Study shows a common pain medication can disrupt assisted reproduction in horses

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A recent study has discovered that phenylbutazone, a non-steroidal anti-inflammatory drug (NSAID) common in equine medicine for pain relief, can affect the ability of mare’s oocytes (egg cells) to become viable embryos.¹ The study, out of the Texas A&M School of Veterinary Medicine and Biomedical Sciences (VMBS) in College Station, found administration of phenylbutazone for 10 consecutive days at 4.4 mg/kg (orally, 1-2 times daily) to be associated with decreased ability for immature equine oocytes to undergo in vitro maturation and develop to the blastocyst stage following intracytoplasmic sperm injection (ICSI).2 The ability of a mare’s egg cells to become viable embryos is a crucial part of assisted reproduction in horses.¹

“In horses, the process of in vitro fertilization (IVF) is more complex than it is in humans,” Luisa Ramírez-Agámez, DVM, a PhD candidate in the VMBS Department of Large Animal Clinical Studies, said in a news release.¹ “First, a mare’s oocytes need approximately 30 hours to mature in the laboratory once they have been collected before they can be fertilized. Then, we have to inject the eggs with sperm to induce fertilization, a process known as ICSI.

“We discovered that [phenylbutazone] can affect both the ability of a mare’s eggs to mature correctly when cultured and whether the fertilized eggs will develop into a viable embryo. In either of those cases, the eggs affected by [phenylbutazone] cannot be used in assisted reproduction,” Ramírez-Agámez added.¹

These findings are significant because of the time and money that horse owners often invest in assisted reproduction. For horse owners who make their livings from their herds, and to those who wish to produce offspring from their favorite horses to extend the bloodline, assisted reproduction is invaluable. Additionally, it’s common for chronically lame mares who are unable to support pregnancies to be used as egg doners. According to Ramírez-Agámez, the latter animals may be among the most impacted.¹

“Mares who are chronically lame are likely going to be on [phenylbutazone ] because it helps with pain management–especially in the musculoskeletal system–which, according to our results, will hinder their ability to participate in assisted reproduction programs,” Ramírez-Agámez said.¹ She added that they hope to identify a phenylbutazone alternative one day with similar levels of pain management, but no interference with reproduction.¹

Some positive news from the study is that the negative effect from the drug on reproduction appeared transient, wearing off within a matter of weeks. Investigators noted there to be no differences regarding in vitro maturation, cleavage, or blastocyst rates 30- and 77-days post-treatment.²

Ramírez-Agámez expressed concern regarding the possible implications of her discovery regarding humans. She has also expressed her interest in one day collaborating with researchers in human medicine to explore any possible impact that this discovery could have on IVF in women.¹

References

1. Common equine painkiller disrupts assisted reproduction technique efficiency in mares, Texas A&M research finds. News release. Texas A&M University School of Veterinary Medicine and Biomedical Sciences. August 13, 2024. Accessed August 13, 2024. https://vetmed.tamu.edu/news/press-releases/equine-painkiller-disrupts-assisted-reproduction/
2. Ramírez-Agámez L, Hernández-Avilés C, Whitfield-Cargile CM, Coleman MC, Love CC. 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;223:53-58. doi:10.1016/j.theriogenology.2024.04.017