Abstract
The in vitro and in vivo release characteristics of a controlled-release hydrogel prostaglandin polymer pessary were compared during an eight hour observation period in 24 patients using a pessary designed to release PGE2 1.0mg/hr. and in 25 patients using a pessary designed to release PGE2 0.6mg/hr. PGE2 release rate in vitro followed a linear and quadratic pattern while release rate in vivo was described by a quadratic pattern. The differences were predominately due to less hydrogel swelling of the pessary in vivo. Pre-soaking the polymer pessary in saline prior to vaginal insertion to increase hydrogel swelling did not influence release characteristics in vivo, but PGE2 release was increased by amniotomy. No differences in PGE2 release rate or absorption across the vaginal epithelium were demonstrated for polymer pessaries of different release profiles and PGE2 release was not related to the degree of cervical ripening. During the course of these studies technical difficulty was experienced with pessary removal. Clinical benefits in cervical ripening were assessed by treating 33 primiparae with an unfavourable cervix (Bishop score < 6) with a polymer pessary designed to release PGE2 0.6mg/hr. on the evening before planned induction. Controlled release of PGE2 was not associated with an exclusively cervical effect as 52% of those treated commenced labour during the ripening process. Those who required a second treatment prior to the onset of labour were randomly allocated to receive an amniotomy and oxytocin titration or a further polymer pessary. The second treatment to delivery interval was shorter for those receiving an amniotomy and oxytocin titration and seven out of eight patients who received a second polymer pessary later required oxytocin augmentation. These results suggest that there is little benefit to be gained from repeated prostaglandin treatments. There was a 3.7% incidence of excessive uterine activity associated with the use of the polymer pessary in studies conducted in this thesis. In all cases removal of the pessary resulted in a return to normal uterine activity. The results of this research suggest that some cases of rapid labour could be avoided by removal of the pessary following amniotomy or spontaneous rupture of membranes but an adequate retrieval mechanism is necessary. Prostaglandin-induced cervical ripening under tocolytic cover was investigated in a double blind trial with 60 nulliparae requiring induction of labour whose modified Bishop score was < 6. Women received either 8mg salbutamol or an identical placebo orally, 30 minutes before vaginal administration of 2mg prostaglandin E2 gel. Women in the salbutamol group experienced less uterine activity over the subsequent 12 hours compared with those given placebo and fewer (35%) commenced labour compared with the placebo group (62%). However the change in cervical score was significantly less in the salbutamol group (mean 3.0 sd 3.1) than the placebo group (mean 5.8, sd 3.2) and the prostaglandin to delivery interval in the salbutamol group (mean 26.1 h, sd 6.49 h) was significantly longer than in the placebo group (mean 19.3 h sd 7.95 h). The first stage of labour lasted > 10 h in 11 women in the salbutamol group, compared with 5 in the placebo group. Side effects attributable to salbutamol occurred in 10% of the treated women but in none of their fetuses and fetal outcome was satisfactory and similar in both groups. These findings suggest that salbutamol can suppress prostaglandin-induced uterine activity during cervical ripening which could be an advantage in induction of labour where a planned delivery is preferred. However the poorer outcome of labour in salbutamol treated women mitigates against this approach.