URINARY VASCULAR ENDOTHELIAL GROWTH-FACTOR CONCENTRATIONS IN WOMEN UNDERGOING GONADOTROPIN TREATMENT

A recently identified cytokine, vascular endothelial growth factor (VE GF, vascular permeability factor) has been implicated in ovarian hyper stimulation syndrome in women undergoing assisted reproduction. We pos tulate that circulating and urinary VEGF values increase following gon adotrophin stimulation, in parallel with the increased ovarian vascula rity. A VEGF radioimmunoassay was developed using iodinated VEGF as tr acer, a goat anti-VEGF serum as antiserum and recombinant human VEGF a s standard. The specificity of the assay was confirmed by comparing th e reverse phase high-performance liquid chromatography (HPLC) pattern of VEGF immunoactivity in urine and urine spiked with recombinant VEGF . Urine was concentrated 5-fold prior to measurement by the radioimmun oassay. VEGF:creatinine ratios in early morning urine samples were use d to monitor daily urinary VEGF concentrations based on its high corre lation (r = 0.77, P < 0.001) with VEGF concentrations in 24 h urine co llections. No diurnal variation in VEGF:creatinine ratios was detected . VEGF:creatinine ratios were determined daily from nine women undergo ing gonadotrophin-releasing hormone (GnRH) agonist/gonadotrophin treat ment. In a further 16 women, early morning urine samples were collecte d in the peri-ovulatory period. A significant increase (P < 0.005, n = 25) was observed in VEGF:creatinine ratios following human chorionic gonadotrophin (HCG) administration. VEGF:creatinine ratios correlated poorly (r < 0.34) with plasma oestradiol, follicle number and size. It is concluded that urinary VEGF/creatinine ratios increase following H CG stimulation.