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

Fertil Steril. 2008 Oct;90(4 Suppl):1511-6. doi: 10.1016/j.fertnstert.2007.09.028. Epub 2007 Dec 31.

Abstract

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.

Animal(s): Female Wistar rats.

Intervention(s): Female Wistar rats (22 days old) were divided into four groups: group 1 (control group; n = 10) received 0.1 mL of intraperitoneal (IP) saline from days 22-26; group 2 (mild-stimulated group; n = 10) received 10 IU of pregnant mare serum gonadotropin (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 4 consecutive days from day 22 and 30 IU hCG on the fifth day to induce OHSS; group 4 was treated the same as group 3, but received 2 muL (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 killed on day 26.

Main outcome measure(s): Number of antral and luteinized follicles, ovarian weight, semiquantitative vascular endothelial growth factor (VEGF) and COX-2 immunohistochemistry.

Result(s): There were no differences in the ovarian weight between groups 1 and 2. Group 3 showed significantly increased ovarian weight that was suppressed, in group 4, by meloxicam. There was no difference in the number of antral follicles among the four groups. In the mild-stimulated and OHSS groups, the granulosa cells (GC) 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 (OHSS group) showed increased COX-2 immunoreactivity that was diminished in the meloxicam-treated group. Meloxicam treatment did not affect the hormone-induced increase in serum E(2) levels seen in OHSS rats.

Conclusion(s): 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 Inhibitors / therapeutic use*
  • Down-Regulation*
  • Female
  • Gene Expression / drug effects
  • Humans
  • Incidence
  • Meloxicam
  • Organ Size
  • Ovarian Hyperstimulation Syndrome / drug therapy
  • Ovarian Hyperstimulation Syndrome / epidemiology
  • Ovarian Hyperstimulation Syndrome / metabolism
  • Ovarian Hyperstimulation Syndrome / prevention & control*
  • Ovary / drug effects
  • Ovary / metabolism
  • Rats
  • Rats, Wistar
  • Thiazines / pharmacology*
  • Thiazoles / pharmacology*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Cyclooxygenase 2 Inhibitors
  • Thiazines
  • Thiazoles
  • Vascular Endothelial Growth Factor A
  • Cyclooxygenase 2
  • Meloxicam