Horse medication may hinder equine assisted reproduction

Researchers at Texas A&M’s School of Veterinary Medicine & Biomedical Sciences have uncovered that phenylbutazone, a commonly used non-steroidal anti-inflammatory drug in horses, may impair a mare’s egg cells, or “oocytes,” from becoming viable embryos, a critical step in equine assisted reproduction.

This finding, published in the journal Theriogenology, is particularly important given the significant investments horse owners make in assisted reproduction.

Like humans, horses sometimes require scientific intervention to reproduce. However, the reproductive process in horses presents unique challenges that necessitate special procedures for successful pregnancies.

“In horses, in-vitro fertilization is more intricate than in humans,” said Luisa Ramirez-Agamez, a Ph.D. candidate in the VMBS’ Department of Large Animal Clinical Sciences, who specializes in equine reproduction. “Mare oocytes need about 30 hours to mature in the lab after collection before fertilization. Then, the eggs must be injected with sperm to induce fertilization, a method known as Intracytoplasmic Sperm Injection.

“We found that phenylbutazone, or bute, can negatively impact both the maturation of mare oocytes and the development of fertilized eggs into viable embryos,” Ramirez-Agamez explained. “Eggs affected by bute cannot be utilized in assisted reproduction.”

Assisted reproduction is crucial for many horse owners, particularly those who rely on their herds for income or want to preserve the lineage of prized horses. Some mares, unable to carry a pregnancy due to chronic lameness, may donate eggs that are fertilized in a lab and carried by a surrogate.

“This is particularly relevant to our findings,” said Ramirez-Agamez. “Chronically lame mares often receive bute for pain management, especially for musculoskeletal issues, which, as our results indicate, compromises their ability to participate in assisted reproduction programs.

“In future studies, we aim to identify an alternative to bute that provides effective pain relief without interfering with reproduction,” she added.

The effect of bute on equine oocytes seems to diminish over time.

“We collected eggs at three, 33, and 77 days after bute administration,” she said. “Eggs collected three days post-treatment couldn’t produce embryos, but those collected after 33 days were successful. We aim to determine more precisely how bute affects egg quality in upcoming research.”

Looking ahead, Ramirez-Agamez is keen on exploring potential collaborations with human medicine researchers due to the implications her findings may have for IVF in women.

“NSAIDs are often prescribed during IVF to delay ovulation,” she noted. “In a typical cycle, women produce one egg, but since IVF is both costly and time-consuming, hormones are used to stimulate the production of multiple eggs, which NSAIDs help by preventing early ovulation.”

However, given her recent findings on NSAIDs and equine reproduction, Ramirez-Agamez wonders if these drugs could also have unintended negative effects on human IVF.

“While NSAIDs are generally viewed as beneficial for IVF in women, our results suggest they may not be as harmless in equine reproduction,” she said. “Some NSAIDs, such as Banamine, can cause anovulatory follicles in horses, where the follicles fail to release egg cells as expected.

“Although this isn’t observed in women, and NSAIDs are considered safe, our discovery that bute can prevent fertilized eggs from developing into embryos raises questions about whether similar effects could occur in women,” she concluded. “This is something I am eager to investigate further.”