Vascular endothelial growth factor production by circulating immune cells is elevated in ovarian hyperstimulation syndrome

Sir, We read with interest the study by Kosaka et al. (2007), on vascular endothelial growth factor (VEGF) production by circulating immune cells in ovarian hyperstimulation syndrome (OHSS) patients. In this study, they demonstrated an elevated basal VEGF production by peripheral blood mononuclear cells of OHSS patients and concluded that their study provides ‘new evidence’ to suggest that circulating immune cells are involved in the pathogenesis of OHSS. Surprisingly, our 10 years of research on controlled ovarian hyperstimulation, OHSS and systemic inflammation went unnoticed (Orvieto, 2004). In our studies, we have suggested that the hyperstimulated human ovaries produce and secrete factor/s, which cause OHSS, probably by activating a systemic inflammatory response. This notion was based on the similarity of vascular leak syndrome to the clinical picture of OHSS (Orvieto et al., 1995), the significantly higher cytokines' concentration in the follicular fluid at the time of oocyte retrieval in patients in whom OHSS subsequently developed (Orvieto and Ben Rafael, 1998), and the neutrophil and endothelial activations following hCG administration (Orvieto et al., 1999, 2000, 2001).