Prediction of ovarian hyperstimulation syndrome: Challenging the estradiol mythos

Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially life-threatening complication of ovulation induction. The syndrome almost always presents either after hCG administration in susceptible patients or during early pregnancy. Despite many years of clinical experience, the pathophysiology is poorly understood and there is no reliable test to predict patients who will subsequently develop severe OHSS. Nevertheless, excessive estradiol (E₂) levels are commonly used as a predictor for the development of severe OHSS. The aim of this debate is to challenge this E₂ mythos by demonstrating the reported versatility in the chosen E₂ level in which patients develop OHSS; present pathophysiological evidence which paradoxically supports a preventive rather than a detrimental effect of E₂ against OHSS, followed by a possible explanation which may sort out the aforementioned chaos. Additional studies are required to elucidate the pathophysiology of OHSS which may ultimately lead to new strategies in the prediction, prevention and treatment of severe OHSS.