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


METHODS
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).


METHODS
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 (upsilon(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 upsilon(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.
Alvarez
Claudio
C
Instituto Valenciano de Infertilidad, University of Valencia, Plaza de la Policía Local, 3, 46015 Valencia, Spain.
Martí-Bonmatí
Luis
L
Novella-Maestre
Edurne
E
Sanz
Roberto
R
Gómez
Raúl
R
Fernández-Sánchez
Manuel
M
Simón
Carlos
C
Pellicer
Antonio
A
D000328:Adult; D001201:Ascites / Q000378:metabolism; D000077465:Cabergoline; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004311:Double-Blind Method; D004873:Ergolines / Q000627:therapeutic use*; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects*; D006107:Granulosa Cells / Q000187:drug effects; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008184:Luteal Cells / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D016471:Ovarian Hyperstimulation Syndrome / Q000517:prevention & control*; D010053:Ovary / Q000098:blood supply; D011247:Pregnancy; D011446:Prospective Studies; D017448:Receptors, Dopamine D2 / Q000819:agonists; D012039:Regional Blood Flow / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018491:Dopamine Agonists; D004873:Ergolines; D006454:Hemoglobins; D017448:Receptors, Dopamine D2; D000077465:Cabergoline