trimester termination of pregnancy. The preparations were administered 8 hours before curettage. The number of complete and incomplete abortions, ease of passage through the cervical canal, as measured by a tonometer before and 8 hours after the administration of prostaglandin, the degree of pain experienced and the quantity of analgesics required, plus the frequency of systemic side effects were all always assessed by one trialist. With regard to the rate of abortion and cervical softening, the administration of 0.1mg Sulprostone gel proved the most effective method. However, in comparison with the others, it also caused the greatest degree of pain and necessitated the greatest use of analgesics. The softening effect of the prostaglandin E2 gel was significantly less and in this group there were two cases of cervical lesion due to tenaculum laceration. The intracervical application of 0.05mg Sulprostone gel is to be recommended for pre-operative ripening of the cervix before termination of pregnancy in the first trimester, as it effectively dilates the cervix and does not cause systemic side effects or pain in the lower abdomen, enough to make treatment necessary. To examine the effectiveness and safety of outpatient vaginal administration of isosorbide mononitrate (IMN) to induce cervical ripening.
                A prospective, double-blind, placebo-controlled, randomized clinical trial was conducted on 102 singleton term pregnant women with unfavorable cervices who were randomly assigned to receive outpatient intravaginal IMN or placebo before admission for induction of labor. The main outcome variable was time from hospital admission to delivery. Secondary outcomes included fetal and maternal morbidity, labor characteristics, and incidence of cesarean delivery.
                The admission-delivery interval was 13.45+/-6.63 and 20.12+/-8.19 h (P=0.0001) for the IMN and placebo groups, respectively. Of the IMN patients 62.75% needed prostaglandins for cervical ripening versus 90.2% with placebo (P=0.002). The incidence of tachysystole was significantly lower in the IMN group (P<0.05) but there were no significant differences in cesarean delivery rate, neonatal outcomes, and incidence of hyperstimulation.
                Outpatient use of IMN resulted in shorter admission to delivery interval, and was associated with less prostaglandin use and lower incidence of uterine tachysystole.
NO donors are superior to placebo or no treatment, but inferior to prostaglandins for first-trimester cervical ripening, and associated with more side effects.