Targeting the vascular endothelial growth factor system to prevent ovarian hyperstimulation syndrome

VEGF antagonist for the prevention of ovarian hyperstimulation syndrome: Current status

“…Among the selected preventive methods, discontinuing gonadotropin therapy (coasting), withholding human chorionic gonadotropin (hCG) and intravenous albumin administration were by far the most popular choices. 4 Embryo Cryopreservation, another strategy, though useful for avoiding the late form of this syndrome due to endogenous hCG production, does not prevent early OHSS development due to exogenous hCG administration. So the search for an ideal pharmacotherapy for the prevention of this potentially deadly complication remained.…”

“…With the better understanding of its pathophysiology and the pivotal role of VEGF implicated in the causation of OHSS, Cabergoline (Cb2) a dopamine agonist with its anti VEGF activity has been demonstrated to be an effective and safe drug, for the prevention of this disorder. 4 The aim of this article is to briefly review the pathogenesis of OHSS, concentrating mainly on the causative role of vascular endothelial growth factor and the rationale for the use of cabergoline, for the prevention and treatment of this syndrome due to its role as a VEGF antagonist.…”

Prevention and management of ovarian hyperstimulation syndrome

“…The dopamine-receptor agonist, cabergoline, partially inhibits the ovarian VEGF receptor 2 (VEGFR-2) through a decrease in its phosphorylation levels; such inhibition, in turn, decreases the VEGFR-2-induced vascular permeability, without affecting luteal angiogenesis [5]. Several trials have now demonstrated that cabergoline administration (0.5mg/day) from the day of hCG administration in high risk women can reduce the incidence and severity of early OHSS in GnRH agonist IVF cycles, while not compromising pregnancy rates [27].…”

“…This facilitates a shift in fluid from the intra-to the extra-vascular compartment and the induction of a state of hypovolaemic hyponatremia with haemoconcentration. Although various systemic and local vasoactive mediators contribute to the pathogenesis of OHSS, vascular endothelial growth factor (VEGF) appears to be critical to the development of the condition [5]. VEGF is involved in corpus follicular growth, luteum function, angiogenesis, and vascular endothelial stimulation.…”

“…In response to human chorionic gonadotrophin (hCG), VEGF mediates the vascular permeability of OHSS the cardinal feature of the syndrome [5]. It is this induction by hCG that ensures OHSS is primarily self-limiting in those who are not pregnant but also why it may persist into the first trimester due to ongoing stimulation of the ovaries.…”