Abstract
Background17alpha-hydroxyprogesterone caproate (17P) administration reportedly improves outcome for women with a previous spontaneous preterm delivery. This study, using in vitro strips of human uterine smooth muscle, aimed to investigate the direct non-genomic effects of 17P on spontaneous and induced contractions in tissues obtained during pregnancy, and in the non-pregnant state.MethodsBiopsies of human myometrium were obtained at elective cesarean section, and from hysterectomy specimens, and dissected strips suspended for isometric recordings. The effects of 17P (1 nmol/L -10 micro mol/L) on spontaneous and agonist-induced (oxytocin 0.5 nmol/L for pregnant, phenylephrine 10 μmol/L for non-pregnant) contractions were measured. Integrals of contractile activity, including the mean maximal inhibition values (MMI) observed at the maximal concentration, were compared with those from simultaneously run control strips.ResultsThere was no significant direct effect exerted by 17P on pregnant or non-pregnant human myometrial contractility. The MMI ± SEM for spontaneous contractions in pregnant myometrium was 4.9% ± 7.2 (n = 6; P = 0.309) and for oxytocin-induced contractions was 2.2% ± 1.3 (n = 6; P = 0.128). For non-pregnant myometrium, the MMI ± SEM for spontaneous contractions was 8.8% ± 11.0 (n = 6; P = 0.121) and for phenylephrine induced contractions was -7.9% ± 6.5 (n = 6; P = 0.966).ConclusionsThe putative benefits of 17P for preterm labor prevention are not achieved, even partially, by a direct utero-relaxant effect. These findings outline the possibility that genomic effects of 17P, achieved over long periods of administration, are required for its reported therapeutic benefits.
Highlights
Preterm delivery constitutes a major problem in obstetric practice because of the large associated contribution to perinatal mortality and morbidity [1,2]
It has been recently reported that weekly injections of 17-alpha-hydroxyprogesterone caproate (17P), in women who have had a previous spontaneous preterm delivery, significantly reduces the risk of preterm delivery before 37, 35 and 32 week's gestation [4]
The aims of this study were focused on the latter mechanism i.e. to investigate the direct effects of 17P on contractions of isolated human myometrium, both spontaneous and agonist-induced, in tissue obtained during pregnancy and in the non-pregnant state
Summary
Preterm delivery constitutes a major problem in obstetric practice because of the large associated contribution to perinatal mortality and morbidity [1,2]. Reproductive Biology and Endocrinology 2004, 2:80 http://www.rbej.com/content/2/1/80 a delay in the interval to delivery, of time periods up to a week, they did not reduce the incidence of preterm delivery at different gestational ages [3] Their use, in comparison to placebo, was not associated with any benefit in terms of objective measures of neonatal wellbeing or morbidity. While evidence for the use of progestational compounds for prevention of preterm delivery, and recurrent miscarriage, has been conflicting [5,6,7], meta-analysis restricted to trials of 17P has suggested a significant reduction in the preterm delivery rate This reported benefit of 17P, while being a welcome development in therapeutic strategies for preterm labor, has raised many questions in relation to whether the same benefit would apply to low risk groups, and the potential effects, if any, from the castor-oil injection of placebo used [8,9]. The aims of this study were focused on the latter mechanism i.e. to investigate the direct effects of 17P on contractions of isolated human myometrium, both spontaneous and agonist-induced, in tissue obtained during pregnancy and in the non-pregnant state
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