The non-ergot derived dopamine agonist quinagolide in prevention of early ovarian hyperstimulation syndrome in IVF patients: a randomized, double-blind, placebo-controlled trial

Abstract

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.

Figure 1

Trial schedule and overview.

Figure 2

Disposition of patients by trial visit. N indicates the number of patients attending the trial visits/undergoing the trial procedures. Patients who stopped trial medication prematurely were discontinued from the trial, but may have undergone procedures related to the controlled ovarian hyperstimulation cycle (e.g. OR and embryo transfer) outside the trial; these patients are not included in Fig 2. End-of-trial visits were scheduled both for patients who completed the trial and patients who discontinued early (three patients were lost to follow-up after negative βhCG test).

Figure 3

Mean serum prolactin concentrations (ng/ml) during the trial.

Figure 4

Moderate/severe early OHSS rate according to the patient's pregnancy status in the trial cycle; no clinical pregnancy (a) and clinical pregnancy (b); and percentage of patients with ultrasound evidence of ascites within the initial 9 days after hCG administration according to the patient's pregnancy status in the trial cycle; no clinical pregnancy (c) and clinical pregnancy (d).

Figure 5

Mean peritoneal fluid (cm²) according to the patient's pregnancy status in the trial cycle; no clinical pregnancy (a) and clinical pregnancy (b).

Figure 6

Percentage of patients with onset of a gastrointestinal adverse event (a) and percentage of patients with onset of a central nervous system adverse event (b) [Day 1 corresponds to hCG administration, Day 3 to OR and Day 6 to OR + 3].