The non-ergot derived dopamine agonist quinagolide in prevention of early ovarian hyperstimulation syndrome in IVF patients: a randomized, double-blind, placebo-controlled trial.
BACKGROUND
Ovarian hyperstimulation syndrome (OHSS) seems to be induced by the ovarian release of vascular endothelial growth factor (VEGF), which increases vascular permeability. Dopamine agonists inhibit VEGF receptor phosphorylation and thereby decrease vascular permeability.


METHODS
A randomized, double-blind, placebo-controlled, multicentre study assessing three oral doses (50, 100, 200 microg/day) of the non-ergot derived dopamine agonist quinagolide started on the day of human chorionic gonadotrophin (hCG) and continued for 17-21 days without dose-titration in comparison to placebo in preventing moderate/severe early OHSS (onset < or =9 days after hCG administration) in 182 IVF patients with > or =20 but less than 30 follicles > or =10 mm.


RESULTS
The incidence of moderate/severe early OHSS was 23% (12/53) in the placebo group and 12% (6/51), 13% (7/52) and 4% (1/26) in the quinagolide 50, 100 and 200 microg/day groups, respectively. The moderate/severe early OHSS rate was significantly lower with all quinagolide groups combined compared with placebo [P = 0.019; OR = 0.28 (0.09-0.81)]. The incidence of ultrasound evidence of ascites among patients with no clinical pregnancy was significantly reduced from 31% (8/26) with placebo to 11% (8/70) with all quinagolide groups combined [P = 0.033; OR = 0.29 (0.10-0.88)], although there was no difference for those with clinical pregnancy. Quinagolide did not have a detrimental effect on pregnancy or live birth rates. The incidence of gastrointestinal and central nervous system adverse events increased with increasing doses of quinagolide.


CONCLUSIONS
Quinagolide appears to prevent moderate/severe early OHSS while not affecting treatment outcome. The effect is more marked in patients who did not achieve a clinical pregnancy. Quinagolide administered in high doses without dose-titration is associated with poor tolerability. ClinicalTrials.gov Identifier: NCT00329693.
IVI Valencia, Plaza de la Policía Local, 3, 46015 Valencia, Spain. crisbusso@hotmail.com
Cristiano
C
Busso
Manuel
M
Fernández-Sánchez
Juan Antonio
JA
García-Velasco
José
J
Landeras
Augustín
A
Ballesteros
Elkin
E
Muñoz
Sandra
S
González
Carlos
C
Simón
Joan-Carles
JC
Arce
Antonio
A
Pellicer
D000328:Adult; D000634:Aminoquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001201:Ascites / Q000517:prevention & control; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects; D006801:Humans; D007231:Infant, Newborn; D016471:Ovarian Hyperstimulation Syndrome / Q000097:blood / Q000517:prevention & control*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011388:Prolactin / Q000097:blood; D020554:Sperm Injections, Intracytoplasmic; D016896:Treatment Outcome; D055815:Young Adult
D000634:Aminoquinolines; D018491:Dopamine Agonists; C046650:quinagolide; D011388:Prolactin