The differences of mechanisms between normal luteal formation and occurrence of ovarian hyperstimulation syndrome

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Vascular endothelial growth factor(VEGF) is well known to stimulate both the growth of endothelium and vascular permeability. VEGF expression in the ovary is also reported to increase during normal luteal formation. In this study we investigated the mechanisms of the occurrence of ovarian hyperstimulation syndrome(OHSS).The expression of VEGE and VEGF receptors(R) was extremely stimulated in the ovaries of OHSS rat models compared with corpora lutea of pseudopregnant rats. Vascular permeability examined with Evans blue was markedly increased in the ovaries of OHSS rats. Gonadotropin releasing hormone agonist(GnRHa) treatment blocked the increase of VEGF-VEGFR expression and vascular permeability of the ovaries of OHSS rats.Tight junction proteins of endothelium are reported to play a pivotal role in vascular permeability. As there are known to be several sorts of tight junction proteins, we checked the expression of such proteins in the ovaries of OHSS rats.Claudin-5 and occludin protein were significantly decreased in the ovaries OHSS rats. However, GnRHa treatment blocked the decrease in both proteins. Moreover, we clinically experienced that the continuation at GnRHa prevented the occurrence of OHSS during in vitro fertilization and embryo transfer.In summary, the decreased expression of claudin-5 and occludin caused by excess expression of VEGF-VEGFR was speculated to change from normal luteal formation into the occurrence of OHSS.