Vascular endothelial growth factor, nitric oxide, and leptin follicular fluid levels correlate negatively with embryo quality in IVF patients

Abstract

Objective(s): To measure vascular endothelial growth factor (VEGF), nitric oxide (NO) and leptin levels in individual ovarian follicles and to examine their relationships with perifollicular blood flow, follicular metabolic indices, and the developmental potential of the corresponding oocyte and embryo. Design: Prospective study. Setting: Academic, tertiary care institution. Patient(s): Unselected IVF patients. Intervention(s): Color-pulsed Doppler analysis of perifollicular blood flow; determination of partial pressure of oxygen (pO 2), partial pressure of carbon dioxide (pCO 2), and pH and VEGF, leptin and NO levels in follicular fluid. Main Outcome Measure(s): Fertilization and day 3 embryo morphology and cleavage. Result(s): Fifty-five follicular fluid samples from 16 patients were studied. Mean follicular fluid levels were as follows: VEGF, 1,046 ± 863.7 pg/mL (range, <63–3,332.7 pg/mL); NO 3/NO 2, 34.2 ± 12 μM (range, 16.4–76.1 μM); and leptin, 20.1 ± 12.1 ng/mL (range, 3.3–52.2 ng/mL). Vascular endothelial growth factor had a negative correlation with embryo morphology ( r = −0.28, P=.01). Leptin demonstrated a negative correlation with follicular pO 2 ( r = −0.42, P=.005) and a positive correlation with follicular pCO 2 ( r = 0.36, P=.02). Follicular leptin levels correlated positively with VEGF levels ( r = 0.46, P=.008) and with NO 3/NO 2 levels ( r = 0.39, P=.006). Conclusion(s): Vascular endothelial growth factor, NO and leptin appear to be markers of follicular hypoxia and suboptimal embryo development. Whether fluctuations of these regulatory factors determine or reflect changes in the follicular microenvironment affecting oocyte developmental potential remains to be elucidated.