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Basics ⬇

Basics

Definition

Complaint that occurs in bitches historically showing abnormal cycling, copulation failure, conception failure, or pregnancy loss.

Pathophysiology

  • Normal fertility-requires normal estrous cyclicity with ovulation of normal ova into a patent, healthy reproductive tract; fertilization by normal spermatozoa; implantation of the conceptus into the endometrium; formation of the normal zonary placenta; and maintenance of pregnancy in the presence of high progesterone concentration throughout the approximately 2-month gestation.
  • Breakdown in any of these processes causes infertility.

Systems Affected

Reproductive

Signalment

  • Animals of all ages; more common in old animals.
  • Dogs >6 years old-more likely to have underlying cystic endometrial hyperplasia; may be predisposed to uterine infection and failure of conception or implantation.
  • Dog breeds predisposed to hypothyroidism-may have a higher prevalence; include golden retrievers, Doberman pinschers, dachshunds, Irish setters, miniature schnauzers, Great Danes, poodles, and boxers.

Signs

Historical Findings

  • Failure to cycle.
  • Failure to cycle normally-shortened interestrous interval (interestrous interval 4 months or less).
  • Failure to copulate, poor semen quality or lack of functional spermatozoa.
  • Failure to become pregnant and/or maintain pregnancy after normal copulation. Persistent estrus (>3 weeks).

Physical Examination Findings

  • Negative pregnancy exam after mating
  • Positive pregnancy with no subsequent parturition

Causes

Animals acquired when already mature-possibility of previous ovariohysterectomy.

Dogs

  • Insemination at the improper time in the estrous cycle-most common
  • Subclinical uterine infection
  • Cystic endometrial hyperplasia
  • Male infertility factors
  • Hypothyroidism
  • Hypercortisolism
  • Anatomic abnormality
  • Chromosomal abnormality
  • Abnormal ovarian function
  • Brucella canis
  • Silent estrus

Cats

  • Similar causes to those of dogs
  • Lack of sufficient copulatory stimulus to induce ovulation
  • Systemic viral or protozoal infection

Risk Factors

  • B. canis (dogs)
  • Hypothyroidism (dogs)
  • Hypercortisolism (dogs and cats)-endogenous or exogenous
  • Systemic viral infection (dogs and cats)-canine herpesvirus; FeLV; FIV
  • Systemic protozoal infection (dogs and cats)-e.g., toxoplasmosis
  • Any chronic, debilitating disease condition (dogs and cats)
  • Congenital vaginal anomaly (dogs and cats)
  • Old age

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

Historical Information

  • Extremely useful in distinguishing causes.
  • Is the patient cycling? Primary anestrus = no overt estrous cycle by 2 years of age; secondary anestrus = no overt estrous cycle within 1 year of a normal cycle.
  • Has the patient conceived or given birth in the past? If so, how recently? Litter size? Percentage of stillbirths? Percentage of litter weaned?
  • Is the patient free of systemic viral or protozoal infection?
  • Is the patient capable of normal copulation?
  • Was the patient bred to a male of proven fertility (i.e., litter whelped within previous 6 months) at the proper time of the estrous cycle?
  • Did the patient ovulate during the estrous cycle and maintain progesterone concentration consistent with pregnancy during the entire gestation?
  • Is the bitch euthyroid?

CBC/Biochemistry/Urinalysis

Usually normal

Other Laboratory Tests

Serologic Test for B. canis (Dogs)

  • Rapid slide agglutination test-used as a screen; sensitive but not specific.
  • If positive results-recommend recheck by an agar gel immunodiffusion test (Cornell University Diagnostic Laboratory, 607-253-3900) or bacterial culture or PCR of whole blood or lymph node aspirate.

Serum Progesterone Measurement

  • Should remain high throughout gestation.
  • May measure at the time of examination.
  • If concentration <2 ng/mL in mid-gestation and pregnancy loss occurs, insufficient luteal function indicated (hypoluteodism) [see Abortion, Spontaneous (Early Pregnancy Loss)-Dogs, and Premature Labor].
  • Concentration >2 ng/mL-may indicate diestrus; silent heat-estrus with no overt behavioral or physical changes; or pathologic production of progesterone from a luteal ovarian structure, functional ovarian neoplasm, or the adrenal gland.
  • Quantitative (chemiluminescence, fluorescence, enzyme immunoassay) progesterone assay is important to detect levels <2.0 ng/mL. Rapid in-hospital assays are least accurate between 2 and 5 ng/mL.

Dogs

  • Progesterone may be measured during proestrus and estrus to predict ovulation time and optimize breeding management.
  • Concentration and ovulation-1–1.9 ng/mL, probable ovulation in 3 days (recheck); 2–2.9 ng/mL, ovulation in 2 days; 3–3.9 ng/mL, ovulation in 1 day; 4–10 ng/mL, ovulation that day.
  • Optimal breeding day for single breeding to produce maximum litter size-2 days after ovulation.
  • Day of ovulation from onset of proestrus or estrus extremely variable; not well correlated with standing behavior (see Breeding, Timing).

Cats

  • Progesterone may be measured after breeding to assess induction of ovulation.
  • Concentration >2 ng/mL-indicates functional luteal tissue.

Other Tests

  • Bacterial culture for uterine organisms (dogs and cats)-vaginal discharge originating in the uterus during proestrus or estrus is collected directly by hysterotomy or transcervical catheterization, or indirectly from the anterior vagina using a guarded swab.
  • Thyroid hormone testing (dogs)-may measure resting serum concentration of T3 or T4 and cTSH.
  • Serologic testing-canine herpesvirus and toxoplasmosis [see Abortion, Spontaneous (Early Pregnancy Loss)-Dogs]; FeLV, FIV, and toxoplasmosis [see Abortion, Spontaneous (Early Pregnancy Loss)-Cats].
  • Karyotype (dogs and cats)-performed on heparinized blood samples of patients with primary or persistent anestrus; look for chromosomal abnormalities that can cause abnormal sexual differentiation (testing done by Molecular Cytogenetics Laboratory, Texas A&M University, (979)-862-2879/458-0520; Veterinary Genetics Laboratory, Univ. Calif. Davis, (530) 752-2211) (see Sexual Development Disorders).
  • Serum cortisol assay (dogs and cats)-if the resting serum concentration is high, investigate the underlying cause.
  • Semen evaluation (dogs and cats)-direct evaluation to rule out oligospermia or azoospermia recommended; alternatively, may test-breed the male to another female to prove fertility; rule out azoospermia in tomcat by finding spermatozoa in a vaginal flush or swab specimens from the queen or in urine collected by cystocentesis from the tom. (See Infertility, Male-Dogs.)
  • Serum AMH/progesterone, LH/estrogen for determination of ovarian presence.

Imaging

  • Radiography and ultrasonography-normal ovaries and a non-gravid uterus usually not visible with radiography; normal ovaries and non-gravid uterus visible with newer high-resolution equipment and frequency near-field imaging; large ovaries may indicate cystic ovarian disease or neoplasia; visible uterus may indicate cystic endometrial hyperplasia.
  • Positive-contrast procedures-vaginography in dogs; hysterography in dogs and cats; performed prepuberally or when the patient is in estrus; may reveal anatomic abnormality (e.g., abnormal structure and impatency) (see Vaginal Malformations and Acquired Lesions).
  • Ultrasound-may diagnose pregnancy as early as 20–24 days after ovulation; useful for documenting pregnancy loss; useful for detecting suspected cystic ovarian or neoplastic ovarian disease, cystic endometrial hyperplasia, and intraluminal fluid.

Diagnostic Procedures

  • Laparotomy (dogs and cats)-assess anatomy of the tubular tract and gonads.
  • Hysterotomy-to obtain a direct uterine culture specimen; biopsy of the uterus or ovaries.

Treatment ⬆ ⬇

Treatment

Medications ⬆ ⬇

Medications

Drug(s) Of Choice

  • Antibiotics (dogs and cats)-for uterine infection; choice depends on bacterial culture and sensitivity test of the uterus or of vaginal discharge during proestrus or estrus.
  • L-Thyroxine-for thyroid insufficiency; dogs: 0.01–0.02 mg/kg PO q12h; prognosis for future fertility with return to euthyroid state guarded.

Gonadotropin Therapy

  • For induction of ovulation.
  • GnRH, which causes release of endogenous LH from the pituitary, or hCG, which has LH-like activity.
  • Cats not adequately stimulated to ovulate at the time of copulation-GnRH (25 µg/cat IM or hCG 250 IU/cat IM) at time of breeding.
  • Ovarian cystic disease-cats: GnRH (25 µg/cat IM) or hCG (250 IU/cat IM); dogs: GnRH (50 µg/dog IM) or hCG (1,000 IU/dog half IV, half IM); causes ovulation or luteinization of cystic ovarian tissue.
  • Estrus induction (dogs)-diethylstilbestrol (5 mg q24h PO for 9 days or until signs of proestrus induced); bromocriptine (20 µg/kg q12h PO for 21 days); cabergoline (5 µg/kg q24h PO for up to 30 days or until signs of proestrus induced); deslorelin (2.1 mg implant, Ovuplant; placed in vestibule; must have progesterone <0.5 mg/mL at start; implant removed after ovulation confirmed: progesterone >10 ng/mL).
  • Estrus suppression (dogs)-megestrol acetate (2 mg/kg PO daily for 8 days if begun within first 3 days of proestrus or 0.5 mg/kg PO daily for 32 days if begun in anestrus) or mibolerone (dose dependent on body weight; 30 µg PO daily for dogs weighing 0.5–12 kg, 60 µg daily for 12–23 kg, 120 µg daily for 23–45 kg, 180 µg daily for greater than 45 kg and for German shepherd dogs and their crosses).

Contraindications

  • Treatment with progestins, including megestrol acetate, contraindicated in bitches with cystic endometrial hyperplasia or history of progesterone-dependent disease.
  • Treatment with mibolerone contraindicated in Bedlington terriers and other breeds with familial liver disease.
  • All hormonal therapies contraindicated in potentially pregnant bitches.

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

  • L-Thyroxine (dogs)-blood concentrations of T3 and T4 rechecked after 1 month of supplementation to ensure adequate absorption of medication and resumption of a euthyroid state.
  • Ultrasonography (dogs and cats)-to definitively diagnose pregnancy; monitor gestation.
  • Progesterone assay (dogs and cats).

Miscellaneous ⬆

Miscellaneous

Associated Conditions

  • Infertility caused by endocrinopathy-signs of dermatologic abnormality (e.g., alopecia with thyroid insufficiency or hypercortisolism); systemic signs of disease (e.g., polydipsia and polyuria with hypercortisolism).
  • Bitches with a vaginal anatomic abnormality-persistent or recurrent urinary tract disease or vaginitis.

Zoonotic Potential

B. canis infection-organism is less readily shed if affected animals are gonadectomized; stress good hygiene.

See Also

See “Causes”

Abbreviations

  • FeLV = feline leukemia virus
  • FIV = feline immunodeficiency virus
  • GnRH = gonadotropin-releasing hormone
  • hCG = human chorionic gonadotropin
  • LH = luteinizing hormone
  • T3 = triiodothyronine
  • T4 = thyroxine
  • TSH = thyroid stimulating hormone

Author Lynda M.J. Miller and Maria Soledad Ferrer

Consulting Editor Sara K. Lyle

Acknowledgment The author and editors acknowledge the prior contribution of Margaret V. Root Kustritz.

Client Education Handout Available Online

Suggested Reading

Johnston SD, Root Kustritz MV, Olson PN. Clinical approach to infertility in the bitch. In: Canine and Feline Theriogenology. Philadelphia: Saunders, 2001, pp. 257–273.

Johnston SD, Root Kustritz MV, Olson PN. Clinical approach to the complaint of infertility in the queen. In: Canine and Feline Theriogenology. Philadelphia: Saunders, 2001, pp. 486–495.

Meyers-Wallen VN. Abnormal and unusual estrous cycles. Theriogenology 2007, 68:1205–1210.