Recovery of Oxytocin Responsiveness in Pregnant Human Myometrial Explants After Oxytocin-Induced Desensitization: an In-vitro Analysis of Oxytocin Receptor Expression and Signaling

• Status: Recruiting
• Trial end date: 2021-06-01
• Target enrollment: 0
• Participant gender: Female

Summary

Postpartum hemorrhage (PPH) is a leading cause of maternal mortality and morbidity worldwide, and is caused most commonly by poor uterine muscle contraction after delivery of the baby and placenta. The first line agent used in the prevention and treatment of PPH is oxytocin, which acts by binding with the oxytocin receptor (OTR) found on myometrial cells to cause uterine contraction.

Oxytocin is also used for the augmentation of labor when spontaneous labor has been deemed ineffective. It is administered intravenously at progressively higher doses, until effective contractions are achieved and vaginal delivery results. However, if augmentation is determined to have failed, a Cesarean delivery (CD) is performed.

One of the potential problems with oxytocin use during delivery is that it loses its effectiveness if the uterus has previously been pre-exposed to its high doses and/or for a prolonged duration during labor. This phenomenon is termed OTR desensitization, and can result in the attenuation of myometrial contractility induced by subsequent oxytocin administration, as well as PPH due to poor uterine tone. Furthermore, oxytocin can produce potentially fatal maternal hemodynamic adverse effects when administered at high doses, so it is advantageous to be able to use as low a dose as possible to obtain good uterine muscle tone.

The objective of this study is to get a better understanding of the signaling pathways governing desensitization, resensitization and contractility in pregnant human myometrium. The investigators wish to investigate the effects of increasing recovery period on the expression patterns of the OTR and its signaling pathways in desensitized pregnant human myometrium.

This study will help shed light on the molecular mechanisms responsible for desensitization and oxytocin-induced myometrial contractility, and will provide some insight into potential therapeutic targets to reduce the incidence of PPH and complications associated with using increasing concentrations of oxytocin.

The hypothesis is that the expression and phosphorylation patterns of the OTR and downstream proteins will be altered in desensitized myometrium, and that these patterns will change with increasing rest periods and re-exposure to oxytocin.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
• Treatments: Oxytocin

Criteria

Inclusion Criteria:

• Patients who give written consent to participate in this study

• Patients with gestational age 37-41 weeks

• Non-laboring patients, not exposed to exogenous oxytocin

• Patients requiring primary Cesarean delivery or first repeat Cesarean delivery

Exclusion Criteria:

• Patients who refuse to give written informed consent

• Patients who require general anesthesia

• Patients who had previous uterine surgery or more than one previous Cesarean delivery

• Patients with any condition predisposing to uterine atony and postpartum hemorrhage, such as abnormal placentation, multiple gestation, preeclampsia, macrosomia, polyhydramnios, uterine fibroids, bleeding diathesis, chorioamnionitis, or a previous history of postpartum bleeding

• Emergency Cesarean section in labor

• Patients on medications that could affect myometrial contractility, such as nifedipine, labetolol or magnesium sulphate.