Plasma Levels of Soluble Vascular Endothelial Growth Factor Receptor-1 May Determine the Onset of Early and Late Ovarian Hyperstimulation Syndrome

Background: Ovarian hyperstimulation syndrome (OHSS) is a life-threatening condition associated with ovarian stimulation. Its pathophysiology is unknown and its treatment continues to be empirical. Early (E)- and late (L)-OHSS occur in women at risk, though not in all cases. Vascular endothelial growth factor (VEGF) is related to increased vascular permeability in OHSS. We analysed the dynamics of the VEGF system in E- and L-OHSS.

Methods: A prospective cohort of women undergoing IVF-ICSI treatment were divided into groups. E-OHSS: Nonpregnant patients classified as women not at risk (group 1) (n = 11) and patients at risk who did not (group 2) (n = 18) and did (group 3) (n = 8) develop severe OHSS. Blood was drawn on the day of ovum retrieval (day 0) and 3, 6, 10 and 14 days later. L-OHSS: Single pregnancies classified as women who did not (group 4) (n = 8) and did develop (group 5) (n = 4) OHSS. Single pregnancies after oocyte donation (OD) (n = 4) were compared with groups 4 and 5 (IVF-ICSI). Blood was obtained weekly (weeks 4-12). Total VEGF (VEFG-A), free (f)-VEGF and soluble VEGF receptor 1 (sVEGFR-1) in plasma and in serum alpha2-macroglobulin (M) were also measured.

Results: Group 3 showed significantly (P < 0.05) higher VEFG-A and f-VEGF than group 1 on day 6 because of lower sVEGFR-1 secretion. Similarly, group 5 had significantly (P < 0.05) more VEFG-A and f-VEGF and less sVEGFR-1 than group 4. Oocyte donation was associated with decreased sVEGFR-1 secretion, and alpha2M was not relevant in OHSS development.

Conclusion: In E- and L-OHSS, the ability to secrete sVEGFR-1 and bind VEGF seems to be the determinant factor in OHSS. f-VEGF acts locally in the ovary.