| Summary: | The importance of the appropriate timing of parturition is highlighted by the fact that preterm labour accounts for 85% of the deaths of normally formed babies. In addition, there are clinical situations where induction of labour is required. Attempts to reduce the incidence of preterm labour and facilitate induction require an understanding of the normal processes of labour at term. In this thesis the physiology of parturition is considered, with emphasis on prostaglandin biosynthesis and metabolism, and the regulation thereof, processes which are thought to be pivotal in the mechanism of labour. The physical and biochemical changes associated with cervical ripening are discussed, as are mediators of this process. Finally, the current understanding of ovine parturition and potential similarities with humans is reviewed. The laboratory studies described employ the techniques of explant and cell culture of fetal membranes, namely amnion and chorion, to investigate firstly the changes in synthesis and metabolism of prostaglandins E2 and F2a (PGE2, PGF2a) that occur within these tissues in association with labour. Prostaglandin production by amnion is increased without any effect on metabolism by chorion. The effect of amniotic fluid on prostaglandin synthesis and metabolism in cell culture was then explored, and, having demonstrated that amniotic fluid from labouring women stimulates PGE2 and PGF2a production, the mechanisms controlling the response to amniotic fluid were investigated, and found to be dependent on new protein synthesis and protein kinase C. In the clinical situation pharmacological ripening of the cervix was studied in two randomised, placebo-controlled clinical trials. The efficacy of recombinant human relaxin and mifepristone (RU 486) was investigated in women with an unfavourable cervix, modified Bishop score < 4, in whom induction of labour was indicated. Vaginal administration of relaxin (1,2 and 4 mg) was without effect on cervical ripening. The first part of a dose finding study with mifepristone demonstrated that a dose of 50 mg may have some preparatory effect on the cervix with regard to ripening, but that a higher dose is required for successful induction of labour.
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