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Dopamine Agonist Cabergoline Reduces Hemoconcentration and Ascites in Hyperstimulated Women Undergoing Assisted Reproduction

Instituto Valenciano de Infertilidad (C.A., E.N.-M., R.G., M.F.-S., C.S., A.P.), University of Valencia; Departments of Obstetrics and Gynecology (A.P.) and Radiology (L.M.-B.), Hospital Universitario Doctor Peset, University of Valencia; and Department of Radiology (L.M.-B., R.S.), Hospital Quirón, 46015 Valencia, Spain

Address all correspondence and requests for reprints to: Prof. Antonio Pellicer, Instituto Valenciano de Infertilidad, Plaza de la Policía Local, 3, 46015 Valencia, Spain. E-mail: apellicer{at}ivi.es; antonio.pellicer{at}uv.es.

Context: Ovarian hyperstimulation syndrome (OHSS) results from increased vascular permeability (VP) caused by ovarian hypersecretion of vascular endothelial growth factor (VEGF), which activates its receptor-2. In animals, the dopamine receptor 2 agonist cabergoline (Cb2) inactivates VEGF receptor-2 and prevents increased VP.

Objective: Our objective was to test whether Cb2 reduces VP and prevents OHSS in humans.

Design: We conducted a prospective, randomized, double-blind study on oocyte donors at risk of developing OHSS (>20 follicles, >12 mm developed, and >20 oocytes retrieved).

Interventions: Cb2 0.5 mg/d (n = 37) or a placebo (n = 32) was administered from the day of human chorionic gonadotropin (d 0) until d 8. Ascites (a pocket of peritoneal fluid > 9 cm² in lithotomy position), hemoconcentration, and serum prolactin were recorded. Pharmacokinetic studies with magnetic resonance employing the transfer constant rate (K^trans, measure of permeability) and the extravascular extracellular space (_e, marker of cellular leakage) were performed to measure VP objectively.

Results: Hematocrit (P < 0.01), hemoglobin (P = 0.003), and ascites (P = 0.005) were significantly lower on d 4 and 6 after treatment with Cb2 as compared with placebo. The incidence of moderate OHSS was 20.0 and 43.8%, respectively (P = 0.04). Magnetic resonance studies showed an increase in VP and extravascular leakage of fluid 5 d after human chorionic gonadotropin injection that was significantly prevented with Cb2 (K^trans P = 0.04 and _e P = 0.001, respectively).

Conclusions: Given that Cb2 is a well-established and safe medication, this study provides proof of concept for the use of dopamine agonists in the prevention of OHSS in women undergoing assisted reproduction.

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