Study shows “Bute” can temporarily disrupt assisted breeding in horses

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 Research from Texas A&M University has found that phenylbutazone (“bute”), one of the most
commonly used pain-relief medications in horses, can interfere with artificial breeding techniques, especially at the crucial stages of egg maturation, fertilisation, and early embryo development.

This finding is particularly important for mares involved in assisted reproductive technologies (ART), such as intracytoplasmic sperm injection (ICSI) or embryo transfer. Many donor mares, especially older mares retired from competition or horses working through chronic lameness, may be receiving long-term bute to manage pain. 

Phenylbutazone is a non-steroidal anti-inflammatory drug (NSAID) widely used to manage lameness. While highly effective for pain, the Texas A&M team discovered that it can temporarily reduce the ability of a mare’s egg cells (oocytes) to develop properly in laboratory conditions.

In horses, assisted reproduction is more difficult than in humans. Mature oocytes must be collected, cultured for around 30 hours, and then fertilised by injecting an individual sperm directly into the egg, a process known as ICSI. If the egg fails to mature or the early embryo fails to grow, it cannot be used.

The research team tested the effect of a 10-day course of oral bute on oocyte quality. Oocytes were collected using transvaginal ultrasound-guided aspiration and evaluated shortly after treatment, then again one month and two-and-a-half months later. Cumulus–oocyte complexes (COCs), the small clusters of egg cells and surrounding support cells, were matured in vitro and fertilised using ICSI.

Key findings included:

Immediately after treatment (3 days post-bute):

• Oocytes from treated mares were less likely to be recovered and mature normally.
• Cleavage (early embryo division) rates were significantly lower.
• No fertilised oocytes from bute-treated mares developed into blastocysts, whereas 28% of those from untreated mares did.

Later in recovery (33 and 77 days post-treatment):

• Differences between groups disappeared.
• Oocytes collected after these intervals matured and developed at normal rates.

This means that bute’s negative effect on reproduction is real but temporary. A waiting period of at least one month after stopping bute appears to allow oocyte quality to return to normal.

This study suggests that:

• Egg collections performed shortly after a course of bute may fail, wasting both time and significant financial investment.
• Planning ART procedures around medication withdrawal could improve success rates.
• A minimum 30-day washout period may be advisable before oocyte aspiration.

Future research will explore whether other NSAIDs offer safer alternatives that do not interfere with reproduction.

For more details, see:

Luisa Ramírez-Agámez, Camilo Hernández-Avilés, Canaan M. Whitfield-Cargile, Michelle C. Coleman, Charles C. Love,

Treatment of mares with the non-steroidal anti-inflammatory drug (NSAID) phenylbutazone transiently affects in vitro maturation of equine oocytes and blastocyst development after Intracytoplasmic Sperm Injection (ICSI),

Theriogenology (2024), Vol 223, Pp 53-58

https://doi.org/10.1016/j.theriogenology.2024.04.017