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CHAPTER 61

Disorders of Canine Reproduction

| Margaret V. Root Kustritz

DISORDERS OF INFERTILITY 2. Estrus, or standing heat, is defined cytologically as


complete cornification, with >50% of the cells ap-
Infer tility in the Bitch pearing anuclear.
3. Six days after ovulation, cornified cells are sloughed,
Definition and the onset of diestrus is signaled by an abrupt
I. Infertility in the bitch is defined as lack of pregnancy after return to noncornified vaginal cytology (Holst and
ovulation of normal ova into a patent, healthy reproductive Phemister, 1974).
tract and insemination with normal semen near the time of D. Ovulation timing is best performed by measurement
ovulation. of serum progesterone.
II. Normal estrous cycling is a prerequisite of normal fertility 1. Serum progesterone concentration is 2 ng/mL 2 days
in the bitch. before ovulation and 4 to 10 ng/mL on ovulation
A. Primary anestrus is the lack of obvious estrous cycling day (Box 61-1) (Johnston and Root, 1995).
by 24 months of age. 2. Luteinizing hormone (LH) can be measured using
B. Secondary anestrus is the lack of estrous cycling within a commercially available semiquantitative assay
12 months of a previous estrous cycle. (Status-LH; Synbiotics, San Diego, Calif.).
C. Normal interestrous interval (number of days between 3. Serum LH concentration >1 ng/mL occurs (on
onset of proestrus and the subsequent proestrus) average) 2 days before ovulation.
averages 5 to 8 months in dogs but may range from III. Subclinical uterine infection is a reported cause of infertility
4.5 months (German shepherd dogs, rottweilers) to 12 in bitches.
months (basenjis, wild dog crosses). A. Infection may cause conception failure by creating a
hostile environment for the ova and spermatozoa, or
Causes and Clinical Signs
I. Primary or secondary anestrus may arise from malnutri-
tion, stress, lack of exposure to cycling bitches, systemic Box 61-1
disease, previous ovariohysterectomy, silent heat (normal
Use of Serum Progesterone Concentration to
ovarian activity without external signs), or chromosomal
Determine Ovulation Day in the Bitch
abnormalities (Johnston, 1991).
II. Improper breeding management (mistimed or inadequate Serum Progesterone
number of breedings), the most common cause of apparent Concentration (ng/mL) Event, Recommendation
infertility in bitches that are cycling normally, is reported in <1.0 Well before ovulation—recheck in
40% to 50% of infertility cases (Johnston et al., 1994). several days
A. The average bitch ovulates about 12 days after first signs 1.0-1.9 ±3 days before ovulation—
of vulvar swelling and exudation of serosanguineous recommend recheck
vaginal discharge; however, ovulation may occur as 2.0-2.9 2 days before ovulation
early as 3 to 4 days or as late as 25 to 26 days after 3.0-3.9 1 day before ovulation
proestrus onset. 4.0-10.0 Ovulation day
B. Breeding by day of the cycle alone yields pregnancy NOTE: Optimal breeding day is
rates as low as 78% (England, 1992). 2 days after ovulation
C. Secretion of estrogen from the mature preovulatory >10.0 with cornified 1-5 days after ovulation—breed
follicle stimulates division of vaginal epithelial cells. vaginal cytology immediately
1. Cytological specimens contain an increasing per- >10.0 with noncornified Diestrus—too late to breed this
centage of cornified cells as dogs progress through vaginal cytology season
proestrus.
603
604 SECTION 8 | Reproductive System

by causing early embryonic death (see Pregnancy Loss


Box 61-2
later in this chapter).
1. Because the canine uterus is inaccessible to most Diagnostic Scheme for Infertility in Bitches
practitioners without performing laparotomy and Is Normal Estrous Cycling Occurring?
hysterotomy, culture samples taken from the cranial
vagina during estrus have traditionally been used No Yes
to infer the presence of uterine infection (Bjurstrom 1. Evaluate husbandry 1. Assess fertility of male dog.
and Linde-Forsberg, 1992; Bjurstrom, 1993). and nutrition. 2. Obtain serum chemistry
2. Requesting quantitative culture results, with the as- 2. House with cycling profile, complete blood
sumption that heavy growth of a single organism bitches. count, urinalysis to assess
is indicative of reproductive tract infection, may 3. Obtain serum chemistry general health.
enhance accuracy. profile, complete blood 3. Perform serologic testing for
3. Some breeders require negative vaginal cultures of count, urinalysis to canine brucellosis (see
breeding bitches before introduction to the male, assess general health. Table 61-1).
but this is an illogical practice and is discouraged. 4. Evaluate thyroid 4. Optimize breeding
B. Canine brucellosis is a specific uterine infection asso- hormones: concurrent management with
ciated with infertility (see Pregnancy Loss later in this measurement of free measurement of serum
chapter). thyroxine by dialysis progesterone.
IV. Hypothyroidism has been associated with infertility in the and canine thyroid- 5. Perform quantitative anterior
bitch. stimulating hormone vaginal culture during
A. It may cause primary anestrus, prolonged or irregular for assessment of proestrus. Treat with
interestrous intervals, prolonged proestrus, decreased hypothyroidism appropriate antibiotic therapy
intensity or duration of estrous cycles, galactorrhea, (Panciera, 1994; throughout proestrus and
and increased incidence of spontaneous abortion. Peterson et al., 1997). estrus if necessary.
B. Many dogs with reproductive dysfunction secondary 5. Perform serial vaginal
to hypothyroidism exhibit no extrareproductive clinical cytology to monitor
signs (Reimers, 1983; Johnson et al., 1997). for silent heat.
V. Hypoluteoidism is a proposed cause of infertility and 6. Consider karyotyping.
pregnancy loss in dogs. 7. Perform serologic testing
for canine brucellosis
Diagnosis (see Table 61-1).
I. The recommended diagnostic tests depend on the presence
Modified from Johnston SD, Olson PN, Root MV: Clinical approach to infertility in the
or absence of normal estrous cycling in the bitch (Box 61-2). bitch. Semin Vet Med Surg (Small Anim) 9:2, 1994.
II. Cases refractory to standard diagnostic tests may benefit
from the following tests:
A. Uterine biopsy via laparotomy and hysterotomy to
look for cystic endometrial hyperplasia, an age-related C. Measure canine thyroid-stimulating hormone and free
change in the uterine lining that may interfere with im- thyroxine in serum to assess for hypothyroidism.
plantation and placentation and predispose the bitch D. Perform vaginal cytological examination weekly and/or
to uterine infection progesterone assays monthly to identify silent heat.
B. Direct uterine culture via laparotomy and hysterotomy E. Submit whole blood or tissue for a karyotype to
(often performed at the time of uterine biopsy) determine if the bitch has a normal chromosome
C. Abdominal ultrasonography to assess the uterus complement.
1. The normal, nonpregnant canine uterus is not F. Attempt estrus induction.
visible as a distinct entity on ultrasonography. 1. Diethylstilbestrol 5 mg PO SID for 6 to 9 days or
2. If the uterus is visible, and especially if the uterine until proestrus is induced
lining can be visualized as a fluffy gray layer, then 2. Cabergoline 5 mg/kg PO SID for 7 to 10 days or
cystic endometrial hyperplasia is present. until proestrus is induced
3. Efficacy of estrus induction protocols: variable in
Treatment dogs
I. Attempt to convert primary and secondary causes of II. Minimize improper breeding practices by optimizing the
anestrus. time of breeding.
A. Ensure the bitch is on a proper plane of nutrition and A. Optimal breeding time is 2 days after ovulation.
is not stressed by the environment in which she is B. If dogs are to be bred by natural service, then they are
housed or by overwork. mated every other day while the bitch allows the male
B. Perform a complete blood count, serum chemistry to mount.
profile, and urinalysis to assess for treatable systemic C. If the number of breedings by natural service is limited
diseases. in number, or if artificial insemination with fresh or
CHAPTER 61 | Disorders of Canine Reproduction 605

chilled semen is intended, then vaginal insemination 2. Pass a polypropylene urinary catheter through the
is performed 2 and 4 days after ovulation. cervix and into the uterus, and inject the semen
D. If frozen-thawed semen is to be used, then intrauterine through the catheter.
insemination is undertaken 3 or 4 days after ovulation.
III. Institute appropriate antibiotic therapy for subclinical Monitoring of Animal
uterine infection. I. Prognosis for return to fertility varies with the cause.
A. Retrieve a culture specimen from the anterior vagina A. Proper breeding management, with collection of serial
of the estrous bitch early in proestrus; moderate to vaginal cytology specimens and measurement of serum
heavy growth of a single organism is significant. progesterone concentrations, is corrective of apparent
B. Treat with an appropriate antibiotic based on sensitiv- infertility in 40% to 50% of cases.
ity testing until the bitch enters diestrus, as evidenced B. Diagnosis and treatment of subclinical uterine infec-
by lack of vulvar discharge and standing behavior, or tion with appropriate antibiotic therapy is the next
abrupt onset of noncornified vaginal cytology. most common corrective therapy for infertility.
C. Empiric antibiotic treatment without culture is not C. Brucellosis is an irreversible cause of infertility in
recommended. bitches.
IV. Canine brucellosis is not curable in dogs; no recom- D. Hypothyroidism may be a reversible cause of infer-
mended treatment exists for infertility caused by Brucella tility with proper supplementation with thyroxine;
canis. however, bitches with hypothyroidism are not good
A. Euthanize Brucella-positive bitches housed in a kennel candidates for breeding.
situation. E. Abnormal chromosome complement is an irreversible
B. Individually housed bitches may be treated by per- cause of infertility in bitches.
forming ovariohysterectomy and administering tetra- II. The owner may benefit from a discussion regarding poten-
cycline 30 mg/kg PO BID for 28 days and streptomycin tial heritability of the cause of the animal’s infertility, as
20 mg/kg IM SID for 14 days. well as the wisdom of removing subfertile animals from the
1. Oral enrofloxacin may be used to treat canine breeding program.
brucellosis, but no specific dose regimen has been
described.
2. Antibiotic therapy induces remission, but does not Infer tility in the Male Dog
eradicate the organism.
C. Canine brucellosis is a zoonotic disease; therefore Definition
caution owners of Brucella-positive bitches of possible I. Infertility in the male dog is defined as complete inability
human transmission, especially if pediatric, geriatric, to effect pregnancy in normal females bred multiple times
or immunosuppressed persons live in the household. near the time of ovulation (Ellington, 1994).
V. Start thyroid supplementation. II. Subfertility is defined as the siring of litters infrequently or
A. Supplement with l-thyroxine 0.01 to 0.02 mg/kg PO the siring of litters containing few pups for that particular
BID. breed.
B. Recheck serum concentration of thyroxine 4 to 6 weeks
after treatment is instituted. Causes and Clinical Signs
C. Hypothyroidism may be hereditary in dogs, so advise I. Lack of normal breeding behavior and poor libido
owners that bitches with hypothyroidism are not good A. Inability to copulate
candidates for breeding. 1. Failure of normal copulation in dogs may have
VI. Bitches with apparently normal reproductive tracts, nor- behavioral or physical causes.
mal estrous cycling, no evidence of intrauterine infection, 2. Behavioral causes include introduction to a non-
negative brucellosis serology, and normal thyroid hormone receptive female, attempting to breed to a dominant
status may benefit from intrauterine insemination. female that will not allow the male to mount, and
A. Intrauterine insemination is performed surgically or inexperience or apprehension (Root Kustritz, 2005).
with endoscopy. 3. Intact male dogs that have been disciplined through-
B. Surgical intrauterine insemination requires general out their lives whenever exhibiting mounting and
anesthesia and laparotomy. thrusting behavior are unlikely to show normal
1. Exteriorize the uterine body and horns, and inject breeding behavior at the desired time.
semen through the uterine wall with a 22-gauge 4. Physical causes for failure of normal copulation
needle or catheter and syringe. include prostate disease and any painful condition
2. Hold off the injection spot briefly, and close the of the spine or hind limbs that prohibits the male
abdomen routinely. from mounting, thrusting, and maintaining the
C. Endoscopic intrauterine insemination requires neither copulatory lock.
general anesthesia nor sedation. B. Inability to ejaculate
1. Pass a long, narrow-diameter, rigid endoscope the 1. Lack of ejaculation may have behavioral or physical
length of the vagina to visualize the cervix. causes.
606 SECTION 8 | Reproductive System

2. Behavioral causes for an ejaculation include lack of 3. The normal percentage of progressively motile sper-
sexual maturity, inexperience, and apprehension. matozoa is >70%.
3. Conversely, some very experienced stud dogs will C. Calculate the total number of spermatozoa in the
not ejaculate in the absence of an estrous teaser ejaculate. The hemacytometric method described is
bitch. more accurate than computer-assisted systems (Kuster,
4. Subordinate males may refuse to mount a bitch they 2005).
perceive to be dominant. 1. Measure concentration of spermatozoa by dis-
5. Physical causes for lack of ejaculation include pensing semen with the capillary pipette into the
prostate disease, any painful condition of the spine diluent container provided with the white blood
or hind limbs, or retrograde ejaculation (ejaculation cell Unopette kit. Dispense the diluted semen into a
of semen into the urinary bladder instead of hemacytometer chamber.
antegrade, through the penile urethra). 2. The number of spermatozoa in one of the nine large
II. Poor semen quality (Table 61-1) squares of the hemacytometer grid visible under the
III. Prostate disease μ10 objective of the light microscope is the con-
A. Benign prostatic hypertrophy, prostatitis, and prostatic centration in millions (millions of spermatozoa per
neoplasia may be associated with pain during prostatic milliliter).
contraction. 3. The total number of spermatozoa is the more valua-
B. Prostatic contraction occurs whenever the male is ex- ble number, because concentration varies with the
cited and throughout ejaculation (Olson et al., 1987). amount of prostatic fluid collected in the ejaculate.
a. The total number is calculated by multiplying
Diagnosis concentration (millions of spermatozoa per milli-
I. Collect historical data. liter) by volume collected (milliliters per ejaculate).
A. Determine whether normal copulation is occurring. b. The normal total number of spermatozoa is
1. Causes of abnormal copulation include pain in the 300 million to 2 billion.
spine or pelvic limbs and prostate disease.
2. Behavioral incompatibilities between the bitch and
male dog may also preclude normal copulation.
B. Determine whether normal ejaculation is occurring. Box 61-3
1. Causes of abnormal ejaculation include pain in the Diagnostic Scheme for Infertility in Male
spine or pelvic limbs, prostate disease, and appre- Dogs
hension on the part of the male.
2. Retrograde ejaculation of semen into the urinary Are Normal Copulation and Ejaculation Occurring?
bladder may appear as lack of ejaculation. Yes No
a. Diagnosis requires collection of a urine sample 1. Measure serum thyroid 1. Investigate the prostate by
by cystocentesis after semen collection. hormones: concurrent rectal palpation,
b. Compare the numbers of spermatozoa in the measurement of free quantitative culture of
antegrade ejaculate and in the urine sediment. thyroxine by dialysis seminal fluid, and
II. Perform a complete physical examination. and canine thyroid- ultrasonography and
A. Evaluate the dog for any evidence of systemic disease stimulating hormone radiographic imaging, with
and clinical signs of hypothyroidism, such as weight for assessment of possible fine-needle
gain and bilaterally symmetrical alopecia (Box 61-3). hypothyroidism aspirate or biopsy.
B. Prostate disease is diagnosed by rectal palpation of the (Panciera, 1994; 2. Investigate sites of pain in
prostate, culture of seminal fluid, and imaging of the Peterson et al., 1997). the spine or hind limbs by
prostate, either by retrograde urethrography or ultra- 2. Perform serological testing complete physical
sonography (see Chapter 53). for canine brucellosis examination and
III. Collect and evaluate semen. (see Table 60-3). radiography.
A. Note color and turbidity of sample. 3. Collect and evaluate 3. Assess for behavioral
1. Normal semen is milky white. semen (see Table 60-3). problems described in text.
2. Red or brown discoloration indicates contamina- 4. Investigate the prostate 4. Assess for retrograde
tion with fresh or old blood, and yellow discoloration by rectal palpation, ejaculation by collection of
indicates contamination with urine. quantitative culture of a urine sample by
3. A clear sample is indicative of azoospermia. seminal fluid, and cystocentesis after breeding
B. Evaluate percentage of progressive motility of sperma- ultrasonography and or semen collection.
tozoa. radiographic imaging,
1. Examine an unstained, undiluted drop of semen with possible fine-needle
under the μ10 objective of a light microscope. aspirate or biopsy.
2. Make a subjective assessment of percentage of sper-
matozoa moving forward. Data from Meyers-Wallen (1991), Olson (1991), and Olson et al. (1992).
CHAPTER 61 | Disorders of Canine Reproduction 607

TA BL E 61-1

Types of Semen Abnormalities Described in the Dog


DEFINITION CAUSES DIAGNOSIS

Azoospermia: ejaculation of Pretesticular causes include Physical examination findings: abnormally small,
seminal fluid containing hypothyroidism, fever (as may be soft, or firm testes may have been damaged and
no spermatozoa seen with illness), drug therapy may not regain function
Testicular causes include intersex Measurement of alkaline phosphatase in seminal
states, bilateral cryptorchidism, fluid: concentration of >5000 IU/L indicates
direct testicular injury, indirect complete ejaculation with no outflow obstruction
testicular injury following increased (Frenette et al., 1986)
intrascrotal temperature as may Measurement of thyroid hormones: concurrent
occur with testicular neoplasia or measurement of thyroxine by dialysis and canine
inguinal hernia, orchitis thyroid-stimulating hormone for assessment of
Post-testicular causes include outflow hypothyroidism (Panciera, 1994; Peterson et al.,
obstruction of the epididymes 1997)
Serologic testing for canine brucellosis:
The rapid slide agglutination test (Synbiotics, San
Diego, Calif.) is a good screening test that is
accurate as early as 8-12 weeks after infection
Negative results with this test are accurate; positive
tests must be rechecked with a nonagglutination
method
The preferred nonagglutination method in the
United States is the agar gel immunodiffusion
(AGID) test available at Cornell University
Ultrasonography of the scrotum
Culture of seminal fluid: quantitative culture is
performed and finding of >10,000 bacteria/mL of
a single organism is considered significant
Perform serum chemistry profile, complete blood
count, and urinalysis to assess for systemic diseases
Oligozoospermia: a total Prostate disease Prostate diagnostic tests (see Box 61-3)
number of spermatozoa in Orchitis Culture of seminal fluid
the ejaculate <300 million Serology for canine brucellosis
Dogs with a low number of Measurement of serum thyroid hormones
spermatozoa in the ejaculate Serum chemistry profile, complete blood count, and
are not necessarily infertile urinalysis to assess for systemic disease
A total of 250 million normally
shaped spermatozoa must be
introduced into the bitch over
the fertile period from 3 days
before to 4 days after ovulation
to reliably effect pregnancy
(Mickelsen et al., 1993)
Teratozoospermia: <80% Orchitis Culture of seminal fluid
normally shaped spermatozoa Testicular neoplasia Ultrasonography of the scrotum
in the ejaculate Contaminated semen collection Re-collection with different equipment
equipment Prostate diagnostic tests
Prostate disease
Asthenozoospermia: <70% As for oligozoospermia As for oligozoospermia
progressively motile
spermatozoa in the ejaculate
608 SECTION 8 | Reproductive System

D. Evaluate the percentage of morphologically normal A. Euthanize Brucella-positive male dogs housed in a
spermatozoa. kennel situation.
1. Place a drop of undiluted semen on one end of a B. Individually housed dogs may be treated by performing
glass slide, smear it out as for a blood smear, and castration and administering tetracycline 30 mg/kg PO
allow it to air dry. BID for 28 days and streptomycin 20 mg/kg IM SID
2. Examine the slide under oil immersion (μ100 objec- for 14 days.
tive of the light microscope) and evaluate 100 sper- C. Antibiotic therapy induces remission but does not
matozoa. eradicate the organism.
3. The normal percentage of morphologically normal D. Canine brucellosis is a zoonotic disease, so caution
spermatozoa is >80%. owners of Brucella-positive dogs of possible human
IV. Perform serological testing for canine brucellosis (see Table transmission, especially if pediatric, geriatric, or im-
61-1). munosuppressed persons live in the household.
V. Cases refractory to standard diagnosis and therapy may V. Start thyroid supplementation.
benefit from testicular fine-needle aspirate or biopsy. A. Supplement with thyroxine 0.01 to 0.02 mg/kg PO
A. Testicular fine-needle aspiration requires that the dog BID.
be sedated. B. Recheck serum concentration of thyroxine 4 to 6 weeks
1. Using a 20-gauge needle on a 10-mL syringe, insert after treatment is instituted.
it on the testicular midline, and apply suction while C. Hypothyroidism may be hereditary in dogs, so advise
the needle is directed in several directions (Dahlbom owners that dogs with hypothyroidism are not good
et al., 1997). candidates for breeding.
2. Submit the sample for histological examination.
3. Ongoing spermatogenesis, inflammation, and neo- Monitoring of Animal
plasia may be identified. I. Prognosis for return to fertility varies with the cause.
4. Because testicular architecture is not maintained, A. Behavioral causes of lack of normal copulation or ejacu-
complete information about spermatogenesis is not lation may be overcome with administration of GnRH
obtained with this technique. (as described previously) or circumvented by use of
B. Testicular biopsy is performed with the animal under artificial insemination.
general anesthesia. B. The prognosis is better for dogs with poor semen
1. Exteriorize the testis through a prescrotal incision. quality than for dogs with azoospermia.
2. Incise through the tunica albuginea with a scalpel C. The prognosis is better for dogs with normal testicular
blade, and shave off the tissue that bulges through size and consistency than for dogs with testicular
the incision. atrophy or fibrosis.
3. Place the tissue in modified Bouin’s or Zenker’s II. A definitive prognosis for future fertility may be made after
fixatives rather than formalin. testicular biopsy. If spermatogenic cells are absent from
4. Evaluate for the presence of the hierarchy of sper- the seminiferous tubules, or if a significant percentage of
matogenesis within the seminiferous tubule, as well the seminiferous tubules are atrophied or fibrotic, then
as for inflammation and neoplasia. infertility is irreversible in that animal.
III. Brucellosis is an irreversible cause of infertility.
Treatment IV. Hypothyroidism may be a reversible cause of infertility
I. Behavioral causes of poor libido may be overcome. with proper supplementation with thyroxine; however,
A. Administer gonadotropin-releasing hormone (GnRH) dogs with hypothyroidism are not good candidates for
at 1 to 2 mg/kg IM 1 hour before attempted breeding breeding.
or semen collection (Purswell, 1994).
B. This method is not to be used routinely in valuable
stud dogs, because frequent artificially enhanced serum DISORDERS OF PREGNANCY
testosterone concentrations may exert negative feed-
back on the pituitary, producing an eventual decline in Pregnancy Loss
serum testosterone concentration and reduced sper-
matogenesis. Definition
II. Retrograde ejaculation is treated with sympathomimetic I. Early embryonic death (death of the fetuses with subse-
drugs (e.g., pseudoephedrine 4 to 5 mg/kg PO 1 and 3 quent resorption in the first half of gestation) is indistin-
hours before attempted breeding or semen collection) to guishable from lack of conception.
effect antegrade ejaculation (Root et al., 1994). II. Abortion (fetal death with expulsion of the fetus and
III. Treatment of prostate disease varies with the specific placental tissues) occurs in the second half of gestation.
abnormality present (see Chapter 53). III. Birth of stillborn pups or retention of nonviable pups in
IV. Canine brucellosis is not curable in dogs, and no recom- the uterus without onset of parturition can also be defined
mended treatment exists for infertility caused by B. canis. as pregnancy loss.
CHAPTER 61 | Disorders of Canine Reproduction 609

Causes II. Signs specific to the reproductive tract include exudation


I. Bacterial causes of purulent or bloody vaginal discharge from the vulva.
A. Brucella canis may cause pregnancy loss
1. Transmission usually occurs by ingestion of aborted Diagnosis
tissues or urine excreted from infected males or I. Diagnostic testing both of the bitch and any pups is bene-
females (Carmichael and Joubert, 1988). ficial in determining the cause of pregnancy loss (Box 61-4)
2. Transient lymphadenopathy and colonization of (Purswell, 1992).
many tissues occurs, especially in the reproductive II. Mycoplasma spp. and Ureaplasma spp. are difficult to grow
tract (Johnson and Walker, 1992). in culture, and differentiating pathologic from non-
3. The classic presentation is abortion late in gestation. pathologic isolates is also difficult.
4. Birth of stillborn or weak pups and persistent dis- III. Hypoluteoidism is diagnosed by measurement of serum
charge of purulent vaginal discharge may also be progesterone concentrations during pregnancy.
seen. A. Weekly measurement of serum progesterone concen-
5. Infertile bitches infected with canine brucellosis tration is recommended in bitches with a history of
may be asymptomatic. possible hypoluteoidism, for the first 6 to 8 weeks after
B. Miscellaneous bacteria implicated in canine preg- breeding.
nancy loss include Campylobacter spp., Salmonella spp., B. If serum progesterone falls to <10 ng/mL, then daily
Escherichia coli, and Streptococcus spp. (Johnston and monitoring of serum progesterone concentration is
Raksil, 1987). recommended.
II. Viral causes C. Treatment is instituted with progesterone supplemen-
A. Canine herpesvirus tation if serum progesterone concentration falls to
1. Canine herpesvirus can be transmitted by aerosol, <5 ng/mL.
via licking, or venereally.
2. Most infected adult animals are asymptomatic or Treatment
have mild vesicular lesions of the genitalia. I. Canine brucellosis is not curable in dogs.
3. Animals at greatest risk are naive bitches exposed to A. Antibiotic therapy can be tried, but the infection
the virus in the last 3 weeks of gestation. usually persists and the dog may exhibit bacteremia
4. Necrotizing placentitis develops, with subsequent when stressed months to years after therapy.
birth of stillborn, macerated, mummified, or weak B. Brucellosis is a zoonotic disease and may be reportable
pups of various sizes, often all within the same litter in the state or country where the disease is diagnosed.
(Poste and King, 1971). C. Neutering minimizes shedding of the organism in
B. Other viruses: parvovirus and canine distemper virus urine.
III. Mycoplasma spp. and Ureaplasma spp. D. Eradication of canine brucellosis in a kennel may re-
A. Mycoplasma spp. and Ureaplasma spp. are ubiquitous quire euthanasia of affected animals.
organisms that lack a rigid cell wall. II. Treatment of the bitch for a bacterial cause of pregnancy
B. They have been associated with infections of the repro- loss often is not useful at the time she is aborting.
ductive tract and pregnancy loss and also are part of the A. Even if the cause can be identified, the pups are not
normal vaginal flora (Doig et al., 1981). viable; therefore pregnancy loss is allowed to continue,
IV. Protozoal causes (Toxoplasma gondii) with monitoring to ensure its completion and normal
A. Toxoplasmosis infection is uncommon in dogs and is a uterine involution.
very uncommon cause of pregnancy loss. B. Antibiotic therapy to prevent sepsis in the bitch is
B. Pups have been experimentally infected with toxo- instituted as needed.
plasmosis transplacentally. C. Mycoplasma spp. and Ureaplasma spp. infections can
C. Dogs that lose pregnancies from toxoplasmosis may be treated with tetracycline, which is contraindicated
be clinically ill from systemic disease (Dubey et al., during pregnancy, and with enrofloxacin, which is not
1990). approved for use during pregnancy.
V. Hypoluteoidism and hypolutemia III. Treatment of the bitch with canine herpesvirus rarely is
A. Hypoluteoidism is a hypothesized cause of pregnancy necessary.
loss in dogs. A. Treat viremic pups by increasing environmental tem-
B. The corpora lutea are the sole sources of progesterone, perature to decrease replication of the virus within the
which is required throughout pregnancy. pups.
C. If the corpora lutea fail prematurely, then progesterone B. An infected bitch should not lose more than one litter
concentrations decline and pregnancy loss occurs. to canine herpesvirus, apparently because she retains
enough memory cells to allow an adequate immune
Clinical Signs response if she is reexposed to the virus.
I. Most bitches have nonspecific clinical signs, including IV. Bitches with documented hypoluteoidism are treated with
anorexia, lethargy, and fever. progesterone (in oil) 2 mg/kg IM every 3 days, or with
610 SECTION 8 | Reproductive System

Box 61-4
Diagnostic Scheme for Pregnancy Loss in Dogs
Is the Bitch Pregnant and, If So, Are the Pups Viable?
Abdominal ultrasonography is the diagnostic method of choice for this assessment, but radiographs may be used after 45 days from
breeding to give some idea of fetal viability.
Yes No
1. Serological testing for canine brucellosis is performed (see 1. If the pups are not viable, expulsion of the pups is allowed
Table 60–3). to continue, and the bitch is monitored with abdominal
2. Serum progesterone concentration is measured. Serum ultrasonography and/or abdominal palpation to ensure
progesterone concentration of <10 ng/mL at midgestation, complete loss of the pregnancy and normal involution of the
and <5 ng/mL anytime before the last 2 to 3 days of uterus. Expulsion of uterine contents may be augmented
gestation, is suggestive of poor luteal function. with oxytocin or prostaglandin F2a.
3. A sample of the vaginal discharge of the bitch is submitted for 2. A sample of the vaginal discharge of the bitch is submitted
aerobic culture, and empirical treatment is instituted with for aerobic culture.
amoxicillin-clavulanate at 14 mg/kg PO BID. 3. Serologic testing for canine brucellosis is performed.
4. Continuing viability of the pregnancy is monitored weekly, 4. Any nonviable pups passed or stillborn pups are submitted
preferably with abdominal ultrasonography. for necropsy. Pups that died from canine herpesvirus have
5. If nonviable pups are passed, they are submitted for necropsy. pathognomonic hemorrhagic lesions on the major
abdominal organs. Contents of the stomach can be cultured
to identify what organisms were in the pup’s amniotic fluid.
5. Serologic testing for canine herpesvirus may be performed
on the bitch, but the antigenicity of the virus is poor, so low
titers do not indicate lack of exposure.

altrenogest (Regumate) 0.088 mg/kg PO SID (Purswell, Dystocia


1991; Eilts, 1992).
A. Therapy must be withdrawn (to mimic the normal de- Definition
cline in progesterone) in the last 2 to 3 days of gestation. Dystocia comes from the Greek words dys, meaning abnormal,
B. Bitches receiving altrenogest may have poor milk and tokos, meaning birth, and is abnormal parturition.
production in early lactation.
Causes
Monitoring of Animal I. Maternal causes
I. All breeding bitches are tested for canine brucellosis twice A. Uterine inertia
yearly, even if they are not actively being bred. 1. Primary uterine inertia is lack of initiation of
II. The poor antigenicity of canine herpesvirus and the varia- second-stage labor by the bitch.
bility of titers because of environmental and host factors 2. Secondary uterine inertia is the lack of progression
preclude regular serologic testing as a means of defining of second-stage labor as the uterine muscle fatigues.
naive and exposed dogs (Ronsse et al., 2004). B. Obstruction of passage, as might be seen in a bitch with
III. In dogs with a history of pregnancy loss from bacterial an artificially narrowed birth canal after pelvic fracture
infections, obtain quantitative culture of the cranial vagina C. Abnormality of pregnancy, such as uterine torsion
early in proestrus, with administration of appropriate anti- II. Fetal causes
biotic therapy throughout proestrus and estrus while the A. Developmental abnormality, such as hydrocephalus
cervix is open. B. Obstruction of passage from relative or absolute over-
IV. Cleanliness of the environment must be assessed. size of the pup
V. Bitches with a history of hypoluteoidism are monitored C. Malpresentation
via weekly serum progesterone assays during subsequent 1. Both cranial (head and extended forelimbs) and
pregnancies. caudal (tail and extended hind limbs) presentation
A. Serum progesterone concentrations of <10 ng/mL at is normal in the dog.
midgestation or <5 ng/mL anytime before the last 2 to 2. Examples of malpresentation include breech presen-
3 days of gestation are suggestive of poor luteal func- tation (caudal presentation with the hind limbs
tion. flexed) and cranial presentation with only one or
B. Empiric administration of progesterone to pregnant neither forelimb extended.
dogs is not desirable, because progestogens are terato- III. Breeds at increased risk for dystocia: Pekingese, Chihuahua,
genic and nonviable pups need to be expelled. Scottish terrier, dachshund, Yorkshire terrier, miniature
CHAPTER 61 | Disorders of Canine Reproduction 611

poodle, Pomeranian, and English bulldog (Gaudet and II. Pharmacological therapy
Kitchell, 1985) A. Oxytocin causes uterine contractions and contributes
to cervical dilatation.
Clinical Signs
1. It also promotes placental separation.
I. An obvious malpresentation is present. 2. Oxytocin is not to be used unless the cervix is open
II. The bitch has been in first-stage labor for >12 hours, in (pup or significant vaginal discharge passed) and
weak and intermittent second-stage labor for >4 hours, no present obstruction exists (as determined by
or in hard second-stage labor for >30 minutes before abdominal radiography).
delivering any pups. 3. The recommended dose is 2 to 5 IU SC, IM.
III. It has been >2 hours since the last pup was born. 4. If no response to oxytocin is seen after three doses
IV. Abnormal vaginal discharge is present. (administered at 20- to 30-minute intervals), then
A. Frank blood indicates hemorrhage. institute some other form of therapy (Wallet Darvelid
B. Black or green discharge indicates placental separation and Linde-Forsberg, 1994).
and is most valuable as an indicator before the first B. Hypocalcemic bitches with no signs of eclampsia other
pup is born. than dystocia may benefit from parenteral calcium
V. The pregnancy is a high-risk one (e.g., former pelvic gluconate at 5 to 10 mL SC, IM.
fracture, predisposed breed, known single-pup litter). C. Oxytocin and calcium are often given together, because
Diagnosis calcium may potentiate the effects of oxytocin.
I. At the minimum, diagnosis of dystocia requires a good D. Some reports suggest that bitches in dystocia may re-
history, a physical examination including a digital vaginal spond to parenteral dextrose; however, hypoglycemia
examination, and a lateral abdominal radiograph. has not been reported as a cause of dystocia in the
II. Abnormalities that may be noted on physical examination bitch.
are as follows: III. Surgical therapy
A. The bitch appears systemically ill. A. Surgical treatment of dystocia is via cesarean section.
B. Abnormal vaginal discharge is present (see previous B. Use anesthetic agents with a short half-life and agents
discussion). that can be reversed in the pups.
C. Digital vaginal examination findings are abnormal (no 1. Premedicate with atropine 0.04 mg/kg IM.
pup in the birth canal or vagina, very large pup palpable 2. Examples of suitable induction agents include thio-
in birth canal or vagina, obvious malpresentation). pental 4 to 8 mg/kg IV (to effect) or oxymorphone
III. Abnormalities are found on radiography. 0.1 to 1.0 mg/kg IV (to effect).
A. Extremely large pup(s) 3. Intubate and maintain on inhalant anesthesia; iso-
B. Dead pups: gas within or around fetuses, collapse of flurane is the inhalant anesthesia of choice.
axial skeleton and/or skull C. No contraindications exist to ovariohysterectomy at
C. Large number of pups remaining in a fatigued bitch the time of cesarean section.
IV. Obtain an abdominal ultrasound if viability of the pups D. Ovariohysterectomy at the time of cesarean section is
is in question. recommended if uterine rupture has occurred or if the
A. Fetal heart rate of <150 beats per minute is indicative owner has no further plans to breed the bitch.
of fetal distress.
Monitoring of Animal
B. Lack of visible movement or heart beats at term is
indicative of fetal death. I. The prevention of dystocia requires good client education.
V. Measure serum calcium. II. Feed the bitch a well-balanced diet and provide consistent
A. Serum calcium <7 mg/dL is diagnostic of hypocalcemia. exercise throughout pregnancy.
B. Hypocalcemia causes dystocia by prohibiting normal III. Stress good breeding management to optimize litter size.
muscle contraction. A. Vaginal cytological examination and measurement of
VI. Evaluate labor with an external whelping monitor, which serum progesterone concentration allow determination
may suggest a decrease in fetal viability or show an abnor- of ovulation day.
mal pattern of uterine contractions (Whelp Watch; Vet B. Optimal litter size is achieved by breeding 2 days after
Watch Corporation [888-200-8044]). ovulation.
IV. Provide the bitch with a stress-free, sanitary whelping
Treatment environment.
I. Manipulation
A. If a pup is palpable within the birth canal, then manip- Pseudocyesis
ulation may allow it to pass.
B. Use caution when manipulating pups, because limb Definition
dislocation and skin tearing may occur. I. Pseudocyesis is mammary development, lactation, and be-
C. Clamps, forceps, and other instruments have been de- havior typical of whelping, nursing, and mothering in
scribed for relief of dystocia but must be used with nonpregnant bitches at the end of diestrus.
extreme caution. II. The term false pregnancy is a misnomer.
612 SECTION 8 | Reproductive System

A. All bitches undergo a hormonal false pregnancy, with III. Testosterone cypionate at a dose of 0.5 to 1.0 mg/kg IM
luteal production of progesterone for an approximately may decrease milk production in dogs.
2-month diestrus, regardless of breeding or pregnancy IV. Prolactin inhibitors decrease milk production in dogs.
status. A. Bromocriptine is administered at a dose of 30 mg/kg
B. The terms pseudocyesis or false whelping more accu- PO SID for 16 days, with the most common side effect
rately describe this phenomenon. being emesis.
III. Pseudocyesis is a normal reproductive phenomenon in B. Cabergoline is administered at a dose of 1.5 to 5.0 mg/kg
dogs and is not associated with reproductive tract disease. PO SID for 2 to 8 days, with emesis as a rare side effect.
V. Ovariohysterectomy is not curative of a given episode of
Causes and Clinical Signs pseudocyesis but prevents subsequent episodes.
I. All bitches produce luteal progesterone for approximately VI. Short-term tranquilization may be necessary in aggressive
2 months after ovulation, which causes mammary devel- animals.
opment. A. Diazepam is the drug of choice.
II. The abrupt decline in serum progesterone at the end of B. Phenothiazine tranquilizers (e.g., acepromazine) and
diestrus stimulates release of prolactin from the anterior butyro-phenone tranquilizers (e.g., haloperidol) are
pituitary, with subsequent mothering behavior and lacta- not recommended, because they may stimulate pro-
tion. lactin release and worsen clinical signs.
III. Onset of pseudocyesis can be triggered by withdrawal of
exogenous progestogen therapy or by a decline in en- Monitoring of Animal
dogenous progesterone after ovariohysterectomy during I. Pseudocyesis is not associated with uterine disease and may,
diestrus. in fact, be a historical indicator of normal ovarian function
IV. Physical changes of pseudocyesis include distention of the in the bitch.
mammary glands and exudation of serous fluid or normal II. Age at onset of pseudocyesis is variable, and a given bitch
milk from the mammae. may not exhibit signs of pseudocyesis after every estrous
V. Behavioral changes include nesting behavior, mothering of cycle.
inanimate objects, and possible aggression. III. Increased incidence of pseudocyesis in a given bitch may
be associated with predisposition to malignant mammary
Diagnosis neoplasia, presumably because of inflammatory changes
I. Diagnosis of pseudocyesis is based on a history of having and release of free radicals within the distended mammary
been in estrus approximately 2 months before presenta- tissue (Verstegen and Onclin, 2003).
tion, as well as the presence of the previously mentioned
clinical signs.
II. If breeding occurred, or if the owner is unsure if the bitch POSTPARTUM DISORDERS
was bred, then perform abdominal radiography to rule out
pregnancy and imminent whelping. Eclampsia
III. Diagnose secondary mastitis if the mammary glands are
enlarged, hot, and painful (see Chapter 60). Definition
I. Eclampsia is hypocalcemia arising from inadequate stores
Treatment of usable calcium in the extracellular compartment.
I. Spontaneous remission occurs in most cases within 2 to II. Eclampsia is also known as postpartum hypocalcemia and
3 weeks of onset of clinical signs. puerperal tetany.
A. Do not milk out the mammary glands, because in-
creased intramammary pressure inhibits prolactin re- Causes and Pathophysiology
lease and continuing milk production. I. Hypocalcemia occurs most commonly in small breed dogs
B. Wrapping the mammary glands with an elastic bandage nursing large litters, especially at peak lactation (2 to 3
may hasten this pressure effect and protects the dis- weeks postpartum) (Kaufman, 1986).
tended glands from trauma. II. Eclampsia can also occur during parturition and may
II. Megestrol acetate (Ovaban) at 2.5 mg/kg PO SID for 8 days precipitate dystocia.
is the only therapy approved for treatment of pseudo- III. The disorder develops because the bitch’s body is incapa-
cyesis in dogs. ble of drawing enough calcium from intracellular sources,
A. Signs resolve with treatment but very often recur when such as bone, and cannot ingest enough oral calcium to
the drug is withdrawn. meet the excessive demands of lactation.
B. Side effects of progestogen therapy include increased IV. Supplementation with oral calcium during pregnancy may
appetite and changes in temperament. predispose bitches to eclampsia during peak lactation.
C. Progestogens are not given to bitches with a history of V. Excessive calcium intake during pregnancy causes down-
mammary neoplasia, diabetes mellitus, or pyometra. regulation of the bitch’s own calcium regulatory system and
D. The author does not recommend the use of megestrol subsequent clinical hypocalcemia when calcium demand is
acetate for treatment of pseudocyesis in dogs. high.
CHAPTER 61 | Disorders of Canine Reproduction 613

Clinical Signs II. Metritis is not synonymous with pyometra, which is pri-
I. Eclampsia is characterized by progressive neurologic changes, mary cystic endometrial hyperplasia with secondary bac-
with initial tremors followed by ataxia and disorientation, terial infection that occurs during or after diestrus.
collapse with seizures, and, finally, coma and death (Drobatz
and Casey, 2000). Causes and Clinical Signs
II. Elevated body temperature (>40.5° C [105° F]) may be I. Metritis is caused by an ascending infection with vaginal
present. aerobic organisms after normal parturition, or after abor-
tion, fetal infection, dystocia, and/or retention of placentas.
Diagnosis II. Clinical signs include fever, anorexia, depression, neglect
I. Putative diagnosis is made by signalment (small breed dog, of pups, and exudation of foul-smelling purulent discharge
nursing large litter), history (2 to 3 weeks postpartum), from the vulva.
and clinical signs as described previously.
II. Confirmatory diagnosis requires demonstration of total Diagnosis
serum calcium concentration <7 mg/dL. I. Cytological examination of the vulvar discharge: inflam-
mation, contains numerous polymorphonuclear leukocytes
Differential Diagnosis (some of which may be degenerative) and bacteria
I. Differential diagnoses for seizures in dogs include idio- II. Aerobic culture and sensitivity of the vulvar discharge to
pathic epilepsy, meningoencephalitis, and toxicities (see guide antibiotic therapy
Chapter 22). III. Complete blood count to demonstrate neutrophilia with a
II. Evaluate dogs for hypoglycemia that do not respond to left shift (common)
empiric treatment with calcium. IV. Abdominal radiographs or ultrasonography to diagnose
retention of placentas and/or fetuses
Treatment V. Serological examination for canine brucellosis
I. Mild tremors, ataxia, and disorientation in the lactating
bitch Differential Diagnosis
A. Provide 10% calcium gluconate 0.2 to 0.4 mL/kg IM, I. Other causes of purulent vulvar discharge in the post-
SC. partum bitch include brucellosis and vaginitis.
B. Dispense oral calcium carbonate or calcium gluconate II. Rule out other causes of uterine disease (see Chapter 57).
(1 to 3 g/day) with concurrent vitamin D.
C. Puppies may continue to nurse unless signs worsen or Treatment
recur. I. Administer an appropriate antibiotic, based on culture and
II. Severe tremors, ataxia or disorientation, or seizures in a sensitivity testing, for 14 days.
bitch at peak lactation II. While awaiting culture results, start on a broad-spectrum
A. Administer 10% calcium gluconate 1 to 10 mL IV, to antibiotic, such as ampicillin at 20 mg/kg PO TID.
effect, while ausculting the heart. III. Evacuate the uterine contents by administration of oxytocin
B. Stop administration of calcium if any cardiac abnor- at 1 IU/kg IM or prostaglandin F2a (Lutalyse) at a dose
mality is evident. of 0.25 mg/kg SC.
C. If hyperthermia is present, then gradually cool the bitch. IV. Perform ovariohysterectomy on bitches that become septic
D. Provide a depot of 10% calcium gluconate 0.2 to (as evidenced by worsening clinical signs, hypoglycemia,
0.4 mg/kg IM, SC, and dispense oral calcium carbonate and positive blood cultures) and on bitches that are not
or calcium gluconate (1 to 3 g/day), with concurrent intended for future breeding.
vitamin D, when the animal is discharged. V. Bitches with mineralized retained fetal tissue may require
E. Remove pups from the bitch for 24 hours, or perma- hysterotomy or ovariohysterectomy for its removal.
nently if signs recur during the same lactation.
Monitoring of Animal
Monitoring of Animal I. Vaginal discharge resolves within 3 weeks postpartum or
I. If signs worsen or recur, then the puppies are removed 2 weeks after institution of appropriate antibiotic therapy.
from the bitch and either hand raised (<4 weeks of age) or II. Properly treated, metritis should have no effect on future
weaned (>4 weeks of age). fertility of bitches left intact.
II. Bitches with a history of eclampsia may benefit from oral
calcium supplementation during lactation after subsequent
whelpings. Subinvolution of Placental Sites

Metritis Definition
Subinvolution of placental sites (SIPS) is exudation of sero-
Definition sanguineous, noninflammatory vulvar discharge beyond the
I. Metritis is a primary bacterial infection of the uterus that time normal postpartum lochia generally is present (>3 weeks
occurs postpartum. postpartum).
614 SECTION 8 | Reproductive System

Causes and Pathophysiology II. Monitor hematocrit weekly, because bitches rarely become
I. Histological examination of placental sites in affected anemic to an extent requiring transfusion of whole blood.
bitches reveals eosinophilic protrusions of nodular epithe- III. The serosanguineous vulvar discharge of SIPS may persist
lium with necrosis and hemorrhage from failure of normal until onset of the subsequent proestrus.
thrombosis and occlusion of endometrial blood vessels. IV. SIPS rarely recurs after subsequent whelpings.
II. Underlying cause is unknown.
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