Vascular endothelial growth factor antagonist reduces the early onset and the severity of ovarian hyperstimulation syndrome

Abstract

Background: Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of controlled ovarian stimulation (COH) during assisted reproductive technology (ART) protocols. This syndrome is a result of ovarian expression of vascular endothelial growth factor (VEGF), which increases vascular permeability.

Objectives: To evaluate the efficiency of prophylactic and therapeutic use of cabergoline in women with higher risk of developing OHSS.

Materials and methods: In this prospective randomized study, 146 women undergoing in vitro fertilization (IVF) cycles with GnRH agonist protocols with a higher risk of OHSS diagnosed during the HCG day administration (more than 18 follicles observed larger than 12mm in diameter during COH and/or estradiol levels of 3000-3500pg/ml, previous episodes of OHSS). Women were randomly divided in two groups. The first group included 78 women who received 0.5mg per day of cabergoline (Dostinex^®) orally for 7 days starting from hCG administration day. The second group included 68 women who received no medication treatment. Overall, in each group 25 patients have developed OHSS. This defines subgroup 1 that includes 25 cases of OHSS obtained in group 1 and subgroup 2 where 25 cases of OHSS obtained in group 2. Early OHSS was defined as being when the onset of the syndrome was initiated during the first 9 days after hCG administration and late OHSS was defined as being when the onset of the syndrome was initiated from 10 days after hCG administration. Outcome measures of this study were the incidence of moderate and severe OHSS, early or late OHSS and pregnancy rates.

Results: There was no evidence of a statistically significant reduction in the incidence of OHSS in cabergoline group (32.05% vs. 36.76%; P>0.05). Late OHSS was observed in 60.6% of cases in cabergoline group while 39.4% of cases in the other group (P=0.036). Early OHSS decreased significantly (P<0.05) in the cabergoline group. Severe OHSS cases were more common within subgroup 2 than subgroup 1 (32% vs. 8%, P=0.000). There was no difference in clinical pregnancy rates (PR) and miscarriages rates between the two subgroups.

Conclusions: The cabergoline administration (Dostinex^®) for patients with high-risk of OHSS can reduce the rate of early OHSS and its severity in GnRH agonist IVF cycles, but cannot prevent the incidence of OHSS.

Keywords: Cabergoline; IVF outcome; Ovarian hyperstimulation syndrome; Résultats FIV; Syndrome de l’hyperstimulation ovarienne; VEGF.