Predicting and preventing ovarian hyperstimulation syndrome (OHSS): the need for individualized not standardized treatment

Abstract

Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of controlled ovarian stimulation (COS) as part of assisted reproductive technologies (ART). While the safety and efficacy of ART is well established, physicians should always be aware of the risk of OHSS in patients undergoing COS, as it can be fatal. This article will briefly present the pathophysiology of OHSS, including the key role of vascular endothelial growth factor (VEGF), to provide the foundation for an overview of current techniques for the prevention of OHSS. Risk factors and predictive factors for OHSS will be presented, as recognizing these risk factors and individualizing the COS protocol appropriately is the key to the primary prevention of OHSS, as the benefits and risks of each COS strategy vary among individuals. Individualized COS (iCOS) could effectively eradicate OHSS, and the identification of hormonal, functional and genetic markers of ovarian response will facilitate iCOS. However, if iCOS is not properly applied, various preventive measures can be instituted once COS has begun, including cancelling the cycle, coasting, individualizing the human chorionic gonadotropin trigger dose or using a gonadotropin-releasing hormone (GnRH) agonist (for those using a GnRH antagonist protocol), the use of intravenous fluids at the time of oocyte retrieval, and cryopreserving/vitrifying all embryos for subsequent transfer in an unstimulated cycle. Some of these techniques have been widely adopted, despite the scarcity of data from randomized clinical trials to support their use.

Figure 1

The pathogenesis of OHSS. Human chorionic gonadotropin (hCG) stimulates a high number of granulosa-lutein cells leading to the increased production of vascular endothelial growth factor (VEGF) mRNA (Figure 1A); VEGF receptor-2 (VEGFR-2) mRNA production in the granulosa-lutein and endothelial cells is also increased in response to hCG. High amounts of VEGF are produced and released from the granulosa-lutein cells and bind to VEGFR-2 on the endothelial cell membranes. Downstream signaling augments vascular permeability (Figure 1B). Adapted from Soares et al [7].