OHSS can occur when drugs are used to stimulate the ovaries to produce the eggs needed for fertilization in IVF treatment. The ovaries become larger than normal, and there can be a build-up of fluid in the abdomen. In severe cases there may also be hemoconcentration (decrease of the fluid content of the blood, with a resulting increase in its concentration), and kidney and liver damage; this can be life-threatening. Although OHSS has been known for many years, until now it has been treated empirically and the underlying causes have been little understood.
Animal models had shown that increased vascular permeability (VP), a factor in OHSS, was associated with an increased expression in the ovary of vascular endothelial growth factor (VEGF), responsible for the growth of blood vessels. The binding of VEGF to its receptor VEGFR2 increases VP. "We knew that dopamine and its agonists also reverse increased VP in hyperstimulated animals", said Dr. Alvarez, "so we decided to see whether it could prevent OHSS in women undergoing ovarian stimulation for ART."
Dopamine agonists are widely used in gynaecological conditions, especially in patients with hyperprolactinemia - a condition where the presence of abnormally high levels of the hormone, prolactine, can cause a number of disorders affecting fertility – and their safety record is good. So Dr. Alvarez and his team began a study of 54 egg donors, who were randomly allocated into two groups immediately after administration of human chorionic gonadotropin (hCG), a drug used to induce ovulation.
The study group received 0.5 mg of the dopamine agonist cabergoline and the control group took placebo. The women were monitored every 48 hours from day 0 (the day hCG was given) to day 8. There were significant differences between the two groups.
"We found that cabergoline reduced hemoconcentration, ascites (excess fluid in the space between the membranes lining the abdomen and abdominal organs) and the incidence of moderate to severe OHSS in women at risk," said Dr. Alvarez. "Our next move will be to study the action of dopamine agonists in more detail, and to proceed to bigger studies of their effects in clinical trials. We hope that our work will enable us to better understand the mechanism of development of this serious complication of ART treatment, and to be able to treat it effectively."