For breeders, few things are more frustrating than a mare that simply won’t get in foal. Despite advances in veterinary care and reproductive management, pregnancy rates remain inconsistent, and for many operations, the underlying reasons aren’t always clear.
According to Carleigh Fedorka, a PhD graduate from the University of Kentucky and a current faculty member at Colorado State University specializing in equine reproductive immunology, the industry’s biggest challenge is both common and widely misunderstood.
“From both a personal and a global veterinary perspective, the biggest problem is endometritis,” she noted adding that roughly 15 to 20% of mares are affected. “This is when the uterus doesn’t have a normal immune response after breeding, which leads to prolonged inflammation. And that inflammation can prevent pregnancy or lead to early embryonic loss.”
One of the most critical and often overlooked factors in early pregnancy is timing.
“If you go into the physiology of pregnancy, the early embryo lives in the oviduct for about six days after ovulation, so you have about six days to get that uterus happy and healthy,” says Fedorka. “If these mares don’t have that normal immune response, then they can still have a pretty angry uterus when the embryo gets to the uterus, causing pregnancy failure, early embryonic loss, and even problems later in pregnancy.”
In other words, it’s not just about successful breeding, it’s about what happens immediately afterward.
As veterinarians look for more effective ways to manage this narrow window, attention has increasingly turned to immune-based therapies. One such option is Settle, an immunomodulator designed to help regulate the mare’s inflammatory response following breeding. In studies, it has been shown to eliminates endometritis in up to 70% of mares.
Rethinking the Cause of Inflammation
Historically, many breeders and farm managers have assumed that uterine inflammation is caused by infection and treated it accordingly.
“We used to call these mares ‘dirty’ and reach for antibiotics right away,” Fedorka says. “But we now know that’s not always the case. Inflammation can be triggered by bacteria, but it can also be caused by sperm, seminal plasma, or even sterile solutions like the saline that we lavage our mares with, they can cause this improper immune response.”
This shift in understanding has significant implications. Treating every case with antibiotics is not only ineffective in some situations but also contributes to growing concerns around antimicrobial resistance.
“We’re getting a good grasp of antimicrobial resistance,” she added. “So we’re really trying to train this next generation of practitioners to be very careful with the diagnostics that they perform and the treatment options that they reach for.”
Why Some Mares Struggle and Others Don’t
At the heart of the issue is the mare’s immune system.
“The immune system’s job is to eliminate anything foreign,” Fedorka explains. “That includes bacteria and sperm, but the embryo is also foreign, because it’s only 50% the mare’s DNA.”
In a healthy mare, the immune response is carefully regulated. Inflammation ramps up quickly after breeding to clear contaminants, then subsides before the embryo enters the uterus. But in problem mares, that system breaks down.
“There’s a variety of reasons,” explained Fedorka noting that about 20% of mares are simply not easy to breed. “There’s a really strong correlation with increasing age and increasing risk. There’re other things like mares that have multiple foals because every time that a mare carries a foal, the broad ligaments that hold up that uterus are going to get stretched ever so slightly, and that mare’s just going to have a harder time resolving that inflammation.”
But some young and healthy mares with no obvious issues can still struggle.
“There’s a subset of mares that on paper are totally normal, they’re young and they’re maidens. They shouldn’t have problems, but their immune system is just screwed up. It’s not the easiest thing to figure out if they do or don’t have it until you just breed the mare and see that they fail to resolve that inflammation,” she notes.
The Challenge of Diagnosis
One of the biggest frustrations for breeders is that these issues often only become apparent after breeding.
“We usually don’t know that these mares are going to have a problem until you’ve bred them and they blow with what we call luminal fluid that you can see on ultrasound after you’ve bred them. Then it really becomes some investigative work on whether or not you can help that mare get rid of all of that inflammation,” says Fedorka.
At that point, diagnostics such as uterine culture and cytology become critical, not just to confirm inflammation, but to determine whether bacteria are actually involved.
Standard approaches to managing post-breeding inflammation include oxytocin to stimulate uterine contractions and lavage to flush the uterus.
“But they don’t always work, particularly in mares with immune regulation issues,” Fedorka says.
And when inflammation isn’t caused by bacteria, antibiotics offer little benefit.
In these cases, veterinarians are increasingly looking at therapies that support the mare’s immune response rather than defaulting to antimicrobials.
A Shift Toward Immune-Based Solutions
Among the immunomodulators gaining traction is Settle, a product Fedorka has evaluated in multiple research studies.
“It is really good at signalling for those immune cells to come in and attack the foreign particle. We have shown that by giving Settle at the time of breeding or a day prior to breeding that we can reduce bacterial infiltration into the uterus. We’ve also shown that it affects a lot of those immune signalling molecules that these mares just don’t do on their own.”
This dual action is key.
“We see it reduce our white blood cells. We see it reduce the amount of fluid that’s in the uterus, and then we see it activate the immune signalling molecules,” she says. “I do think that the coolest part about Settle is that we also see an impact on bacteria. Because Settle can actually help clear out those bacteria, it can stand in place of an antimicrobial and allows the practitioner to not even have to reach for that antibiotic.”
Timing and Practical Use
For breeders and veterinarians, timing is critical.
“We see peak activity about 12 hours after administration, but we have seen pronounced effect even 3 days later.”
In practice, she often recommends its use early in the diagnostic process.
“It’s a great option to use while you’re waiting for culture results,” she says. “Sometimes you won’t get the results back from them for 72 hours. So maybe give that dose of Settle then, and then once you get your culture and cytology back, make a different plan or stay on that plan, but very few of these products have been found to both kill bacteria and help with the inflammation.”
It has also been studied in postpartum mares, where supporting uterine recovery can improve the chances of a successful return to breeding.
A More Targeted Approach to Fertility
As research continues to evolve, the industry is moving toward more precise, evidence-based reproductive management.
“If you understand what’s driving the problem, you can make much better decisions and improve outcomes,” Fedorka said. And for the 20% of mares that aren’t straightforward, that understanding can make all the difference.
About NovaVive Inc.
NovaVive Inc. is a private Canadian immunobiology company that acquired an advanced veterinary immunotherapeutic platform based on mycobacterium cell wall fraction (MCWF) technology with regulator-approved products for cattle, horses and dogs. These products are currently sold to veterinarians in the USA, Canada, Australia, New Zealand, and the UAE. The Company’s head office is in Ontario, Canada and the products are manufactured in Georgia, USA.
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