Veterinary Vertex

Comfort Without Compromise: Phenylbutazone and Mare Fertility

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Challenging conventional wisdom in equine reproduction, this episode explores revolutionary research about phenylbutazone's impact on embryo production in mares. When previous studies claimed mares on "bute" had zero successful embryos via intracytoplasmic sperm injection (ICSI), Dr. Kristen Loncar and her team questioned these findings based on their own clinical success. Their subsequent investigation reveals surprising results with significant implications for veterinary practice and equine welfare.

Dr. Loncar walks us through the evolution of transvaginal follicle aspiration and ICSI technology, which has transformed from a last-resort procedure for problem mares to an efficient breeding method for both aging broodmares and performance horses. She explains how their research tested various phenylbutazone formulations—liquid (oral and IV) and paste—finding no significant decrease in blastocyst rates compared to control groups. This groundbreaking discovery resolves a critical ethical dilemma: veterinarians no longer need to choose between managing a mare's pain and pursuing reproductive success.

The conversation delves into fascinating aspects of equine reproductive medicine, future research directions, and the potential role of AI in analyzing embryo development. Whether you're a practicing veterinarian, breeder, or horse owner, this episode provides essential insights into managing aging or arthritic mares while preserving their reproductive potential. Listen now to discover how science is enhancing both quality of life and reproductive options for horses under veterinary care.

JAVMA article: https://doi.org/10.2460/javma.25.04.0285

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Speaker 1:

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Speaker 2:

You're listening to Veterinary Vertex, a podcast of the AVMA Journals. In this episode we chat about how phenylbutazone treatment of mares does not reduce embryo production via intracytoplasmic sperm injection, with our guest Kristen Lunker.

Speaker 3:

Welcome listeners. I'm Editor-in-Chief Lisa Fortier, and I'm joined by Associate Editor Sarah Wright. Today we have Kristen joining us. Kristen, thank you so much for taking time out of this crazy therogenology time frame in your life to be with us here today. Thanks for having me.

Speaker 2:

I'm really excited about this. All right, let's trot on over. So, kristen, your JABMA article discusses how mares that are undergoing transvaginal follicle aspiration and intracytoplasmic sperm injection can remain on phenylbutazone for comfort and quality of life. Please share with our listeners the background on this article. Yeah, so the whole process of transvaginal aspiration and ICSI has really evolved over the last 20 plus years. Initially it was kind of one of those last-ditch efforts for those mares that are older and had a lot of chronic uterine problems where they couldn't be bred or have embryos fleshed anymore. And now there's been so many advances and it's actually become a really efficient way of making embryos. So we do see a lot more young, healthy mares that can come in so that way, if they're busy training or showing, they can just come in, get aspirated and potentially make multiple embryos from one session. With that being said, we still have a very large population of mares that are older. A lot of them have chronic osteoarthritis issues. I see a lot of laminitic mares that come in anything like that where they really need to be on some sort of non-steroidal plus or minus other medications to be comfortable, be able to ambulate and just have a relatively decent quality of life, just have a relatively decent quality of life. And so last year a paper came out that described that mares having 10 days of butte or phenylbutazone had a 0% blast rate after ICSI. And so at the clinic that I work at we read this paper and we kind of went that doesn't really fit with the clinical picture that we see. You know, we started going down the list and naming all of the mares that we could think of off the top of our head of you know. Okay, this one's been on Butte and this one's been on Butte.

Speaker 2:

And so this project really started, just kind of for our own information we wanted to know were our expectations unrealistic? You know, were we making assumptions that were incorrect? Is it really that detrimental? And part of it was. We wanted to know, since we had some embryos being produced, okay, maybe there was a decrease that we should be expecting and we should kind of figure out. Maybe there was a decrease that we should be expecting and we should kind of figure out what that decrease was, so that when we're talking with clients we can come up with kind of all the facts and have better expectations.

Speaker 2:

So it started off as just an in-house kind of wanting to know situation and it definitely morphed into multiple rounds, multiple types of phenylbutazone. And you know, the great thing was that the mares that we were using in our study we saw no differences and in fact some of the mares that were on phenylbutazone had higher blast rates than the control mares. So at least we kind of got the information we were looking for and have some information that we decided we wanted to share with other veterinarians and other clients so that mares would continue to remain on non-steroidals if they needed them and people wouldn't be scared off of it. I feel like we hear that so commonly on this podcast like hey, like we noticed this one thing but thought differently. So one to like actually investigate and see if there's evidence to prove this. So definitely a cool myth buster, I think, for this episode, which we appreciate.

Speaker 2:

And what are some of the important take-home messages from this article? The biggest take-home is the fact that it does seem to be safe to leave these mares on phenylbutazone. We didn't see any decrease in blastocyst rate. We tested the liquid preparation given orally, which is fairly common in my area. We tested the liquid given IV and we tested one of the paste phenylbutazones in IV and we tested one of the paste phenylbutazones, so there's a number of options that we can still use, and these mares still produced high numbers of blastocysts. So if you have a mare that needs to be on it, she certainly doesn't need to come off just because you're trying to make some embryos.

Speaker 3:

Yeah, such great clinical, really important clinical information. So thank you for sharing that. We have so many great options in veterinary medicine, so many fabulous careers. What sparked your interest in therogenology?

Speaker 2:

That started all the way back in college. I had an amazing professor that taught reproductive physiology and we had a breeding program at the university, and so once you took his class, you could then participate in breeding and foaling out the university horses, and so I just kind of became fascinated at that point. I was then given an opportunity to work at a really well-known large Arabian breeding farm during college and then after that, during vet school, had a number of mentors that kind of showed me you know, you can't actually make a career out of this, which was amazing, and things just kind of kept falling into place. So I ended up doing exactly what I was hoping I could do and didn't think I could.

Speaker 3:

A little bit earlier. Sarah asked you and you nicely articulated what are some of the important take-homes. Mares can stay on phenylbutazone for their comfort and no decrease in embryos. But every time we do a study there's something that surprises us. What do you think surprised your team about this study? I think mostly.

Speaker 2:

I was surprised at how little effect there was Going into it. We thought that there was probably going to be some decrease. There hasn't been a whole lot of work looking at what different types of medications or supplements or anything like that do to the oocyte, and so we know when we give some sort of non-steroidal, when we're trying to breed a mare, we're going to run into some problems. We're going to have potentially increased episodes of hemorrhagic follicles, follicles that fail to ovulate. We'll have increased fluid after ovulating, but we really didn't have any idea what happens to the actual oocyte itself, and so we assumed we'd have some sort of a decrease. We just didn't know what that decrease would be, and the fact that there was no decrease at all was really surprising. Yeah, super valuable information. Thank you again for sharing it with our journals.

Speaker 2:

So what are the next steps to research in this topic? I think there's a couple things that need to be done after this. Although not statistically different, we did see a lower percentage of blasts produced with the paste formulation, so I don't know if that was just a coincidence or what. We tried to use the same paste that was used in the previous study, where they had zero blast produced but it wasn't available. So maybe there's something in the paste, some sort of carrier, that can actually cause problems. So it'd be really interesting to try a number of different brands of the Butte paste to see if that is potentially going to be an issue. And then after that, I mean we use a number of different non-steroidals in veterinary medicine and it would be interesting to see if any of them have effects, since we just did phenylbutazone.

Speaker 2:

Always more questions than answers sometimes. So hopefully we'll see some more work from you, kristen, and do you see a role for AI in this area of research? I'm not really sure about the exact type of studies that we're doing. Just because there's so much physical work, it would be really nice to have a way to design the experiments. You know we wanted to make sure that we had enough numbers that our significance could be accurate and trusted, so it would be nice to have the studies designed that way. And then, obviously, the data analysis is always kind of the hardest part, so that's always nice.

Speaker 2:

I know not really related to this study, but I know there's AI being developed to analyze the blastocysts as they're developing, looking at cellular changes and that sort of thing, to kind of help predict the outcome of each of these embryos, because right now, you know, we kind of grade them based on how well they develop, what they look like at cleavage, how fast they develop. But I know there's AI being developed to really analyze, you know, okay, this one has this chance versus this other one that doesn't have as good of a chance just based on what it looked like at each little teeny, tiny change in the in the process. Very cool. And for those of you just joining us, we're discussing how phenylbutazone treatment of mares does not reduce embryo production via intracytoplasmic sperm injection, with our guest Kristen.

Speaker 3:

Kristen, you talked about your wonderful exposure in undergraduate and then throughout veterinary school, so you have a lot of experience in this field. So how did all that combined training help prepare you to write this article and even really execute the study?

Speaker 2:

So I think I have the training to do the procedures that I've developed at the practice that I'm currently at, and then the training to kind of design an appropriate study for my residency. So I've spent a lot of time aspirating mares, getting more efficient at that, doing the actual ICSI process in the lab, and that's all just been learning on the job. But the residency really prepared me to look at data critically, design studies that have appropriate controls. We did crossovers to try to make everything as even as possible. We tried to make it as blind as possible so there wasn't any sort of bias during the aspiration process or during the injection process. So there's been a lot of steps along the way where you learn different techniques and pick up different methods of doing things, and then, as well, the scientific part is just a whole nother ballgame of difficulty. And luckily I have a lot of people in my life that were good sounding boards and we could bounce ideas off each other and verify that we were doing things kind of as thoroughly as we could. That's great. Sounds like you had a really good team, so that's awesome to hear.

Speaker 2:

Now, kristen, this next set of questions is going to be very important for our listeners. The first one is going to be dealing with the veterinarian's perspective. What is one piece of information the veterinarian should know about final venous zone treatment and embryo production in mares? The biggest thing as a managing vet is to continue to treat the horse. If you have a mare that needs to be on phenylbutazone, make sure she stays on it and maintains quality of life. If I had the choice, I would probably stick with either the IV formulation given IV or given orally versus the paste. I just feel like we don't know quite enough about the paste yet, but since we didn't see a statistically significant difference, if that's your only option, I would absolutely not stop it, just for the sake of aspirating and creating embryos and from the client's perspective.

Speaker 2:

What's one thing clients should know? I think the clients need to be comfortable with the veterinarian's decision to keep the mare on butte as well. We all know how fast information can travel, and so I think that was one of the reasons this study went from let's just see for our own knowledge to we need to make sure we do a thorough job and try to get this published, because we were concerned with the previous article coming out that the mares that were on phenylbutazone produced zero embryos that clients would just latch on to that. You know one fact of not being able to give my mare butte anymore and and that's that. And we absolutely don't want mares to to be uncomfortable, we don't want them to suffer, we don't want any of that. So we want to make sure that clients understand that from a scientific point of view, from a researched point of view, they can absolutely keep their mare on phenylbutazone and you're not going to have an effect on the way she produces embryos.

Speaker 3:

Yeah, you just have to keep reminding them. There's a difference with embryos and other sorts of repro and lots of I mean it's not uncommon to in my field of regenerative medicine oh, they have to come off it before you make PRP, and that's just not true platelet-rich plasma. So yeah, we don't want them to go backwards in lameness or discomfort for sure. As we close, kristen, we like to ask a little bit of a fun fact and if you have it with you, you can show us, because this is all video recordings you know what's the oldest? If you have it with you, you can show us, because this is all video recordings, you know what's the oldest? I'm a little afraid to ask a therogenologist this question, like at all vet schools for listeners, like when you go by that, both the dental and the therogenology, the old equipment, you're like that's terrifying. But Kristen, what's the oldest or most interesting item on your desk or in your desk drawer?

Speaker 2:

Oh, wow, I don't have it on me actually, which is sad. I have the Beatle heartbeat Doppler monitor that my dad bought when my mom was pregnant with me, which I think is super cool. I can't get it to work, but I think it's pretty cool just to have because, you know, it's a little bit of family history. Very cool, and in your field, yeah, yeah, I love that. Very cool, kristen. Well, thank you so much for being here, kristen, and sharing the manuscript with us as well and letting our listeners know what they can expect when they read your article. Absolutely, this has been great. Thank you so much. And to our listeners, you can read Kristen's article on Jabma I'm Sarah Wright with Lisa48. Be on the lookout for next week's episode and don't forget to leave us a rating and review on Apple Podcasts or whatever platform you listen to.

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