NO donors are superior to placebo or no treatment, but inferior to prostaglandins for first-trimester cervical ripening, and associated with more side effects.
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.
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.