Effect of ACE inhibiting therapy in ovarian hyperstimulation syndrome in the rat: histological and immunohistochemical study

ABSTRACT

Ovarian hyperstimulation syndrome [OHSS] has become a common problem since the introduction of assisted reproductive technologies and ovarian stimulation methods into infertility practice. The purpose of the present study was to investigate the possible effects of the angiotensin converting enzyme inhibitor enalapril in the ovarian hyperstimulation syndrome in a rat model. Thirty young adult virgin female rats were randomly divided into 2 experimental and one control groups of ten rats each. Ovarian hyperstimulation was induced in all experimental animals by using 30 IU FSH [sc] for 5 consecutive days, followed by 30 IU of hCG [im] on day 6. Oral enalapril tablets [2mg/kg] were given twice daily to ten rats only [group II] for 6 consecutive days. The remaining ten rats did not receive enalapril [group I]. Control animals received injections of saline solution to mimic the conditions of the study animals. Body weights of animals were recorded on days 1 and 8, and percentage of weight gain was calculated for each group. All animals were sacrificed on day 8, ovaries were removed and weighed to obtain ovarian weight. Histological changes in the ovaries were evaluated, and corpora lutea were counted to estimate the number of ovulations in each ovary. Blood samples were also taken to determine serum estradiol and progesterone levels. In addition, ovaries were subjected to immunohistichemical staining with anti-VEGF antibodies. Administration of the stimulation regimen to group I rats resulted in a significant increase in weight gain, ovarian weight, number of ovulations, serum estradiol and progesterone levels, as well as VEGF immunoreactivity in the ovaries, compared with the control rats. Moreover, a significant positive correlation between ovarian weight and body weight gain was also found in both experimental groups. Enalapril administration, in group II rats, significantly reduced all study parameters, including the VEGF immunohistochemical expression in the ovaries. Angiotensin converting enzyme inhibiting therapy with enalapril was significantly effective in reducing the severity of ovarian hyperstimulation syndrome in the rat model