PROJECT ABSTRACT Nearly a third of pregnant patients in the US undergo induction of labor with oxytocin. Despite it being a commonly used medication on Labor & Delivery units around the world, we have a limited understanding of how to dose oxytocin effectively during labor induction as evidenced by its variable therapeutic index and high failure rate of almost 30%. Exposure to high doses of oxytocin for long periods of time is associated with maternal and neonatal morbidity. When there is abnormal labor progression during an induction, the current standard of care is to titrate oxytocin to reach adequate contractions, defined as Montevideo units (MVU) >200 assessed via an intrauterine pressure catheter (IUPC). The theoretic pathway for oxytocin administration is that it increases maternal serum oxytocin, activating the oxytocin receptor (OXTR) and generating adequate contractions. However, we lack mechanistic understanding of how this pathway is affected by oxytocin dosing and our current definition for adequate contractility is flawed as recent data suggest that MVU is an imprecise predictor of induction success. In this proposal, we test the hypothesis that our strategy for assessing contraction adequacy can be improved by using contraction parameters other than MVU, such as peak pressure, duration, frequency, and area under the curve. We will also test the hypothesis that contraction adequacy is associated with maternal serum oxytocin concentration and that myometrial OXTR function is affected by dose and duration of oxytocin. To test these hypotheses, we propose a prospective cohort study of universal IUPC placement in 605 patients undergoing labor induction to develop a prediction model for completion of the first stage of labor using contraction measures and accounting for oxytocin response (Aim 1). We will collect serial maternal serum in a subset of 84 patients from Aim 1 to correlate serum oxytocin concentrations with contraction measures (Aim 2). We will also assess myometrial OXTR function, expression, and localization as it relates to dose and duration of oxytocin exposure (Aim 3). The results of this clinical and translational study will provide mechanistic understanding of how pregnant patients physiologically and functionally respond to exogenous oxytocin so that we may ultimately titrate oxytocin to optimize labor induction success and reduce maternal and fetal morbidity.