Endometritis

Managing Persistent Post-Breeding

Endometritis

Igor F. Canisso, DVM, MSc, PhDa, Jamie Stewart, DVM, MS

a
,
Marco A. Coutinho da Silva, DVM, MSc, PhDb,*

KEYWORDS
 Mare  Endometritis  Post-Breeding endometritis  Uterine lavage
 Intrauterine fluid

KEY POINTS
 Susceptible mares have impaired uterine defense mechanisms.
 Persistent post-breeding induced endometritis is characterized by abnormal imbalance in
pro-inflammatory and anti-inflammatory cytokines.
 Diagnosis can be made through endometrial histology, culture, cytology, and/or ultra-
sound; each of which have differing advantages and disadvantages.
 The most common management strategies include combinations of therapeutic tech-
niques such as uterine lavage and ecbolic treatments that enhance drainage of the persis-
tent uterine fluid.

INTRODUCTION

Mares have been classified as susceptible and resistant to endometritis based on their
ability to clear bacteria from the reproductive tract following experimental inoculation
through the cervix.1–6 Clinically, mares are classified as susceptible to endometritis
based on the persistent presence of intra-uterine fluid accumulation by 24 to 48 hours
post-breeding.7 For years, it was thought that post-breeding endometritis was solely
caused by infectious agents, particularly bacteria.5,8 However, a seminal study
demonstrated that estrous mares infused with either bacteria (Streptococcus zooepi-
demicus) or spermatozoa presented similar number of neutrophils in the uterine fluid
at 4 hours post uterine infusion.9 The results of this study established the concept that
post-breeding endometritis is a normal physiologic, transient inflammatory response

a
Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois
Urbana-Champaign, 2001 S Lincoln Ave, Urbana, IL 61822, USA; b Department of Veterinary
Clinical Sciences, College of Veterinary Medicine, The Ohio State University, 601 Vernon Tharp St,
Columbus, OH 43210, USA
* Corresponding author.
E-mail address: marco.dasilva@cvm.osu.edu

Vet Clin Equine 32 (2016) 465–480

http://dx.doi.org/10.1016/j.cveq.2016.08.004 vetequine.theclinics.com
0749-0739/16/ª 2016 Elsevier Inc. All rights reserved.
466 Canisso et al

that serves the purpose to clear the uterus from excess of sperm cells, seminal
plasma, debris and bacterial contaminants.5,10
Persistent post-breeding endometritis is a prolonged (ie, longer than 48 h) inflamma-
tory response of the endometrium caused by spermatozoa and is estimated to affect
approximately 10% to 15% of mares.7 In some cases, bacterial contamination may
also be present. Therefore, the objectives of this article are to discuss some of the
most relevant literature concerning persistent post-breeding endometritis and the au-
thors’ clinical experiences managing this condition in ambulatory practice and refer-
ring hospitals.

UTERINE DEFENSE MECHANISMS

Reproductive Tract Barriers to Prevent Uterine Infection
Vulva, vestibule-vagina sphincter, and cervix represent three physical barriers or seals
in the mare reproductive tract to prevent uterine infections. If one of these barriers is
not functional, the mare will be prone to pneumovagina and pneumometra (physome-
tra), causing irritation of the uterus and potential aspiration of bacteria. The vulva, an
outward barrier against infection, should have perfectly apposed lips and be vertically
oriented withe 2/3 of the vulvar length located below the pelvic brim and 1/3 of the
vulvar length above the pelvic brim (Fig. 1).
The vestibule-vagina sphincter is the only barrier that remains functional while the
mare is in estrus and helps to prevent aspiration of air and debris into the cranial va-
gina. However, it is also a common site for lacerations during foaling, and its integrity
and competency should be assessed during breeding soundness examinations.
When performing vaginoscopy, the sphincter should offer some resistance to the pas-
sage of the speculum. While advancing or retracting the vaginal speculum, the
sphincter should close like curtains in front of the opening of the speculum. Another
method consists of physically separating the vulvar lips with hands and fingers as
wide as possible, and listening for any noise of air being aspirated into the cranial va-
gina, which would denote an incompetent vestibule-vagina sphincter. Additionally, if
the vestibule-vaginal sphincter is incompetent, the operator may be able to directly
visualize the vagina and cervix (Fig. 2). The cervix should be free from lacerations
and adhesions, relaxed and open during estrus, and be tight and closed during dies-
trus and pregnancy.

Uterine Immune Response

Following intrauterine deposition of semen, there is initiation of a complement system
which is responsible for chemotaxis and activation of polymorphonuclear neutrophils
(PMNs) to the uterine lumen as soon as 30 minutes after insemination.5,11 The acti-
vated PMNs then function to remove bacteria, debris, and sperm cells from the uterus
through phagocytosis.3,12 Neutrophil extracellular traps (NETs) (ie, extracellular fibers
of DNA) also begin to form and appear to play a major role in the uterine clearance
post-breeding by binding to pathogens but not sperm.13 Rebordão and collabora-
tors14 found that mares suffering from S zooepidemicus or E. coli endometritis formed
NETs in vivo, demonstrating a potential complementary mechanism by which mares
can resist endometritis.14 Further work is still warranted to determine if and how
impaired NET formation occurs in mares susceptible to infectious endometritis. While
NETs may play a crucial role in preventing bacterial endometritis, they also release in-
flammatory mediators that some speculate could lead to endometrial degenerative
disease.15 Overstimulation of NET formation and/or a decrease in NET degradation
have been postulated as potential causes for increased endometrial fibrosis and
 Post-Breeding Endometritis 467

Fig. 1. (A) Normal vulvar conformation in a broodmare. Note the vertically oriented vulva,
perfect apposition of vulvar lips, and 2/3 of the vulvar length is located below the pelvic
brim. (B) The maiden mare represented in this picture has a slightly sunken anus, and vulvar
2/3 of the vulvar length is located above the pelvic brim. The vulvar labia on this mare is very
weak and has minimal fat pad surrounding the vulva making the mare prone to pneumo-
vagina. (C) Vulva of an older broodmare, note the recessed anus and imperfect apposition
of the vulvar lips; (D) Quarter horse mare with torn perineal body; (E) Paint Horse vulvar
squamous cell carcinoma. (F) Older Andalusian mare presenting melanoma in the vulva,
note the imperfect apposition of the labia and deformed vulva as a consequence of these
masses, this mare is prone to air aspiration. Lindsey Rothrock is acknowledged for taking
the picture F to the authors.

subsequent endometrial secretory function impairment,15 though no data currently

exists to support this hypothesis.
After breeding, there is an increase in myometrium contractility likely induced by
PGF2a from endometrium and membranes from activated PMNs (ie, via metabolism
of arachidonic acidic through cyclooxygenases) that aid in eliminating sperm and fluid
through the cervix.16,17 Mares susceptible to endometritis seem to have an impaired
ability to evacuate the uterine fluid after breeding,18,19 which can be harmful to both
sperm and developing embryos.12 Compromised uterine contractility is mediated by
increased endometrial production of nitric oxide, a potent muscle relaxant.20 Nitric ox-
ide was found to be elevated after breeding in mares susceptible to endometritis when
compared to resistant mares.21 While it is clear that nitric oxide plays a role in persis-
tent post-breeding endometritis, it is unclear whether it is causative or an effect of the
underlying pathogenesis.
468 Canisso et al

Fig. 2. Evaluation of the vestibule-vagina sphincter in a broodmare. The sphincter was

incompetent allowing direct visualization of the cranial vagina.

Cytokines also play a key role in modulating inflammatory response in normal mares
and mares susceptible to endometritis. Woodward and collaborators21 found that at
around 6 hours post-insemination, susceptible mares had lower mRNA expressions
of the pro-inflammatory cytokine IL6 and the anti-inflammatory cytokines IL10 and
IL1RA (IL1RN), which occur in response to pathogens and are needed to resolve
inflammation. The same authors also reported that IL1b, a pro-inflammatory cytokine,
was found to be increased at both 2 and 6 hours in both susceptible and resistant ma-
res, suggesting a normal mechanism in the initial transient endometritis response.
Interferon gamma (IFNg) expression, important for initiation of the inflammation
cascade, was both delayed in onset and slower to return to pre-insemination levels
in susceptible mares, consistent with clinical signs of prolonged inflammation and
infertility.21 Cytokine response to inflammation is the first step in recognition and elim-
ination of foreign debris; therefore, an altered local cytokine response, as has been
demonstrated in susceptible mares, likely contributes to impaired uterine clearance
and subsequent infertility in susceptible mares.21 (Fig. 3)
Recently, studies have also suggested that CRISP-3 (unpublished personal
communication M Troedsson) and lactoferrin,22 two highly abundant seminal plasma
proteins, may play a role in protecting viable sperm and opsonizing dead non-viable
sperm following breeding. These studies suggest that the seminal plasma may play
a role in the modulation of post-breeding uterine inflammation and require further
investigation.

DIAGNOSIS

A detailed approach on various diagnostic modalities for endometritis is presented in

Ryan A. Ferris’s article, “Endometritis: Diagnostic Tools for Infectious Endometritis,” in
this issue, thus the reader is referred to consult that article for description of the
various methods, and thus herein we will provide an overview of the most commonly
used diagnostic techniques used as part of the breeding management of mares sus-
ceptible to endometritis.
The diagnosis of endometritis in mares is complicated by its multi-factorial nature.
As previously mentioned, the different causes can overlap leading to a multitude of
problems. Often the diagnosis of persistent post-breeding endometritis is attained af-
ter breeding, and prediction of susceptibility is often limited to reproductive history of
 Post-Breeding Endometritis
Fig. 3. Suggested sequence of events involved in persistent breeding induced endometritis. (From Woodward EM, Troedsson MH. Equine breeding-
induced endometritis: a review. J Equine Vet Sci 2013;33(9):673–82; with permission.)

469
470 Canisso et al

failure to conceive and excessive intrauterine fluid accumulation after breeding.23 Risk
factors for susceptibility (Table 1) can be used to estimate whether a mare presented
for breeding may be susceptible to endometritis. For example, infectious endometritis
may be associated with persistent post-breeding endometritis due to the mare’s
inability to clear excess fluid and debris post-mating. Being able to identify the under-
lying pathology can help to determine the best management strategy, which is the
subject of many recent publications. Historically, diagnosis and treatment of endome-
tritis has been focused in “problem mares”, or those with clinical endometritis. How-
ever, recent work has found the rate of apparently healthy mares with subclinical
endometritis to be as high as 28.6%, highlighting the importance of pre-breeding ex-
aminations in all mares.24

Endometrial Sampling: Cytology, Culture and Histopathology

Endometrial cytology is a quick way to diagnose endometrial inflammation in the mare.
However, an accurate cytologic interpretation relies on a collection technique that
yields a high number of well-preserved cells representative of a large uterine surface
area.25 Endometrial cytology can be performed by guarded cotton swabs, cytobrush,
low-volume uterine lavage, or by recovery of intrauterine fluid with an artificial insem-
ination pipette.
A study demonstrated that cytobrush technique combined with culture decreased
the likelihood of a false negative result26; thus, the use of cytobrush is the preferred
technique over cotton swab for routine diagnosis of endometritis.
When evaluating endometrial cytology, a threshold value of 1% PMN cells per
high-power field and/or culture of a single bacterial isolate was associated with
reduced live foaling rates. These results exhibited high specificity (0.94), meaning
that mares with a negative diagnosis were highly likely to produce live foals, but a
very low sensitivity (0.08), meaning that a mare with a positive diagnosis could still pro-
duce a live foal, but were less likely to than a mare without clinical signs of
endometritis.27
Bacterial culture may provide important diagnostic information in cases of infectious
endometritis or to rule out non-infectious endometritis, as growth of microorganisms

Table 1
Incidence of risk factors for endometritis in Sport Horses (n 5 513 cycles)

# of Estrous Cycles
Risk Factors (% Incidence)
Abnormal breeding history 51(8)
Positive endometrial culture 40(7)
2 cm endometrial fluid prior to breeding 74(12)
Abnormal perineal conformation 89(15)
Abnormal cervix 25(4)
Post-breeding endometrial >1.5 <2 cm 23(4)
Post-breeding fluid 2 cm 120(20)
Post-foaling vulvo-plasty (Caslick procedure) not repaired 29(5)
after episiotomy
Abnormalities of the reproductive tract 46(8)
Post-breeding fluid persistent after 36 h after breeding 72(12)

Adapted from Bucca S, Carli A, Buckley T, et al. The use of dexamethasone administered to mares at
breeding time in the modulation of persistent mating induced endometritis. Theriogenology
2008;70:1093–100.
 Post-Breeding Endometritis 471

has been associated with reduced pregnancy rates.2,27 However, as with any diag-
nostic test, false positives and false negatives may result from poor sampling tech-
niques. One of the most commonly used sampling techniques is a guarded culture
swab, which has the advantages of being cheap, easy, and safe to use. However,
swabs only come into contact with a 1 to 2 cm area of endometrium, making a false
negative result likely.28 A low-volume uterine flush, is a reasonable alternative sam-
pling technique with an estimated sensitivity and specificity of 0.71 and 0.86, respec-
tively.28 While more difficult to perform, this technique shows a sensitivity twice as
high as those reported for uterine swabs (0.34 and 0.33) by Nielsen29 and Overbeck
and colleagues,26 respectively. Since this method of cytologic evaluation of the flush
efflux is timely and not practical for use by clinicians, Christoffersen and colleagues30
described a double-guarded flushing technique, which exhibited a comparable sensi-
tivity (0.75) and specificity (0.72) to the previous technique without the need for eval-
uation of the flush efflux to rule out false-positive samples from contamination. In the
authors’ practices, we used cytobrush and swab culture for routine screening and
reserve small volume uterine lavage culture and cytology for mares with history of sub-
fertility, such as being barren for one or more years and with recurrent embryonic
losses.
Endometrial biopsy is expensive and it is not practical for every case, thus in the au-
thors’ practices, this technique is used as part of the breeding soundness evaluation of
mares and can be used to obtain a sample that will be submitted to aerobic culture, as
previously reported.29 The presence of polymorphonuclear cells in the luminal epithe-
lium and stratum compactum of the endometrium on histology are indicative of inflam-
mation/infection. Kenney & Doig31 introduced a scoring system in which mares were
classified into 4 categories according to the acute and chronic changes observed in
the histopathology of the endometrium. Though this classification system can predict
the ability of a mare to carry a foal to term, it does not determine the ability of the mare
to become pregnant.32,33 Therefore, the use of uterine biopsies to diagnose cases of
post-breeding endometritis is limited.

Ultrasound Examination
In mares with persistent post-breeding endometritis, the major consequence of
impaired uterine clearance is increased uterine fluid retention and persistent inflamma-
tion or edema of the endometrium, which occurs more frequently in older or barren ma-
res and is associated with reduced fertility.34 This may be partially due to the build-up of
nitric oxide in susceptible mares that could cause myometrial relaxation, leading to
decreased clearance of fluids. Intra-uterine fluid accumulation measuring greater
than 2 cm in height on transrectal ultrasound during estrus prior to breeding were
more likely to be susceptible to persistent breeding induced endometritis (Fig. 4).35 Us-
ing an endometrial edema scoring system (0 absent and 4 excessive edema), Rasmus-
sen and colleagues24 found that the mares with a score of 3 (strong edema), or 4
(excessive edema) early in estrus were 5.48 times more likely to have a positive culture
of S zooepidemicus post-breeding than those with a score of 2 (moderate edema).
These results confirm the standard clinical practice of checking mares post-breeding
not only for ovulation, but to assess the presence and type of fluid post-breeding.

MANAGEMENT STRATEGIES FOR SUSCEPTIBLE MARES

Overall treatment for persistent breeding induced endometritis includes a combination

of antimicrobials, correction of anatomic defects and management strategies to con-
trol/modulate uterine inflammation.
472 Canisso et al

Fig. 4. Large echogenic amount of intrauterine fluid accumulation in an older broodmare

post-breeding.

Antimicobials
Antimicrobials may be used in treatment and or prevention of post-breeding induced
endometritis.36 Post-breeding intra-uterine infusion of antimicrobials is a standard
method used to prevent uterine infection mainly in Thoroughbreds mares. However,
there is no evidence-based data supporting that this practice actually improves
conception rates or prevent infection. It is likely that a single antibiotic infusion post-
breeding will not prevent bacterial infection.36
The use of repeated intrauterine infusions of antibiotics may also lead to distur-
bances in the normal vaginal flora which predispose the mare to fungal endometritis.
Thus, the authors’ preference is to use antibiotics systemically whenever is possible.
In this case, antibiotics that reach high levels in the endometrium and uterine lumen
are selected. Tables 2 and 3 list the common antibiotics used to treat mares with
endometritis.

Correction of Anatomic Defects

Mares presenting anatomic defects in the reproductive tract should have these abnor-
malities surgically corrected before breeding. The most common anatomic defects
observed are poor perineal conformation, poor opposition of vulvar lips or lacerations
to the perineal body. Lacerations of the perineal body are often underdiagnosed and
this is one of the common problems we encounter in referral cases of subfertile mares
in our practice. This defect can be easily fixed with a simple surgical procedure as
shown in Fig. 5. If mare is confirmed to have a cervical laceration, pending on the
size and location, the mare may need to undergo surgery. It has been the authors’
experience that if the vaginal portion of the cervical is lacerated most mares are
able to carry and delivery normal pregnancies without the need to fix the cervix. On
 Post-Breeding Endometritis 473

Table 2
Drugs commonly used for intrauterine infusion in mares

Drug Dosage Comments

Amikacin sulfate 1–2 g Buffer with equal volume of 7.5% NaHCO3 or large
volume (150–200 mL)
Ampicillin 1–2 g Gram-negative spectrum, use soluble product at
high dilution, may be irritating when
concentrated; susceptible gram-positive and
gram-negative organisms, including E. coli
Ceftiofur sodium 1g Broad spectrum (S zooepidemicus), reserve for
organisms resistant to other antimicrobials;
susceptible gram-negative and gram-positive
organisms
Gentamicin sulfate 1–2 g Buffer with NaHCO3 or large volume (150–200 mL)
saline solution; susceptible S zooepidemicus
(some isolates), Enterobacter spp, E coli, Klebsiella
spp, Proteus spp, Serratia spp, P aeruinosa, S
aureus
Neomycin sulfate 2–4 g Gram-negative spectrum, useful against E coli and
some Klebsiella spp
Potassium penicillin 5 million units Gram positive spectrum (S zooepidemicus)
Polymyxin B 1 million units Good spectrum against Pseudomonas spp
Ticarcillin 3–6 g Anti-pseudomonas; b-lactam drug; good spectrum
against gram-positive organisms; infuse diluted in
a minimum of 200 mL of saline solution
Ticarcillin 3–6 g Clavulanic acid is a b-lactamase inhibitor, confers
greater activity against Enterobacter spp, S
aureus, Bacillus fragillis, S zooepidemicus; infuse
with a minimum of 150–200 mL saline solution

Data from Canisso IF, Coutinho da Silva MA. Bacterial endometritis. Sprayberry KA, Robinson NE,
editors. In: Robinson’s current therapy in equine medicine. St Louis (MO): WB Saunders; 2015.
p. 683–88.

Table 3
Commonly used systemic antimicrobials for endometritis in mares

Antimicrobial Dosage Route

Amikacin sulfate 10 mg/kg q24 h IV or IM
Ampicillin 29 mg/kg q12 or 24 h IV or IM
Ceftiofur sodium 2.5 mg/kg q12–24 h IV or IM
Ceftiofur crystalline free acid 6.6 mg/kg q4 d IM
Enrofloxacin 5 mg/kg q24 h IV
7.5 mg/kg q24 h PO
Gentamicin sulfate 6.6 mg/kg q24 h IV
Metronidazole 15–25 mg/kg PO
Potassium penicillin 25,000 IU/kg q6 h IV
Procaine penicillin 22,000 IU/kg q12 h IM
Trimethoprim-sulfamethoxazole 30 mg/kg q12 h PO

Data from Canisso IF, Coutinho da Silva MA. Bacterial endometritis. Sprayberry KA, Robinson NE,
editors. In: Robinson’s current therapy in equine medicine. St Louis (MO): WB Saunders; 2015.
p. 683–88.
474 Canisso et al

Fig. 5. Perineal body reconstruction in a Quarter Horse mare following a mild dystocia.
After the mare is blocked with lidocaine, stay sutures are placed and then a flap of the dor-
sal aspect of the vestibule is removed, thereafter, the borders of the incision are sutured
together to form a shelf and then the dorsal aspect closed with simple interrupted absorb-
able suture. The procedure is finished by placing Caslick’s stitches.

the other hand, if the laceration is cranial in the cervix and extensive, surgical correc-
tion may not be possible.
Uterine Lavage
Uterine lavage is commonly used to manage endometritis in mares post-breeding.
Obvious advantages include physical removal of microorganisms, sperm cells, debris,
inflammatory products which may prolong the endometrial inflammation. Lactated
Ringer’s Solution (LRS) is the preferred and most commonly used solution to perform
uterine flushing. Mucolytics and chelators can be used to improve uterine lavage
(Table 4). In a typical post-breeding uterine lavage, 2 L are usually sufficient, but
sometimes three to 5 L may be necessary. While performing uterine lavage, the prac-
titioner needs to ensure that the entire uterus is fully distended to ensure that the whole
surface is flushed, and the lavage is continued until the effluent is clear.
Maiden mares will typically tolerate 1 L of LRS at the time, and broodmares can
easily tolerate 2 L of LRS in their uteri. It is worth noting that some mares may present
signs of mild discomfort (shifting weight, moving hind legs up and body forward) when
2 L of LRS are used. However, the use of 2 L of LRS per flush assures that the entire
uterus is dilated and flushed and facilitates fluid recovery.
Post-breeding uterine lavage is commonly performed with a Bivona-type catheter,
and the balloon inflated to avoid reflux of fluid through the cervix. This procedure is first
performed 6 to 24 hours post-breeding, and repeated daily, if necessary, until deemed
no longer necessary. Mares presenting intra-uterine fluid accumulation pre-breeding
may have uterine lavage performed immediately prior to breeding. The criteria for lav-
aging a mare’s uterus pre- and post-breeding can be based on the mare’s history of
producing excessive amounts of fluid post-breeding, the detection of moderate to
large amounts of intrauterine fluid accumulation (>2 cm depth) with certain defining
features (ie, intrauterine fluid accumulation with high echogenicity), or simply clini-
cian’s preference.
 Post-Breeding Endometritis 475

Table 4
Other treatments used in mares with endometritis

Product Mechanism of Action Comments

Dimethyslsulfoxide (DMSO Postulated to reduce May result in irritation if
10%–20%) endometrial applied in high
inflammation by concentration
scavenging free radical
N-acetylcysteine (5%–10% Postulated to disrupt Anecdotally effective in
solution) disulfide bonds between improving pregnancy
polymers, resulting in rates for barren mares
clearance with history of bacterial
endometritis
Buffered chelators (Tris Postulated to chelate Potentiates the effects of
EDTA and Tricide) divalent cations in the antifungals and
fungal cell membrane, decreases resistance to
resulting in altered antifungals
fungal structural
integrity

Data from Canisso IF, Coutinho da Silva MA. Bacterial endometritis. Sprayberry KA, Robinson NE,
editors. In: Robinson’s current therapy in equine medicine. St Louis (MO): WB Saunders; 2015.
p. 683–88.

We prefer to perform uterine lavage by 6 hours post breeding. It is our clinical expe-
rience that flushing the uterine lumen at this time helps to avoid excessive inflamma-
tory response in susceptible mares. Our anecdotal experiences are supported by
controlled design studies where the authors found that 6 hours post-breeding appears
to be a critical time point for uterine inflammation between susceptible and resistant
mares.17,23 Additionally, sperm transport appears to be completed by 4 hours post-
breeding,37 and fertility should not be affected by uterine lavage performed at or after
4 hours post-breeding.38 As a basic rule, when performing uterine lavage, additional
flushing should be added if the last fluid recovered still appears cloudy and/or contain
mucus strings (Fig. 6).

Ecbolic
Oxytocin and cloprostenol (an analog of prostaglandin F 2 a (PGF2a)) have been
commonly used as ecbolic agents. These drugs stimulate uterine contractility and
eliminate intrauterine fluid accumulation through an open cervix and/or through
lymphatic drainage. Oxytocin is associated with strong uterine contractions for a short
period of time (<45 min); whereas cloprostenol (125–250 mcg/IM) induces a weak but
prolonged uterine contraction (up to 2 h).10,39 In our clinical experience prolonged
uterine contraction appears to be very beneficial for mares with a very pendulous
uterus.
We recommend to begin oxytocin therapy by 6 hours post breeding or pre-breeding
if the mare has intrauterine fluid accumulation. Oxytocin (20 units/IM) is administered
at intervals of 2 to 8 hours. In our practice, susceptible mares may receive oxytocin
every 2 hours. We only use needles with very small calibers, typically a 25 gauge nee-
dle, to prevent a mare from becoming needle-shy or aggressive toward the person
administering the drugs. Smaller doses of oxytocin (10–20 units) are more effective
in inducing uterine contractions than larger doses (40 units), as larger doses induce
tetanic uterine contractions rather than cyclic uterine contractions, thus preventing
uterine evacuation.10
476 Canisso et al

Fig. 6. Severe inflammatory response in a mare highly susceptible to endometritis. This uter-
ine lavage was performed approximately 6 to 8 h post-insemination. The second bag of fluid
(on right) contains less debris; however, flush was continued until effluent was clear.

Cloprostenol should be used with caution as it may be associated with hemorrhagic

anovulatory follicles and is therefore not recommended in older mares with history of
HAF.40 Additionally, cloprostenol should not be given to mares post-ovulation
because it will interfere with CL formation and progesterone secretion.39
Carbetocin, a long-acting oxytocin analog, has been introduced as a potentially
more effective alternative to oxytocin41 or cloprostenol in the breeding management
of mares. However, its use in clinical practice has been rather limited and more
data is needed before specific recommendations regarding its use can be provided.

Prostaglandin E & Misoprostol

Old maiden mares, nervous young maiden mares, and embryo donor mares (used for
embryo donation without carrying foals to term), are very likely to present excessive
post-breeding fluid accumulation due to inadequate cervical dilation during estrus.
The authors recommend managing such mares proactively by performing uterine
lavage 6 hours post breeding. Moreover, prostaglandin E preparations or misoprostol
can be applied on the cervix after uterine lavage to maintain the cervix open. Such ma-
res may also have the cervix gently dilated manually during the lavage. Some clinicians
advocate drawing of the uterine catheter from the uterus with the balloon inflated to
help stretch the cervix.
Prostaglandin E may be purchased as a cream/liquid preparation from compound-
ing pharmacies or human pharmacy and can be applied directly to the cervix (2–
2.5 mg/mare). In addition to not being readily available as a commercial product,
another major disadvantage of this drug is the elevated cost, making it not feasible
to use on all mares. This is in contrast to misoprostol (a synthetic prostaglandin E1
analogue), which is inexpensive and widely available as 100 mcg tablets that can be
crushed, mixed with sterile lube, and directly applied to the cervix. The recommended
dose for this treatment is 1 to 2 mg/mare. However, it is worth to note that a recent
controlled study did not find measureable differences in mares receiving 1 mg intra-
cervically.42 In our practice, we associate the use of misoprostol with manual dilation
of the cervix and which appears to enhance its response. Another controversial
 Post-Breeding Endometritis 477

treatment that has been described to relax the cervix in susceptible mare is
buscopan. Some clinicians advocate using buscopan (N-butylscopolammonium bro-
mide 20 mg/mL) 20 to 40 mg locally in the cervical lumen to aid in stretching the cervix.
The authors’ have used buscopan with variable results, but currently no controlled
data is available to justify its use.

Uteropexy
In Thoroughbreds, assisted reproductive techniques are not allowed, which repre-
sents a challenge to those mares that may have difficulties conceiving due to the pres-
ence of a pendulous uterus. With that in mind, Brink and collaborators43 described a
surgical technique using laparoscopy to imbricate the mesometrium in 5 barren ma-
res. Three out of five mares became pregnant within the same year without any major
intervention. Standard abdominal laparoscopic technique is performed under seda-
tion with the mare standing in stocks. The dorsal aspect of the mesometrium and myo-
metrium and perimetrium are then sutured together by a simple continuous suture
placed 1.5 cm apart (10–14 bites per side). Though the technique has potential to
improve reproduction in the Thoroughbred industry, it does not seem to be widely uti-
lized for unknown reasons. We speculate that this underutilization may be due to finan-
cial constraints of the owners or that most clinicians are unfamiliar with the technique.
Regardless, this technique should be considered as a viable option when indicated.

Breeding Management
Most clinicians’ agree that susceptible mares should be bred with highly fertile semen
whenever possible, and some advocate to breed the mare several days from ovulation
to allow time for the uterine inflammation to subside before the embryo enters the
uterus. Susceptible mares can have semen deposited in the uterine body as deep
horn insemination, with frozen or fresh cooled semen, using either a flexible AI pipette
or hysteroscopy; however, this was associated with lower pregnancy rates in suscep-
tible mares, in contrast to enhanced pregnancy rates in resistant mares.44 Moreover,
mares should be inseminated only once per cycle, in order to decrease the inflamma-
tory stimulus to the endometrium. Thus, the use of ovulation inducing agents is
indicated, such as deslorelin acetate (1.8 mg) or human chorionic gonadotropin
(1500–2500 Units).

Immune Modulators
Glucocorticoids are the most widely used immunomodulatory drugs to manage mares
susceptible to endometritis. Recently, non-traditional immunomodulatory agents such
as platelet-rich plasma, mycobacterium cell wall extract, Propionibacterium acnes,
and Ceragyn have also been used to manage mares with variable success, and these
therapies are being covered in Charles F. Scoggin’s article, “Endometritis: Non-
Traditional Therapies,” in this issue.
Administration of prednisone acetate starting 2 days before breeding was effective
in improving pregnancy rates in mares bred with frozen semen.45 Intravenous admin-
istration of 50 mg dexamethasone (w0.1 mg/kg) within 1 hour of breeding in combi-
nation with common treatment (ecbolics, uterine lavage) reduced persistent
post-breeding endometritis as assessed by decreasing post-mating efflux turbidity
and endometrial edema with no change in the number of PMN cells recovered by small
volume lavage.46 Interesting to note that dexamethasone only improved pregnancy
rates in mares presenting with more than three risk factors (see Table 1).46 This study
demonstrated the importance of case selection when deciding to give dexametha-
sone to mares at breeding time. In our practice, we typically administer 20 to 40 mg
478 Canisso et al

(IV) to mares with history of excessive intrauterine fluid accumulation around breeding
and may repeat the dose at 24 hours after breeding if the mare is presenting excessive
intrauterine fluid accumulation. However, other authors failed to observe improvement
in pregnancy rates in w700 cycles of w350 treated with 10 to 20 mg of
dexamethasone.47
Uterine inflammation post-breeding is a physiologic reaction of the endometrium
to sperm that subsides in 24 to 48 h. Persistence of this inflammatory reaction
beyond 48 h is caused by many different factors alone or in association. Thus, the
clinical approach to manage cases of persistent post-breeding endometritis should
be based on the reproductive characteristics of the individual mare and adapted to
circumvent or improve these faults, in order to maximize pregnancy and foaling
rates.

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