New insights into the pathophysiology of ovarian hyperstimulation syndrome. What makes the difference between spontaneous and iatrogenic syndrome?

Abstract

The recent identification of mutations in the FSH receptor gene, which display an increased sensitivity to hCG and are responsible for the development of spontaneous ovarian hyperstimulation syndrome (OHSS), provides for the first time the molecular basis for the physiopathology of spontaneous OHSS. Based on these recent findings, this paper underlines the differences between spontaneous and iatrogenic OHSS and proposes a model to account for the different chronology between the two forms of the syndrome. In the iatrogenic form, the follicular recruitment and enlargement occur during ovarian stimulation with exogenous FSH, while in the spontaneous form, the follicular recruitment occurs later through the stimulation of the FSH receptor by pregnancy-derived hCG. In both forms, massive luteinization of enlarged stimulated ovaries ensues, inducing the release of vasoactive mediators, leading to the development of the symptoms of OHSS.

Figure 1

Chronology of iatrogenic and spontaneous ovarian hyperstimulation syndrome. In the iatrogenic form, the follicular recruitment and growth occur during the administration of exogenous FSH. In the spontaneous form, the follicular recruitment and enlargement occur later through the promiscuous stimulation, by pregnancy-derived hCG, of a mutated FSH receptor (abnormally sensitive to hCG) or a wild type FSH receptor (in the presence of abnormally high levels of hCG). In both forms, massive luteinization of enlarged stimulated ovaries ensues, inducing the release of vasoactive mediators, leading to the development of the symptoms.