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Basics ⬇

Outline

BASICS

Definition!!navigator!!

Maternal structural/functional defects preventing normal embryonic development from early pregnancy diagnosis at 14–15 days post ovulation to the beginning of the fetal stage at approximately 40 days of gestation.

Pathophysiology!!navigator!!

  • Estimated to be 5–10% in younger mares; much higher in older, subfertile mares
  • The causes and pathophysiology are similar to those of conception failure and include:
    • Embryonic defects or injury
    • Unsuitable uterine environment
    • Regression of CL secondary to endometritis
    • Luteal insufficiency—anecdotal
    • Failure of maternal recognition of pregnancy

Systems Affected!!navigator!!

Reproductive

Signs!!navigator!!

Historical Findings

One or more of the following:

  • Diagnosis of EED by transrectal US at >14 days after ovulation, following previous diagnosis of pregnancy
  • Diagnosis of failure of pregnancy by TRP at >25 days after ovulation, following previous diagnosis of pregnancy
  • History of PMIE
  • History of abortion and/or dystocia
  • Return to estrus after diagnosis of pregnancy
  • Previous exposure to endophyte-infected fescue or ergotized grasses and grains
  • Recent systemic disease

Physical Examination Findings

  • Frequently, at ≤40 days after ovulation, there is no evidence by transrectal US or TRP of a previously diagnosed pregnancy
  • Alternatively, at ≤40 days after ovulation, there can be evidence by transrectal US of embryonic death in a mare previously diagnosed as pregnant
  • Transrectal US evidence of EED includes decreasing embryonic vesicular size, change in appearance of the fluid within the embryonic vesicle, failure to visualize the embryo proper, the absence of a heartbeat at >25 days, and/or cessation of normal embryonic growth and development, with eventual disappearance of pregnancy-associated structures
  • Endometrial folds and/or intrauterine fluid might be visualized in the nonpregnant uterus
  • Luteal structures may or may not be present on the ovaries, and the mare can appear to be cyclic or acyclic, depending on the circumstances
  • There may or may not be a mucoid or mucopurulent vaginal discharge

Risk Factors!!navigator!!

  • Older mares >15 years of age, especially those with moderate/severe endometritis, endometrial periglandular fibrosis, and/or lymphatic cysts
  • Anatomic defects predisposing to endometritis
  • Seasonal effects
  • Foal heat breeding—anecdotal and somewhat controversial
  • Inadequate nutrition
  • Exposure to xenobiotics—fescue toxicosis and ergotism
  • Some heterospecific matings—stallion × jenny
  • Susceptibility to PMIE (conception failure is more likely)
  • Geographic location, especially in relation to endophyte-infected fescue pastures/hay and/or ergotized grasses or grains
  • Preexisting PPID and EMS/IR
  • Severe laminitis
  • Transfer of embryos from older mares or those generated using IVF or other reproductive technologies

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

  • Conception failure
  • Misdiagnosis of pregnancy
  • Pregnancies move (transuterine migration) until fixation at 16 days after ovulation; they also increase in size, and develop/exhibit heartbeats

CBC/Biochemistry/Urinalysis!!navigator!!

  • CBC and serum biochemistry for inflammatory response, or evidence of other organ system involvement if the mare has recently been ill
  • Maternal P4 may be useful at <80 days of gestation (>1 to >4 ng/mL, depending on the reference laboratory). Maternal estrogen concentrations can reflect fetal estrogen production and viability, especially conjugated estrogens, e.g. estrone sulfate

Imaging!!navigator!!

  • Transrectal US should be performed every 2 weeks until at least 60 days of pregnancy in normal mares in order to detect EED
  • It is necessary to follow embryonic growth and development and to distinguish the conceptus from cysts

Other Diagnostic Procedures!!navigator!!

  • Vaginal speculum examination and hysteroscopy if structural abnormalities are suspected in the cervix or uterus
  • Endometrial cytology, culture, and biopsy procedures to assess endometrial inflammation and/or fibrosis
  • Feed or environmental analyses for specific xenobiotics, ergopeptine alkaloids, phytoestrogens, heavy metals, or fescue endophyte
  • A thorough reproductive evaluation is indicated before breeding for individuals predisposed to EED
  • Specialized testing for PPID or EMS/IR
  • Cytogenetic studies to detect chromosomal abnormalities

Pathologic Findings!!navigator!!

An endometrial biopsy can demonstrate the presence of moderate to severe, chronic endometritis, endometrial periglandular fibrosis with decreased normal glandular architecture, and/or lymphatic lacunae.

Treatment ⬆ ⬇

Outline

TREATMENT

Appropriate Health Care!!navigator!!

  • Treat preexisting endometritis before insemination or breeding of mares during physiologic breeding season
  • Mares being bred should have adequate body condition
  • Inseminate or breed foal heat mares if ovulation occurs >9–10 days postpartum and no intrauterine fluid is present
  • Prevention of PMIE
  • Depending on breed restrictions, various forms of advanced reproductive technologies (e.g. zygote, embryo) to retrieve embryos from the oviduct or uterus (days 6–8 after ovulation) for ET, and oocyte retrieval and successful IVF with subsequent ET have been used in some instances
  • Most cases of EED can be handled in an ambulatory situation
  • Increased frequency of US monitoring of follicular development and ovulation to permit insemination closer to ovulation, as well as more technical diagnostic procedures, may need to be performed in a hospital setting

Nursing Care!!navigator!!

Minimal nursing care might be necessary after more invasive diagnostic and therapeutic procedures.

Activity!!navigator!!

  • No restriction unless contraindicated by concurrent maternal disease or diagnostic or therapeutic procedures
  • Preference may be to restrict activity of mares in competition because of the possible impact of stress on pregnancy maintenance, especially in mares with a history of EED

Diet!!navigator!!

Generally no restriction, unless indicated by concurrent maternal disease (e.g. EMS) or nutritional problems, e.g. under- or overnourished.

Client Education!!navigator!!

  • Emphasize the aged mare's susceptibility to conception failure and EED and her refractoriness to treatment
  • Discuss susceptibility of mares with preexisting systemic disease (e.g. PPID and EMS/IR) to EED
  • Inform clients regarding the cause, diagnosis, and treatment of endometritis; the seasonal aspects and nutritional requirements of conception; the role that endophyte-infected fescue and certain heterospecific breedings might play in conception failure

Surgical Considerations!!navigator!!

  • Indicated for repair of anatomic defects predisposing mares to endometritis
  • Certain diagnostic and therapeutic procedures discussed above might also involve some surgical intervention

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

Altrenogest

  • For mares with a history of conception failure or moderate to severe endometritis (i.e. no active, infectious component) or fibrosis—0.044–0.088 mg/kg PO once daily beginning 2–3 days after ovulation or at diagnosis of pregnancy and continued until at least 90–100 days of gestation (taper daily dose over a 14 day period at the end of treatment)
  • Administration can be started later during gestation, continued longer, or used for only short periods of time, depending on serum P4 levels during the first 80 days of gestation, clinical circumstances, and risk factors
  • If used near term, altrenogest is generally discontinued 7–14 days before the expected foaling date

Precautions, Possible Interactions!!navigator!!

  • Use altrenogest only to prevent conception failure of noninfectious endometritis
  • Use transrectal US to diagnose pregnancy at ≥14–16 days after ovulation to identify intrauterine fluid or pyometra early in the disease course for appropriate treatment
  • If pregnancy is diagnosed, frequent monitoring (weekly initially) may be indicated to detect EED
  • Altrenogest is absorbed through the skin, so persons handling this preparation should wear gloves and wash their hands
  • Although supplemental progestins are commonly used widely to treat cases of conception failure, their efficacy is controversial
  • Primary, age-related embryonic defects do not respond to supplemental progestins

Alternative Drugs!!navigator!!

  • Injectable P4 (150–500 mg/day, oil base IM SID) instead of the oral formulation
  • Other injectable and implantable progestin preparations are available commercially for use in other species. Any use in horses of these products is off-label, and little scientific data are available regarding their efficacy
  • Newer, repository forms of P4 are occasionally introduced; however, some evidence of efficacy should be provided prior to use
  • The use of thyroxine supplementation in affected mares is controversial

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

  • Accurate teasing records
  • Reexamination of mares treated for endometritis before breeding
  • Early examination for pregnancy by transrectal US

Prevention/Avoidance!!navigator!!

  • Recognition of at-risk mares
  • Management of endometritis before breeding
  • Removal of mares from fescue-infected pasture and ergotized grasses and grains after breeding and during early gestation
  • Prudent use of medications in bred mares
  • Avoid exposure to known toxicants

Possible Complications!!navigator!!

  • High-risk pregnancy
  • Abortion—infectious or noninfectious

Expected Course and Prognosis!!navigator!!

  • Young mares with resolved cases of endometritis or corrected anatomic abnormalities can have a fair to good prognosis to complete pregnancy
  • Older mares (>15 years of age) with a history of preexisting systemic disease, chronic, moderate to severe endometritis, endometrial periglandular fibrosis, and/or lymphatic cysts, as well as conception failure and/or EED have a guarded to poor prognosis for conception, full-term pregnancy, and delivery of a healthy foal

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Synonyms!!navigator!!

  • Conception failure
  • Infertility
  • Pregnancy reabsorption
  • Reabsorbed pregnancy
  • Sterility
  • Subfertility

Abbreviations!!navigator!!

  • CL = corpus luteum
  • EED = early embryonic death
  • EMS = equine metabolic syndrome
  • ET = embryo transfer
  • IR = insulin resistance
  • IVF = in vitro fertilization
  • P4 = progesterone
  • PMIE = post-mating-induced endometritis
  • PPID = pituitary pars intermedia dysfunction
  • TRP = transrectal palpation
  • US = ultrasonography, ultrasound

Suggested Reading ⬆ ⬇

Ball BA. Embryonic loss. In: McKinnon AO, Squires EL, Vaala WE, Varner DD, eds. Equine reproduction, 2e. Ames, IA: Wiley Blackwell, 2011:2327–2338.

Canisso IF, Stewart J, Coutinho da Silva MA. Endometritis: managing persistent post-breeding endometritis. Vet Clin North Am Equine Pract 2016;32(3):465–480.

Evans TJ. Endocrine disruptive effects of ergopeptine alkaloids on pregnant mares. Vet Clin North Am Equine Pract 2011;27(1):165–173.

Ferris RA. Endometritis: diagnostic tools for infectious endometritis. Vet Clin North Am Equine Pract 2016;32(3):481–498.

Scoggin CF. Endometritis: nontraditional therapies. Vet Clin North Am Equine Pract 2016;32(3):499–511.

Author(s) ⬆

Author: Tim J. Evans

Consulting Editor: Carla L. Carleton