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-2Ralpha, IL-6 and sIL-6R by ELISA.

Results: The mean serum levels of IL-2, sIL-2Ralpha, 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-2Ralpha, IL-6, sIL-6R and VEGF in the OHSS group were 282.5+/-191.5 pg/ml, 26020+/-13 995, 90.5+/-36, 14900+/-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-2Ralpha 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.