Poor responder-high responder: the importance of soluble vascular endothelial growth factor receptor 1 in ovarian stimulation protocols.
This study was designed to detect vascular endothelial growth factor (VEGF) and its soluble receptor (sVEGFR-1) in follicular fluid specimens and to evaluate the importance of sVEGFR-1 with respect to ovarian response to gonadotrophin stimulation. A total of 69 patients was treated for IVF with recombinant human follicle stimulating hormone (FSH). Concentrations of VEGF and sVEGFR-1 were quantified in follicular fluids from oocyte retrievals. Patients were designated to three groups with respect to the number of harvested oocytes: group A, 1-5 oocytes; group B, 6-10 oocytes; group C, >10 oocytes. In group A, 1133 +/- 870 pg VEGF/ml follicular fluid per oocyte were quantified, in group B 426 +/- 262 pg VEGF/ml per oocyte, and in group C 274 +/- 179 pg VEGF/ml per oocyte. Soluble VEGFR-1 concentrations resulted in 1200 +/- 523 pg/ml follicular fluid per oocyte in group A, 255 +/- 193 pg/ml per oocyte in group B, and 79 +/- 69 pg/ml per oocyte in group C. No free sVEGFR-1 could be detected in any follicular fluid. An index to estimate the biological activity of VEGF by dividing VEGF/sVEGFR-1 revealed an increasing availability of VEGF with higher ovarian response to gonadotrophin therapy. In group A this index was 1.03, in group B 1.71, and in group C 3.21. A delicate balance between VEGF and sVEGFR-1 is necessary to allow an adequate ovarian reaction to gonadotrophin therapy. Excess of bio-active VEGF increases the risk for ovarian hyperstimulation syndrome. Excess of sVEGFR-1 results in poor response and goes in parallel with reduced chances for conception.
Department of Gynecological Endocrinology and Reproductive Medicine, University Clinic, RWTH Aachen, Germany. jneulen@post.klinikum.rwth-aachen.de
J
J
Neulen
D
D
Wenzel
C
C
Hornig
E
E
Wünsch
U
U
Weissenborn
K
K
Grunwald
R
R
Büttner
H
H
Weich
D000328:Adult; D000911:Antibodies, Monoclonal / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000627:therapeutic use; D016228:Endothelial Growth Factors / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology / Q000627:therapeutic use; D015571:Follicular Fluid / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008222:Lymphokines / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects*; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D010062:Ovulation Induction / Q000379:methods*; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D000911:Antibodies, Monoclonal; D006063:Chorionic Gonadotropin; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D020794:Receptor Protein-Tyrosine Kinases; D040281:Vascular Endothelial Growth Factor Receptor-1