Inhibition of cyclooxigenase -2 (COX-2) by meloxicam decreases the incidence of ovarian hyperstimulation syndrome in a rat model.

QUINTANA R; KOPCOW L.; MARCONI G.; YOUNG E.; YOVANOVICH, A.; PAZ D.A.

FERTILITY AND STERILITY

Elsevier

Lugar: New York; Año: 2007

0015-0282

Objective: To investigate the effects of selective cyclooxygenase-2 (COX-2) inhibition on the ovarian hyperstimulation syndrome (OHSS) in an experimental model. Design: Controlled laboratory study. Setting: University-affiliated fertility center. Animals: Female Wistar rats Interventions: 22 day-old female Wistar rats were divided into four groups: Group 1 (control group; n = 10) received 0.1 ml of IP saline from day 22 to day 26;  Group 2 (mild-stimulated group; n = 10) received 10 IU of PMSG on day 24 and 10 IU of hCG 48 hours later (day 26); Group 3 (OHSS group; n = 10) was given 10 IU of PMSG for four consecutive days from day 22 and 30 IU hCG on the fifth day in order to induce OHSS; Group 4 was treated in same fashion as Group 3, but received 2 ml (15 mg/ml) of meloxicam 2 hours before the PMSG injection for 4 consecutive days, and 2 hours before the hCG injection on the fifth day. All groups were sacrificed on day 26. Main Outcome Measures: number of antral and luteinized follicles, ovarian weight, semiquantitative VEGF and COX-2 immunohistochemistry Results: There were no differences in the ovarian weight between groups 1 and 2.  Group 3 showed significantly (p < 0.01) increased ovarian weight that was suppressed, in group 4, by meloxicam (p < 0.01). There was no difference in the number of antral follicles among the four groups.  In the mild-stimulated and OHSS groups, the granulosa cells of preovulatory follicles and the stromal cells showed intense VEGF immunoreactivity. The ovaries from the meloxicam treated group showed less immunoreactivity than the OHSS group, indicating  diminished VEGF expression associated with meloxicam treatment. Group 3 (group OHSS) showed increased COX-2 immunoreactivity that was diminished in the meloxicam treated group. Meloxicam treatment did not  affect the hormone-induced increase in serum estradiol levels seen in OHSS rats.  Conclusions: Our results in a rat model suggest that meloxicam has a beneficial effect on OHSS by reducing the increases in ovarian weight and VEGF expression associated with OHSS.  These effects may be mediated by the COX-2 inhibitory capacity of meloxicam.