Oxytocin and vasopressin V(1A) receptors as new therapeutic targets in assisted reproduction.
Embryo transfer, the final stage of IVF/embryo transfer (IVF/ET) treatment, independently influences treatment outcome.Successful embryo implantation following embryo transfer, among other factors, is also dependant on uterine receptivity.Uterine contractile activity may adversely affect the implantation. Although increased contractions have been found in approximately 30% of patients undergoing embryo transfer, to date it has not been a subject to any diagnosis or therapy. Pharmacological tocolytics may be expected to improve pregnancy rates; however, targeting uterine adrenergic receptors, calcium channels or prostaglandin synthesis has since proven ineffective. The novel class of drugs which could be the most useful in this indication is oxytocin antagonists. In animal models, oxytocin significantly reduced embryo implantation rates, and this was reversed by an oxytocin antagonist. In humans, peptidyl oxytocin and mixed vasopressin V1A/oxytocin antagonists have been found to significantly reduce uterine contractions in egg donors undergoing mock embryo transfer. It has further been demonstrated that the vasopressin V1A/oxytocin receptor antagonist atosiban can improve pregnancy success in patients with recurrent IVF failures. This article reviews the uterine oxytocin/vasopressin V1A receptor systems and their potential influence on embryo implantation. It is suggested that the clinical application of oxytocin antagonists might improve results of IVF/ET treatment.
Centre for Reproductive Medicine London (CRM London), Park Lorne, 111 Park Road, London NW8 7JL, United Kingdom. piotr.pierzynski@gmail.com
Piotr
P
Pierzynski
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D010064:Embryo Implantation / Q000187:drug effects; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D007246:Infertility / Q000188:drug therapy; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use; D010121:Oxytocin / Q000037:antagonists & inhibitors / Q000378:metabolism; D011247:Pregnancy; D011759:Pyrrolidines / Q000494:pharmacology / Q000627:therapeutic use; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors*; D027724:Reproductive Techniques, Assisted; D015149:Tocolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014590:Uterine Contraction / Q000187:drug effects; D014667:Vasopressins / Q000037:antagonists & inhibitors / Q000378:metabolism; D014668:Vasotocin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
D065092:Antidiuretic Hormone Receptor Antagonists; D007211:Indoles; D009842:Oligopeptides; D011759:Pyrrolidines; D018045:Receptors, Oxytocin; D015149:Tocolytic Agents; C047046:atosiban; D014667:Vasopressins; D010121:Oxytocin; C082134:relcovaptan; C517339:barusiban; D014668:Vasotocin