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Basics

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BASICS

Definition!!navigator!!

The failure of a mature, dominant follicle to ovulate in the estrus mare.

Pathophysiology

  • Normal development of 1 or 2 mature follicles during estrus
  • Follicular estradiol initiates the LH surge that stimulates prostaglandin production required for ovulation
  • Ovulation failure results when the follicle(s) fails to respond to the LH surge. The follicle(s) continues to enlarge, the antrum becomes hemorrhagic, and granulosa cells luteinize
  • Such follicles are called HAFs, luteinized unruptured follicles, or autumn (fall) follicles

Systems Affected

Reproductive

Incidence/Prevalence

HAFs occur in both the transitional and ovulatory seasons. Incidence in the range 5–20%.

Signalment!!navigator!!

Any breed and age.

Signs!!navigator!!

Historical Findings

  • Mares appear to exit estrus normally
  • May result in enlarged ovarian structures causing pain on palpation, under saddle, or mild colic

Physical Examination Findings

  • TRP and US—failure to ovulate. Follicle may regress or enlarge to form a HAF
  • Failure to respond to ovulation induction with either deslorelin or human chorionic gonadotropin. If the mare ovulates normally in the ensuing days, this is considered failure of induction of ovulation, rather than ovulation failure.

Causes!!navigator!!

HAFs

  • Causes unknown and spontaneous cases cannot be predicted
  • HAF is diagnosed as a dominant follicle in estrus that fails to ovulate, develops intrafollicular hemorrhage, and undergoes remodeling and luteinization over time
  • Can be induced by administration of high doses of COX inhibitors and debatably by shortening diestrus with PGF2α

Luteinized Follicles

In the pregnant mare, eCG causes luteinization of all large follicles, forming accessory CL. In mares that undergo EED after 35 days of gestation, eCG will continue this effect for up to 150 days post ovulation. Mares will appear to enter estrus, the CL will form, but ovulation will not occur.

Risk Factors!!navigator!!

  • Administration of high doses of COX inhibitors in estrus
  • Seasonality (particularly fall)

Diagnosis

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DIAGNOSIS

Differential Diagnosis!!navigator!!

Differentiating Similar Signs

Mild colic signs from other causes.

Differentiating Causes

  • Reproductive records should be reviewed
  • The mare should be examined by TRP and US

Laboratory Tests!!navigator!!

  • Serum progesterone—concentrations >1 ng/mL indicate functional luteal tissue
  • Serum eCG—positive assay can determine if EED occurred after endometrial cup formation

Imaging!!navigator!!

Transrectal US is standard of care for reproductive examinations.

Treatment

TREATMENT

No treatment if related to seasonality.

Medications

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MEDICATIONS

Drug(s) of Choice!!navigator!!

PGF2α (Lutalyse 10 mg IM) or its analogs (cloprostenol 250 μg IM) to induce luteolysis after sufficient luteinization of HAF.

Contraindications!!navigator!!

PGF2α and its analogs are contraindicated in mares with equine asthma and other bronchoconstrictive disease.

Precautions!!navigator!!

  • Horses
    • PGF2α causes sweating/colic-like symptoms due to stimulation of smooth muscle. Institute symptomatic treatment if not resolved in 1–2 h
  • Humans
    • PGF2α should not be handled by pregnant women, or persons with asthma/bronchial disease. Any skin exposure should be washed off immediately

Alternative Drugs!!navigator!!

Cloprostenol sodium (Estrumate; 250 μg/mL IM) is a PGF2α analog. Associated with fewer side effects than natural PGF2. Not currently approved for use in horses.

Follow-up

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FOLLOW-UP

Patient Monitoring!!navigator!!

Mares intended for breeding should be monitored by serial TRP and US.

Possible Complications!!navigator!!

Individual mares may develop more than 1 HAF in a season.

Miscellaneous

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MISCELLANEOUS

Associated Conditions!!navigator!!

Infertility if bred on that cycle.

Pregnancy/Fertility/Breeding!!navigator!!

PGF2α administration to pregnant mares can cause luteolysis and abortion.

Synonyms!!navigator!!

  • Hemorrhagic anovulatory follicles
  • Luteinized unruptured follicles
  • Autumn follicles

Abbreviations!!navigator!!

  • CL = corpus luteum, corpora lutea
  • COX = cyclooxygenase
  • eCG = equine chorionic gonadotropin
  • EED = early embryonic death
  • HAF = hemorrhagic anovulatory follicle
  • LH = luteinizing hormone
  • PGF2α = prostaglandin F2 alpha
  • TRP = transrectal palpation
  • US = ultrasonography, ultrasound

Suggested Reading

Cuervo-Arango J. The effect of treatment with flunixin meglumine at different times relative to hCG administration on ovulation failure and luteal function in mares. Anim Reprod Sci 2011;127:8490.

Ginter OJ, Gastal EL, Gastal MO, et al. Incidence, endocrinology, vascularity, and morphology of hemorrhagic anovulatory follicles in mares. J Equine Vet Sci 2007;27:130139.

Martinez-Bovi R, Cuervo-Arango J. Intrafollicular treatment with prostaglandins PGE2 and PGF2α inhibits the formation of luteinized unruptured follicles and restores normal ovulation in mares treated with flunixin-meglumine. Equine Vet J 2016;48:211217.

Author(s)

Author: Lisa K. Pearson

Consulting Editor: Carla L. Carleton

Acknowledgment: The author and editor acknowledge the prior contribution of Carole C. Miller.