Low-dose histrelin for ovulation induction in mares: a partially randomized crossover pilot study

This partially randomized crossover pilot study evaluated reduced doses of histrelin for ovulation induction in mares and compared intramuscular (IM) administration with pharmacopuncture at the Bai-hui and Yan-chi acupoints. Eleven mares were enrolled, of which nine completed all eight protocols and were included in the analyses. The protocols comprised 250 µg histrelin IM (standard dose), 75 µg IM, 25 µg IM, no intervention, saline at Bai-hui, saline at Yan-chi, 25 µg histrelin at Bai-hui, and 25 µg histrelin at Yan-chi. Ovulation was assessed by transrectal ultrasonography at scheduled examinations until detected, with ovulation within 48 h as the primary outcome. Ovulations first detected at 24 h were excluded from the primary analysis. Ovulation within 48 h occurred in 88.9% (8/9) of observations with 250 µg IM, 87.5% (7/8) with 75 µg IM, 87.5% (7/8) with 25 µg IM, 37.5% (3/8) with no intervention, 50.0% (3/6) with saline at Bai-hui, 100% (9/9) with 25 µg histrelin at Bai-hui, 12.5% (1/8) with saline at Yan-chi, and 87.5% (7/8) with 25 µg histrelin at Yan-chi. Exact 95% confidence intervals were wide, reflecting the small sample size. Exploratory pairwise comparisons with the no-intervention protocol were performed without adjustment for multiple comparisons and should be interpreted cautiously. The findings provide preliminary evidence that reduced histrelin doses, including 25 µg, may induce ovulation within 48 h in mares. However, this study did not demonstrate an advantage of pharmacopuncture over IM administration of the same reduced dose. Larger, fully randomized studies are required to confirm the efficacy of reduced-dose histrelin and determine whether administration at specific acupoints provides any additional effect.