Part 2. Reproductive Complications Affecting Fertility and Pregnancy in the Bitch
Disorders of the Reproductive Cycle
During the normal reproductive cycle of the bitch, increase in the concentration of the hormone estrogen coincides with
the proestrus stage. This elevation in estrogen results in cornification of the cells of the vaginal walls. The subsequent
estrus stage (the acceptance period for mating) occurs when 90% of the vaginal cells are cornified. At the onset of estrus,
estrogen levels begin to decrease while progesterone levels rise. Increase in progesterone levels coincide with the lutenizing
hormone (LH) surge that will herald ovulation within the subsequent 48 hours. Throughout estrus, progesterone levels will
continue to rise and estrogen levels will continue to fall. Loss of estrogen will cause the vaginal cells to revert back to
a non-cornified state. When 50% or less of cells from a vaginal smear appear cornified, then the bitch is in the diestrus
stage and the mating period has ended (for further review refer to "Part 1: The Normal Reproductive Cycle of the Bitch")
The mating cycle of the bitch is, therefore, controlled by strict regulation of hormones. As such, conditions that may
interfere with normal hormone levels will interfere with successful reproduction.
Persistent estrus. Persistent estrus is most often associated with a failure of estrogen levels to decrease during
the estrus stage. Clinical symptoms of this condition present as prolonged (for 21 days or longer): 1) cornification of the
vaginal epithelial cells, 2) mating receptivity (willingness to "stand" for mating) and "tail flagging", and 3) vulvar swelling.
In prior years when exogenous estrogen treatment was used to terminate unwanted pregnancies, this condition was observed frequently
while the bitch was receiving drug treatment. Since estrogen therapy is no longer advocated for pregnancy termination, occurrence
of persistent estrus is now more often associated with endogenous (physiological) sources of estrogen. Such sources may include
developing follicles (especially in bitches that may be treated with gonadotropin therapy to induce estrus), abnormal follicular
cysts, or functional ovarian tumors. Less common sources include pituitary or hypothalamic tumors, or severe liver disease
Diagnosis of persistent estrus may be confirmed by cytological examination of vaginal smears, which will indicate persistent
cornification of 90% or greater of the sampled cells. Monitoring serum estrogen concentrations is not a reliable method for
diagnosing persistent estrus since many bitches cytologically diagnosed do not always demonstrate increased serum estrogen
levels. Monitoring serum progesterone by ELISA may be more useful since a majority of bitches experiencing persistent estrus
fail to demonstrate the normal increase (above 2 ng/ml) in progesterone levels.
Ultrasonography is usually the first step to identify the source of endogenous estrogen. This non-invasive form of diagnostic
imaging may be helpful for detecting ovarian cysts, follicles, or tumors. However, normal ovarian appearance on ultrasound
does not rule out abnormalities. Therefore, in the presence of confirmed persistent estrus where a source cannot be identified
by ultrasound imaging, exploratory laparotomy with biopsy is accepted as the follow-up approach.
In some instances, persistent estrus, particularly those cases associated with follicles or follicular cysts, will resolve
spontaneously without treatment. However, in those cases where the condition persists for longer than 3 weeks, treatment intervention
is warranted. Treatment options for persistent estrus will be based on whether or not the owner has future expectations in
regard to breeding the bitch. Ovariohysterectomy (spaying) is the preferred treatment for persistent estrus in bitches whose
owners have no consideration of breeding. For those owner's who seek to salvage reproductive function within the bitch, alternative
options may be considered.
Injections of gonadotropin-releasing hormone (GnRH) or human chorionic gonadotropin (hCG), both of which induce the ovulation
of ovarian follicles, have been successfully used in limited studies for the treatment of persistent estrus. Following administration
of the treatment regimen, vaginal smears and serum progesterone levels are monitored weekly for indications of onset of diestrus.
When treatment is successful, the cytological exam will show a decrease in the % of cornified cells and serum progesterone
levels will increase within 2-3 weeks. Though ovulation may occur as a result of treatment, breeding is not recommended at
this time. Secondary complications associated with the use of GnRH include the potential for pyometra [for information on
"pometra" please refer to: Robin Camken's Pyometra Links]. Additionally, some bitches that undergo successful therapy may subsequently develop a recurrence of
persistent estrus: a condition which is highly indicative of a tumor. In such instances, ultrasound or laparotomy is indicated.
Though progestin therapy with megestrol acetate (Ovaban) is effective at reducing the symptoms associated with persistent
estrus, progestin therapy should not be used in bitches that will later be bred. Progestin therapy results in a high incidence
of cystic endometrial hyperplasia and pyometra, and therefore when this approach is used, ovariohysterectomy is considered
mandatory within 3 weeks following treatment to prevent these secondary complications. As such, this is not a viable therapeutic
option for owners wishing to preserve reproductive function.
Persistent Proestrus. In this condition, estrogen levels fail to peak during proestrus. As a result, the estrus
stage does not follow the proestrus stage. Though symptoms may appear similar to persistent estrus, examination of the vaginal
epithelial cells shows only 50-90% of the cells in the smear to be cornified. Additionally, serum progesterone levels fail
to reach 2 ng/ml. Treatment of persistent proestrus is the same as for persistent estrus.
Split Estrus. Occasionally, a bitch will enter proestrus and fail to enter estrus or will experience a very short
estrus. If the bitch is bred, conception will usually fail, however, the owner will note that within 3 to 4 weeks the bitch
is demonstrating signs of entering proestrus again. Thereafter, the bitch proceeds normally through the subsequent stages
of reproduction. This condition is known as Split Estrus. Split estrus occurs more commonly in young, first-estrus bitches,
however, older bitches may also be affected. Split estrus usually resolves without the need for treatment. Recurrent incidences
of split estrus in a bitch, however, may suggest chronic premature luteolysis (inability to maintain sufficient elevation
of the serum progesterone concentration) or an underlying health disorder such as hypothyroidism.
Recurrent Estrus (Shortened Interestrus Intervals or Polyestrus). In some cases, bitches will experience only brief
(shorter than 4 months) interludes between estrus cycles. It has been observed that such bitches usually have a higher rate
of infertility. The shortened intervals, however, are believed to be an effect rather than a cause of infertility. For example,
it is believed that these bitches fail to ovulate, perhaps due to insufficient LH production, and as a result serum progesterone
concentrations never get high enough to be recognized by the hypothalamus. This condition is believed to prompt the hypothalamus
to initiate another estrus cycle. Fertile cycles may occur intermittently among infertile cycles, and as such, a bitch may
conceive even after several unsuccessful attempts to breed during prior cycles. One study links recurrent estrus to functional
follicular cysts and suggests that recurrent estrus, like persistent estrus, may respond to gonadotropin-releasing hormone
(GnRH) therapy. Alternatively, mibolerone therapy (Cheque Drops) may be used to increase the interval between estrus cycles.
When persistent estrus follows recurrent estrus, there is an increased suspicion for the presence of either an ovarian or
Primary and Secondary Anestrus (Persistent Anestrus). Some reproductively intact bitches may completely fail to
cycle. Because of the numerous potential causes, the process to diagnose the reason for this abnormality can be quite extensive.
Before undertaking this task, it is first essential to confirm the state of persistent anestrus. Blood samples should be drawn
on a monthly basis for 6-8 months for the purpose of measuring concentrations of serum progesterone. Progesterone levels in
the normal reproductive bitch will rise above 2 ng/ml for 2 months after estrus. Failure to detect increased levels of serum
progesterone over a 6-8 month period in the bitch will strongly suggest a state of persistent anestrus. Additionally, because
functional ovaries will provide a negative control over hormones produced by the pituitary gland, other blood tests to detect
elevated concentrations of lutenizing hormone (LH) or follicular stimulating hormone (FSH) may be indicative of abnormalities
of ovarian development or premature ovarian failure that may bring about persistent anestrus. Once the condition of persistent
anestrus is confirmed, then exploration to identify the underlying cause can be initiated.
Abnormalities of Sexual Differentiation. Genetic errors that effect sexual development of an individual dog may
occur during one of three time points following conception: 1) during chromosomal establishment of gender (chromosome monosomy
[XO], trisomy [XXX or XXY], or chimerism [some cells XX, others XY in the same individual]; 2) when chromosomal gender is
translated into gonadal gender (disagreement between actual chromosomal sex and reproductive organ sex such as when a bitches'
ovaries are XY instead of XX); or 3) during actual development of the reproductive tract and organs (disagreement between
actual chromosomal sex and reproductive organ development such as having an outward appearance of a bitch, but the internal
organs of a male). When any of these situations occur, normal reproductive function is inhibited and there is a permanent
and irreversible state of anestrus. Diagnosis of abnormal sexual differentiation can be confirmed by analyzing the chromosomes,
a process known as karyotyping, from a blood or skin sample of the bitch.
Thyroid Insufficiency. In general, a history of irregularities in the reproductive cycle of a bitch, including
persistent anestrus, "silent heats" (in which only mild bleeding and minimal vulvar swelling are observed), prolonged proestrus,
or ovulation failure, is often indicative of hypothyroidism. Thyroid hormones are involved in numerous positive and negative
feedback loops that have direct and indirect effects on other hormone levels and hence metabolism. In regard to its role in
reproduction, thyroid hormone is indirectly associated with levels of prolactin hormone. As such, insufficient production
of thyroid hormone often leads to increased levels of prolactin. Prolactin, in turn, has an inhibitory effect on gonadotropin-releasing
hormone, which is required for induction of follicular ovulation. Therefore, this is one of possibly several ways in which
thyroid hormone insufficiency indirectly interferes with ovulation. Measurement of thyroid hormones alone often yields ambiguous
results, therefore, for accurate diagnosis of hypothyroidism a complete thyroid profile, which measures: 1) levels of free
thyroid hormone in serum; 2) response to administration of thyroid-stimulating hormone; and 3) levels of antithyroid antibodies,
is recommended. Hormone replacement therapy is successful for restoring normal reproductive cycling within 3 to 6 months,
however, recommendations for breeding bitches with hypothyroidism are guarded since this condition is often associated with
a hereditary immune-mediated disease. (For more information on Hypothyroidism, please refer to Robin Camken's "Hypothyroidism" Health Information Links)
Lymphocytic Oophoritis. This condition is an autoimmune mediated disorder that results in premature ovarian failure.
The autoimmune disease may be isolated to the ovaries or occur in conjunction with a more wide-spread, systemic disease manifesting
as skin lesions or polyarthritis. This disorder is diagnosed by surgical biopsy of the ovaries which reveals follicular degeneration
and lymphocytic infiltration (suggestive of the immune-mediated reaction). Recommended treatment for this disorder is ovariohysterectomy
since immunosuppression using corticosteroids to treat this disease has not been examined in terms of safety and efficacy
in the dog.
Luteal Ovarian Cyst. Ovarian cysts are occasionally found in conjunction with occurrence of persistent anestrus.
It is unknown if this finding is coincidental or if ovarian cysts play a contributory role in persistent anestrus. In any
event, ovarian cysts should be suspected when progesterone levels exceed 2 ng/ml for more than the normal 2 month duration
during a bitches' cycle. Symptoms of abnormal cycling combined with appearance of ovarian enlargement on ultrasound are indicative
of an ovarian cyst but should be confirmed by biopsy. Ovarian cysts usually respond to treatment with prostaglandins; those
that do not respond to drug therapy are treated by surgical excision.
Pituitary Insufficiency. Persistent anestrus occurs commonly in bitches with dwarfism resulting from hereditary
abnormalities of the pituitary gland. Because pituitary function is critical for maintaining endocrine organ (thyroid, adrenal,
ovary) functions, various endocrine abnormalities typically occur concurrently in bitches with this disorder. Additionally,
the bitch will retain the size, haircoat and dentition of a puppy. Because there is a hereditary basis for this disorder,
the recommended treatment for persistent anestrus resulting from pituitary insufficiency is ovariohysterectomy.
Ovarian Aplasia/Hypoplasia. Incomplete development and/or maturation of the ovaries will result in a state of persistent
anestrus. Compromised anatomy of the ovaries and subsequent insufficient production of ovarian hormones result in an inability
to regulate pituitary hormones. As such, chronic elevation of LH and FSH serum concentrations in the bitch is highly indicative
of this disorder. This condition is irreversible and ovariohysterectomy is the usual course of action.
Other Causes for Infertility
Occasionally, attempts to breed a bitch will fail because of physiological defects or simply because the bitch refuses
to accept natural mating. Such causes may originate from one of several factors.
Vaginal/Vestibular Barrier to Breeding. Obstructions of the vaginal tract can occur as a result of abnormal or
attenuated development of the vagina or as a result of vaginal prolapse (when one area of the vagina slides or "telescopes"
within the adjacent area). These conditions may present a source of pain to the bitch during the male's attempts to copulate,
and thus lead to her refusal to allow the male to breed. Conditions such as persistent hymenal remnants, annular strictures,
vaginal hypoplasia, vertical septa bifurcation, and vaginal prolapse can often be diagnosed by physical exam and vaginoscopy.
When attempting to diagnose vaginal abnormalities it is important to note that some conditions may only be observed during
proestrus, estrus, or early diestrus; this is particularly true of some types of vaginal prolapses. Some vaginal/vestibular
abnormalities can be corrected by surgery and/or electrocautery. Alternatively, artificial insemination may be used to circumvent
the problem, however, some abnormalities may compromise normal delivery and thus require delivery of the resulting litter
by cesarean section.
Abnormalities of the Female Tubular Tract. Developmental or acquired obstructions of the female tubular tract occur
rarely but should be considered when evaluating causes for infertility. Improper development or trauma from previous whelping
or cesarean surgeries are potential causes for this disorder. Diagnosis is achieved through laparotomy and distention of the
uterus with saline or by retrograde hysterography which allows visualization of the reproductive tract using a dye for contrast
imaging. Occasionally, correction of this condition may be achieved by surgery.
Incorrect Timing of Ovulation. Probably the most common reason for failed breeding results from the attempt to
breed a bitch at the wrong time of her cycle. Although the average bitch will ovulate on Day 12 after the onset of proestrus,
some bitches may ovulate as early as Day 3 or as late as Day 26 after onset of proestrus. Because the willingness of the bitch
to "stand" for mating coincides with ovulation, attempts to breed a bitch that experiences ovulation early or late in her
cycle around Day 12 will usually result in refusal to breed. Refusal of the stud and/or failure to conceive due to incorrect
timing of breeding can be managed by ovulation testing (refer to "Ovulation Testing" in Part 1).
Mate Preference. In some instances, a bitch may refuse to "stand" for one male but will be receptive to another
male. This problem may be circumvented by performing artificial insemination (see Artificial Insemination in Part 1) 2 days
after ovulation as determined by serum progesterone testing and/or serum LH testing (see "Ovulation Testing" in Part 1)
Conditions Causing Spontaneous Abortion
Spontaneous abortion may occur early or late into the pregnancy of a bitch. When spontaneous abortion occurs during the
first or second trimester of the pregnancy, the fetuses will be resorbed. If prior confirmation of pregnancy (either by ultrasound
or serum relaxin diagnosis--see "Pregnancy Diagnosis" in Part 1) has not been obtained, the owner may suspect failed breeding or
infertility in the bitch. As such, diagnosis of the cause leading to early spontaneous abortions is often challenging.
Spontaneous abortions in the third trimester will result in expulsion of the fetuses and, therefore, greatly narrow the
field for possible causes. Aborted fetuses and placenta should be collected and refrigerated (not frozen). Necropsy of the
fetuses is often helpful for identifying conditions responsible for spontaneous abortion, however, results may not always
provide a definitive explanation. Causes for spontaneous abortions may be either infectious or non-infectious conditions.
The most common causes are discussed here.
Brucellosis. Bacteria of the Brucella sp. are well known for inducing spontaneous abortion in the bitch.
B. canis is the most common of the brucellosis-causing bacterial strains found in dogs and, as such, is routinely screened
for by serological testing as part of the breeding management plan. Limitations to serological testing for B. canis,
however, do exist and typically occur with use of the rapid slide agglutination test (RSAT) or the tube agglutination test
which may result in false-positives or false-negatives. False-positives should be suspected if a dog is asymptomatic or concurrent
blood cultures drawn at the same time as serological samples are negative for bacterial growth. Follow-up assessment with
the agar-gel immunodiffusion (AGID) test will rule-out the possibility of false-positive results.
False-negatives will occur if serological testing is conducted within a 4 week period after the dog has initially contracted
B.canis. Therefore, all negative tests should be confirmed by repeat testing 30 days from the first test before considering
a dog to be free of infection.
B. canis infections in pregnant bitches will typically cause spontaneous abortions between 49 and 59 days after breeding,
however, infections may also induce early spontaneous abortions with resorption of the fetuses, result in stillborn puppies,
or cause death of puppies shortly after birth. A bitch that aborts a litter due to B. canis will demonstrate a brown
or greenish-gray discharge that contains a large number of bacteria that will be infectious to both dogs and humans. Extreme
caution, therefore, should be used when caring for a bitch suspected of harboring B.canis. At such point, collection
of the vaginal discharge and specific culture testing for B.canis is usually sufficient to obtain the diagnosis.
Though B. canis is most often conceived as being transmitted from dog to dog during the actual act of copulation,
the primary mode of transmission actually occurs via oronasal contact with infected body fluids. Therefore, spread of infection
is not limited to breeding contact and as such, once introduced into a breeding kennel, the highly infectious B. canis
will quickly spread through the population. Long-term, multiple treatments with antibiotics may assist in controlling symptoms
and extent of infection within an individual dog, however, antibiotic treatment has limited efficacy for cure and the dog
will remain potentially infectious to other dogs. As such, infected dogs should be neutered and removed from the breeding
kennel environment to prevent spread to other breeding dogs. Retesting should be performed 6 months following completion of
the antibiotic regimen to assess treatment efficacy. The alternative for controlling spread of B. canis is euthanasia
of all confirmed-infected dogs.
Dogs may also become infected with other strains of Brucella sp. that typically infect livestock. Dogs with a history
of spontaneous abortion, negative serological testing for B. canis, and exposure to livestock may harbor one of the
other strains such as B. abortus, B. suis, and B. melitensis. Since serological tests for B. canis
will not cross react with these other Brucella sp., dogs suspected of carrying an alternate strain of Brucella
should be tested specifically for these other strains.
Canine Herpesvirus Infection. Canine herpesvirus infection occurs as a relatively mild viral infection in the average
dog, however, new infection in a pregnant bitch or newborn puppies will usually result in spontaneous abortion or neonatal
fatality. Greatest risk occurs in the last three weeks of pregnancy and the first 3 weeks of birth. The virus is commonly
found in dogs, and as many as 80% to 100% of dogs with a history of high exposure to other dogs (such as show dogs and kennel
dogs) will be found to have life-long, latent states of infection (asymptomatic infection). Bitches that become infected with
herpesvirus during pregnancy will usually experience pregnancy complications resulting in fetal death, fetal mummification,
spontaneous abortion, or premature birth. Newborns that become infected with the virus usually succumb to septicemia. Additionally,
surviving puppies will typically show indications of permanent nerve, kidney and lymphatic system damage. Bitches previously
infected with canine herpesvirus may have normal pregnancies and litters without fatality, but at other times have a spontaneous
abortion or lose puppies following birth. Outcome in bitches harboring infection prior to breeding appears to rely on the
maternal immune system status at the particular point in time.
Serological testing showing any degree of titer for canine herpesvirus infection is considered positive since humoral immunity
to this virus is minimal and short-lived. Monitoring titer, however, may provide an indication of viral "flare-up" at a particular
point in time and may be helpful for assessing immune status and potential pregnancy complications in those bitches that have
previously lost litters to canine herpesvirus complications. Additionally, serological titer is useful for diagnosis of canine
herpesvirus as a cause for spontaneous abortion in the pregnant bitch. When abortion occurs late in the pregnancy, histopathological
examination of tissues from the aborted fetuses can be used to confirm the presence of canine herpesvirus infection.
Treatment for canine herpesvirus, as with most viruses, is extremely limited and there is currently no preventative vaccine
available. Recommendations for reducing risk of new infection in pregnant bitches is to isolate the bitch from other dogs
particularly during the last 3 weeks of pregnancy and to isolate newborn puppies for their first 3 weeks of life. (Canine
Herpesvirus in newborn puppies is often fatal, however, some treatment success has been reported for the following treatment
protocols: Neonatal Herpesvirus)
Toxoplasmosis. The cat is the definitive host for the toxoplasmosis organism, however, dogs may serve as an intermediate
host. As in humans, toxoplasmosis infection in the dog may produce spontaneous abortion, but more commonly causes developmental
problems that will impact upon the puppies in life.
Dogs may become infected with toxoplasmosis by ingesting the organism when eating the feces of an infected cat, by eating
infected meat, or in utero if the dam is acutely infected during the pregnancy (chronic infections in the dam are usually
not transmitted to the fetuses). In the latter instance, if an infected litter survives, the puppies will usually develop
symptoms of neurological, respiratory and gastrointestinal abnormalities.
Diagnosis of toxoplasmosis is accomplished by serological titers sampled 2 weeks apart. A significant increase in the second
titer compared to the first titer is indicative of an acute toxoplasmosis infection. Chronic infections may present a high
baseline titer (initial titer).
Prevention is the recommendation for reducing risk of toxoplasmosis infection in the pregnant bitch. Bitches should not
be exposed to cat feces or raw meat, both of which may pose palatable temptations to the bitch. Since cats only shed toxoplasmosis
during a brief time after exposure, chronically infected cats are not of particular concern.
Mycoplasma and Ureaplasma. These organisms are of the Mycoplasmataceae family and normally inhabit the canine
urogenital and nasopharyngeal tracts. If, however, there is an increase in the number of these organisms in comparison to
the other common organisms also inhabiting the vaginal tract of the bitch, then there is an increase in infertility, spontaneous
abortion resulting in resorption or premature birth, stillbirth, weak puppies, or neonatal death. Bitches kept in large, overcrowded
breeding kennels are at greatest risk for acquiring these infections.
Diagnosis of spontaneous abortion caused by Mycoplasma or Ureaplasma is obtained by vaginal cultures and
cytological examination of the vaginal discharge for signs of inflammatory cells. Cultures may also be obtained from aborted
fetuses for confirmatory results.
Administration of chloramphenicol or tetracyline is effective for Mycoplasma or Ureaplasma infections. These
antibiotics, however, are not safe for pregnant bitches. Therefore, if a bitch is diagnosed with an infection during pregnancy,
before complications occur, Erythromycin, which is less effective against the infection but safer to the developing fetuses
is the recommended treatment.
Miscellaneous Bacterial Infections. The vaginal tract of the bitch houses a multitude of various organisms, anyone
of which may become opportunistic pathogens under certain conditions. Some of these bacterial organisms that have been associated
with spontaneous abortions or post-delivery complications most commonly include Escherichia coli and Streptococcus,
or less commonly Salmonella or Campylobacter (particularly if diarrhea has been observed in the bitch or any
humans in contact with her). Infections can occur in any bitch, however, endometrial hyperplasia that occurs with aging places
older bitches at increased risk for these infections.
Bacterial infections of the uterus and urogenital tract during pregnancy usually present with clouded, sometimes green-tinged
discharge and if left untreated often results in spontaneous abortion. When puppies survive they usually have neonatal conjunctivitis
(infection of the eyes) and often die shortly after birth due to septicemia (systemic infection).
Culture and examination of the vaginal discharge will indicate bacterial infection and processes of inflammation, respectively
(a special culture must be run separately if Campylobacter is suspected). Additionally, the bitch may have a fever.
For treatment, the antibiotic administered will be based on efficacy as determined by sensitivity screening as well as safety
to the developing fetuses if the bitch is still pregnant. When spontaneous abortions occur, care must be taken to ensure that
the uterus is completely evacuated in order to control infection.
Miscellaneous Viral Infections. Spontaneous abortions as a result of viral infections occur infrequently in the
bitch, most likely attributed to the preventative vaccination programs utilized by most breeders as well as the duration of
immunity afforded by anti-viral vaccines. When spontaneous abortions do occur they are most often associated with canine distemper
virus, canine adenovirus and canine herpesvirus. Commercial vaccines are available to protect against canine distemper and
adenovirus and should be administered prior to the proestrus stage to prevent vaccine-associated complications during breeding
and gestation (refer to "Vaccines, Infectious Diseases, and the Canine Immune System" for more information). Currently, there are no commercial vaccines available
to protect against canine herpesvirus (refer to section above on "Canine Herpesvirus").
Noninfectious Causes of Canine Abortion
Progesterone Insufficiency. Bitches for which pregnancy has been confirmed by ultrasound or serum relaxin diagnosis
(refer to "Pregnancy Diagnosis" in Part 1) and subsequently experience spontaneous abortion without evidence
of any of the infectious causes outlined above should be suspected of having progesterone insufficiency (insufficient luteal
phase). Progesterone hormone rises just prior to ovulation and continues to increase to levels above 5 ng/ml during the pregnancy
then will decrease just prior to whelping. This hormone is essential for the maintenance of the pregnancy because it is required
in high levels to suppress the hypothalamus from producing gonadotropin releasing hormone (GnRH). If levels of progesterone
drop below 2 ng/ml, GnRH levels will rise and stimulate the pituitary to release follicular stimulating hormone (FSH) and
lutenizing hormone (LH). FSH and LH will reset the ovarian cycle causing an abrupt termination of the current cycle, thus
resulting in spontaneous abortion. This premature decrease in progesterone will typically occur between 2 and 4 weeks after
breeding. When the condition occurs early in gestation, prior to confirmation of pregnancy, diagnosis is often complicated
because other factors associated with unsuccessful breeding must be ruled out. Bitches for which there is a strong suspicion
of progesterone insufficiency or that are confirmed to be pregnant prior to spontaneous abortion with no evidence of other
conditions should be monitored for serum progesterone levels by ELISA during subsequent pregnancies. In such an instance,
progesterone levels are measured from the time of breeding through the weeks of gestation. If progesterone levels begin to
fall, exogenous progesterone therapy can be administered to maintain the pregnancy. Progesterone therapy is discontinued at
the end of the gestation period with birth occurring within 72 hours after the final injection is administered.
Miscellaneous Causes. Fetal genetic defects may result in resorption or stillbirth of effected fetuses, but generalized
spontaneous abortion typically only occurs if all the fetuses are afflicted. Such defects are diagnosed by chromosome analysis
of the fetal tissue.
Hypothyroidism has been linked to spontaneous abortion in bitches, however, its role in the occurrence of spontaneous abortion
has not been established. In general, bitches with any type of endocrine disorder are discouraged from being bred because
of the hereditary nature of many of these diseases.
Though nutritional deficiencies, particularly manganese deficiency, may lead to fetal demise, the widespread availability
of nutritionally-balanced, commercial dog foods has made this a rare cause for spontaneous abortion. In regard to diet, however,
the practice of calcium supplementation still has implications for producing pregnancy complications, such as uterine inertia
and prolonged gestation, that may increase risk to both the fetuses and the dam.