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Contents

  1. Top of page
  2. Contents
  3. Introduction
  4. Ultrasonography
  5. Uterine Culture and Cytology
  6. New Treatment Strategies
  7. Conclusion
  8. Conflict of interest
  9. Author contributions
  10. References

Rapid physical uterine clearance is paramount for fertility. Mares that are unable to clear the by-products of insemination or foaling quickly may develop post–mating-induced or acute endometritis. If endometritis is not promptly resolved, the infection can become chronic. Endometritis can be difficult to identify because clinical signs, ultrasonographic and laboratory findings can vary between uterine pathogens. Some micro-organisms are associated with an influx of neutrophils and fluid into the uterine lumen while others are associated with only heavy debris on cytological specimens. Identifying the inciting cause may require more than swabbing the endometrium. Culturing endometrial biopsy tissue or uterine fluids are more sensitive methods for identifying Escherichia coli than culture swab while endometrial cytology identifies twice as many mares with acute inflammation than uterine culture swab. While post–mating-induced endometritis is classically treated with uterine irrigation and ecbolics and acute endometritis is treated with either systemic or intra-uterine antibiotics, these therapies are not always effective in resolving chronic uterine inflammation or infections. Mucolytics can be used to break up mucus produced by an irritated endometrium, steroids can modulate the inflammatory response associated with insemination and buffered chelating agents can remove biofilm, a protective mechanism used primarily by gram-negative organisms and yeast to evade the host immune response.


Introduction

  1. Top of page
  2. Contents
  3. Introduction
  4. Ultrasonography
  5. Uterine Culture and Cytology
  6. New Treatment Strategies
  7. Conclusion
  8. Conflict of interest
  9. Author contributions
  10. References

Endometritis in the mare can be divided into acute infectious, chronic infectious or post–mating-induced endometritis. The most critical component in preventing the disease is rapid physical clearance of uterine contents after foaling and mating. Physical clearance can be hindered by anatomical abnormalities such as a pendulous uterus or incompetent cervix or by degenerative changes such as decreased uterine contractility, vascular elastosis or lymphangectasia. Endometritis can also be influenced by the offending pathogen and the mare’s subsequent immunological response to it. Different bacteria express different virulent factors and have different modes of evading the immune response. This can result in an array of clinical signs, ultrasonographic and laboratory findings. Some bacteria such as Escherichia coli tenaciously adhere to epithelial surfaces, preventing their physical removal. Others such as streptococci stimulate production of an inflammatory exudate, interfering with neutrophil phagocytosis. Pseudomonas aeruginosa and some yeast and fungi secrete a biofilm, an adhesive matrix that supports growth and maintenance of bacterial micro-colonies. Biofilms provide inherent resistance to antibiotics and both cellular and humeral immune defences resulting in persistent, chronic infections even after prolonged antibiotic treatment (Costerton et al. 1995; Donlan and Costerton 2002; Otto 2006). Some bacteria or fungi form focal plaques that are not identified by routine swab culture techniques, while others do not produce intra-uterine fluid, the ‘hallmark’ of endometritis. The uterine response to a pathogen also contributes to the establishment and chronicity of infection. During acute and subacute endometritis, mucus production by epithelial cells lining the endometrium, (LeBlanc et al. 2007) (Causey et al. 2000; Causey 2007), is increased; while in chronically inflamed endometria, there is loss of the epithelium and mucus blanket and increased opportunities for bacterial adhesion (Causey et al. 2008). Changes in the production, elasticity or viscosity of endometrial mucus can interfere with the ability of the mucociliary apparatus to remove particulate matter, with sperm migrating to the oviduct or with antibiotic penetration by the endometrium. Because of the many factors affecting fertility, clinicians need to tailor their diagnostics specifically for each individual. Recent data indicate that ultrasonographic and cytological findings from mares with endometritis differ between uterine pathogens and that uterine swabs have lower sensitivity in identifying gram-negative organisms than culture of small volume uterine flushings or endometrial biopsy. Classical treatments for endometritis include uterine irrigation, administration of ecbolics and intra-uterine infusion of antibiotics. These therapies are not effective in all cases of endometritis. Recent clinical studies have shown improved pregnancy rates in chronically infertile mares treated with mucolytics or steroids that modulate the immunological uterine response. In addition, intra-uterine infusion of chelating agents used to penetrate biofilm has been used successfully in clearing chronic gram-negative and yeast endometritis that did not respond to routine therapy. The purpose of this review is to describe clinical findings associated with uterine pathogens and present new uterine culture techniques and treatment strategies for endometritis using mucolytics, steroids or chelating agents.

Ultrasonography

  1. Top of page
  2. Contents
  3. Introduction
  4. Ultrasonography
  5. Uterine Culture and Cytology
  6. New Treatment Strategies
  7. Conclusion
  8. Conflict of interest
  9. Author contributions
  10. References

Accumulation of uterine fluid during the ovulatory period is consistently associated with decreased pregnancy rates. (McKinnon et al. 1988; Pycock and Newcombe 1996; Barbacini et al. 2003). The presence of two or more centimetres of intra-uterine fluid during oestrus or between 6 and 36 h post-breeding are good indicators that a mare is susceptible to mating-induced endometritis (Brinsko et al. 2003) (Troedsson 1997; Bucca et al. 2008). In a recent study, intra-uterine fluid during oestrus was associated with increased numbers of neutrophils in the uterine lumen. Thoroughbred mares with intra-uterine fluid on day 2 or 3 of oestrus were 1.4 times more likely to have >5 neutrophils/400× field on cytological specimens than those with no or mild inflammation (Burleson et al. 2010). However, intra-uterine fluid during oestrus was not always associated with bacterial endometritis. Thoroughbred mares from which the bacterial organisms, E. coli, Staphylococcus aureus, Pseudomonas spp., or bacteria considered to be non-pathogens (micro-coccus, alpha streptococcus or bacillus) were isolated had intra-uterine fluid in <40% of the ultrasonographic examinations (17–39% depending on organism) conducted immediately before the uterine culture was obtained. Intra-uterine fluid was seen more frequently, in 45–55% of the ultrasonographic examinations, when β-haemolytic Streptococcus, Klebsiella pneumoniae, Enterobacter cloacae, or yeast were isolated (Burleson et al. 2010). Other ultrasonographic abnormalities associated with decreased pregnancy rates include abnormal oedema patterns such as excessive oedema pre- or post-mating, an oedema pattern that does not extend throughout the uterine wall (Samper 2009) or the presence of short, thick, hyperechoic lines within the uterine wall signifying either air or exudate.

Uterine Culture and Cytology

  1. Top of page
  2. Contents
  3. Introduction
  4. Ultrasonography
  5. Uterine Culture and Cytology
  6. New Treatment Strategies
  7. Conclusion
  8. Conflict of interest
  9. Author contributions
  10. References

Uterine culture and cytology are common techniques for diagnosis of endometritis, through their respective detection of uterine pathogens and inflammatory cells (neutrophils). If a uterine pathogen is isolated and the mare has more than two neutrophils per 400× field (a positive uterine cytology), she can reliably be diagnosed as having endometritis (Riddle et al. 2007). However, mares may also yield positive uterine cytologies with negative uterine cultures, and vice versa. Recent work indicates that both of the latter scenarios are associated with endometritis and decreased pregnancy rates (Nielsen 2005; Riddle et al. 2007; Bindslev et al. 2008; Nielsen et al. 2008). Mares positive for E. coli, ≥2 organisms, S. aureus and Pseudomonas spp. had fewer cytology specimens with >2 neutrophils per 400× field (range 19–33%) than mares positive for β-haemolytic Streptococcus or Klebsiella (range 50–71.4%) (Burleson et al. 2010; Riddle et al. 2007). Pathogens that were associated with uterine fluid were more likely to have neutrophils on cytology while pathogens not associated with uterine fluid, tended to be negative for neutrophils on cytology. These data indicate that not all uterine pathogens induce an acute neutrophilic response and support the finding that intra-uterine fluid indicates acute inflammation and not necessarily bacterial infection. Other possible causes for an acute neutrophilic uterine response include pneumovagina, refluxing of urine into the uterus, semen and excessive production of endometrial mucus.

To determine the relative importance of culture and cytology, it is helpful to have a ‘gold standard’ for the presence or absence of disease against which the results can be compared, and thereby generate estimates of sensitivity (per cent of disease-positive which test positive) and specificity (per cent of disease-negative which test negative) (LeBlanc and Causey 2009). With this approach, Nielsen (2005) used the presence of neutrophil infiltration of the luminal epithelium and stratum compactum as a gold standard to indicate the presence of disease (endometritis) in 212 uterine biopsies. Against neutrophil infiltration, he compared culture of the endometrial biopsy tissue specimen, swabbing of the endometrium using a guarded culture swab and uterine cytology by smearing the biopsy on a slide. Of the three techniques (biopsy culture, swab culture and cytology), sensitivities were calculated to be 0.82, 0.34 and 0.77, and specificities 0.92, 1.0 and 1.0, respectively. What became apparent was that uterine culture, with a sensitivity of only 0.34, appeared to have a high degree of false negatives in detecting cases of endometritis, and that cytology or culture of a uterine biopsy was twice as sensitive as swab culture in predicting the presence of endometritis. What was also apparent was the high specificity of all three techniques, meaning that there were very few false positives in all three tests. In a more recent study, more mares had a positive cytology but negative uterine culture using a guarded swab (26%) than uterine culture taken from a biopsy (3%) (Nielsen et al. 2008).

Overall, these data indicated that the clinician is confronted with a high rate of false negatives in uterine swab cultures and that methods to improve detection of pathogens required further investigation. LeBlanc et al. (2007) used the same gold standard as Nielsen (2005), but evaluated uterine culture, cytology and indices of inflammation obtained from low-volume uterine flushes, a technique originally reported by Ball et al. (1988). It was hypothesized that more complete sampling of the endometrium might be obtained through such a technique. Using small volume lavage, sensitivity of culture was 0.71 (i.e. double that previously reported for uterine swab cultures), and sensitivity of cytology was 0.80. Specificity of flush culture and cytology were 0.86 and 0.67, respectively. Uterine flush cytology thus tended to under-report inflammation with 70% of positive cultures yielding a negative cytology (a clinical estimation of false positive culture). However, if lack of cytological debris and a clear efflux were added to the definition of a negative cytology, only 11% of positive cultures would have been clinically classified as false. Thus, additional indices available from the flush improved clinical detection of inflammation. Cloudy efflux was highly correlated with the presence of bacteria. The improvement in uterine flush culture sensitivity over swab culture was because of increased detection of E. coli in uterine flush. Isolation of E. coli was characterized by moderate to heavy debris observed on cytology. Therefore, uterine flush culture would appear to be helpful in detecting mares with endometritis because of E. coli.

The findings of these studies were consistent with a large clinical study involving 2123 paired uterine culture and cytology specimens (Riddle et al. 2007). Instead of using biopsy as a gold standard, this study compared culture swab and cytology results to pregnancy rates, a more relevant clinical outcome. Endometrial cytology specimens were collected by rotating the cap of a guarded culture instrument on the endometrial surface. Secretions collected in the cap were tapped onto a glass slide at the stall. The slide was either air dried or fixed with a commercial fixative. Similar to the earlier study (Nielsen 2005), twice as many mares were identified as having endometritis by uterine cytology than uterine culture. In addition, pregnancy rate per cycle was significantly affected by the number of neutrophils per 400× field. Mares with 0–2 neutrophils per 400× field had a per cycle pregnancy rate at 28 days of gestation of 60% compared to 36% for mares with 2–5 neutrophils per field and 23% for mares with >5 neutrophils per field. Isolation of bacteria on culture swab was also associated with a decreased pregnancy rate (36%) even when cytological specimens were normal defined as 0–2 neutrophils per 400× field. These studies stress the importance of interpreting laboratory data in context with clinical findings as the correlation between cytology and culture results varies between micro-organisms recovered. They also indicate that a positive culture, neutrophilic cytology, or abnormal flush alone would indicate a mare as having endometritis.

New Treatment Strategies

  1. Top of page
  2. Contents
  3. Introduction
  4. Ultrasonography
  5. Uterine Culture and Cytology
  6. New Treatment Strategies
  7. Conclusion
  8. Conflict of interest
  9. Author contributions
  10. References

Correcting the defects in uterine defence, neutralizing virulent bacteria and controlling post-breeding inflammation are the goals of successful therapy. This is accomplished by surgically correcting anatomical defects, improving physical drainage after insemination, reducing the length or modulating the inflammatory response to insemination and inhibiting bacterial growth. Post-breeding inflammation is most commonly treated by improving physical clearance of uterine fluid with uterine irrigation followed immediately by administration of either oxytocin (10–25 IU i.v. or i.m.) or cloprostenol (250 μg i.m.) (Brinsko et al. 1990; LeBlanc et al. 1994; Troedsson et al. 1995; Combs et al. 1996; Pycock and Newcombe 1996; Rasch et al. 1996; Knutti et al. 2000; Pycock 2009). In some cases, the uterus is infused with antibiotics post-mating. Bacterial or fungal endometritis are routinely treated for 3–5 days during oestrus with either intra-uterine or systemic antibiotics in combination with uterine irrigation (LeBlanc 2009). Emphasis here will be on the use of mucolytics, chelating agents and administration of steroids for modulating the inflammatory response.

Mucolytics

Not all infections respond to uterine irrigation and antibiotic treatment. Treatment failure may be because of continual contamination of the uterus because of anatomical abnormalities in the caudal tract, degradation of antibiotic in uterine exudates, or biofilm production by the micro-organism. Previous work indicates that mucus secretion increases during experimental uterine inflammation (Freeman et al. 1990), and in mares with delayed uterine clearance and bacterial endometritis (Causey et al. 2000, 2008). Mares with chronic endometritis have an increase in the thickness of the mucus ribbon overlying the endometrium, increased staining intensity of both intracellular and extracellular mucus, and epithelial cell loss (Causey et al. 2008). Excessive mucus or exudate can interfere with antibiotic penetration, can render aminoglycosides chemically inert or may interfere with sperm transport to the oviduct. Treatment with a mucolytic agent may help clear mucus and increase effectiveness of intra-uterine antibiotics. Solvents and mucolytic agents have been added to uterine irrigation fluids in an attempt to clear exudate, mucus or biofilm. Agents used include Dimethyl sulfoxide (DMSO), kerosene and N-acetylcysteine (NAC). Each compound appears to have some beneficial effects. Barren mares (n = 16) infused with a 30% solution of DMSO after breeding tended to have higher pregnancy rates than mares infused with saline (Ley et al. 1989). Intra-uterine DMSO therapy also resulted in a significant improvement in endometrial biopsy classification in 18 of 27 mares; whereas only two of 18 barren mares improved following intra-uterine saline treatment. In contrast, intra-uterine infusion of 50 ml of commercially available kerosene in 26 mares with varying degrees of endometrial pathology induced diffuse moderate to severe endometritis, severe diffuse oedema and production of a serum-like exudates. (Bracher et al. 1991) Half of the mares exhibited mild to severe necrosis of luminal epithelium. Mares were subsequently bred on the next cycle and surprisingly, 50% of the mares with Category II or III biopsy scores carried foals until term. Although kerosene was associated with significant inflammatory changes, pregnancy may have been established because mucus and exudate were removed via destruction and necrosis of uterine epithelium.

N-acetylcysteine is a mucolytic agent that disrupts disulphide bonds between mucin polymers, thereby reducing the viscosity of mucus. In addition, NAC possesses antioxidant and possibly some antimicrobial properties (Zuin et al. 2005; Estany et al. 2007; Duru et al. 2008). NAC has been used to treat respiratory diseases such as pneumonia, the pulmonary component of cystic fibrosis in humans, meconium impactions in both humans (Weller and Williams 1986; Burke et al. 2002) and equine neonates and meconium aspiration pneumonia in equine neonates.(Morresey 2008) Multiple studies support its beneficial anti-oxidative properties especially in chronic inflammatory diseases (Kasielski and Nowak 2001; Zuin et al. 2005; Estany et al. 2007; Duru et al. 2008). We have recently evaluated its effect on the endometrium and epithelium (Gores-Lindholm et al. 2009). Endometrial biopsies were obtained from 12 fertile and 10 barren mares before and after infusion of a 3.3% solution of NAC (day 1) and compared to biopsies obtained from mares infused with saline. The uterus of all mares was irrigated with 2 l of lactated Ringer’s solution on days 2 and 3 and a second biopsy obtained. Endometrial biopsies were given a Kenney grade by a board certified veterinary pathologist (Kenney 1978) and changes in epithelial architecture and mucus blanket were measured by image analysis. Data indicated that NAC was not harmful to the endometrium and that it may counteract the irritating effect of saline, as reflected through increased cell height in control mares. As further evidence that NAC does no harm and may be beneficial, 20 thoroughbred mares each bred 2–5 times in 2007 or 2008 and with a history of endometritis were mated naturally to commercial stallions in Central Kentucky in late May and June 2008. Mares received a 0.6% solution of N-acetylcysteine (ACE) either the treatment cycle before (n = 10) or in the 48 h before breeding (n = 10) in addition to conventional treatments. Infusion before breeding was associated with higher than expected pregnancy rates as 17 of 20 mares (85%) conceived and foaled in 2009. Before this study, the rationale for using NAC as a uterine infusion had been the removal of inspissated secretions, exudate and biofilm, (i.e. as a mucolytic). However, because increased vaginal mucus viscosity is documented to inhibit sperm forward progression in cows (Rutllant et al. 2005), it is also speculated that NAC may improve sperm transport in mares with excessively viscous mucous secretions by breaking the cross-linking disulphide bridges between mucin polymers.

Bacterial and yeast biofilms

Antibiotic failure in chronic endometritis may be because of biofilm produced by some gram-negative bacteria, yeast and fungi. Bacterial biofilms consist of a heterogeneous community of different bacterial species, surrounded by an extracellular matrix, that co-exist in a symbiotic relationship (Walker 2008). Such biofilms are found throughout the human body, e.g. the oral cavity, the skin, the intestines and the vagina. In most cases, the inhabitants of this community are considered as normal flora and serve as a protective mechanism to prevent the colonization of frank and opportunistic pathogens. If the balance of this biofilm community is upset or disrupted, pathogens may colonize, proliferate and cause disease (Walker 2008). Biofilms confer antibiotic resistance and therefore contribute to treatment failure. A number of theories have been advanced to account for this increased resistance (Costerton et al. 1995; Shapiro 1998; Donlan and Costerton 2002; Soto et al. 2006). One is simply that the antibiotic is unable to penetrate the extracellular matrix of the biofilm. Another is that antibiotics are less active on biofilms because of the lower rate of metabolism and growth. A currently popular theory is that there are ‘persister cells’ within the biofilm community. Persister cells are defined as a small subpopulation of essentially invulnerable cells that neither grow nor die in the presence of bactericidal agents and exhibit multi-drug tolerance or resistance to antibiotics (Walker 2008).

Pseudomonas aeruginosa is a potent biofilm producer and is often cultured from the uterus of mares with chronic endometritis. Other equine pathogens that produce biofilm and can be isolated from the uterus include Staphylococcus epidermis, E. coli, E. cloacae and a number of yeast and fungi. These organisms more commonly cause endometritis in older, pluriparous barren mares that have anatomical defects than in young, fertile mares, although uterine defences can be broached in the latter resulting in chronic infection. Infections by these organisms can be difficult to treat, are often refractory to a 3–5 day course of antibiotics and may result in a population of bacteria colonizing the uterus that is highly resistant to the drug initially used for treatment. Work in other species and in the mare has shown that buffered chelating agents (Tris-EDTA, Tricide®) may potentiate the actions of antimicrobials, dissolve exudate and break up biofilm.

Buffered chelators such as first generation Tris-EDTA (ethylenediamine tetraacetic acid (3.5 m)–tromethamine 50 mm;) (Blue et al. 1974; Wooley and Blue 1975; Wooley and Jones 1983; Ashworth and Nelson 1990; Farca et al. 1993; Sparks et al. 1994; Foster and DeBoer 1998) and third generation Tricide® (8 mm disodium EDTA dehydrate and 20 mm 2-amino-2-hydroxymethyl-1,2-propanediol; Medical Molecular Therapeutics, LLC Georgia Biobusiness Center, Athens, Georgia 30602; tricideinfo@yahoo.com) potentiate the actions of antimicrobials (Weinstein et al. 2006). They have been shown to enhance the bactericidal effects of antimicrobials in dogs with refractory otitis (Blue et al. 1974; Farca et al. 1993; Sparks et al. 1994), pyoderma (Farca et al. 1993), osteomyelitis (Ashworth and Nelson 1990), multiple fistulas (Bjorling and Wooley 1982; Ashworth and Nelson 1990), rhinitis (Wooley et al. 1979) and cystitis (Wooley et al. 1974; Farca et al. 1993). Isolates of Pseudomonas collected from the uterus of mares with chronic endometritis exhibited decreased growth and/or death when exposed to Tris-EDTA solution (Kirkland et al. 1983). Others have shown that addition of Tris-EDTA to gentamicin in vitro improved killing of P. aeruginosa by 1000-fold more than treatment with only gentamicin (Wooley et al. 1984). Addition of Tris-EDTA to penicillin, ampicillin, oxytetracycline, neomycin and amikacin has also been shown to be synergistic (Weinstein et al. 2006). A recent study showed that Tricide®, a third generation buffered chelating agent, increased in vitro activity of antifungal drugs against common fungal pathogens isolated from eyes of horses with mycotic keratitis (Weinstein et al. 2006). The mechanism of action of buffered chelating agents is not completely understood but it is speculated that the chelating agent (EDTA) chelates calcium and/or magnesium from the outer membrane of bacteria, thereby altering the integrity and permeability of the cell wall. Damage to the cell wall interferes with the effectiveness of the bacterial efflux pump and facilitates osmotic collapse. Unlike bacteria, fungal cell walls are composed mainly of polysaccharides (beta-glucans and chitin) and protein. It is hypothesized that removal of divalent cations in the cell wall by third generation chelating agents may alter membrane proteins that are important in maintaining the construction and maintenance of the polysaccharides in the wall (Weinstein et al. 2006).

Buffered chelating agents must come in direct contact with the bacterial cell wall to kill the organism so the volume of solution needed for infusion will vary with the size of the uterus. Doses ranging from 200 to 500 ml are recommended. The chelating agent binds to the bacteria within minutes resulting in cell death and accumulation of debris so the uterus should be lavaged within 12 h to remove these by-products. Our current recommended therapy for gram-negative bacteria and yeast repeatedly isolated from the uterus of a mare with endometritis is to infuse 250–500 ml of Tricide® or Tris-EDTA into the uterus on day 1, lavage the solution out within 24 h and examine the efflux. If the efflux is cloudy or has mucus strains, the chelating agent is infused into the uterus again on day 2. Antibiotics are then begun on day 3 following uterine irrigation and continued daily for a minimum of 5 days.

Modulation of the inflammatory response

Fluid may accumulate within the uterine lumen during oestrus because it is not physically drained through the cervix, production is increased because of chronic inflammation, or because the mare is refluxing urine into her uterus. Degenerative uterine changes such as vascular elastosis may also contribute to fluid accumulation. Vascular elastosis appears to indirectly reduce fertility through a reduction in endometrial perfusion, and through disturbances in uterine drainage caused by reduced venous return in capillary beds (Schoon et al. 1999; Esteller-Vico et al. 2007; Liu et al. 2008). For the past 20 years, treatment of post–mating-induced endometritis has emphasized methods for improving physical drainage. However, modulation of the immune response with steroids given around the time of mating has been shown to increase pregnancy rates in mares with fluid accumulation or uterine inflammation (Bucca et al. 2008; Papa et al. 2008). Immunomodulation may help restore homeostatic local inflammatory mechanisms through reducing pro-inflammatory cytokines. This may be especially helpful in older mares that may be suffering from inflamm-aging. Inflamm-aging is a low grade, systemic inflammatory response associated with advanced age in humans and horses that is characterized by increased inflammatory cytokine production (Adams et al. 2008, 2009). Peripheral blood mononuclear cells collected from old horses have been shown to produce more inflammatory cytokines than young horses; moreover, fat old horses have even greater frequencies of lymphocytes and monocytes producing inflammatory cytokines than thin, old horses. Weight loss in old, fat mares reduced the per cent of IFNγ- and TNFα-positive lymphocytes and monocytes and serum levels of TNFα protein. When weight and fat increased in these old horses, there was a significant increase in inflammatory cytokine production (Adams et al. 2008, 2009).

Single dose dexamethasone administered within one hour of mating and daily prednisolone administration given before and after mating have improved pregnancy rates in mares with uterine fluid (Bucca et al. 2008; Papa et al. 2008). A single injection of dexamethasone administered within one hour of mating (50 mg, IV; approximately 0.1 mg/kg) combined with routine post-breeding therapies (uterine irrigation, ecbolic drugs and in some cases intra-uterine antibiotics) resulted in increased pregnancy rates in mares with a history of fluid accumulation after ovulation and in mares with cervical incompetence (Bucca et al. 2008). Treated mares exhibited decreased uterine oedema, decreased intra-uterine fluid and an increase in uterine fluid clarity. Although dexamethasone did not increase pregnancy rates in the general population, pregnancy rates were increased in mares that had three or more risk factors for susceptibility to endometritis. Risk factors included abnormal reproductive history, abnormal perineal conformation, vulvoplasty not repaired after foaling, an incompetent cervix, positive endometrial culture, ≥ 2 cm of endometrial fluid before breeding, endometrial fluid post-mating between 1.5 and 2.0 cm, or a fluid volume ≥ 2 cm, and endometrial fluid persisting more than 36 h after mating. Increased pregnancy rates were also observed in mares with a history of intra-uterine fluid accumulation following oral administration of acetate 9-alpha-prednisolone (0.1 mg/kg) given at 12 -h intervals for 4 days beginning 48 h before breeding (Papa et al. 2008). In contrast, administration of dexamethasone (10 or 20 mg, IM) 6–12 h after insemination did not improve pregnancy rates of warmblood mares (n = 783 cycles) with a history of intra-uterine fluid retention (Vandaele et al. 2008). A plausible cause for the different results is that steroids block both the cyclooxygenase and the 5-lipoxygenase pathways of inflammation. The 5-lipoxygenase pathway includes leukotriene B, a potent neutrophil chemotactic factor found in uterine fluids of susceptible mares after mating (Watson et al. 1988a,b). Reducing neutrophil chemotaxis and the number of neutrophils recruited into the uterus post-mating may diminish the severity and length of the inflammatory response. Candidates for steroid use should be chosen carefully as misuse in mares with bacterial endometritis may exacerbate the infection.

Conclusion

  1. Top of page
  2. Contents
  3. Introduction
  4. Ultrasonography
  5. Uterine Culture and Cytology
  6. New Treatment Strategies
  7. Conclusion
  8. Conflict of interest
  9. Author contributions
  10. References

Not all uterine pathogens produce a neutrophilic response and intra-uterine fluid, the classic signs of uterine inflammation and may therefore require diagnostic methods other than culture swab for identification. Swabbing endometrial biopsy tissue or the efflux obtained from a small volume uterine flush is more sensitive in identifying uterine pathogens than is the culture swab. As pathogens induce different uterine responses and have developed different methods for evading the immune response, treatment with mucolytics or buffered chelating agents can improve treatment success. Some bacterial pathogens that invade the uterus produce biofilm that can confer antibiotic resistance thereby contributing to a prolonged chronic endometritis. Steroids can also be administered to some mares that accumulate fluid before and after breeding in an attempt to dampen the uterine immune response to insemination.

References

  1. Top of page
  2. Contents
  3. Introduction
  4. Ultrasonography
  5. Uterine Culture and Cytology
  6. New Treatment Strategies
  7. Conclusion
  8. Conflict of interest
  9. Author contributions
  10. References
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