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

Overview

• This study explored the use of lower doses of the hormone histrelin to induce ovulation in mares.
• It compared traditional intramuscular (IM) injection with pharmacopuncture (injection at specific acupuncture points) to see which method might be more effective.

Study Objective

• To determine if reduced doses of histrelin can effectively induce ovulation within 48 hours in mares.
• To compare the efficacy of intramuscular administration with pharmacopuncture at two acupuncture points: Bai-hui and Yan-chi.

Study Design

• Partially randomized crossover pilot study involving eleven mares.
• Nine mares completed all eight treatment protocols and were included in the analysis.
• Treatments included various doses of histrelin intramuscularly (250 µg, 75 µg, 25 µg), no intervention, saline injections at Bai-hui and Yan-chi points, and 25 µg histrelin injected at Bai-hui and Yan-chi points.
• Each mare experienced all protocols in a crossover manner to control individual variability.

Treatment Protocols

• Standard Dose IM: 250 µg histrelin intramuscular injection.
• Reduced Dose IM: 75 µg and 25 µg histrelin intramuscular injections.
• Control Protocols: No intervention and saline injections at Bai-hui and Yan-chi acupoints.
• Pharmacopuncture: 25 µg histrelin injected directly at Bai-hui and Yan-chi acupoints.

Assessment Method

• Ovulation was monitored using transrectal ultrasonography at scheduled intervals.
• Primary outcome was occurrence of ovulation within 48 hours after treatment.
• Ovulations detected exactly 24 hours post-treatment were excluded from the primary analysis to avoid ambiguity.

Results

• High ovulation rates (approximately 88%) were observed in intramuscular histrelin groups at all doses: 250 µg (88.9%), 75 µg (87.5%), 25 µg (87.5%).
• Pharmacopuncture with 25 µg histrelin yielded varied results depending on acupoint:
• Bai-hui point showed 100% ovulation (9/9).
• Yan-chi point had 87.5% ovulation rate (7/8).
• Saline injections alone had inconsistent ovulation rates: 50% at Bai-hui, 12.5% at Yan-chi.
• No intervention control had a much lower ovulation rate of 37.5%.
• Wide confidence intervals reflected the small sample size, indicating uncertainty around estimates.
• Exploratory pairwise comparisons versus no intervention were conducted but without adjustments for multiple comparisons, so caution is needed when interpreting these.

Conclusions

• Reduced doses of histrelin, even as low as 25 µg, appear to effectively induce ovulation within 48 hours in mares.
• No clear advantage was found for pharmacopuncture over traditional intramuscular injection of the same reduced dose.
• The pharmacopuncture method did not demonstrate consistent added benefit based on the selected acupoints.
• This pilot study provides preliminary data but highlights the need for larger, fully randomized trials to confirm these findings.
• Future research should also explore whether targeting specific acupoints may improve efficacy beyond standard IM administration.

Study Limitations

• Small sample size (nine mares in analysis) limits the statistical power and precision of estimates.
• Partially randomized and pilot nature means the results are preliminary and exploratory.
• Non-adjustment for multiple comparisons increases risk of false positive findings.
• Excluding ovulations detected exactly at 24 hours could affect outcome interpretation.

Implications for Veterinary Practice

• Lower doses of histrelin may be a viable, cost-effective option for inducing ovulation in horses.
• Standard intramuscular administration remains effective; pharmacopuncture does not yet show clear benefits.
• Veterinarians may consider lower dose protocols but should await larger confirmatory studies before changing practice.