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In-vitro intermittent exposure to oxytocin preserves myometrial responsiveness to oxytocin
Abstract Number: F-10
Abstract Type: Original Research
Introduction: Postpartum hemorrhage (PPH) secondary to uterine atony is a leading cause of maternal morbidity. Prolonged continuous infusion of oxytocin during labor may induce oxytocin receptor desensitization, which attenuates the response of the myometrium to further oxytocin. The literature comparing pulsatile (intermittent) vs continuous oxytocin administration for labor augmentation is inconsistent with regards to maternal outcomes.[2,3] Furthermore, PPH has not been investigated as a primary outcome. We aimed to determine the effect of intermittent vs continuous oxytocin exposure on the extent of myometrial desensitization.
Methods: Following written informed consent from patients undergoing elective cesarean deliveries, this in-vitro study was undertaken using myometrium dissected into 6 strips. Each strip was mounted in a single organ bath with physiological salt solution (PSS) under homeostatic conditions and allocated to one of 3 groups 1) control (no pretreatment); 2) continuous (oxytocin 10-5M pretreatment for 2h ); or 3) intermittent (pretreatment with oxytocin 10-5M and PSS alternating every 15min for 2h). After pretreatment, a dose-response to oxytocin 10-10M to 10-5M was performed and contractile parameters measured. The primary outcome was motility index (MI, frequency x amplitude).
Results: Eighteen women were recruited and 86 successful experiments performed (control n=29, continuous n=28, intermittent n=29). The mean (SE) MI (√g.contractions/10min) in the control, continuous and intermittent groups were 2.34 (0.09), 1.78 (0.09) and 2.13 (0.11), respectively (Fig 1). The MI was significantly reduced in the continuous group when compared to the control (p<0.01) and intermittent group (p=0.01). There were no significant differences in MI in the intermittent vs control group (p=0.17).
Discussion: Human myometrium remains more responsive to subsequent oxytocin following intermittent exposure to oxytocin, compared to continuous exposure. Intermittent exposure to oxytocin may preserve oxytocin responsiveness by minimizing oxytocin receptor desensitization, or by facilitating receptor resensitization. These results suggest that pulsatile (intermittent) oxytocin administration for labor augmentation may prevent uterine atony and PPH. Further clinical trials should be considered.
References: 1) AJOG 2003;188:497-502; 2) Clin Exp Obstet Gynecol 2000;27:21-3; 3) AJOG 2012; 206:230.e1-8; 4) Anesthesiology 2013;119:552-61