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Basics ⬇

Outline

BASICS

Definition!!navigator!!

Includes normal/abnormal causes; 1 or both ovaries achieve a size significantly larger than considered normal, detected by TRP and/or US.

Pathophysiology!!navigator!!

Physiology

  • Estrous cycles/ovulatory period normally occurs spring and summer
  • Light duration is the predominant influence on ovarian activity
  • Outside the optimal season for breeding activity, gonad size and activity waxes and wanes
  • Reproductive activity initiated at puberty
    • GnRH increases in the springtime, increasing FSH/LH leading to ovarian activity
    • A lag time of 60–90 days follows the winter equinox for increasing light to be reflected in regular estrous cycles/ovulation
    • After the summer solstice, day length decreases, GnRH tapers, LH/FSH decrease, until levels are insufficient to complete maturation and/or induce ovulation
  • Persistent follicles in vernal (spring) transition
    • Variable sizes through transition; late vernal (spring) transition follicles may regress after persisting for a month or more
    • May stimulate ovulation late in vernal transition by administration of hCG
  • Persistent follicles in fall (autumnal) transition
    • Early in fall transition can induce additional ovulations, especially if identified early in fall transition and follicles ≥35 mm
    • All will eventually regress (decrease in size) as daylight wanes; mare enters into winter anestrus (bilateral small, inactive ovaries)

Normal Ovary, Persistent Follicles

  • Most common LOS cause
  • May be single or multiple, present on 1 or both ovaries
  • Normal structures that will resolve if left alone

Normal Ovary, Hematoma

  • Second most common LOS cause
  • Enlargement resolves without assistance over time
  • PGF treatment may stimulate earlier initiation of estrous cyclic activity. Often slower to luteinize than a normal-sized CH; often requires longer (6–14+ days) to become responsive
  • Hematoma can harm ovarian stroma if repeated due to successive pressure inside ovarian tunic

Abnormal Ovary, Tumors, and Other Causes

  • Hormone treatments fail to elicit desired response
  • TRP/US—appearance inconsistent with normal ovarian structures
  • Systemic illness
  • Identify cell type on histopathologic examination of tissue following OVX

Systems Affected!!navigator!!

Reproductive

Genetics!!navigator!!

N/A

Incidence/Prevalence!!navigator!!

Persistent Follicles

  • Potentially 80% of reproductively normal mares
  • ≈20% of Northern Hemisphere mares experience year-round estrous cycle activity, albeit may be some variation from the “norm” of 21 days

Hematoma

Less common, a few cases a year will be recognized within a normal population of mares; ovulatory season.

Tumors

GCT/GTCT—most common ovarian tumor, but rare.

Signalment!!navigator!!

  • Females of breeding age
  • All breeds

Signs!!navigator!!

Persistent Follicles

  • Seasonal component—during 1 of the 2 transition periods
  • Usually extended periods (1+ month) of teasing in (receptive to stallion)
  • Estrus behavior longer than during a normal estrous cycle (>12–14 days in the spring)
  • TRP/US—presence of follicles, multiple, variable size; follicular appearance is normal
  • May increase in size/diameter with time, the increase is slower than with dominant follicles (5–6 mm/day) during the ovulatory period

Causes!!navigator!!

Persistent Follicles

Day length relationship: Vernal (spring) transition before sufficient LH; Autumnal (fall) transition after LH decreases.

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

Ovaries During Pregnancy (>37–40 Days’ Gestation)

  • Endometrial cups with subsequent equine chorionic gonadotropin production, secondary follicles luteinize to become secondary corpus lutea. Pregnant mare ovaries become bilaterally enlarged
  • Mare's behavior may mimic aggression of some mares with a GCT/GTCT
    • Most likely related to increased circulating testosterone (fetal gonads), may be >100 pg/mL by 60–90 days gestation.
    • Testosterone peaks at ≈200 days’ gestation; returns to basal levels by time of foaling

Ovarian Hematoma

  • Occurs following ovulation; the CH increases to a size substantially larger than the follicle that preceded it
  • Acute pain associated with rapid stretch of the ovarian tunic (short-term colic)
  • Post ovulation (2–4 days), the mare's behavior is that of diestrus, i.e. normal (teases out; rejects the stallion's advances); blood P4 rises (>1 ng/mL) by 5–6 days post ovulation, ovulation confirmation
  • Contralateral ovary is normal
  • US of hematoma—eventually similar to a CH, albeit a large one
  • Resolution—time or PGF treatment. Complete luteinization may be slow; thus delayed response to PGF (>6 to 14+ days post ovulation)

GCT/GTCT

  • TRP characterized by unilateral gonad enlargement (tumor growth rate varies significantly by case)
    • Surface of tumor remains smooth, may exhibit gentle lobulations
    • Ovulation fossa disappears (fills in) early in tumor's development
    • Over time, contralateral ovary shows evidence of suppression; the number/size of follicles decreases, then total volume/size of parenchyma decreases
    • Chronic GCT/GTCTs may have a contralateral ovary so small to be difficult for the novice to detect during TRP
    • Rare contralateral ovary will continue with follicular activity and ovulations
  • Elevation of circulating levels of AMH and inhibin with GTCT
  • Behavior
    • Mares typically exhibit 1 of 3 primary behaviors—chronic anestrus, increased aggression, persistent estrus, a reflection of the specific tumor cell type involved, with a possible steroid hormone component
    • Mares rarely exhibit pain (in contrast to a hematoma) due to more gradual stretch of ovarian tunic.
    • May exhibit discomfort at the trot or refuse to go over jumps due to painful stretching of the mesovarium; behavioral change (pain, anger, reticence to perform) possible

Teratoma/Dysgerminoma

  • Rare, not hormonally active
  • TRP of contralateral ovary is normal. Surface of teratoma may exhibit somewhat sharper protuberances reflective of its contents
  • No effect on behavior or estrous cycle activity
  • Teratoma is benign

Dysgerminoma

  • Rare
  • Initial presentation for intermittent chronic colic, weight loss, stiff extremities
  • Presence of tumor may only be discovered once mare's health deteriorates due to metastases
  • Potentially highly malignant

Cystadenoma

  • Unilateral, no effect on contralateral ovary
  • No effect on behavior
  • Appearance—large, cystic structures, may confuse early on with persistent follicles, remains nonresponsive to hCG
  • Rare hormonal impact; elevated testosterone

Ovarian Abscess

  • Rare
  • Early reports may have been associated with attempts to reduce the size/number of persistent follicles via flank approach aspiration
  • Contralateral ovary normal
  • No effect on behavior or estrous cycle activity

CBC/Biochemistry/Urinalysis!!navigator!!

N/A

Other Laboratory Tests!!navigator!!

GCT/GTCT

Diagnostic tests and sensitivity of detection:

  • Sensitivity for circulating inhibin levels (>0.7 ng/mL) in 80% of GCT/GTCTs
  • Sensitivity for testosterone (>50–100 pg/mL) in 48% of affected mares
  • Combining results of inhibin with testosterone levels raises the level of confidence to 84%
  • Progesterone levels are usually <1 ng/mL in the absence of luteal tissue
  • AMH—98% sensitivity of detection (greater than for inhibin or testosterone). AMH originates from the granulosa cells of normal ovaries (in both cycling and pregnant mares) as well as GCTs. The systemic levels of AMH in mares with GCTs are elevated above those produced by normal ovaries. Its normal reference range is ≤4.2 ng/mL

Ovarian Hematoma

Blood progesterone will increase by 5–7 days of hematoma formation.

Dysgerminoma

  • Reports of hypertrophic pulmonary osteoarthropathy
  • Radiography, biopsies for metastasis

Imaging!!navigator!!

US

Important adjunct tool to evaluate/differentiate cases of LOS

  • Persistent follicle—except for larger size, appearance is similar to normal follicle
  • Hematoma
    • Recent—fluid-filled space
    • By 2–10 days hyperechoic areas began to appear; ongoing clotting of blood, contraction of clot, invasion of luteal cells
    • Eventually takes on uniform hyperechoic appearance of a large CH
  • GCT/GTCT
    • Multicystic spaces, can appear quite irregular; fluid pockets range from a few millimeters to multiple centimeters
    • Size/location of tumor during US scan can range from readily accessible off tip of uterine horn to very pendulous (dependent on weight stretch of mesovarium)
    • Recorded weights ranged from <1 to 45+ kg
    • When detected, majority will be <30 cm diameter
  • Teratoma
    • Variable echogenicity, reflecting the nature of its contents, i.e. soft tissue, fluid, hair, bone, teeth

Other Diagnostic Procedures!!navigator!!

Blood hormone evaluations are a valuable adjunct (Table 1).

Pathologic Findings!!navigator!!

  • Neoplasms can potentially arise from any ovarian tissue type
  • Classification based on the origin and surface epithelium—sex cord–stromal tissue, germ cell, mesenchymal tissue
  • GCT/GTCT—sex cord–stromal tumor, endocrine effects, specific in mare: inhibin and AMH are produced by granulosa cells (GTCT)
  • Teratoma—many tissue types, including germ cells, within the mass; can include hair, skin, respiratory epithelium, tooth, bone. Metastases not a routine concern in the mare
  • Cystadenoma—from epithelium; forms cystic neoplastic masses
  • Dysgerminoma—from germ cells, analogous to seminoma of the testis; cells are arranged in sheets and cords with a dense population of large pleomorphic cells; all malignant

Treatment ⬆ ⬇

Outline

TREATMENT

Nursing Care!!navigator!!

  • None specific to conditions
  • General postoperative medical care recommended following an OVX

Client Education!!navigator!!

  • Explain need for serial examinations (TRP/US) to reach accurate diagnosis of LOS; avoid unnecessary OVX
  • Vast majority of LOS cases are due to persistent follicle(s) and hematoma
  • GCT/GTCTs are the most common tumor causing ovarian enlargement, but are still rare
  • History
    • Season—during transitional periods, persistent follicle(s) is first to rule out
    • Estrous activity—e.g. a mare recently showing estrus is now out of estrus, acutely painful, enlarged ovary is detected. Hematoma is the first to rule out
    • Response to treatment—progesterone supplementation, prostaglandin, hCG
    • Behavior changes—prolonged anestrus, increased aggression, nymphomania
  • Serial TRP
    • At interval of 7–10 days, may require 3–5 examinations (if not doing endocrine testing)
    • Avoid too frequent examinations (if interval too short unlikely significant increase or decrease in size of affected ovary); avoid unnecessary cost/surgery
      • Examine 2x within the span of a potential estrus period—(1) compare affected and contralateral ovary, (2) rate of size increase, (3) activity of opposite gonad
  • US is a most effective tool to evaluate the internal characteristics of the enlarging gonad
  • Circulating hormone levels
    • Inhibin, testosterone, progesterone, AMH
    • Ovarian tumor endocrine panel—evaluate most likely rule-outs

Surgical Considerations!!navigator!!

OVX

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

Hematoma

  • No treatment, wait for ovary to regress in size and other follicular activity to develop, or
  • PGF2α 5–10 mg IM when >7–10 days post ovulation
  • May be unresponsive to treatment within first 2+ weeks (may need to repeat PGF)
  • Successful treatment is noted by the mare returning to estrus within 2–5 days

Persistent Follicles

  • Can elect “no treatment, but for time,” wait for estrous activity to begin (vernal transition) or cease (fall transition) on its own
  • To shorten duration of spring transition
    • Regu-Mate- do not start treatment before significant follicular activity is present. In transition, mare experiences behavioral, not physiologic, estrus. See chapter Abnormal estrus intervals. Wear protective gloves. Dosed PO at 0.044 mg/kg (1 mL/50 kg (110 lb) body weight) daily for 15 days. Delivered by dose syringe PO or place on grain at feeding time
    • hCG 2500–3000 IU IV; may induce ovulation late in vernal transition. Wait until a follicle of ≥35 mm is present; ovulation within 36–44 h
    • Deslorelin (GnRH analog) injection. Ovulation within 38–60 h; a decapeptide, it does not stimulate antibody production as can hCG. A subset of mares will experience persistent anestrus if PGF is administered 1 week after deslorelin administration
    • P+ (150 mg P4 + 10 mg estradiol-17β)—10 day treatment; results in more effective ovulation and follicular suppression than P4 alone. Administered IM daily. PGF on the last day of treatment. Approximately 80% of mares will ovulate 8–10 days after PGF. hCG may be used once a ≥35 mm follicle is present (induce ovulation)
    • Other P4 products are available—P4 in oil (IM); Bio Release P+ LA (long-acting) and P+ in oil (50 mg/mL P4 + 3.3 mg/mL estradiol-17β IM); P+ microspheres—2 week interval of administration

Precautions!!navigator!!

  • Some behavior changes can be dramatic; use caution around mares showing aggressive behavior; consider individual paddock, distance from other mares in estrus, separation from foals, stallions
  • Large ovarian tumors develop extensive blood supplies. Intraoperative time can be increased due to time required to properly ligate vessels supplying the tumor; increases surgical risks

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

Routine postoperative care for OVX.

Prevention/Avoidance!!navigator!!

N/A

Possible Complications!!navigator!!

  • Any operative procedure/anesthesia holds potential risk for death
  • GCT/GTCT—time from OVX to resumption of estrous cycle activity is influenced by the time of year and length of suppression
    • Usually <1–3 years
    • Rare cases of permanent suppression
    • Rare case of remaining ovary developing into a GCT/GTCT
    • A few mares with GTCT will continue to develop follicles and ovulate on the contralateral ovary

Expected Course and Prognosis!!navigator!!

Prognosis, Poor

  • Dysgerminoma—potential for metastasis
    • Usually advanced state of disease by the time of diagnosis

Prognosis for Future Reproduction, Good

  • Hematoma—large size returns nearly to normal over 1–6 months
    • Rare hematoma will destroy remaining ovarian tissue secondary to pressure within the ovarian tunic.
    • Some mares develop a hematoma on subsequent cycles within a season
  • Persistent follicles—100% resolution with time and season

Prognosis for Life, Good

  • GCT/GTCT
  • Abscess
  • Cystadenoma
  • Teratoma

Recommendation for OVX

  • GCT/GTCT—removal of affected gonad for reproductive function to return, prognosis fair to good depending on size of tumor, surgical route, duration of suppression of contralateral ovary
  • Cystadenoma—reported testosterone production
  • Abscess, teratoma—dysfunctional ovary

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Associated Conditions!!navigator!!

  • Dysgerminoma—hypertrophic osteoarthropathy developing secondary to metastatic dysgerminoma
  • Behavior changes with GCT/GTCT

Age-Related Factors!!navigator!!

  • Of breeding age
    • Hematoma
    • Persistent follicles
  • Tumors
    • No age limitation

Abbreviations!!navigator!!

  • AMH = anti-Müllerian hormone
  • CH = corpus haemorrhagicum
  • FSH = follicle-stimulating hormone
  • GCT = granulosa cell tumor
  • GnRH = gonadotropin releasing hormone
  • GTCT = granulosa–theca cell tumor
  • hCG = human chorionic gonadotropin
  • LH = luteinizing hormone
  • LOS = large ovary syndrome
  • OVX = ovariectomy
  • P4 = progesterone
  • PGF = prostaglandin F (natural prostaglandin)
  • TRP = transrectal palpation
  • US = ultrasonography, ultrasound

Author(s) ⬆

Author: Carla L. Carleton

Consulting Editor: Carla L. Carleton