title: Inhibition of cyclooxygenase-2 (COX-2) by meloxicam decreases the incidence of ovarian hyperstimulation syndrome in a rat model.
abstract: OBJECTIVE
  To investigate the effects of selective cyclooxygenase-2 (COX-2) inhibition on the ovarian hyperstimulation syndrome (OHSS) in an experimental model.
  
  
  METHODS
  Controlled laboratory study.
  
  
  METHODS
  University-affiliated fertility center.
  
  
  METHODS
  Female Wistar rats.
  
  
  METHODS
  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.
  
  
  METHODS
  Number of antral and luteinized follicles, ovarian weight, semiquantitative vascular endothelial growth factor (VEGF) and COX-2 immunohistochemistry.
  
  
  RESULTS
  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.
  
  
  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.
authors.affiliation: Instituto de Ginecología y fertilidad (IFER), Buenos Aires, Argentina.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Quintana
authors.forename: Laura
authors.initials: L
authors.lastname: Kopcow
authors.forename: Guillermo
authors.initials: G
authors.lastname: Marconi
authors.forename: Edgardo
authors.initials: E
authors.lastname: Young
authors.forename: Carola
authors.initials: C
authors.lastname: Yovanovich
authors.forename: Dante A
authors.initials: DA
authors.lastname: Paz
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015994:Incidence; D000077239:Meloxicam; D009929:Organ Size; D016471:Ovarian Hyperstimulation Syndrome / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism / Q000517:prevention & control*; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D013843:Thiazines; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; D000077239:Meloxicam