Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening iatrogenic complication of ovarian stimulation. Severe forms complicate 1–3% of IVF cycles (1). It is characterized by a massive ovarian enlargement together with a fluid shift into extravascular compartments responsible for the development of ascites, sometimes pleural and/or pericardial effusion, hypovolemia, oliguria, and hydroelectrolytic disorders. Several factors such as histamine, serotonin, prostaglandins, prolactin, cytokines including the interleukins, tumor necrosis factor alpha, endothelin-1 and vascular endothelial growth factor (VEGF) are thought to be involved in triggering of increased vascular permeability after ovulation stimulation. Vascular endothelial growth factor (VEGF), which promotes angiogenesis and vascular permeability, is probably the principle factor involved in the pathogenesis of OHSS (2). VEGF was demonstrated to be secreted from progesterone-producing granulosa cells in the ovarian follicles, and the VEGF production is stimulated by HCG (3). So, it is evident that hCG is the main trigger for its development. Therefore, the ideal method to avoid OHSS occurrence is cancelation of the cycle, which unfortunately leads to a financial and psychological impact. How to reach an OHSS-safe IVF? In the last decades, there were several trials aiming at a more successful and OHSS-safe IVF. Since the pathophysiology of OHSS is poorly understood, scientific effort should search for a reliable predictive test for patients prone to OHSS before starting stimulation and testing its validity. Such as, a possible gene mutation in the FSH receptor gene, which displays an increased sensitivity to hCG and may be responsible for the development of spontaneous ovarian hyperstimulation syndrome (OHSS), (4). Another possible option is the pre-treatment measurement of