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.

Bilateral Pleural Effusion as Unique Manifestation of Atypical Ovarian Hyperstimulation Syndrome

“…Although the etiology of OHSS is unknown, the physiopathology is an increase of vascular permeability to high molecular weight proteins due to mediators such as Vascular Endothelial Growth Factor (VEGF), produced by granulosa cells, which depends on hCG [2,4,7,8]. This causes displacement of fluids and proteins from intravascular space to third space, with intravascular volume depletion, hypotension, oliguria, ascites and hemoconcentration [4].…”

“…Given the possible recurrence of the syndrome in future cycles of stimulation in this patient, it will be necessary to consider preventive measures, such as: cancel the cycle before administering hCG with less follicles or lower levels of estradiol to the previous cycle; reduce dose of hCG: embryo cryopreservation to avoid the production of endogenous hCG; and delayed transfer [8,14]. Other secondary prophylaxis strategies (albumin administration, corticosteroids or dopamine agonists) are controversial [14,15].…”

“…Its etiology and pathogenesis are still uncertain but clinical manifestations are due to an increase of vascular permeability and extravasation of fluid in a third space [2,3]. Ascites is usual, however, pleural effusion is uncommon as isolated manifestation [4][5][6].…”

Severe Ovarian Hyperstimulation Syndrome Complicated by <i>Stenotrophomonas maltophilia</i> Peritonitis: A Case Report and Literature Review

“…These symptoms result as a consequence of ovarian stimulation, which results in ovarian enlargement and the accumulation of exudative ascites (20). Gastrointestinal symptoms are believed to occur due to the effects of human chorionic gonadotropin (21).…”

Current Medical Strategies in the Prevention of Ovarian Hyperstimulation Syndrome

“…Targeting the VEGF/ VEGFR2 pathway by the administration of pharmacotherapy through low doses of dopamine agonists might be the most appropriate way to prevent OHSS in high-risk patients. Th e proposed mode of action appears to be through partial blockage of VEGFR2 specifi c phosphorylation sites involved in the development of vascular permeability without aff ecting tyrosine sites or activating angiogenic activity 43 . It is likely that decreased VEGF secretion leads to less VEGFR2 activation and lower amounts of phosphorylated VEGFR2 resulting in inhibition of increased vascular permeability and OHSS prevention 44 .…”