Human follicle fluid vascular endothelial growth factor concentrations are correlated with luteinization in spontaneously developing follicles

Vascular endothelial growth factor (VEGF) is a cytokine that inducesangiogenesis. Angiogenesis is a prominent histologic component of theluteinization process. Luteinization is also characterized by granulosacell progesterone secretion in response to the luteinizing hormone (LH)surge. Local VEGF production in human pre-ovulatory follicles, induced byLH, was postulated to be a luteinization mediator in women. To investigatethis hypothesis, serum and fluid from the dominant follicle of 31 healthyregularly cycling multiparous women undergoing laparoscopic sterilizationwere obtained. VEGF was measured by enzyme- linked immunosorbent assay, andLH and progesterone were measured by radioimmunoassay. Follicle aspirationwas performed at a median of 13 days from the last menstrual period (range11-17 days). The median pre- ovulatory follicle diameter was 16 mm (range11-23 mm). Follicle fluid VEGF concentrations (mean 6900 pg/ml, range1200-17 100 pg/ml) were correlated positively with follicle fluidprogesterone concentrations (mean 10 176 nmol/l, range 636-66780 nmol/l,r=0.62, P=0.002). This correlation was even tighter (r=0.87, P < 0.0001)when only samples from the 22 women in the earliest stages of follicleluteinization were considered. In these women serum LH concentrations werealso correlated with follicle fluid VEGF concentrations (r=0.51, P=0.02).Our findings demonstrate the close dynamic relationship between VEGFproduction and early luteinization in human follicles during normalnon-stimulated cycles.