Dopamine agonist cabergoline reduces hemoconcentration and ascites in hyperstimulated women undergoing assisted reproduction

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 cm(2) 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 (v(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 v(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.