College of Veterinary Medicine

VM 551 SAM - Urogenital System

Female Reproduction



Pregnancy prevention

 Methods to prevent pregnancy include
  • ovariohysterectomy
  • treatment with megesterol acetate
  • treatment with mibolerone (no longer commercially available)

Ovariohysterectomy is the removal of the ovaries and uterus. The positive aspects of performing ovariohysterectomy include:

  • no unwanted puppies
  • no heat cycles
  • a lower incidence or prevention of some diseases including mammary tumors, pseudopregnancy and pyometra
  • lower license fees in some areas

Potential negative aspects of performing ovariohysterectomy include: 

  • permanence, the owners cannot later change their mind
  • some animals will gain weight due to a reduced metabolic rate although this can be controlled by reduced caloric intake and exercise
  • surgical and anesthetic risks. Risks are increased during an estrus cycle and during pregnancy due to increased blood supply.
  • urinary incontinence. Sympathetic alpha receptors in the urethra which maintain urethral tone and urinary continence, are more sensitive to stimulation in the presence of estrogen. As estrogen levels decrease after ovariohysterectomy, some dogs will develop urinary incontinance due to reduced tone of urethral muscle, months to years after the surgery. The incontinence usually occurs when the dog is sleeping and the dog is not aware that she is leaking urine. The incontinence may be controlled by the administration of estrogens or alpha agonists including ephredrine and phenylpropanolamine. (more information on urinary incontinence)
  • perivulvar dermatitis. Bitches that have heavy musculature in the rear (like bulldogs) may have recession of the vulva between folds of tissue. Small amounts of urine may accumulate on the skin around the vulva causing dermatitis. During estrus, the vulva enlarges and becomes more prominent so air circulation around the vulva is improved and urine is less likely to accumulate in folds of skin around the vulva. Bitches who have never had a heat (estrus) cycle are more likely to have a small, recessed vulva. If this problem develops it is easily managed by excising some skin around the vulva to make the vulva more prominent and improve air circulation to keep the perivulvar area dry. Perivulvar infections can ascend into the urinary tract and be a source of urinary tract infection.

Megestrol acetate (OvabanR) is a synthetic progesterone. It is ~92-97% effective in preventing ovulation and signs of heat. The mechanism of action is to inhibit follicle stimulating hormone (FSH) and lutenizing hormone (LH). It is the only progestin approved for estrus control in dogs in the US.

There are 2 administration protocols for dogs:

  • proestrus
  • anestrus
cornified epithelial cells and RBC

Within the first 3 days of proestrus, an oral dose of 1 mg/lb is administered by mouth for 8 days. If megesteral is administered too early, the first post-treatment heat cycle may occur early. If accidental mating occurs during the first 3 days of treatment DO NOT MISMATE with estrogens due to increasing the risk of development of pyometra. If mating occurs after the first 3 days of therapy continue megesterol; the pregnancy should be prevented.

parabasal cells

If the bitch is between heat cycles (anestrus) megesterol is administered for 32 days at a dose of 0.55 mg/kg (0.25 mg/lb) starting at least one week prior to anticipated onset of estrus. Vaginal cytology may help identify impending estrus. If there is cytologic evidence of proestrus (RBC), wait a few days until proestral bleeding is apparent and begin treatment using the proestrus regime.

Allow a nontreated cycle before using megesteral a second time. The manufacturers recommend that Megesteral not be used in the first estrus cycle because of sexual immaturity and variability in response.

Side effects of megesterol may include:

  • increased appetite resulting in weight gain
  • mammary enlargement and rarely lactation
  • pyometra may develop
  • diabetes mellitus
  • acromegaly
  • adrenocortical supression
  • progesterones can have "sedative" effects and some patients will have a decreased activity level

Megesterol is not approved for use in cats although there are protocols in the literature.

It is suggested that no more than 2 consecutive cycles be suppressed.

A subdermal implant of levonorgesterol (Norplant) has been shown to supress estrus for 12 months in cats. Norplant is not approved for use in dogs or cats.

Androgens

Mibolerone is no longer available. Other testosterones have been used for estrus suppression but are not approved.

GnRH Agonists

A slow release subcutaneous implant of Deslorelin has been shown to suppress reproductive function in male and female dogs and cats. This product is not available but is being researched.

Sclerosing Agents

The injection of a sclerosing agent into the testes will result in azoospermic ejaculates. Neutersol®, ( Zinc Gluconate/Arginine) is an FDA-approved injectable sterilant used for chemical castration of male dogs 3 to 10 months of age.

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Mismating

A bitch may be presented after accidentally being breed by a male. The administration of a drug to prevent pregnancy is called mismating.

There are no products which are approved for mismating. There is the potential for development of serious side effects from estrogens administered to prevent pregnancy. You should be prepared to present the risks of mismating to the owners and to discuss alternative methods to terminate pregnancy. Vaginal cytology should be performed to look for spermatozoa to confirm that mating took place.

 

cornified epithelial cells

 Confirm that the majority of the vaginal epithelial cells are cornified, indicating the influence of increased levels of estrogen. 65% of bitches will have sperm in a vaginal smear 24 hours after breeding and 50% of bitches will have sperm in a vaginal smear 48 hours after breeding.

Estrogens can be highly effective (but not 100% effective) in preventing pregnancy if given within 5 days after mating. If estrogens are to be used they, should be given as soon as possible. Estrogens alter the transport of the ova through the oviduct and alter the uterus to provide an unfavorable environment for implantation and growth of the ova.

Estradiol cypionate (ECP) is administered at a dose of 0.01-0.02 mg/lb up to 1 mg total. ECP is not approved for this use.

The potential complications of estrogen treatment include:

  • prolonged signs of estrus. If the bitch is breed again after estrogen administration DO NOT give a second dose.
  • bone marrow suppression due to the inhibition of pleuripotential stem cells resulting in irreversible pancytopenia. Dogs are more sensitive than cats to the bone marrow suppressive effects of estrogens
  • pyometra within 1-6 weeks after administration of estrogens

Alternatives to estrogen administration include:

  • ovariohysterectomy. There is less blood flow to the reproductive tract in early pregnancy than during estrus, so it is recommended to wait until the bitch completes her heat cycle and spay her in early pregnancy.
  • prostaglandin induced abortion. Prostaglandin F2 alpha is luteolytic in bitches which means it will cause regression of the corpus luteum which produces progesterone which supports pregnancy. Prostaglandin F2 alpha will cause fetal resorption if administered at ~20 days of gestation and will cause abortion if given at ~30 days of gestation. By waiting 20 to 30 days after breeding, an ultrasound can be performed to see if the bitch did become pregnant. Prostaglandins are not approved for this use.
  • Dexamethasone administered at 0.5 m/kg IM q 12hr x 10 days terminated pregnancy in an experimental study.

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Louisiana State theriogenology notes on estrus control

Louisiana State theriogenology notes on pregnancy prevention


Diseases of the female genital tract

Pseudopregnancy

The "dictionary definition" of pseudopregnancy, also called false pregnancy or pseudocyesis, is the retention of the corpus luteum in a non pregnant animal for the same duration as the corpus luteum is retained during pregnancy.

By this definition, all dogs are pseudopregnant after every heat period, mated or not. In the dog, the term pseudopregnancy is accepted to mean that the bitch shows clinical signs mimicking those of pregnancy about 8 weeks after estrus, even though she is not pregnant.

The cause of clinical pseudopregnancy is unknown. It may result from high levels of prolactin stimulated by an abrupt decline in progesterone. Colony dogs have a very low incidence of false pregnancy. The clinical signs vary in intensity from mild to very obvious and include:

  • mammary development
  • milk letdown (lactation)
  • nervousness and excitability
  • nesting behavior
  • weight gain

The signs may be so convincing that the owners actually think the dog is pregnant. Bitches have a tendency to repeat this behavior during subsequent heat cycles. The signs can subside without treatment but if treatment is given the treatment should reduce the signs of false pregnancy without stimulating the mammary glands.

Drugs used in treating false pregnancy can alter a normal pregnancy or mask a pyometra so these conditions should be ruled-out before use.

Treatments include:

  • ovariohysterectomy
  • tranquilizers
  • megestrol acetate - OvabanR , 2.5 mg/kg for 8 days by mouth

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Cystic endometrial hyperplasia and pyometra complex

Both estrogen and progesterone are involved in the development of cystic endometrial hyperplasia and pyometra. Cystic endometrial hyperplasia has been produced by administering 10 mg of progesterone daily for 60 days to ovariectomized bitches. Pyometra has been produced by giving 4 cycles of 5 mg stilbestrol for 10 days followed by 25 mg of progesterone for 20 days.

Progesterone stimulates endometrial gland proliferation, functionally closes the cervix, and inhibits myometrial contractility. When given to diestrual bitches progesterone may induce pyometra. Cystic endometrial hyperplasia is the exaggerated response of the uterus to progesterone. Pyometra occurs when excessive inflammatory exudate and mucus accumulate in the uterus.

Estrogen cannot cause pyometra alone, but it enhances the progestational effects on the uterus.

Bacteria complicate rather than initiate pyometra. Secondary infection is common. E. coli is the most common organism involved. Strep, staph, proteus, klebsiella, or pseudomonas may be present.

Pyometra most often occurs in bitches over 6 years of age, but may occur as early as after the first heat cycle. There is no breed predisposition. Clinical signs vary with the patency of the cervix; signs are more severe if the cervix is closed and the diagnosis may be more difficult to make as there is no obvious vaginal discharge.

Clinical signs begin 2 to 12 weeks following estrus. Historical complaints may include:

  • purulent vaginal discharge if the cervix is open
  • PU-PD
  • depression
  • vomiting
  • weight loss

Physical examination may reveal:

  • variable temperature: normal, subnormal or fever
  • abdominal and uterine enlargement (avoid forceful palpation - can lead to rupture)
  • dehydration
  • depression
  • purulent vaginal discharge if the cervix is open. The bitch may groom excessively resulting in redness around the vulva. She may keep the area free of discharge.

Laboratory findings may include:

  • neutrophilia. The most elevated neutrophil counts occur when the cervix is closed. A variable degree of left shift and toxicity of the neutophils may be present.
  • normocytic, normochromic anemia is observed in ~ 25% of cases
  • elevated serum albumin reflects dehydration
  • azotemia which is usually prerenal in origin from dehydration
  • elevated serum globulins reflect antigenic stimulation
  • low urine specific gravity is due to e coli antigens inducing a state of nephrogenic diabetes insipidus. Often the urine specific gravity is hyposthenuric (<1.007).
  • proteinuria. Proteinuria may be due to the presence of a concurrent urinary tract infection and be secretory in nature or may be due to development of immune complex glomerulopathy and be glomerular in origin.
  • vaginal cytology discloses neutrophils and bacteria

Radiology may disclose an enlarged uterus as a homogenous tubular structure of fluid density in the caudal abdomen. Ultrasound may provide accurate visualization of uterine loops to differentiate pyometra from pregnancy.

The initial treatment is to correct dehydration and stabilize the patient before initiating more specific treatment. Antibiotics are indicated based on uterine culture results. Prior to results of the culture, treatment should be directed against e coli.

Ovariohysterectomy is a definitive treatment of pyometra. Medical therapy using prostaglandin F2alpha is a well described, but not approved, alternative treatment. Prostaglandins cause an increase in contractility of uterine muscle and lysis of the corpus luteum resulting in decreased circulating progesterone levels. Prostaglandin F2alpha is dosed at 0.10 mg/kg, 0.25 mg/kg or 0.50 mg/kg SQ for 3-5 days. Treatment can be repeated in 2 weeks if vaginal discharge still present.

Immediate reactions to prostaglandins include restlessness, salivation, vomiting, and defecation. If the cervix is closed there is a risk of uterine rupture resulting in sepsis. Additionally if the cervix is closed, uterine contents may be forced up the oviducts which may cause damage leading to infertility.

Pyometra tends to reoccur on subsequent cycles. Therefore, it is recommended to breed the bitch the next cycle.

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Acute Metritis

Acute metritis is inflammation of the post partum uterus. It may occur due to uterine trauma during parturition with subsequent infection. Gram negative bacilli are most frequently causative. Acute metritis may also be caused by retention of fetal membranes or a fetus. Infrequently metritis occurs after artificial insemination or natural breeding.

History includes recent parturition which frequently was complicated, anorexia, depression and loss of maternal instincts.

Physical findings include:

  • fever
  • foul smelling vaginal discharge
  • tense abdomen
  • sometimes concurrent mastitis.

Laboratory abnormalities include:

  • neutrophilia with left shift and toxic neutrophils
  • hemoconcentration evidenced by increased TP and PCV
  • prerenal azotemia
  • vaginal cytology may show degenerate neutrophils, endometrial cells, debris, mucus, and bacteria.

A culture of the discharge should be obtained. Treatment is with systemically administered antibiotics, supportive fluid therapy and oxytocin or prostaglandins to promote uterine evacuation. Ovariohysterectomy may be necessary.

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Subinvolution of placental sites (SIPS)

Subinvolution of placental sites (SIPS) is a failure of the sites of placental attachment in the uterus to involute. The etiology is unknown. It is not a common disorder and is most often seen in young bitches.

Bitches with SIPS appears normal except for the presence of a mild to moderate serosanguinous discharge which lasts beyond the normal post partum lochia of 3-4 weeks. Palpation of the abdomen reveals discrete, oblong uterine enlargements which are the sites of placental attachment. Clinical pathology is normal. Vaginal cytology discloses RBC, WBC, parabasal cells, cell debris, and bacteria. Vaginal culture yields growth of mixed normal vaginal flora.

Spontaneous remission may occur. The discharge is a good bacterial growth media and secondary metritis may occur therefore antibiotics may be indicated. Ovariohysterectomy is curative.

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Puppy vaginitis

Prepubertal bitches may have a small quantity of white vaginal discharge. This is usually of no consequence, requires no treatment and will resolve with first estrus cycle.

 

Vaginal hyperplasia During estrus, vaginal tissues may become hyperplastic and protrude through the vulva. Vaginal hyperplasia is more common in brachycephalic breeds such as Boxers and Bostons. The hyperplastic tissue will regress at the end of the heat cycle but may return the next heat. The tissue may appear healthy or may become necrotic if the tissue dries and is self mutilated. It may be necessary to place an Elizabethan collar on the dog to prevent self trauma. The protruding tissues should be kept clean and moist. It may be necessary to amputate the hyperplastic tissue if it becomes necrotic. Vaginal hyperplasia must be differentiated from tumors which are not associated with estrus cycles. It is common for this to recur with each estrus cycle.

Vulvovaginal stenosis, hymenal remnant, paramesonephric septal remnant

Each of these findings result in a narrowed region of the vulva or vagina which may be asymptomatic or result in problems during breeding or may result in apparent urinary incontinence. The bitch may truly be incontinent if other congenital abnormalities are present or they may pool urine anterior to the narrowed region which leaks out when they change positions. A digital vaginal exam discloses a narrowing of the vaginal vault in close proximity to the urethral orifice. A hymenal remnant is a thin, ventrodorsal band of tissue in the vestibule, paramesonephric septal remnants appear as ventrodorsal bands that appear to be continuous with both the vestibular and vaginal mucosa, and a vulvovaginal stenosis is as an annular constriction at the vestibulovaginal junction. It is difficult to pass a urinary catheter in bitches with any of these findings. If symptomatic, the treatment is to digitally or surgically breakdown the stricture.

Transmissible venereal tumor (TVT) affects both sexes after sexual maturity and is transmitted by breeding. It is a vascular, flesh colored mass with serosanguinous preputial discharge and a possible secondary bacterial infection. Treatment can be surgical excision or chemotherapy. Spontaneous regression does occur, and the prognosis in all treatment is usually good. The response to chemotherapy is rapid.

 

 

 

 

 

 

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Mammary hypertrophy

Mammary hypertrophy results in diffuse or local nonpainful firm swellings of one or more mammary glands. It is a benign fibroglandular proliferation and can be seen in male and female cats receiving progestogen such as megestrol acetate. Mammary hypertrophy must be differentiated from mammary neoplasia. All mammary masses in the queen should be biopsied due to the aggressive behavior of mammary neoplasia.

Mammary tumors

Mammary tumors are the most common malignant neoplasm in the bitch (41.7% of all neoplasms). High risk breeds include the poodle, Brittney spaniel, English spaniel, English setter, cocker spaniel and Boston terrier. Low risk breeds include Boxers and Chihuahuas. There is an increased incidence of mammary neoplasia with increasing age. Performance of ovariohysterectomy at a young age results in a lower incidence of mammary neoplasia.

  • Before first estrus - 0.5% risk of intact bitches
  • One estrus cycle - 8% risk of intact bitches
  • 2-4 estrus cycles - 26% risk of intact bitches
  • After 4 estrus cycles - same risk as intact bitches

Approximately 50% canine mammary neoplasms are malignant. Metastasis occurs by direct invasion into adjacent tissues, hematogenous and lymphatic routes. Metastasis occurs widely including regional nodes, lung, kidney, liver, heart, bone, and brain. Several histologic types of mammary tumors occur. The histologic appearance within the same tumor and between tumors on the same dog can vary markedly.

Fine needle aspiration cytology of mammary neoplasia can be misleading due to the heterogenous microscopic appearance. Biopsy is preferred over aspiration cytology in order to obtain a larger and "hopefully" more representative sample. If possible, perform excisional rather than incisional biopsy.

Thoracic radiographs should be performed to evaluate the patient for thoracic metastases prior to surgery. Abdominal radiographs and/or ultrasound are used to search for intraabdominal metastases. CBC, biochemical profile and urinalysis should be performed to evaluate the patient for general organ health which may be impacted by metastasis or concurrent disease.

Surgical removal is the major component of treatment. Adjunctive radiation therapy, or chemotherapy may have an impact on residual disease. The type of surgery appears NOT to influence prognosis. Surgery ranges from "lumpectomy" to total resection of both mammary chains with regional node removal. Remove as much tissue as required to remove palpable disease. Ovariohysterectomy at time of neoplasm excision does not appear to impact survival or mortality.

Factors influencing prognosis are size, ulceration, rate of growth, fixation to skin or muscle, and histologic appearance.

Mammary neoplasia in the cat occurs with increased frequency in older queens. Early neutering is protective. An intact queen has a 7 fold higher relative risk of mammary cancer than the animal neutered at a young age. Most tumors occur in the first 2 pair of glands, are carcinomas and are very malignant. Aggressive surgical removal is recommended. No studies evaluating various surgical nodes are available. Chemotherapy may be used postoperative although there is little data to support that chemotherapy increases survival.


Excellent site on Small Animal Reproduction at Louisiana State University



Last Edited: Jul 26, 2007 8:53 AM
CVM Course Websites  Washington State University, Pullman, WA 99164-7010, 509-335-9515, Safety Links