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Basics ⬇

Outline

BASICS

Definition!!navigator!!

Persistence of a CL post ovulation such that the normal return to estrus is delayed.

Pathophysiology!!navigator!!

  • Post ovulation, the CL forms and secretes P4
  • In mares, the CL is refractory to a single injection of PGF2α to cause luteolysis until >5 days post ovulation; however, serial injections can cause luteolysis in <5 days
  • In the absence of pregnancy, endogenous PGF2α is produced and released by the endometrium approximately 14–15 days post ovulation to initiate luteolysis
  • The lifespan of the CL is prolonged in idiopathic/spontaneous cases, or uteropathic cases (pyometra, EED) where P4 > 1 ng/mL
    • The cause is likely failure of normal PGF2α production, and not insensitivity of the CL to PGF2α
  • Persistent CL can affect 8–10% of cycles during the season, and up to 25% of cycles in the fall transition period with a CL lifespan of approximately 2 months

Systems Affected!!navigator!!

Genetics!!navigator!!

N/A

Signalment!!navigator!!

Postpubertal mares of any breed.

Signs!!navigator!!

Historical Findings

Failure to return to estrus at the expected time interval in the cyclic mare.

Physical Examination Findings

  • The physical examination is usually normal
  • Transrectal palpation and US are used to assess the reproductive tract:
    • 1 or more CL can be visualized as a uniformly hyperechoic area within the ovary
    • If ovulation was recent, the CL may appear as a corpus haemorrhagicum, with a hypoechoic, blood-clot appearance to the center
    • In diestrus, the uterus and cervix should be toned
    • Pregnancy should be noted if present
    • Abnormal findings (uterine fluid, cysts) should be noted in the mare's examination record
  • Vaginoscopy is used to examine the vaginal vault for abnormal content and the cervix for pathology

Causes!!navigator!!

Diestrus Ovulation

Diestrus ovulations (after day 10 of the cycle) can occur spontaneously in mares, resulting in an immature CL being present at the time of normal luteolysis (day 14–15).

Pregnancy

CL function continues in the presence of a conceptus until placental progestogens take over pregnancy maintenance (100–120 days).

EED

  • EED after maternal recognition of pregnancy will delay luteolysis (owing to lack of PGF2α secretion)
  • If EED occurs after endometrial cup formation (35–40 days post ovulation), cyclicity will not resume until endometrial cup regression and production of eCG ceases (120–150 days post ovulation)

Uterine Infections/Endometrial Degeneration

Pyometra, endometritis, and endometrial degeneration can affect endometrial function, inhibiting normal production/secretion of PGF2α.

Iatrogenic/Pharmaceutical

  • Gonadotropin-releasing hormone agonist (deslorelin) implants (not available in the USA) to induce ovulation have been associated with prolonged interovulatory intervals in the absence of pregnancy if they are not removed after ovulation. These effects are not seen with injectable formulations
  • Oxytocin can prolong CL function when administered 60 IU IM daily from day 7 to day 14 post ovulation or for 29 days at any time in the cycle
  • Placement of intrauterine glass marbles has prolonged CL lifespan up to 90 days in some mares
    • This treatment is no longer recommended owing to risk of complications (some marbles have shattered; uterine reactions—endometritis) and variable efficacy
  • Intrauterine infusion of plant oils has also prolonged CL function in some mares

Lactation

Persistent CL can develop following the first postpartum ovulation, particularly if mares foal during winter or are in poor body condition.

Risk Factors!!navigator!!

N/A

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

Differentiating Similar Signs

Diagnosis is based on finding a normal, nonpregnant, diestrus reproductive tract coupled with a history of failure to show estrus behavior >2 weeks post ovulation and a serum progesterone concentration of >1 ng/mL. Serial TRP and US (with or without teasing) are the cornerstones to proper interpretation of the reproductive cycle of an individual mare.

Differentiating Causes

  • Pregnancy and/or EED can occur in any mare that had proximity to a stallion
    • Pregnancy should be ruled out prior to any invasive diagnostics or treatments
  • Pyometra/endometritis are diagnosed by TRP, US, uterine culture, and cytology/biopsy
    • See chapters Endometritis and Pyometra
  • History of a normal foal heat followed by reproductive quiescence can be due to either prolonged diestrus or lactational anestrus, particularly if foaling occurred in winter without artificial light supplementation
    • These can be differentiated by TRP and US
  • Performance mares may have been treated with oxytocin or have had an intrauterine marble placed to suppress estrus
    • History, TRP, and US are used to diagnose; the marble may appear with a faint shadow outline with US
    • Hysteroscopy can identify marble fragments and facilitate removal
  • All other cases of prolonged CL for which a cause cannot be identified are considered idiopathic/spontaneous

CBC/Biochemistry/Urinalysis!!navigator!!

N/A

Other Laboratory Tests!!navigator!!

  • Serum P4—concentrations >1 ng/mL indicate functional luteal tissue
  • Serum eCG—positive assay can determine if EED occurred after endometrial cup formation

Imaging!!navigator!!

N/A

Other Diagnostic Procedures!!navigator!!

Uterine cytology, culture, and endometrial biopsy are useful to diagnose and treat pyometra and endometritis. See chapters Endometritis and Pyometra.

Pathologic Findings!!navigator!!

N/A

Treatment ⬆ ⬇

Outline

TREATMENT

  • Idiopathic/spontaneous prolonged CL is treated with PGF2α
  • Pregnancy should be definitively ruled out prior to treatment
  • Uteropathic causes of prolonged diestrus should be treated according to the inciting cause
  • Endometrial biopsy may stimulate endogenous PGF2α release

Appropriate Health Care!!navigator!!

N/A

Nursing Care!!navigator!!

N/A

Activity!!navigator!!

N/A

Diet!!navigator!!

N/A

Client Education!!navigator!!

N/A

Surgical Considerations!!navigator!!

N/A

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

PGF2α (Lutalyse (Pfizer) 10 mg IM) or its analogs are used to stimulate luteolysis:

  • Mares with a responsive CL at the time of treatment typically exhibit estrus within 2–4 days and ovulate within 6–12 days, depending on the status of the ovarian follicular wave at the time of treatment
  • 2 doses of PGF2α given 5 days apart are useful, if TRP and US cannot easily or safely be accomplished. This regimen ensures that immature/nonresponsive luteal tissue present at the time of the first injection has time to mature and is able to respond to the second injection

Contraindications!!navigator!!

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

Precautions!!navigator!!

  • Horses
    • PGF2α causes sweating/colic-like symptoms due to stimulation of smooth muscle
    • 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

Possible Interactions!!navigator!!

N/A

Alternative Drugs!!navigator!!

Cloprostenol sodium (Estrumate (Schering-Plough Animal Health) 250 μg/mL IM) is a PGF2α analog.

  • This product is used in similar fashion to natural PGF2α and has been associated with fewer side effects
  • While it is not currently approved for use in horses, it is in broad use in the absence of an alternative

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

  • Serial TRP and US (with or without teasing) are recommended to monitor the mare's reproductive tract function
  • Serum progesterone concentrations can be measured post treatment, but provide little additional information than what US can provide

Prevention/Avoidance!!navigator!!

N/A

Possible Complications!!navigator!!

Prolonged nonpregnant periods and/or infertility.

Expected Course and Prognosis!!navigator!!

N/A

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Associated Conditions!!navigator!!

N/A

Age-Related Factors!!navigator!!

N/A

Zoonotic Potential!!navigator!!

N/A

Pregnancy/Fertility/Breeding!!navigator!!

  • PGF2α administration to pregnant mares can cause luteolysis and abortion
  • Definitively rule out pregnancy before administering this drug or its analogs

Synonyms!!navigator!!

N/A

Abbreviations!!navigator!!

  • CL = corpus luteum
  • eCG = equine chorionic gonadotropin
  • EED = early embryonic death
  • P4 = progesterone
  • PGF2α = prostaglandin F2α
  • TRP = transrectal palpation
  • US = ultrasonography, ultrasound

Suggested Reading ⬆ ⬇

Coffman EA, Pinto CR. A review on the use of prostaglandin F2α for controlling the estrous cycle in mares. J Equine Vet Sci 2016;40:34–40.

Ginther OJ, Castro T, Baldrighi JM, et al. Defective secretion of prostaglandin F2α during development of idiopathic persistent corpus luteum in mares. Domest Anim Endocrinol 2016;55:60–65.

Ginther OJ, Baldrighi JM, Castro T, et al. Concentrations of progesterone, a metabolite of PGF2α, prolactin, and luteinizing hormone during development of idiopathic persistent corpus luteum in mares. Domest Anim Endocrinol 2016;55:114–122.

Vanderwall DK, Parkinson KC, Rigas J. How to use oxytocin treatment to prolong corpus luteum function for suppressing estrus in mares. J Equine Vet Sci 2016;36:1–4.

Author(s) ⬆

Author: Lisa K. Pearson

Consulting Editor: Carla L. Carleton

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