Investigating the Effect of Pulsatile Administration of Oxytocin on the Desensitization of Human Myometrium In-vitro
Condition: Postpartum Hemorrhage
MeSH terms: Postpartum Hemorrhage; Hemorrhage
Study type: Interventional

Summary: 
      Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity and mortality worldwide
      and is caused most commonly by poor uterine muscle (myometrium) tone after delivery. The
      first line agent used in the prevention and treatment of PPH is oxytocin.

      Women who require augmentation of labor with intravenous oxytocin because of inadequate labor
      progression have been shown to be at increased risk of PPH. Typically, for augmentation of
      labor, oxytocin is used as a continuous infusion, with no consensus on the initial dose, its
      increments or maximal limit. High concentration continuous oxytocin infusions are not without
      theirs risks, which include hyperstimulation, fetal distress, as well as uterine rupture.

      Studies have shown the clinical benefits of pulsatile oxytocin delivery for labor induction
      and augmentation with regards to requirement of less total oxytocin, similar uterine
      contractility and similar rates of caesarean delivery when used for labor induction and
      augmentation. However, the rate of PPH as a primary outcome measure has not been
      investigated. Therefore we currently do not know the effect of pulsatile oxytocin delivery on
      the rate of PPH.

      The investigators hypothesize that the effect of myometrial desensitization following
      pulsatile oxytocin exposure would be lower when compared to continuous oxytocin exposure.
      These results will help in establishing whether myometrial contractility and sensitivity to
      oxytocin can be better preserved by delivery of pulsatile oxytocin, rather than continuous
      oxytocin for labor induction and augmentation, and thereby result in less PPH.
    

Detailed description: 
      Typically labor can be augmented by exposure to high levels of continuous oxytocin, for
      prolonged periods. The increased incidence of uterine atony and PPH following exogenous
      oxytocin administration during labor augmentation is related to myometrial oxytocin receptor
      desensitization to oxytocin.

      Human clinical trials have shown the benefits of pulsatile oxytocin administration for labor
      induction and augmentation, which include requirement of less total oxytocin, similar uterine
      contractility and similar rates of cesarean delivery. However, the outcome of the effect on
      PPH is not currently known.

      Characterization of the effect of pulsatile oxytocin on the desensitization of myometrium
      when compared to the effect of continuous oxytocin, may provide guidance for the delivery of
      pulsatile oxytocin for labor induction and augmentation to protect against the otherwise
      higher risk of PPH. Furthermore, the delivery of pulsatile oxytocin may be considered in
      subgroups who are already at higher risk of PPH, and require labor augmentation.

      The investigators' previously validated in-vitro model provides a solid foundation for the
      study of myometrial contractility under controlled conditions, without any confounders that
      could be encountered in clinical settings.

      The results of this study will provide insight into the level of desensitization of human
      myometrium following exposure to pulsatile oxytocin. Based on oxytocin dose-response curves
      after pretreatment to continuous oxytocin and pretreatment to pulsatile oxytocin, we will be
      able to determine the extent of desensitized myometrium following each delivery method.
    

Intervention name(s): Oxytocin
Intervention type(s): Drug
Intervention description(s): Oxytocin, 100 micromolar solution
Other intervention name(s): pitocin
Intervention MeSH terms: Oxytocin
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Uterine contraction; Oxytocin desensitization