Inhibition of cyclooxygenase-2 (COX-2) by meloxicam decreases the incidence of ovarian hyperstimulation syndrome in a rat model.
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.
Quintana
Ramiro
R
Instituto de Ginecología y fertilidad (IFER), Buenos Aires, Argentina.
Kopcow
Laura
L
Marconi
Guillermo
G
Young
Edgardo
E
Yovanovich
Carola
C
Paz
Dante A
DA
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
D052246:Cyclooxygenase 2 Inhibitors; D013843:Thiazines; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; D000077239:Meloxicam