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Improves Mare Fertility

Canadian veterinarians now have another option for treating endometritis in their clients’ mares. Canada is the latest country in which Settle® immunotherapy has received regulatory approval for sale. The product is also approved and available in the USA, Australia, New Zealand, and UAE. 

Settle® is CFIA-approved as a stand-alone injectable treatment to stimulate the mare’s immune system to decrease inflammation and eliminate bacteria (without antibiotics). A single dose (1.5ml) has been shown effective for a positive outcome.  

Endometritis is inflammation of the uterine lining. It’s the greatest cause of mare infertility, affecting up to 15 percent of broodmares. Uterine inflammation creates a hostile environment in which sperm or embryos cannot thrive. This inflammation can occur at or around the time of breeding and/or postpartum. It can be caused by bacterial, fungal, or yeast infection, or by sperm, seminal plasma, or sterile solutions such as saline or lactated Ringers solution. 

In the challenge study for product registration, Settle® showed efficacy in treating endometritis caused by Streptococcus zooepidemicus, the most common cause of the disorder. In the challenge study, a single dose of Settle® was administered either intravenous or intra-uterine 48 hours post-inoculation with S. zooepidemicus.  

In this challenge study, endometritis was observed in all placebo-treated mares at seven days post-ovulation, whereas treatment with Settle® resulted in elimination of endometritis in 70 percent of mares at seven days post-ovulation. Additionally, both routes of treatment were found effective. 

Settle® is manufactured using mycobacterium cell wall fraction (MCWF) as the active ingredient. It is a potent immunomodulator, and in multiple research studies, Settle® has been found to stimulate innate and specific immune responses, as needed to address underlying challenges in the broodmare. 

Research with Settle® for Post-Breeding Endometritis 

Research studies have demonstrated that Settle® decreases pro-inflammatory cytokine production (IL-1β, IL-8) (Fumuso et al. 2006; 2008; Woodward et al. 2014). 

Research has also shown that Settle® increases anti-inflammatory cytokine production (IL-10) (Fumuso et al. 2007). 

Two research studies demonstrated that Settle® decreases PMN infiltration resulting in decreased fluid in the uterus (Fumuso et al. 2007; Christoffersen et al. 2014). 

Another two studies demonstrated that Settle® treatment results in decreased bacterial infiltration in the uterus (Fumuso et al. 2010; Christoffersen et al. 2014). 

A single administration of Settle® to problem mares within 24 hours of breeding has been shown to normalize the immune response and enhance bacterial clearance without the use of medically important antibiotics. 

Research with Settle® for Postpartum Endometritis 

A study conducted by the Gluck Equine Research Center (U. Kentucky) demonstrated that a two-dose regimen of Settle® in postpartum mares hastened involution of the uterus, decreased the magnitude of bacterial growth and time to negative culture, decreased mucosal inflammation, and shortened the number of days to ovulation (Fedorka et al., 2020). 

Another study demonstrated that Settle® enables normal pregnancy at foal heat when administered as a single dose post-foaling (Fumuso et al. 2003). 

Research with Settle® for Endometrial Cups 

A research study by the Gluck Equine Research Center (U. Kentucky) and Rood & Riddle Equine Clinic demonstrated that with repeated hysteroscopic-guided injections of endometrial cups, Settle® caused a significant reduction in peripheral eCG concentrations and hastened the return to oestrus in treated mares (Fedorka et al. 2024).  

Additionally, the average Settle®-treated mares in this study developed a pre-ovulatory follicle 24 days after initiation of treatment, indicating that these mares are able to be rebred within a month of pregnancy loss/termination. 

Summary 

Settle®, manufactured by NovaVive Inc., has been proven safe when administered in conjunction with both natural and AI breeding. It is compatible with hormones and other conventional reproductive treatments. It’s also compatible with spermatozoa (it can be added to semen extender or administered at the same time as breeding). Most importantly, Settle® can replace medically important antibiotics in the broodmare.

About NovaVive Inc.

NovaVive Inc. is a private Canadian immunobiology company founded in July 2014. The company 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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