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15: 17P vehicle, castor oil, exerts a uterotonic effect in human myometrium in pregnancy

      Objective

      There is evidence that the clinical use of 17 Hydroxyprogesterone caproate (17P) in women at high risk of preterm delivery (PTD), results in a reduction in the rate of PTD, and a reduced risk of serious neonatal morbidity. The mechanism by which 17P exerts this effect is unknown. The possibility that the vehicle for 17HP, castor oil, exerts an independent effect on human uterine contractility, has previously been questioned, and is hitherto unknown. The aim of this study was to evaluate the potential effects on contractility of exposure of isolated human myometrial preparations, obtained during pregnancy, to castor oil.

      Study Design

      Biopsies of human myometrium were obtained at elective cesarean section (n=8). Dissected myometrial strips suspended under isometric conditions, had contractility induced, for a 30 minute period using oxytocin (0.5nM). Strips were removed from the tissue bath and inserted in Castor Oil or physiological salt solution (PSS), for a 30 minute period. Strips were then re-suspended under isometric conditions and exposed to further oxytocin challenge. Contractile integrals were expressed in relation to the first challenge, and compared between study and control groups.

      Results

      Strips exposed to castor oil demonstrated increased contractile activity elicited by oxytocin after the castor oil exposure (165.53%± 17.03%, n=8, P=0.004), in comparison to that measured prior to its exposure. For strips exposed to PSS only, the second oxytocin challenge reduced contractile activity (72.57%±7.48%, n=8, P=0.003). Comparison of the contractile activity, between castor oil and PSS exposed strips, revealed a significant increase in contractile activity for those exposed to castor oil (p<0.001).

      Conclusion

      These findings indicate that exposure of human myometrial preparations to castor oil results in an enhanced state of contractility in this in vitro model, in comparison to control experiments. The use of castor oil as placebo for 17P studies may be linked to increased contractility, and higher preterm delivery rates, among the placebo arm.