Ovarian hyperstimulation syndrome is correlated with a reduction of soluble VEGF receptor protein level and a higher amount of VEGF-A

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening condition associated with increased vascular permeability. The vascular endothelial growth factor (VEGF) system and its receptors have been identified as the main angiogenic factors responsible for increased capillary permeability and are therefore discussed as crucial for the occurrence of OHSS. Recently, a number of soluble receptors for the VEGFs have been detected (sVEGF-Rs) and it has been shown that these sVEGF-Rs compete with the membrane-standing VEGF-R to bind VEGFs. METHODS: We analyzed the serum levels of soluble VEGF-R1, -R2 and -R3 in 34 patients suffering from OHSS and in 34 controls without this disease. In a subgroup analysis, we correlated the severity of the OHSS with the detected amounts of VEGF-R1, -R2 and -R3. In addition, we determined the amount of total VEGF-A in the samples. RESULTS: All the three soluble VEGF receptors tended to be higher in the control group compared with that in the OHSS group but this difference only reached significance for sVEGF-R2 (mean +/- SEM: 15.5 +/- 0.6 versus 13.8 +/- 0.5 ng/ml, respectively, P < 0.05). In the subgroup analysis, sVEGF-R2 levels decreased as the severity of OHSS increased (OHSS-I: 16.8 +/- 1.9 ng/ml and OHSS-III: 12.7 +/- 1.0 ng/ml, P < 0.05) Moreover, the serum levels of total VEGF-A were higher in the OHSS group than those in the controls (537.7 +/- 38.9 versus 351 +/- 53.4 pg/ml, respectively P < 0.05). CONCLUSIONS: We propose that VEGF-A plays a role in the occurrence of OHSS, that the amount of biologically available VEGF-A is modulated by sVEGF-Rs and that different combinations of VEGF-A and sVEGF-R levels might contribute to the severity of OHSS.