Effects of combined use of steroidal and non-steroidal anti-inflammatory drugs on endometrial condition after artificial insemination

Abstract

Post-breeding endometritis is a physiological reaction to semen and should resolve within 36 to 48 hours. Failure of uterine defense mechanisms to eliminate antigens and inflammatory products from the uterus effectively results in persistent endometritis with a detrimental effect on fertility (Canisso et al. Internal Journal of Molecular Sciences. 2020; 21(4), 1432). This study was designed to evaluate the effect of combinations of systemic NSAIDs on the uterine inflammatory response in mares after AI. Twenty-eight females were used. They were submitted to four treatments (n=7) randomly distributed: TAIE - AIE (0.1 mg/kg of Dexamethasone; IM); TAINE - AINE (1.1 mg/kg Phenylbutazone; IV); TAIE+AINE - two classes of associated anti-inflammatory drugs (0.1 mg/kg of Dexamethasone and 1.1 mg/kg of Phenylbutazone; IV) and TC – Control (NaCl 0.9% saline solution; IV). Gynecological examinations were performed three times a week and when follicles with a diameter of ≥ 35 mm were detected, ovulation was induced using 500 mg of histrelin acetate (Strelin®). The mares were inseminated 36 hours after ovulation induction with refrigerated semen. Immediately after AI, treatments were applied to each experimental group. Eight and 24 h post-AI, samples were collected foruterine cytology and ultrasound was performed to verify the presence of intrauterine fluid. The standard for considering the presence of endometritis was >5% PMN/endometrial cells or >5 PMN/field, in addition to the presence of intrauterine fluid greater than 2 cm. All mares underwent pregnancy diagnosis by transrectal ultrasound 25 days after AI. There was a difference between TAIE and the other treatments eight hours after AI in relation to PMN/endometrial cells (p <0.0001). However, in relation to the number of PMN/field there was a difference only between TAIE and TAIE+AINE (p<0.05). Twenty-four hours after AI, for PMN/endometrial cells, there was a difference between TAIE and TAINE (p<0.01), TAIE and TC (p<0.01), TAINE and TAIE+AINE (p<0.05), TAIE+AINE and TC (p<0.01) and for PMN/field between TAIE and TC (p<0.01) and TAIE+AINE and TC (p<0.01). The results obtained between the two evaluation criteria were discrepant and greater reliability was observed in the evaluation of PMN/endometrial cells. IN conclusion, the combined use of two anti-inflammatory classes (TAIE+AINE) was effective in improving the endometrial condition at 24 hours post-AI in normal mares.