Endometritis in the mare Flashcards

1
Q

Endometritis is a common cause of poor fertility in the mare. It occurs following uterine contamination during covering, artificial insemination, reproductive examination, parturition and as a result of poor conformation.

What are the types of endometritis:

A
  1. Venereal Infectious Endometritis
  2. Non-venereal Infectious Endometritis
  3. Persistent Post-mating Endometritis
  4. Chronic Degenerative Endometritis
  5. Chronic Infectious Endometritis
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2
Q

Three major pathogens cause venereal endometritis in the mare. What are they?

A

Taylorella equigenitalis - causing the notifiable Contagious Equine Metritis (CEM)

Klebsiella pneumoniae - tests can be performed to identify capsule types 1, 2 and 5 which are sexually transmitted

Pseudomonas aeruginosa - there is no available test to differentiate strains so all must be treated as pathogenic

Equine Viral Arteritis (EAV) and Equine Herpes Virus 3 (EHV-3) are also classified as venereal infections however they do not cause endometritis or prevent conception.

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3
Q

What is the presentation of venereal endometritis in the mare?

A

The mare may present with vaginal discharge (raging from scant to copious) in an acute infection. However she may also present in a carrier state, in which case there may be no outward clinical signs. Stallions are usually sub-clinical carriers of disease. All three bacteria prevent conception.

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4
Q

Discuss Non venereal infectious endometritis?

A

This occurs following infection during covering, reproductive examination or foaling.

History of infertility or early embryonic death and short cycles.

There may also be evidence of vaginal discharge.

Infection causes by :

  • Bacterial Infection - Streptococcus zooepidemicus, Escherichia coli or Staphylococcus aureus
  • Fungal Infection
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5
Q

Discuss Persistent post mating endometritis?

A
  • more common in older and multiparous mares
  • They present with a history of short cycling and often an vaginal discharge approximately two weeks post-cover.
  • A transient inflammatory response is normal in the mare post-cover, however a normal immunological response is mounted and the infection cleared before the embryo exits the fallopian tube. In the cases of persistent post-mating endometritis the inflammation persists longer than 72-96 hours so that when the embryo enters the uterus the environment is still unsuitable for embryonic development, resulting in early embryonic death.
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6
Q

Discuss Chronic degenerative endometritis?

A
  • Older mares or following repeated inflammation of the uterus.
  • Definitive diagnosis can only be achieved by biopsy, which will show degenerative change of the uterus histologically.
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7
Q

Discuss Chronic infectious endometritis?

A
  • Normally an underlying conformational condition such as pneumovagina predisposes the mare to chronic infectious endometritis.
  • Definitive diagnosis is again by biopsy which should show infiltration of the endometrium with lymphocytes and plasma cells.
  • Infection caused by :
    • Bacterial - Streptococcus zooepidemicus, Escherichia coli
    • Fungal - more common if there is a history of multiply intra-uterine antibiotic treatments
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8
Q

What may show in clinical exam diagnosis of endometritis?

A

Clinical examination may reveal vulval discharge or matted tail hairs.

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9
Q

What may show in vaginal exam diagnosis of endometritis?

A

Vaginal examination should identify any discharge and increased vascularity of the tissue. Conformational abnormalities resulting in e.g. pneumovagina and urovagina may be evident.

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10
Q

What may show in ultrasound exam diagnosis of endometritis?

A

Ultrasound examination of the uterus - more than 2 cm of fluid with abnormal character suggests endometritis.

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11
Q

What may show in clitoral and endometrial swabs of endometritis?

A

Clitoral and endometrial swabs should be taken for culture and sensitivity. Clitoral swabs should be taken if a chronic venereal infection is suspected. Guarded endometrial swabs should be taken during oestrus to identify either acute venereal infections or the causative organism of other endometrial infections and evidence of inflammation. A high level of neutrophils is indicative of endometritis. The mare should be confirmed as not pregnant before taking an endometrial swab.

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12
Q

What may show in Uterine flush of endometritis?

A

the uterus should be flushed with 100mls of fluid which can then be examined cytologically for evidence of inflammatory cells and bacteria.

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13
Q

What may show in Endometrial endoscopy of endometritis?

A

can be performed to visualise and assess the endometrium.

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14
Q

When is a uterine biopsy indicated in endometritis cases?

A

Uterine biopsy - this should be performed after all other tests have failed to reach a diagnosis or to definitively diagnose endometriosis or chronic infectious endometritis. A single sample should be representative if the uterus feels normal on palpation. If an abnormality is detected on examination per rectum then samples should be taken from both normal and abnormal sites.

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15
Q

What is the treatment for endometritis?

A

A combination of multiple therapies should be used to collectively resolve the inflammation within the uterus and treat existing infections:

  1. Uterine lavage with copious amounts of fluid. This is beneficial because it: removes contaminants such as bacteria and purulent material; stimulates uterine contractions to aid clearance and causes mechanical irritation to the endometrium aiding healthy neutrophil recruitment
    1. 2-3 litres of saline or lactated ringers solution should be administered using a uterine flushing catheter and then drained back into the bag and inspected. Dilute Povidone iodine can also be used as a cheap alternative
  2. Antibiotics (intrauterine or systemic). Antibiotic type should be guided by culture and sensitivity and activity of the drug in the uterus where possible. The length of the treatment should be proportional to the severity of infection.
  3. Administration of ecbolics to stimulate uterine contractility and clearance of infection - oxytocin and prostaglandin analogues
  4. Hormonal therapy- Oestradiol Benzoate and PG can be used to aid the clearance of infection. They are more effective during oestrus.
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16
Q

What is the management for susceptible mares?

A
  1. Identify problem mare
  2. Plan a single insemination using a stallion with high fertility rates approximately 1-2 days prior to ovulation. Semen extender may be delivered intra-uterine before cover.
  3. Ultrasound the uterus in the first 12 hours post-cover. The character and volume of fluid present should be assessed.
  4. Remove uterine contaminants via lavage and antibiotic infusion. Administer oxytocin 8 hours after treatment.
  5. Repeat ultrasound examination after 24 hours.

Treatments should not be repeated if possible as this may introduce infection.

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17
Q

What is the aetiology of Contagious equine metritis?

A
  • Taylorella equigenitalis Taylorella equigenitalis, a gram negative, coccobacillus that does not grow serologically on conventional media.
  • Pin-point colourless colonies after 3-7 days microaerophilic culture on enriched ‘chocolate’ agar.
  • Two strains exist, streptomycin resistant and sensitive.
  • Contact with a carrier stallion, mare, or fomite spread by handlers and vets.
  • Natural breeding or artificial insemination.
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18
Q

How is Contagious equine metritis diagnosed?

A

Presenting problems

  • Failure to conceive.
  • Vulvar discharge.
  • Endometritis, cervicitis.
  • Swab from endometrium, cervix or clitoral fossa and sinuses → bacteriological culture required (PCR test may provide a quicker result if available).
  • Complement fixation test carried on blood 20-45 days after breeding.

Client history

  • Failure to conceive.
  • Early return to estrus.

Microbiology

  • Most reliable method of diagnosing T. equigenitalis Female: bacterial venereal disease screening Male: bacterial venereal disease screening.
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19
Q

How should bacterial venereal pathogen screening be done in mares and stallions?

A

Mares:

  • Narrow tipped swabs must be used to effectively sample the clitoral sinuses and regular swabs for sampling other sites. Place swabs deep in Amies charcoal medium and keep cold until submitted at an approved laboratory within 24-48 h of collection.
  • Clitoral swabs may be taken at any stage of the cycle or pregnancy (endometrial swabs must not be taken during pregnancy as breaching the cervix is likely to cause abortion).
  • In acute cases, endometrial smears that are Dif-Quik stained can be examined for the presence of the coccobacilli within the polymorphonuclear leukocytes. Although not diagnostic, extremely presumptive of infection!

Stallions:

  • With penis fully extended and erect swab 4 sites - urethral fossa and sinus, urethra, preputial folds and pre-ejaculatory fluid.
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20
Q

What are the Differential Diagnosis of contagious equine metritis?

A
  • Endometritis - other bacterial causes (failed uterine defense mechanisms) - bacterial by common pathogens, eg Streptococcus zooepidemicus.
  • Other bacterial venereal pathogens Pseudomonas aeruginosa and Klebsiella pneumoniae
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21
Q

What are the Clinical signs of Contagious equine metritis?

A
  • Profuse grayish mucoid vulval discharge approximately 2 days post-breeding and lasts up to 2 weeks in untreated cases.
  • Lowered conception rates.
  • Chronic infections → little vulvar discharge + early return to estrus.
  • Endometritis Uterus: endometritis - bacterial.
  • Vaginitis Vagina: bacterial infection.
  • Cervicitis.
  • Abortion (rare).
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22
Q

What is the treatment of contagious equine metritis?

A

Standard treatment

  • Isolate all suspect cases and cease breeding.
  • Notify State and Federal health officials (USA) or DEFRA and appropriate breed societies (UK) if positive CEMO cultured.
23
Q

What is the treatment of contagious equine metritis in the female?

A
  • Intrauterine infusion Therapeutics: intra-uterine of 50-100 ml crystalline penicillin solution Penicillin G (5-10 million units) for each of 5 days (alternatives include soluble ampicillin and amoxicillin Therapeutics: antimicrobials).
  • Clean out clitoral sinuses and scrub with 4% solution of chlorhexidine Chlorhexidine then pack the fossa with nitrofurazone 0.2% soluble ointment or suitable alternative daily for 5 days
  • Re-establish normal clitoral flora with actively growing broth cultures of commensal organisms collected by clitoral swabbing a normal mare.
  • Where there is chronic endometritis +/- salpingitis a 7-10 day course of systemic antibiotics is indicated, eg intramuscular procaine penicillin Therapeutics: antimicrobials.
  • Clitoral sinusectomy: if repeated courses of medical treatment prove unsuccessful → surgery to remove the clitoral sinuses
24
Q

What is the treatment of contagious equine metritis in the male?

A
  • Treat with the penis fully extruded and erect.
  • Wash with 4% chlorhexidine solution paying particular attention to the urethral fossa, sinus and folds of the prepuce.
  • Pack with nitrofurazone ointment or suitable alternative.
  • Repeat daily for 5 days.
  • Re-establish normal penile flora with actively growing broth cultures of commensal penile organisms
25
Q

How should contagious equine metritis be monitored?

A

Monitoring

  • Take series of swabs preferably 7 days apart (clitoral and endometrial from mares, urethra/urethral fossa/prepuce from stallions).
  • Three consecutive negative results are regarded as confirmation of elimination of infection.
  • Test breed a stallion to two culture and antibody negative mares and maintain mares for evidence of infection both by culture and serology.

Subsequent management Monitoring

  • Check first three mares bred to a stallion cleared of T. equigenitalis for evidence of CEM infection.
26
Q

How is contagious equine metritis controlled?

A

In the UK, the HBLB Codes of Practice for the Control of Contagious Equine Metritis and other venereal diseases of the horse should be adhered to by all owners of mares and stallions entering a breeding program.

Test all mares before breeding.

Practice strict reproductive and veterinary hygiene techniques Female: examination - minimal contamination.

Use disposable and sterile equipment and supplies.

Levels of testing depend on whether mares are classified as ‘high’ or ‘low’ risk.

High risk mares:

  • Have been infected by T. equigenitalis in the last 5 years.
  • Were infected >5 years ago but not mated since.
  • Were bred to stallions that were CEM positive in the last season.
  • Are imported mares from countries OTHER THAN Canada, France, Germany, Ireland, Italy, UK and USA.
  • Are mares from the above countries that have been bred to stallions from countries not listed.

Low risk mares:

  • All other mares.
27
Q

What is the prognosis of contagious equine metritis?

A
  • Occurrence of the carrier state in mare and stallion means that the prognosis must be guarded. Stringent adherence to the HBLB Codes of Practice will minimize the risk of an outbreak.
  • Early intrauterine antimicrobial therapy can resolve infection quickly with less likelihood of carrier state occurring.
  • Antimicrobial treatment is likely less effective in clearing chronic low grade infections with less pronounced clinical signs.

The carrier state may occur in up to 20% of animals regardless of treatment.

28
Q

Discuss Post-partum metritis?

A

Serious condition of mares with RFM following dystocia or following aided delivery

Should be treated urgently to prevent P3 movement

Treatment

  • Attempt to cause placental separation should be made
  • Removal of uterine fluid using scooping and/or lavage with 1-2 litres saline and immediate drainage by siphonage
  • Broad spectrum antibiotic systemically
  • Local infusion of antibiotic into the uterus and systemic use.
  • NSAIDs
  • Vasodilators etc
  • Treatment is repeated daily until the pus and placental debris have disappeared
29
Q

What is the aetiology of Pyometra in the mare?

A
  • some interference with the usual process of fluid clearance from the uterus; a sequel to endometritis; cervicitis; cervical adhesions following previous dystocia; functional failure of the cervix to relax (so called ‘fibrotic cervix’; persistent corpus luteum)
  • Uncertain.
  • Associated with bacteria and fungi found in endometritis cases Uterus: endometritis - bacterial.
  • Most commonly associated with Streptococcus zooepidemicus Streptococcus spp.
  • Also implicated are:
    • Pseudomonas aeruginosa Pseudomonas aeruginosa.
    • Escherichia coli Escherichia coli.
    • Actinomyces spp.
    • Pasteurella spp Pasteurella multocida.
    • Propionibacterium spp.
  • Often mixed infections.
  • Occasionally discharged material is sterile.
30
Q

What are the predisposing factors for equine pyometra?

A
  • Cervical or caudal uterine adhesions.
  • Trauma.
  • Cervicitis.
  • Functional closure of the cervix (so called ‘fibrotic cervix’; persistent corpus luteum).
  • Uterine therapy with irritating agents.
  • Reduced endometrial resistance.
  • Hot, dry, dusty regions.
  • Some types of dystocia
31
Q

What is the diagnostic plan for equine pyometra?

A

Rectal palpation

Distended uterus with various amounts of fluid.

Uniformly enlarged horns, thin-walled and atonic, or usually thick-walled and doughy.

Examination of cervix

Vaginoscopic Female: vaginoscopy, digital Vagina and cervix - manual examination:

Discharge may be visible coming through external os of cervix.

Presence of damage and adhesions.

2D Ultrasonography

Uterus contains typically hyperechoic fluid with ‘scintillating’ particles throughout both horns and body .

Retained functional corpus luteum sometimes, but not always, presents.

Fluid/aspirate analysis

Viscid brownish/cream pus containing many degenerate leukocytes and bacteria: pyometra.

Viscid grayish fluid, bacteriologically sterile, eosinophilic and amorphous: mucometra.

Microbiology

Uterine bacterial/fungal culture.

Bacteria or fungi typical of endometritis may be cultured.

Endometrial cytology.

Biopsy

Endometrial biopsy is indicated to obtain prognostic information before treatment Endometrium: biopsy.

Deep, chronic changes in the endometrium.

Endometrial atrophy.

Endometrial hyperplasia.

Hematology

Mild neutropenia Blood: neutrophils.

Mild anemia Blood: packed cell volume (PCV).

Sometimes mild lymphopenia Blood: lymphocytes.

32
Q

Discuss Confirming diagnosis of pyometra?

A

Discriminatory diagnostic features

  • History.
  • Clinical signs

Definitive diagnostic features

  • Ultrasonography.
  • Uterine cytology/culture.
  • Endometrial biopsy

Gross autopsy findings

  • Uterus contains varying amounts of pus.
  • Damage most severe in body of uterus.
  • Endometrial surface smooth and glistening.
  • Endothelium rough and granular

Histopathology findings

  • Endometritis of varying type and severity.
  • Atrophy and fibrosis of endometrium
33
Q

Discuss Differential diagnosis for pyometra?

A
  • Bacterial endometritis Uterus: endometritis - bacterial.
  • Pregnancy 80-120 days.
  • Fungal endometritis.
  • Metritis-laminitis-septicemia complex Metritis-laminitis-septicemia complex.
  • Mucometra.
  • Cystic glandular hyperplasia.
  • Endometrial neoplasia, eg leiomyoma.
34
Q

What is the initial treatment for pyometra?

A

Initial symptomatic treatment

  • Drain and flush accumulated material using frequent, large-volume saline, antibiotic, and hydrogen peroxide flushes Therapeutics: intra-uterine. Repeat lavage until quality of recovered fluid improves and uterus stays empty and normal flush fluid recovery is achieved.
  • Break cervical or endometrial adhesions, if present, and treat with local corticosteroid preparations to prevent recurrence.
  • If cervix remains patent administer 20 iu oxytocin Oxytocin IM or PGF 2α 10 mg IM or PGF 2α analogue cloprostenol 250 µg IM to encourage uterine clearance plus luteolysis.
35
Q

How should pyometra be monitored?

A
  • Uterine ultrasonography.
  • Vaginal speculum examination.
  • Endometrial biopsy.
  • Uterine fluid.
  • Clinical signs.
36
Q

What is the subsequent management of pyometra?

A

Treatment

  • Hysterectomy may be considered in mares with chronic pyometra not intended for breeding:
  • Technically difficult.
  • Reported complications include reduced defecation, mild abdominal pain, incisional infections.
37
Q

What is the prognosis for equine pyometra?

A
  • Generally poor for reproductive performance.
  • Treatment usually results in only temporary resolution.
  • Reversion occurs spontaneously or after mating.
  • Usually best to retire mare from breeding.
  • Mares showing estrus and having normal uterine ultrasonography have a slightly better prognosis for a return to breeding.
  • Prognosis poor if chronic case:
    • Severe cervical and/or intrauterine adhesions.
    • Deep chronic inflammatory endometrial changes.
    • Endometrial atrophy.
38
Q

What are the reasons for pyometra treatment failure?

A
  • Most cases result in loss of use of mare for breeding.
  • Cervical or uterine adhesions which recur having been broken down.
  • Severe endometritis.
  • Endometrial atrophy.
  • Loss of endometrial defense mechanisms.
39
Q

Discuss case one

Mare sick post-foaling, has foul smelling vulval discharge and echogenic fluid within uterus?

A

Diagnosis: metritis

Aetiology: RFM

Diagnostic plan: vaginal examination- see if there were any retained foetal membranes present. If there is pus in the uterus this can be manually excavated.

Treatment:

  • Attempt to cause placental separation should be made
  • Removal of uterine fluid using scooping and/or lavage with 1-2 litres saline and immediate drainage by siphonage
  • Broad spectrum antibiotic systemically
  • Local infusion of antibiotic into the uterus and systemic use.
  • NSAIDs
  • Vasodilators etc
  • Treatment is repeated daily until the pus and placental debris have disappeared
40
Q

Discuss case two

Mare develops uterine fluid accumulation within uterus after breeding

A

Diagnosis: post mating endometritis

Aetiology: could be an infectious cause due to venereal pathogen introduction or introduction of commensal bacteria into the uterus during mating. Depends on the age of the horse

Diagnostic plan: swab the uterus with a sterile swab for cytology and bacteriology. Take a biopsy of the endometrium.

Treatment: antibiotics, lavage, oxytocin

41
Q

Discuss case three

Mare presents barren at the beginning of the breeding season with uterus containing echogenic fluid

A

Diagnosis: chronic endometritis

Aetiology: occurs in older mares following repeat incidences of inflammation. Can occur in older mares due to pneumovagina, Occur due to anatomical abnormalites of vulva.

Diagnostic plan: Definitive diagnosis can only be achieved by biopsy, which will show degenerative change of the uterus histologically.

Treatment: treat the primary cause

42
Q

Discuss case 4?

Mare has persistent large volume uterine fluid, frequent vulval discharge when in oestrus, and has long interval between oestrus

A

Diagnosis: pyometra

Aetiology: as sequel to endometritis, inability of the uterus to clear fluid. CL presence

Diagnostic plan: ultrasonography: presence of stipples, aspirate the fluid through vaginoscopy, vagninoscopy to see fluid coming from the cervix.

Treatment: lyse CL

43
Q

What can be seen in all these pictures?

A

Can see common to all is fluid in the lumen of the uterus.

Apart from lochia discharge immediately post part partum fluid in uterus is indicative of disease.

2 times in cycle when uterus can get contaminated: 1 when open at oestrus (in some species) 2 Parturition.

44
Q

Discuss the normal process at breeding of the reproductive tract in the mare?

A
  • At normal breeding cervix is open, large penis deposits sperm directly into the uterus.
  • In all normal mares there will be a short duration inflammatory response. What you see is influx of neutrophils into the uterus and of course as the uterus is dilated there will be uterine contractions against the fluid that has been deposited.
  • In normal female where sperm deposits there is a transient contamination of the uterus which is resolved quickly by normal immune response and uterine contractions (sperm and bacteria, seminal plasma pushed out by 12hours post breeding)
  • Small proportion of sperm make their way quickly to the fallopian tube and not in the lumen of the uterus and can on to fertilise.
  • Although millions of sperm are deposited on a few hundred make it to the fallopian tubes.
  • By About day 7 fertilised embryo enters the uterus and by this time the inflammation has resolved at 12 hours and an environment in which pregnancy can be establish= normal situation.
45
Q

Discuss the aetiology of post-breeding endometritis?

A
  • Post breeding endometritis is when this situation becomes abnormal.
  • Often some underpinning abnormality not being able to resolve the initial contamination which makes them susceptible.
  • Old mares often susceptible and find that their uterus hangs over front of pelvis so when fluid is deposited it has to drain out against gravity as it is cranially hanging over the pelvis (AKA the dependent uterus).
  • The other thing is they may have an abnormal cervix (fibroses) will prevent fluid being pushed out of repro tract.
  • May also have uterine disease (can take biopsies to diagnoses amount of glandular and fibrostissue) may over secrete and under contract.
  • A mare with the above abnormalities will: not establish a pregnancy because the sperm + bacteria + seminal plasma + smegma and she cannot expel that material so she gets bacterial growth, massive pouring in of neutrophils and see persistent fluid in the lumen of the uterus.
  • Sperm are still safe in tubes and the mare still gets fertilised but the embryo can’t survive in this pool of pus environment (hostile environment) so mare does not stay pregnant.
  • She is now in the luteal phase also with an infection in the mare there is PG production and the mare will come back into oestrus sooner than she would have done = short cycle every 16-18 days. This cycle increases oestrogen which causes contractions to increase, resistance to increase and an increased chance of endometritis resolving.
46
Q

What do we do to treat post-breeding endometritis?

A
  • We can lavage her to removed that fluid and pus (1.5 litres saline via Foley catheter)
  • Aspirate fluid out
  • PGs for spasmogenic effect at this point of cycle
  • Oxytocin to promote drainage (not many receptors at this time though)
  • Control bacterial growth-intrauterine (pen trep)

This mare has a contaminated uterus not a systemic infection

  • Other things maybe to dilate the cervix if it had adhesions to promote drainage
  • Could manually lift the uterus
  • Do not re-breed at this cycle if this mare has not ovulated as we will just contaminate the uterus again.
  • Examine daily and do these same treatments if we want to get her pregnant again
47
Q

If you’re anticipating post breeding endometritis what can you consider doing?

A
  • AI would be a good choice
  • Clean stallions penis to reduce amount of smegma
  • Clean mares vulva before she is bred
  • Could breed mare early (if we breed early we increase the number of treatment days before ovulation occurs, the sperm can wait in the fallopian tubes until she ovulates for up to 6-7 days and may survive to go on to fertilise)
48
Q

What species can get post-breeding endometritis?

A

Any species where sperm is deposited into the uterus get post-breeding endometritis (mare and pig common and seen in dogs)

49
Q

Mare sick post-foaling, has foul smelling vulval discharge and echogenic fluid within uterus we would use a similar treatment to post breeding metritis but what needs to be considered in addition?

A

In addition need to think about laminitis so need to use:

  • NSAIDs
  • Systemic antibiotics
  • Laminitis treatments
  • Fluids?
50
Q

Mare presents barren at the beginning of the breeding season with uterus containing echogenic fluid. What does she have?

A

She has chronic endometritis Infection introduced from last breeding, last foaling or she has poor conformation.

51
Q

What would you do to treat chronic endometritis?

A

Do not breed it won’t get pregnant need to resolve pus in uterus first othersie ejaculate will die in pus.

Treatments available

  • Remove fluid (lavage, aspirate)
  • Promote drainage
  • Control bacteria
  • Dilate cervix
  • Lift uterus
52
Q

Mare has persistent large volume uterine fluid, frequent vulval discharge when in oestrus, and has long interval between oestrus. She has a pyometra. What is the pathogenesis of pyometra?

A
  • Infected mare will have a PG release resulting in a short cycle. They short cycle repeatably and in some the problem will resolve but for some of them despite that they are short cycling the infection persists.
  • The mare with a pyo will have had multiple short cycles and then have had a long cycle. The inference is that in early phases of disease uterus produces PGs despite coming back into oestrus the infection persists into next period after 3-4 cycle the uterus no longer produces PGs and CL is not lysed and persists.
  • She is now just like a cow and this is when we call it a pyometra because there is persistence of the CL
53
Q
A