Overview

• Ovulatory failure is a breakdown in the process of the release of oocytes from follicles with resultant corpus luteum formation and progesterone production.
• Ovulatory failure may present with nymphomania or prolonged anestrus.
• Bitches with nymphomania, decreased interestrous interval, have prolonged estrogen production and may present with signs of estrogen toxicity, including dermatologic or hematologic abnormalities.

Signalment

• Intact bitch or queen of any age, but there is a greater predisposition in older females.
• Ovulatory failure is reported in 1.2% of bitches presented for breeding management.
• No reported breed predisposition for anovulation; follicular cysts reported more commonly in Malamute, German shepherd, golden retriever, Bouvier des Flandres, and Labrador retriever.
• Heritability unknown.

Signs

• Prolonged proestrus or estrus
• Edematous vulva
• Sanguineous vulvar discharge (bitch)
• Nymphomania
• Anestrus
• Decreased interestrous interval
• Bilaterally symmetrical alopecia (progressive, non-pruritic)
• If neoplasia: enlarged abdomen ± palpable cranial-midabdominal mass ± ascites
• If chromosome abnormality: genitalia ranges from infantile or ambiguous to normal to enlarged clitoris or os clitoris; small stature; anestrus

Causes & Risk Factors

• Failure of release of gonadotropin-releasing hormone or luteinizing hormone from the hypothalamus or pituitary, respectively.
• Failure of receptors on the follicular wall to respond to LH.
• Failure of the follicles to produce adequate estrogen to illicit a surge in GnRH.
• Functional follicular cysts: may mimic a normal estrous cycle initially, but estrus persists and ovulation does not occur.
• Immune-mediated oophoritis.
• Cachexia or obesity.
• Stress (performance, travel, kennel).
• Addison's disease.
• Cushing's disease.

Differential Diagnosis

• Prolonged proestrus (up to 30 days) or estrus (up to 30 days).
• Split heat: the anovulatory cycle will be followed by a normal, fertile, ovulatory cycle in 1–8 weeks.
• Hypoluteoidism.
• Granulosa cell tumor or serous cystadenoma: ± palpable abdominal mass; enlarged ovary on ultrasound, often with a honeycomb appearance; ± ascites; ± bilaterally symmetrical alopecia, hyperpigmentation, lichenification if endocrinologically functional.
• Ovarian senescence.
• Immune-mediated oophoritis
• Chromosomal abnormality: intersex, hermaphrodites, pseudohermaphrodites, chimeras, mosaics may develop follicles that either go on to ovulate or simply regress.
• Exogenous estrogen administration or exposure.

CBC/Biochemistry/Urinalysis

If estrogen toxicity exists: normochromic, normocytic anemia; thrombocytopenia; initial leukocytosis followed by leukopenia

Other Laboratory Tests

• Progesterone <4–10 ng/mL over multiple samplings once vaginal cytology exceeds 70% anucleated superficial cells. It often hovers around 3–5 ng/mL for a prolonged period of time and never exceeds 10–12 ng/mL.
• Karyotyping is indicated in cases of suspected chromosomal abnormality.

Imaging

• Radiology may be beneficial if an ovarian mass is present. A large soft tissue density may be noted mid-abdomen. If ascites is present, a loss of general abdominal detail or ground glass appearance may be present.
• Ultrasonography is extremely helpful to evaluate ovarian structures: multiple anechoic structures on the ovary may be considered follicles; anechoic structures >1 cm are considered cystic; enlarged ovaries may be neoplastic; anechoic structures with thickened walls may indicate luteinization (partial or complete) of follicular structures; serial (daily) ultrasonography is necessary to document ovulation; use of color doppler to assess ovarian follicular blood flow (increased with follicles, minimal with luteal structures).

Diagnostic Procedures

Exploratory laparotomy to examine the ovaries or to obtain ovarian biopsies: the ovarian bursa must be opened to visualize the ovary.

Drug(s)

• Ovulation induction may be attempted once cytology reaches >70% anucleated cells and follicles are >4–5 mm (toy to small-breed canine), 5–7 mm (medium to large-breed canine), 7–10 mm (giant-breed canine), or 2–3 mm (feline).
• Ovulation-inducing agents: GnRH 1.1–2.2 µg/kg IM or IV or 25 µg/cat IM. May repeat daily for 1–3 days in bitches, single dose for queens; hCG 500–1,000 IU/dog IM or 500 IU/queen IM, may repeat in 2–3 days if ovulation does not occur; GnRH and hCG may be given concurrently; deslorelin implant (2.1 mg implant; Ovuplant^®) placed in the mucosa of the vulvar lip using a lidocaine block and removed with a similar block and sharp dissection, remove implant once ovulation is documented (progesterone >10 ng/mL); cervical stimulation in queens, may be performed starting at the time of initial induction medication and repeated several times daily for 24–48 hours.

Associated Conditions

Bilaterally symmetrically non-pruritic alopecia with significantly prolonged estrus.

Pregnancy/Fertility/Breeding

• Depending on etiology, anovulation may be hereditary; discuss with owner prior to breeding.
• The cycle after an anouvlatory cycle may be normal, necessitating no treatments.

See Also

• Infertility, Female-Dogs
• Sexual Development Disorders

Abbreviations

• GnRH = gonadotropin-releasing hormone
• hCG = human chorionic gonadotropin
• LH = luteinizing hormone

Internet Resources

Concannon PW, England G, Verstegen III J, Linde-Forsberg C, eds., Recent Advances in Small Animal Reproduction. International Veterinary Information Service, Ithaca NY, www.ivis.org.

Author Cheryl Lopate

Consulting Editor Sara K. Lyle