What's new in the pathogenesis and prevention of ovarian hyperstimulation syndrome?

Abstract

Several pathophysiological mechanisms have been proposed for the development of ovarian hyperstimulation syndrome (OHSS), such as activation of the ovarian renin-prorenin-angiotensin system, release of ovarian cytokines and nitric oxide, but numerous reports now attest to the role of vascular endothelial growth factor (VEGF), an endothelial cell mitogen, as an important mediator of the syndrome. Luteinizing hormone (LH) or human chorionic gonadotrophin (hCG) regulates VEGF production by the ovary. Formation of multiple follicles, as seen in regimens of ovarian stimulation used for in vitro fertilization (IVF), and intensified sensitivity towards human menopausal gonadotrophin (hMG) and hCG, as seen in women with polycystic ovaries (PCO) or polycystic ovary syndrome (PCOS), result in increased serum VEGF concentrations, probably due to enhanced VEGF production by the ovaries. It is possible that the hypersecretion of VEGF in women with PCO is due to an increase in the number of VEGF secreting cells or that the cells individually hypersecrete VEGF. This hypothesis was tested by in vitro studies on granulosa lutein cells. After the cells were stimulated with gonadotrophins and hCG, VEGF production was higher in granulosa cells obtained from women with PCO compared with those obtained from women with normal ovaries under similar culture conditions. The studies performed in vivo and in vitro were consistent with increased VEGF expression as a constitutive feature of PCO. Increased VEGF may be responsible for the fluid shift from the vascular bed to the extravascular space, which characterizes OHSS. Prevention of OHSS focuses on predicting the possibility of developing OHSS. Markers such as serum oestradiol concentrations and number of follicles on the day of hCG administration, the presence of PCO and the number of oocytes retrieved may be subject to inter-observer and inter-operator variations. As individual markers of OHSS, each of these factors predicts less than a quarter of cases of the syndrome. It has been shown that a combination of pretreatment diagnosis of PCO along with number of follicles on the day of hCG administration and ‘VEGF rise’ gives the highest prediction rates for the risk of developing OHSS. Neither pathogenesis nor prevention and treatment of OHSS are specific. Therefore, at present, OHSS remains a condition that cannot be avoided altogether.