title: Physiology and pathology of ovarian hyperstimulation syndrome.
abstract: Ovarian hyperstimulation syndrome (OHSS) occurs when ovaries primed with follicle-stimulating hormone/leuteinizing hormone (LH) are subsequently exposed to human chorionic gonadotropin (hCG). The ultimate pathophysiological step underlying this clinical picture is increased vascular permeability (VP). With the administration of hCG, the expression vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) mRNA increases significantly rising to a maximum coinciding with peaked VP. Immunohistochemistry shows the presence of VEGF and VEGFR-2 proteins in the granulosa-lutein and endothelial cells of the entire corpus luteum. These findings suggest that the syndrome can be prevented by inducing ovulation with LH or gonadotropin-releasing hormone analogs, which prevent VEGF overexpression. Also, coadministration of a dopamine agonist inhibits phosphorylation of the receptor VEGFR-2. In a trial of 69 oocyte donors, the incidence of moderate OHSS was 20% with the dopamine agonist cabergoline and 44% with a placebo ( P = 0.04). Another dopamine agonist, quinagolide, was also effective in nonpregnant patients, but those pregnant did not benefit from dopamine agonist administration. In conclusion, the pathophysiological mechanisms involved in OHSS show that targeting VEGF/VEGFR2 is an effective preventive approach to treat the syndrome. Pharmaco-prevention through dopamine agonists is effective only in nonpregnant high-risk OHSS women. Embryo cryopreservation plus dopamine agonist administration might be the most appropriate way to prevent OHSS in high-risk patients.
authors.affiliation: Instituto Universitario IVI, Universidad de Valencia, Valencia, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Gómez
authors.forename: Sergio R
authors.initials: SR
authors.lastname: Soares
authors.forename: Cristiano
authors.initials: C
authors.lastname: Busso
authors.forename: Juan A
authors.initials: JA
authors.lastname: Garcia-Velasco
authors.forename: Carlos
authors.initials: C
authors.lastname: Simón
authors.forename: Antonio
authors.initials: A
authors.lastname: Pellicer
mesh_terms: D000818:Animals; D018491:Dopamine Agonists / Q000627:therapeutic use; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008954:Models, Biological; D016471:Ovarian Hyperstimulation Syndrome / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology* / Q000517:prevention & control; D010062:Ovulation Induction / Q000009:adverse effects / Q000379:methods; D011247:Pregnancy; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D018491:Dopamine Agonists; D005300:Fertility Agents, Female; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2