FOLLICULAR-FLUID VASCULAR ENDOTHELIAL GROWTH-FACTOR CONCENTRATIONS ARE ELEVATED IN WOMEN OF ADVANCED REPRODUCTIVE AGE UNDERGOING OVULATION INDUCTION

Objective(s): To determine whether follicular fluid (FF) from women of advanced reproductive age had a relative deficiency of the angiogenic cytokine vascular endothelial growth factor/vascular permeability fac tor. Furthermore, we sought to determine whether luteinized granulosa cells secrete vascular endothelial growth factor/vascular permeability factor in response to hypoxia. Design: Retrospective cohort study. Se tting: University teaching hospital. Patients: Women undergoing follic ular aspiration after superovulation in preparation for IVF-ET. Women of advanced reproductive age consisted of 21 women greater than or equ al to 38 years old (range, 38 to 46 years); 15 subjects less than or e qual to 30 years served as the control population. Intervention(s): Gr anulosa cells and FF were collected by transvaginal aspiration 35 hour s after hCG. Granulosa cells from two women were cultured for 24 and 4 8 hours in M199 + 10% fetal bovine serum in 1% O-2-5% CO2-94% N-2 (hyp oxic) or 95% air-5% CO2 (normoxic) without or with 0.1 mol/L cobalt ch loride. Main Outcome Measure(s): Pooled FF vascular endothelial growth factor/vascular permeability factor concentrations and media vascular endothelial growth factor/vascular permeability factor accumulation a t 24 and 48 hours were determined. Result(s): Follicular fluid vascula r endothelial growth factor/vascular permeability factor concentration s were higher in advanced reproductive age women compared with younger women (3,735 +/- 2,155 versus 2,205 +/- 952 pg/mL, mean +/- SD). Accu mulation of vascular endothelial growth factor/vascular permeability f actor at 24 and 48 hours was 391 +/- 54 and 744 +/- 2 pg/mL in media m aintained in 5% CO2 and air. Cobalt chloride induced a marked increase in vascular endothelial growth factor/vascular permeability factor (2 ,008 +/- 52 pg/mL at 24 hours and 3,630 +/- 519 pg/mL at 48 hours). An intermediate but significant increase in vascular endothelial growth factor/vascular permeability factor (733 +/- 35 pg/mL at 24 hours and 2,675 +/- 864 pg/mL at 48 hours) was observed with 1% O-2 compared wit h normoxic controls. Conclusion(s): After hMG and hCG administration t he FF from women of advanced reproductive age showed increased vascula r endothelial growth factor/vascular permeability factor concentration s compared with younger women. Increased vascular endothelial growth f actor/vascular permeability factor concentrations could be consistent with a hypoxic environment within follicles of older women. (C) 1997 b y American Society for Reproductive Medicine.