Elevated levels of interleukin-2, soluble interleukin-2 receptor alpha, interleukin-6, soluble interleukin-6 receptor and vascular endothelial growth factor in serum and ascitic fluid of patients with severe ovarian hyperstimulation syndrome

Abstract

Objective: To investigate the possible role of vascular endothelial growth factor, interleukin-2, soluble interleukin-2 receptor alpha, interleukin-6 and soluble interleukin-6 receptor in the pathogenesis of ovarian hyperstimulation syndrome. Study design: The study group consisted of 10 healthy women who developed severe ovarian hyperstimulation syndrome, group A ( n=10), following ovarian stimulation by long GnRHa/hMG protocol for IVF. A control group B=10 patients underwent stimulation with the same protocol and did not develop OHSS. Blood and ascitic fluid samples were assayed for VEGF, IL-2, sIL-2Rα, IL-6 and sIL-6R by ELISA. Results: The mean serum levels of IL-2, sIL-2Rα, IL-6, sIL-6R and VEGF in OHSS group were 297.5±190, 6588±5566, 40.6±16.6, 5280±3326 and 492±165 pg/ml as compared to 50.8±17.4, 1100±391.6, 8.5±3.5, 516±342 and 167±31.3 pg/ml in the control group, respectively, P<0.001. The mean ascitic fluid IL-2, sIL-2Rα, IL-6, sIL-6R and VEGF in the OHSS group were 282.5±191.5 pg/ml, 26 020±13 995, 90.5±36, 14 900±2789 and 660±359 pg/ml as compared to 32±14.8, 1206±429.4, 12.6±1.7, 614±240 and 151±20.5 pg/ml, respectively, P<0.001. Conclusions: The significantly high levels of VEGF in patients with severe OHSS suggest that VEGF is a major capillary permeability agent in OHSS. Elevated levels of IL-6 in serum and peritoneal fluid support the hypothesis that IL-6 may serve as a marker of OHSS. Although serum and ascitic fluid levels of IL-2 were elevated, accumulating evidence does not support a pivotal role for IL-2 in the pathogenesis of OHSS. However, it may have a peripheral role in mediating an increase in vascular permeability. Soluble IL-2Rα and sIL-6R may be considered to be involved in OHSS. However, the patho-physiologic mechanism is the subject of further investigations. Clinical application of VEGF-receptors in the management of OHSS is awaited with interest.