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


METHODS
Prospective study.


METHODS
Academic, tertiary care institution.


METHODS
Unselected IVF patients.


METHODS
Color-pulsed Doppler analysis of perifollicular blood flow; determination of partial pressure of oxygen (pO2), partial pressure of carbon dioxide (pCO2), and pH and VEGF, leptin and NO levels in follicular fluid.


METHODS
Fertilization and day 3 embryo morphology and cleavage.


RESULTS
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); NO3/NO2, 34.2+/-12 microM (range, 16.4-76.1 microM); 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 pO2 (r = -0.42, P = .005) and a positive correlation with follicular pCO2 (r = 0.36, P = .02). Follicular leptin levels correlated positively with VEGF levels (r = 0.46, P = .008) and with NO3/NO2 levels (r = 0.39, P =.006).


CONCLUSIONS
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.
Barroso
G
G
Jones Institute for Reproductive Medicine and Eastern Virginia Medical School, Norfolk, USA.
Barrionuevo
M
M
Rao
P
P
Graham
L
L
Danforth
D
D
Huey
S
S
Abuhamad
A
A
Oehninger
S
S
D002970:Cleavage Stage, Ovum; D004624:Embryo Transfer; D004622:Embryo, Mammalian / Q000648:ultrastructure; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005260:Female; D005307:Fertilization in Vitro; D015571:Follicular Fluid / Q000378:metabolism*; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D008222:Lymphokines / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000378:metabolism*; D011785:Quality Assurance, Health Care; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D020738:Leptin; D008222:Lymphokines; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D009569:Nitric Oxide