Nitric oxide (NO) plays a fundamental role in cervical ripening and it is synthesized in the human cervix. We studied the effect of the dinoprostone on cervical NO release in pregnant women, and we investigated the relationship between cervical NO metabolites, cervical length, and Bishop score. Seventy-seven women underwent induction of labor at ≤37 weeks of gestation, due to post-term pregnancy (23.8%), oligohydramnios (36.3) or preeclampsia (29.9%). Cervicalfluid samples for NO metabolites (NOx), Bishop score, and cervical length were assessed immediately before (time 0 [TO]) and 6 hours after (T6) the local application of dinoprostone, a commercially available prostaglandin E2 (PGE2) analog. The mean patients’ age was 34 ± 3.2 years, mean gestational age at enrollment was 284 ± 9.2 days, and nulliparous represented 31.2%) of the study population. At time 0, Bishop score was less than 4 in 74% (57/77) of the subjects, mean cervical length was 28.6 ± 5.8 mm, mean NOx concentration was 208.6 ± 103.8 μM/mL; 6 hours later, at T6, the mean cervical length decreased to 19.5 ± 8.8 mm, and the mean NOx concentration increased up to 316.7 ± 240.9 μM/mL. Data were unaffected by parity or by regular uterine contraction patterns. A statistically significant positive correlation was found between changes in cervical NOx levels and Bishop score modification (P <.01; r =.494), as well as between the modification of NO metabolites concentration and cervical shortening (P <.01; r =.307). Prostaglandin (PG)-induced cervical ripening is associated with local NO release. NO plays an active role in cervical remodeling since it positively correlates with both cervical shortening and Bishop score increase. NO oxide and PG are the two pathways that, cross activating each other, trigger the cascade of events responsible of cervical ripening.

The aim of this study was to compare the clinical effects of preinduction cervical ripening by using two ways of dinoprostone administration. In a prospective, open-label trial, 144 consecutive nulliparous women with a Bishop score <4 who required induction of labour at term were randomised to receive dinoprostone via either a vaginal insert (10 mg over 12 h) or a cervical gel (0.5 mg, twice in 12 h). If labour did not start by 24 h after this preinduction, patients received 2 mg vaginal dinoprostone gel followed 6 h later by oxytocin infusion. The main outcome measure was the rate of caesarean sections (CS). Secondary measures were: changes in Bishop score at 6 h and 12 h, delivery within 12 h and 24 h, need for oxytocin for induction, failure of induction (delivery after >48 h), need for pharmacological interventions to manage tachysystole/hyperstimulation, length of stay in hospital. The CS rate was lower in the vaginal insert group (22.9%) than in the cervical gel group (34.3%), though the difference did not reach statistical significant difference (P = 0.13). The indications for CS overlapped between the groups. The rate of vaginal delivery within 12 h and 24 h was similar, as was the rate of failure of induction. More women in the gel group (41.4% versus 24.3%) required the use of oxytocin (OR = 2.21; 95% CI = 1.07-4.55). Tachysystole or hyperstimulation in the vaginal insert group (7) was twice that with cervical gel (4). Four women in the vaginal insert group and three in the cervical gel group reported infectious complications. A long stay in hospital (>4 days) was less frequent with vaginal inserts (21.4 versus 38.6%; OR = 0.43, 95% CI = 0.19-0.97). The more challenging preinductions of labour at term are associated with increased obstetric interventions such as a high CS rate and a more frequent requirement for oxytocin inductions. In terms of success and failure, vaginal inserts releasing dinoprostone do not differ from dinoprostone given by the traditional cervical route. However, the use of vaginal inserts reduces the need for obstetric interventions and allows shorter periods in hospital.