Oxytocin and cabergoline alleviate ovarian hyperstimulation syndrome (OHSS) by suppressing vascular endothelial growth factor (VEGF) in an experimental model.

Abstract

Ovarian hyperstimulation syndrome (OHSS) is a life-threatening complication of ovarian stimulation in reproductive medicine. Here, we aimed to investigate the role of oxytocin (OT) and cabergoline in the prevention and alleviation of the OHSS in an animal model. Thirty-five female immature Wistar rats were randomly assigned to five groups. The control group (n = 7) received saline only for five consecutive days. Remaining twenty-eight rats received 10IU of pregnant mare serum gonadotropin (PMSG) followed by 30IU of human chorionic gonadotropin (hCG) to induce OHSS. Group 2 (n = 7) was managed with no additional intervention after the induction of OHSS. Group 3 (n = 7) received 100μg/kg cabergoline 2h before the PMSG injection for four consecutive days and 2h before the hCG injection on the fifth day. Group 4 (n = 7) and group 5 (n = 7) received 80μg/kg and 160μg/kg OT after induction of OHSS, respectively. Oxytocin was administered 2h before the PMSG injection for four consecutive days and 2h before the hCG injection on the fifth day. Body and ovary weight, vascular permeability (VP), VEGF expression in the ovaries, and levels of VEGF in the peritoneal fluids were examined in all animals. Cabergoline and OT reduced body weight, ovary weight, and VP compared to that of the OHSS group (p < 0.05). VEGF expressions in ovaries and peritoneal VEGF levels were decreased in cabergoline and OT groups compared to that of the OHSS groups (p < 0.001 for cabergoline and OT-80μg/kg; p < 0.00001 for OT-160μg/kg). However, there was no statistically significant difference in these parameters between the OT and cabergoline groups. Both OT and cabergoline were active in the alleviation of OHSS through suppression of VEGF and VP. Overall, we conclude that OT is effective for downregulation for VEGF and improvement in vascular permeability in OHSS.