Endometritis is a condition involving inflammation of the uterine lining, and is a very common cause of infertility in broodmares. Mares with endometritis develop fibrosis and inflammation that prevent embryonic development, resulting in failure to conceive or early embryonic loss.

Endometritis comes in two major types: infectious endometritis, caused by bacterial or fungal infections, and persistent breeding-induced endometritis, in which the uterine lining reacts to seminal fluid within the uterus. The conditions have similar treatment approaches, and mares are sometimes affected by both forms of the condition.

Symptoms of endometritis are subtle, typically manifesting as an inability to conceive despite multiple breeding attempts. Some mares may have uterine fluid accumulation prior to or after breeding, vaginal discharge, or early embryonic loss after successfully conceiving.

Diagnostic testing aims to identify the type of endometritis and its severity, to determine an appropriate treatment protocol. Common diagnostics include bacterial or fungal culture, uterine lining biopsies, and ultrasound examination of the uterus.

Endometritis treatment may include antibiotics, repeated uterine lavages, surgical procedures, medications to treat underlying problems within the uterus, and changing breeding strategies. With appropriate management, many mares can successfully conceive despite having endometritis.

Endometritis in Horses

Endometritis refers to inflammation of the uterine lining, also known as the endometrium. It is one of the most common causes of infertility in broodmares.

Infectious endometritis affecting approximately 25-60% of barren mares, while persistent breeding-induced endometritis (PBIE) affects around 15% of all broodmares. [1]

Some mares have components of both types of endometritis, requiring extensive diagnostic investigation and treatment to improve their chances of conceiving.

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Infectious Endometritis

Infectious endometritis occurs when there is an abnormality in the uterus’ ability to clear contamination. Without being able to remove contaminants from the uterus, bacterial or fungal pathogens proliferate, causing inflammation.

The most common bacteria involved in infectious endometritis are: [2][3][4]

  • Streptococcus equi zooepidemicus
  • Staphylococcus
  • Escherichia coli

These pathogens reside in the environment or are part of the normal reproductive flora in horses, and gain access to the uterus through the cervix.

The most common fungal organisms present in the uterus of mares with endometritis are: [4]

  • Yeast (Candida spp.)
  • Aspergillus spp.
  • Mucor spp.

Fungal organisms are detected in 1-5% of mares with infectious endometritis. Certain physical conformations or the use of antibiotics to treat or prevent endometritis can allow fungi to colonize the reproductive tract. [4]

Pathophysiology

Under normal conditions, the uterine environment is relatively sterile due to a firmly closed cervix preventing bacterial entry, and uterine contractions to remove any contaminants that do accumulate. [4]

For infectious endometritis to occur, there must be a failure in the protective mechanisms of the uterus, or the amount of bacteria present must overwhelm the ability of the uterus to clear the infection.

Major predisposing factors include:

  • Poor vulvar conformation, allowing feces or urine to contaminate the reproductive tract
  • Abnormalities in closure of the cervix, allowing bacterial entry
  • Inability to contract the uterus to clear contaminants, usually associated with increased mare age or having multiple previous foals
  • Immunosuppression reducing the efficacy of the local immune system. [1][3]

After the bacteria enter the reproductive tract, they often form a biofilm – a layer of bacteria adherent to the uterine lining. Within a biofilm, bacteria are resistant to antibodies produced by the immune system and to antibiotics, making treatment challenging. [4]

Over time, inflammation caused by the bacteria results in fibrosis, or scarring, of the uterine lining. [4] Fibrosis prevents embryos from implanting in the uterine lining, and impairs nutritional support of the embryo if it does implant.

Persistent Breeding-Induced Endometritis

Persistent breeding-induced endometritis (PBIE) is similar to infectious endometritis, however inflammation develops in response to sperm within the uterus rather than bacteria. [4][5] In some cases, bacteria are also introduced during breeding, resulting in PBIE and infectious endometritis occurring simultaneously.

In normal mares, sperm within the reproductive tract stimulates inflammation which triggers uterine contractions and an immune response to remove any potential contaminants introduced into the reproductive tract by the sperm. These mechanisms restore the sterile environment of the uterus within 24 to 36 hours, in preparation for the embryo to implant in the uterine wall. [4][6][7]

In mares with poor clearing mechanisms, such as inability to contract the uterus or immunosuppression, sperm and other contaminants remain within the uterus for longer than 36 hours. [4][5] The sperm continue to stimulate inflammation, which ultimately results in fibrosis of the uterine lining.

Risk Factors

Older mares are most at risk for endometritis for several reasons. Aging is associated with weakening of the uterine muscles, reducing contractile ability during the post-breeding period or if contaminants enter the uterus.

Similar changes can occur in the cervix, resulting in incomplete closure of the cervix allowing for bacterial entry. [4]

Older mares can also develop degeneration of the uterine lining due to aging, resulting in fibrosis without infectious endometritis or a PBIE event. [3]

Clinical Signs

The major symptom of endometritis is infertility, usually noticed as failure to conceive after multiple breeding attempts. Other symptoms of endometritis include: [3][13]

  • Uterine fluid build-up before and/or after breeding
  • Early embryonic loss after successful breeding
  • Vaginal discharge
  • Vaginitis (inflammation of the vagina)
  • Shorts intervals between estrus (heat) cycles
  • Excessive endometrial edema (swelling) after mating

Some mares have subclinical endometritis, meaning they exhibit few or no overt symptoms. In such cases, the condition is often diagnosed during reproductive evaluations or when the mare repeatedly fails to conceive.

Diagnosis

Mares bred for several cycles in a row that fail to become pregnant likely have undiagnosed endometritis. Diagnostic testing focuses on identifying the type of endometritis and the severity.

Your veterinarian may conduct several of the following to confirm a diagnosis of endometritis: [1][3][4][8]

  • Breeding history
  • Assessment of vulvar conformation
  • Vaginal speculum examination of the cervix
  • Ultrasound examination of the uterus
  • Cytology (sampling of cells) of the endometrium
  • Biopsy (sampling of tissue) of the endometrium
  • Bacterial or fungal culture
  • Endoscopy examination of the uterus

Endometrial Biopsies

The gold standard for the diagnosis of endometritis is the endometrial biopsy, where a sample of the uterine lining is submitted for evaluation.

Under the microscope, pathologists can evaluate inflammation, the presence of fibrosis, lymphatic and vascular changes, and whether the uterine lining is appropriately developed for the mare’s seasonal cycle. [3][9]

In cases of PBIE, taking samples before and after breeding can identify inflammation and uterine lining changes resulting from the effect of sperm. [3]

Kenney-Doig Scale

Pathologists use the Kenney-Doig scale to evaluate endometrial biopsies, which provides a prediction of the mare’s ability to carry a foal to term successfully.

There is some controversy about the efficacy of the Kenney-Doig scale as a predictor of mare fertility, and the consistency of categorization between pathologists. [9] However, it is currently the best method available for classifying severity of endometritis. [1][3]

  • Category I mares have minimal changes on biopsies, and have an over 80% chance to conceive and carry a foal to term.
  • Category IIA mares have a foaling success rate of 50-80%, due to mild increases in inflammation or fibrosis in the uterine lining.
  • Category IIB mares have a success rate of 10-50%. These mares have moderate inflammation and fibrosis, or the presence of other conditions such as vascular and lymphatic changes.
  • Category III mares have a less than 10% chance of carrying a foal to term, even with appropriate management. These mares are typically considered barren.

Treatment

The best treatment plan for endometritis in mares depends on the type and severity of endometritis. Since multiple factors can contribute to endometritis, a wide array of treatments may be required to restore a healthy uterine lining.

Infectious Endometritis

Antibiotics

Antibiotics are the primary form of treatment for bacterial endometritis. Generally, veterinarians prefer intrauterine lavage with antibiotics over using systemic antibiotics, as there are fewer side effects and the antibiotic is delivered directly to the target area. [1][4]

The type of antibiotic used is based on culture and sensitivity results, where the bacteria isolated from the reproductive tract are tested against several antibiotics to determine the most effective treatment. [4] Common antibiotics include: [1]

  • Amikacin
  • Penicillin G
  • Gentamicin
  • Ceftiofur

Bacteria causing endometritis commonly form biofilms, which require specific treatment to remove. In most cases, antibiotics are unable to kill bacteria within biofilms. [4]

To break up biofilms, most veterinarians use DMSO or Tris-EDTA in combination with antibiotics. [4] Other treatments that improve the efficacy of antibiotics include hydrogen peroxide and N-acetylcysteine. [4][10]

Antifungals

Similar to bacterial endometritis, treatment of fungal endometritis involves intrauterine lavages of antifungals. Common antifungals include nystatin, clotrimazole or amphotericin B, and in some cases these antifungals may be combined with Tris-EDTA. [3][4]

Antifungals may also be applied to the vagina and clitoris as these may harbor a reservoir of fungi that cause reinfection. [4]

Other treatments

Some studies have shown intrauterine kerosene can strip the uterine lining entirely, allowing for regeneration of the lining over the following 21 days. [4][11]

There is also some evidence to support the use of regenerative therapies, such as stem cells and platelet-rich plasma, in restoring the endometrial lining. [11]

Poor Vulvar Conformation

Poor vulvar conformation is a major predisposing factor to endometritis, by allowing feces or urine to contaminate the reproductive tract.

The most common treatment to address conformation issues is a Caslick’s procedure. In this procedure, veterinarians surgically close the lips of the vulva near the top to prevent feces from accessing the reproductive tract.

Mares that have extreme urine pooling within the vagina may require a urethral extension, where the urethra is lengthened to prevent backflow of urine into the reproductive tract. [1][3][10]

Poor Uterine Tone

Mares with infectious endometritis and PBIE can benefit from ecbolic agents, which are drugs that increase muscle tone. In mares with poor uterine tone, these drugs can improve muscle contractions to increase removal of contaminants from the uterus.

The main ecbolic agents used in the treatment of endometritis are oxytoxin and cloprostenol. [3][10][11]

Poor Cervical Opening

In mares with PBIE, inability to open the cervix completely allows fluid to accumulate within the uterus. [3][10]

Prostaglandin treatment applied directly to the cervix can relax the cervix and allow improved fluid drainage.

Prolonged Inflammatory Response

After breeding a mare, the immune system plays an important role in removing seminal fluid from the uterus to prevent inflammation. In mares with PBIE, the inflammatory response persists, and eventually results in fibrosis of the uterine lining.

Immunomodulatory medications, such as glucocorticoids, can reduce inflammation and improve pregnancy rates in PBIE mares. [3][10][11] These medications must be used cautiously, as they also increase the risk of bacterial endometritis. [3]

Severe Endometrial Fibrosis

Category III mares are considered barren, meaning they are unable to conceive or sustain a pregnancy to term. Even if mares successfully form an embryo, the extensive fibrosis often results in early embryonic loss. [3]

There are few treatments available for this degree of fibrosis, and usually mares are reproductively retired or are used for embryo transfer only. [3]

Breeding Strategies

Mares with infectious endometritis or PBIE often require additional management during breeding season to maximize their chance of conceiving a foal.

Preventative Treatments

The goal of preventative treatment is to remove seminal fluid and contaminants promptly after breeding, so that the embryo has a healthy uterine lining to attach to five days after fertilization. [12]

In many mares, a single dose of oxytocin, which increases uterine tone, is enough to allow the uterus to clear fluid and contaminants on its own. [12]

In mares with significant fluid accumulation, uterine lavages can remove the excess fluid to reduce contamination. These lavages can begin as soon as 4 hours after breeding, and can be repeated multiple times over the following 3-4 days if fluid is still present. [10][12]

Altered Breeding Protocols

Mares with PBIE may benefit from altering the normal breeding protocols to minimize the risk of inflammation in the uterus. One of the most common changes is breeding the mare only once per estrus cycle, to reduce the amount of seminal fluid within the uterus. [3][10]

Some practitioners advocate for breeding the mare as close to ovulation as possible, so that the inflammation in the uterus has time to resolve before the embryo reaches the uterine lining. [10]

Deep horn insemination may also benefit susceptible mares, as the seminal fluid is deposited locally and is less likely to affect the entire uterus. [10][12]

Natural Breeding vs Fresh vs Frozen Semen

Switching semen sources can benefit mares with PBIE and infectious endometritis by reducing their risk of contamination.

For mares with infectious endometritis, artificial insemination (AI) with fresh, cooled, or frozen semen reduces the risk of bacterial contamination compared to natural breeding, as the tools used for AI are sterile. [12]

The mare’s vulva can also be sterilized prepared prior to breeding. If natural breeding must be used, some veterinarians infuse semen extender containing antibiotics into the uterus prior to natural breeding to reduce the risk of infection. [3]

In mares with PBIE, frozen semen is more inflammatory than fresh or cooled options, as the freezing process reduces the amount of seminal plasma. [12] Seminal plasma has anti-inflammatory properties which benefit mares with PBIE, even though the volume of semen used is higher. [12]

Summary

  • Endometritis is an inflammation of the uterine lining that is a common cause of infertility in mares.
  • The condition can be triggered by bacterial or fungal infections or by the mare’s reaction to seminal fluid.
  • Diagnosis typically involves ultrasound of the uterus, biopsy of the endometrium and bacterial or fungal cultures. Treatment options include antibiotics, antifungals, and surgical interventions.
  • Mares affected by endometritis require specialized breeding strategies to ensure successful conception.

With appropriate treatment and management, most mares with endometritis are able to successfully carry a foal to term. Working closely with your veterinarian provides the best chance for successful conception.

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References

  1. McKinnon. A. O. et al., Equine Reproduction. Wiley-Blackwell, 2010.
  2. Díaz-Bertrana. M. L. et al., Microbial Prevalence and Antimicrobial Sensitivity in Equine Endometritis in Field Conditions. Animals. 2021. View Summary
  3. Lavoie. J.-P., Ed., Blackwell’s five-minute veterinary consult. Equine, Third edition. Hoboken, NJ: Wiley-Blackwell, 2019.
  4. Morris, H.L.A. et al., Equine Endometritis: A Review of Challenges and New Approaches. Reproduction. 2020. View Summary
  5. Troedsson. M. H. T. and Woodward. E. M., Our Current Understanding of the Pathophysiology of Equine Endometritis with an Emphasis on Breeding-Induced Endometritis. Reproductive Biology. 2016. View Summary
  6. Morrell. J. M. and Rocha. A., A Novel Approach to Minimising Acute Equine Endometritis That May Help to Prevent the Development of the Chronic State. Front. Vet. Sci. 2022. View Summary
  7. Woodward. E. M. and Troedsson. M. H., Equine Breeding-Induced Endometritis: A Review. Journal of Equine Veterinary Science. 2013.
  8. Katila. T., Evaluation of Diagnostic Methods in Equine Endometritis. Reproductive Biology. 2016. View Summary
  9. Westendorf. J. et al., IIB or Not IIB, Part 1: Retrospective Evaluation of Kenney–Doig Categorization of Equine Endometrial Biopsies at a Veterinary Diagnostic Laboratory and Comparison with Published Reports. J Vet Diagn Invest. 2022. View Summary
  10. Canisso. I. F. et al., Endometritis: Managing Persistent Post-Breeding Endometritis. Veterinary Clinics of North America: Equine Practice. 2016. View Summary
  11. Scoggin. C. F., Endometritis: Nontraditional Therapies. Veterinary Clinics of North America: Equine Practice. 2016. View Summary
  12. Maischberger. E. et al., Equine Post-Breeding Endometritis: A Review. Ir Vet J. 2008.
  13. LeBlanc, MM. Causey, RC. Clinical and subclinical endometritis in the mare: both threats to fertility. Reprod Domest Anim. 2009. View Summary