Ci. Friedman et al., FOLLICULAR-FLUID VASCULAR ENDOTHELIAL GROWTH-FACTOR CONCENTRATIONS ARE ELEVATED IN WOMEN OF ADVANCED REPRODUCTIVE AGE UNDERGOING OVULATION INDUCTION, Fertility and sterility, 68(4), 1997, pp. 607-612
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.