Role of vascular endothelial cell growth factor in ovarian hyperstimulation syndrome

Controlled ovarian hyperstimulation with gonadotropins is followed by Ovari an Hyperstimulation Syndrome (OHSS) in some women. An unidentified capillar y permeability factor from the ovary has been implicated, and vascular endo thelial cell growth/permeability factor (VEGF) is a candidate protein, Foll icular fluids (FF) from 80 women who received hormonal induction for infert ility were studied, FFs were grouped according to oocyte production, from g roup I (0-7 oocytes) through group IV (23-31 oocytes), Group IV was compris ed of four women with the most severe symptoms of OHSS. Endothelial cell (E C) permeability induced by the individual FF was highly correlated to oocyt es produced (r(2) = 0.73, P < 0.001), Group IV FF stimulated a 63+/-4% grea ter permeability than FF from group I patients (P < 0.01), reversed 98% by anti-VEGF antibody, Group TV fluids contained the VEGF165 isoform and signi ficantly greater concentrations of VEGF as compared with group I (1,105+/-8 7 pg/ml vs, 353+/-28 pg/ml, P < 0.05). Significant cytoskeletal rearrangeme nt of F-actin into stress fibers and a destruction of ZO-1 tight junction p rotein alignment was caused by group IV FF, mediated in part by nitric oxid e. These mechanisms, which lead to increased EC permeability, were reversed by the VEGF antibody, Our results indicate Chat VEGF is the FF factor resp onsible far increased vascular permeability, thereby contributing to the pa thogenesis of OHSS.