Small animal theriogenology notes

CANINE - FEMALE

Anatomy

• Ovaries - Not routinely palpable or visible by ultrasound in normal bitches

• Uterine tubes

• Uterus - Bicornuate - Not routinely palpable or visible by ultrasound in normal non-pregnant bitches

• Cervix - Abdominal - Tightly closed except during estrus, the peripartum period, or in the presence of uterine disease

• Vagina - Extremely long - The dorsal median postcervical fold obscures the external cervical os. Formed from the paramesonephric (Mullerian) ducts

• Vestibule - Forms junction with the vagina just cranial to the urethral papilla - Forms from the urogenital sinus - The ventral portion is the clitoral fossa.  

Gross anatomy of the bitch reproductive tract

Gross image of an ovary within the bursa

Gross image of an ovary outside of the bursa

Techniques

• Vaginal cytology

• Vaginal epithelial cells mature to keratinized squamous epithelium under the influence of estrogen. Estrogen concentrations rise through proestrus and peak just prior to the onset of standing heat. Cornification (=keratinization) of the vaginal epithelium develops gradually, paralleling estrogen concentrations. You can interpret the population of vaginal epithelial cells, WBCs and bacteria collected on a swab of the dorsal vaginal surface during the estrous cycle to try to predict reproductive events, and can do vaginal cytology at any time to assess for reproductive tract pathology and as a bioassay for estrogen.

• Technique - Moisten a cotton-tipped swab with water or saline (this is not a sterile procedure). You may use a standard length swab since changes in cytology are the same throughout the vagina. Insert at the dorsal commissure of the vulva, advance craniodorsally till the swab goes over the ischial arch, then advance cranially. Roll the swab against the dorsal vaginal surface, pull it straight out, roll onto a glass slide, allow to air dry, and stain with new methylene blue or DiffQuik.

Diagram showing how to collect a vaginal cytology specimen

Interpretation - Four cell types exist. Parabasal and intermediate cells are the two non-cornified cell types, and superficial cells and anuclear squames are the two cornified cell types. There is a gradual increase in percent cornification as the dog progresses from proestrus to estrus, and a abrupt return to complete non-cornification at the onset of diestrus. Swabs from early proestrus and diestrus look exactly alike.

• Vaginal culture

• Direct uterine culture is only possible via laparotomy with hysterotomy. The vulvar discharge present during proestrus and estrus originates in the uterus, so indirect uterine culture can be performed by anterior vaginal culture during proestrus or estrus. Use a long guarded culture instrument. Insert as for collection of a vaginal cytology specimen. Be aware that there is a large population of normal flora present in the vagina.

• Vaginoscopy

• Instruments used = vaginoscope, endoscope, otoscope. Insert as for collection of a vaginal cytology specimen. Vaginoscopy allows visualization of the vaginal mucosa, and assessment for source of discharges, presence of masses, foreign objects, vaginal anomalies, etc. Vaginoscopy will not allow visualization of the external cervical os.

• Hormone assay

• Estradiol - Estradiol is not routinely measured in serum. It is present in very low concentrations (pg/ml) and the assay sensitivity may be above this. Concentrations of serum estradiol vary greatly even within one animal. It is generally better to use vaginal cornification as a bioassay.

• Progesterone - Progesterone can be measured by enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), or chemiluminescence assay. ELISA tests can be run in-house, but the accuracy is not good. These tests are semi-quantitative; the Premate progesterone assay (Synbiotics) gives results of low (< 3 ng/ml) or high (> 3 ng/ml). RIAs must be sent out but the accuracy is excellent. RIAs can be done at any commercial or hospital laboratory.

Estrous cycle

• Puberty and estrous cycling- Female dogs reach puberty, defined as the first observed heat, from 6 to 24 months of age, with an average onset of 10 to 12 months of age. Small breeds come into heat earlier than large breeds. The pubertal estrus may be a split or false heat. You may induce an early pubertal estrus by housing a young bitch with cycling females. Bitches cycle, on average, every 7 months. Some breeds cycle more frequently (German Shepherd dogs and Rottweilers may cycle as frequently as every 4.5 to 5 months) and some less frequently (Basenjis, dingos and wolf-crosses cycle yearly).

• Stages

1. Proestrus

2. Length = 9 days average, range 0 to 17 days

3. Physical changes and behavior = The vulva is enlarged and firm. Vulvar discharge ranging in character from serous to serosanguinous is present. Male dogs will be attracted to the bitch but she does not stand for breeding, and often tucks her tail under tightly, sits down, or turns on the male dog.

Comparative images of the vulvas of an anestrous bitch and a proestrous bitch

Endocrinology = This is the follicular stage of the cycle. Estrogen concentrations rise during proestrus and peak at the end of this stage. Serum progesterone and luteinizing hormone (LH) concentrations are low.

Vaginal cytology = RBCs may be present throughout the stage. PMNs are present early in this stage but disappear as estrus nears and the vaginal epithelium thickens. The vaginal epithelial cell population gradually changes from completely non-cornified to completely cornified. Cornification will be complete about 2 days before estrogen peaks, about 4 days before standing heat begins.

Early proestrous vaginal cytology

Late proestrous vaginal cytology

1. Estrus

2. Length = 9 days average, range 3 to 21 days

3. Physical changes and behavior = The vulva may become less turgid as the bitch enters standing heat. The vulvar discharge may become straw-colored but can range from serous to serosanguinous in a normal bitch. Estrus, or standing heat, is defined by the behavior of the bitch; standing = remaining motionless as the male investigates her hindquarters, flagging = deflection of the tail laterally and muscular elevation of the vulva.

4. Endocrinology = Estrogen concentrations fall at the beginning of estrus. This decrease in estrogen, along with a preovulatory rise in progesterone, is necessary for appearance of breeding behaviors in the bitch, and presumably elicits the LH surge. A surge of LH is released from the pituitary on or about the first day of estrus, and causes ovulation of a primary oocyte 2 days later. Great variation in time of ovulation exists in the normal dog. After ovulation, CLs form and progesterone production begins. Measurement of serum LH is not routinely performed. However, measurement of serum progesterone concentrations easily can be performed and this data used to optimize breeding management.

5. Vaginal cytology = The vaginal epithelial cell population is completely cornified, with greater than 50% of the cells anuclear squames. No PMNs or debris are present. Intra- and extracellular bacteria are commonly present. RBCs may or may not be present. Vaginal cytology cannot be used to predict ovulation time prospectively; however, vaginal cytology changes abruptly as the bitch enters the next stage of the cycle, diestrus, with this change consistently occurring 6 days after ovulation.

Estrous vaginal cytology

Thickness of the vaginal epithelium in anestrus

Thickness of the vaginal epithelium in estrus

1. Diestrus

2. Length = 60 days average, range 50 to 80 days

3. Physical changes and behavior = There are no characteristic physical changes or behaviors in diestrus. Small amounts of mucoid vulvar discharge may be present. Some bitches still stand to be bred early in this stage.

4. Endocrinology = Bitches maintain the CL for about 60 days whether they were bred or not at that cycle. Progesterone concentrations are high throughout. Diestrus ends with a decline in serum progesterone to less than 2 ng/ml. This is associated with whelping if bitch is pregnant, false pregnancy or no outward signs if she is not. The CL is the sole source of progesterone during pregnancy in the bitch.

5. Vaginal cytology = On the first day of diestrus, the vaginal epithelial cell population abruptly shifts to complete non-cornification. There may be a large number of PMNs present, and metestrum cells (non-cornified cells containing leukocytes) and/or foam cells (non-cornified cells containing vacuoles) may be present.

Diestrous vaginal cytology 

1. Anestrus

2. Length = About 4.5 months average, so counting the approximately 2.5 months of proestrus, estrus and diestrus, the overall interestrous interval averages 7 months. This is a period of reproductive quiescence with no characteristic physical, behavioral or endocrinologic changes. Vaginal cytology reveals only a scant number of cells, all of which are non-cornified at this stage.

Anestrous vaginal cytology

Breeding management

1. Ovulation timing

• Prospective methods

• * Count days from estrus onset - Poor! Great variability exists between normal bitches although most bitches remain consistent as individuals; in one study evaluating 390 cycles in 102 bitches, duration from proestrus onset to ovulation did not vary significantly from one cycle to the next for a given dog.

• * Progesterone assay - Progesterone begins its normal rise at the time of the LH surge that stimulates ovulation. Serum progesterone concentrations are about 2 ng/ml on the day of the LH surge, and 4 to 10 ng/ml on ovulation day. Knowing this, we can measure serial serum progesterones in a dog, and watch for the time of its rise to predict ovulation. Once progesterone begins to rise, reaching a concentration of about 2 ng/ml, ovulation will occur in 2 days. In dogs with a history of poor fertility despite having been bred at the right time, some clinicians do not trust the absolute values and instead watch for an "ovulatory jump" in progesterone, which usually means an increase by 3 ng/ml or more from one day to the next.

If I do not know the history of the bitch, I usually ask to first see her when the owner perceives her as having been in heat for 4 to 5 days. I start with vaginal cytology and only draw blood for progesterone assay if it is greater than 60 to 70% cornified. The earliest I have known a bitch to ovulate was 4 days from the onset of proestrus. The latest was 32 days from the onset of proestrus.

* Luteinizing hormone (LH) assay - Because the LH peak lasts at most one day, blood samples must be drawn daily and at about the same time of day to increase chance of identifying the LH surge. This is cumbersome and expensive for the owner. One practitioners recommends freezing leftover serum from progesterone assays and running the LH test on samples believed to be indicatve of the LH surge, as a way to verify progesterone results without undue inconvenience or expensive to the owner.

* Breeding history - As far as is known, most bitches will ovulate on or about the same day of their cycle from one heat to the next.

* Change in lining of the vagina as noted vaginoscopically - In proestrus, the vaginal folds will be pink and edematous. In estrus, the vaginal folds will be white and wrinkled.

Vaginal folds during estrus

• Retrospective methods

* Diestrous smear - The abrupt transition from the complete cornification seen on cytology during estrus to the complete non-cornification seen in diestrus happens 6 days after ovulation.

* Whelping history - Gestation length is 62 to 64 days from ovulation. If good records are kept of the date of onset of heat and subsequent date of whelping, subtraction of 63 calendar days from parturition equals date and day of the estrous cycle when ovulation occurred.

1. Breeding timing

2. Sperm must undergo capacitation within the female tract; this requires about 7 hours. Normal sperm can remain viable in a normal female tract for up to 7 to 9 days. The ovulated oocyte is a primary oocyte which must undergo 2 meiotic divisions before fertilization can occur. This maturation process takes about 2 days. After maturation, the oocyte remains viable for 4 to 5 days.

3. Best conception rate occurs when the bitch is bred from 4 days before to 3 days after ovulation; best litter size is achieved when the bitch is bred 2 days after ovulation.

4. There are 2 possible breeding strategies:

5. * Breed every other day while the bitch stands

6. * Breed once, 2 days after ovulation

Normal canine breeding behavior

Estrus suppression

• Ovariohysterectomy (OHE)

• Advantages: Prevents conception, signs of heat, appearance of uterine disease, confers protection against later mammary cancer if the dog is spayed before or shortly after the first estrus.

• Disadvantages: Cost, risk of anesthesia, permanent contraception, estrogen-responsive urinary incontinence, perivulvar dermatitis and obesity may be sequelae.

• Progestogens - Progestogens exert negative feedback on the hypothalamus and pituitary, preventing release of gonadotropins and ovulation. The only progestogen currently approved is megestrol acetate (Ovaban - Schering). As of this writing, it is no longer commercially available. The drug can be dispensed through human pharmacies under other brand names. It can be used in 2 ways:

• * Anestrus - 0.25 mg/lb po x 32 days

• * Proestrus - 1.0 mg/LB PO x 8 days, begun within first 3 days of cycle

• Return to heat is extremely variable with a range of 2 to 9 months. Megestrol acetate should not be given to a bitch on her first cycle or for more than 2 consecutive cycles. If used as directed, there is no adverse effect on fertility. It is contraindicated in bitches with predisposition to progesterone-dependent disease conditions, e.g. previous pyometra, mammary nodules, or diabetes mellitus.

• Androgens - Androgens act by exerting negative feedback on the pituitary, preventing release of gonadotropins and ovulation.

• The only androgen currently approved is mibolerone. As of this writing, this drug is on indefinite backorder. Mibolerone has no progestational or estrogenic effects. Treat with 30 mcg/25# BW PO SID up to 1.8 ml daily for the length of time the dog is to kept out of heat (German Shepherd Dogs should get 1.8 ml daily regardless of body weight). Mibolerone must be started at least 30 days before the next estrus is due to begin. Return to estrus after the drug is withdrawn is variable, with an average of 70 to 90 days (range 7 to 240 days). This drug is not recommended for use in the pubertal heat, or for use in breeding bitches. No adverse effects on fertility have been reported. The drug is contraindicated in Bedlington terriers, bitches with androgen-dependent disease (e.g. perianal adenomas), or those with renal or hepatic dysfunction. Side-effects include clitoral hypertrophy and vaginitis.

•      Testosterone often is used to suppress estrus in racing Greyhounds. While under racing stress, low doses (5 mg testosterone per os daily or 50 mg injectable testosterone esters monthly) suppress heat in the bitch.

Pregnancy termination

     Up to 1/3 of bitches presented for pregnancy termination are not pregnant. If you choose to see a bitch immediately after a supposed breeding, be aware that absence of spermatozoa on a vaginal swab does not mean she was not bred. In general, methods that terminate pregnancy prior to day 40 of gestation result in absorption of fetuses while those after day 40 result in expulsion of fluid or tissues. Puppies passed after about day 55 of pregnancy may be alive and should be euthanized when passed.

• OHE

• Method: Physically remove the gravid uterus and both ovaries

• Pros: 100% effective, protection against future mammary neoplasia, ovarian and uterine disease

• Cons: Surgical and anesthetic risk, cost, permanent contraception, post-surgical complications

• Estrogen ("mismate" shot)

• Method: Estrogen slows movement of ova through the uterine tube, causes degeneration of ova, and alters the endometrium, affecting implantation

• Pros: Low cost, effective if given mid-estrus to early diestrus (post-ovulation)

• Cons: May induce pyometra, ovarian cystic disease and/or pancytopenia, ineffective if given at wrong stage of cycle, prolongs standing heat

• Prostaglandin (PGF-2a, Lutalyse)

• Method: PGF-2a causes lysis of the CL with a subsequent decline in serum progesterone concentrations, and causes uterine contractions.

• Pros: Effective at all stages of gestation after the fifth day of diestrus (250 mcg/kg SQ BID x 4 days), fertility unaffected

• Cons: High cost, side-effects of hypersalivation, emesis and defecation, may cause early return to estrus. The GI side-effects may be minimized by concurrent administration of atropine (0.025 mg/kg SQ).

• Dexamethasone

• Method: Mimics normal decrease in progesterone induced at time of whelping (see Endocrine induction of parturition)

• Pros: Effective after day 30 to 35 of pregnancy, can be given orally so dog need not be hospitalized (0.2 mg/kg BID x 10 days). Abuse potential minimal.

• Cons: Short-term side-effects include PU/PD and vulvar discharge.

• Miscellaneous

• * Mifepristone (RU 486) or aglepristone (Alazine) - Blocks progesterone receptors

• * Prolactin inhibitors - Bromocriptine (Parlodel - human product) or cabergoline (Dostinex - veterinary product)

• * Combination therapy can be used, such as bromocriptine and prostaglandin

Pregnancy

• General information

• Fertilization occurs in the oviduct. The embryo enters the uterus as a morula day 8 to 12, and implantation occurs day 17 to 18. Dogs form an endotheliochorial zonary placenta with marginal hematomas containing the green pigment uteroverdin.

Gross image of a normal canine placenta

Gestation length = 62 to 64 days from ovulation. Due to variability in the time of ovulation compared to time of standing behavior in the bitch and the long time sperm are viable in the female reproductive tract, gestation length from a single breeding can range from 58 (bred late) to 71 days (bred early).

Pregnancy endocrinology - Progesterone must be present to maintain pregnancy. All progesterone is produced by the CL in dogs. No pregnancy specific gonadotropins are released.

Pregnancy management - Bitches are not handled in any different way in the first half of pregnancy. After mid-gestation, bitches should be exercised but not encouraged to jump as in agility or hunting. Diet can be altered after mid-gestation to a puppy or performance diet, with 28 to 32% protein, 17 to 22% fat, and omega-3 and omega-6 fatty acids.

• Pregnancy diagnosis - This is confounded by the fact that all bitches maintain the CL and undergo a prolonged luteal phase. Endocrinologic tests and assessment of physical changes are unreliable.

• * Palpation - Abdominal palpation should be performed from 28 to 35 days of gestation. Accuracy is poor in a tense or obese animal.

Demonstration of how to palpate for pregnancy

* Radiography - Less than 42 days of gestation you can see an enlarged uterus but cannot differentiate pregnancy from uterine disease. You can first see calcification days 42 to 45 from ovulation (variable number of days from breeding). Late in gestation, radiography is the best predictor of fetal number, and can be used to estimate fetal age and to assess for fetal death (chart below taken from Rendano V, et al. Vet Rad 1984;25:132).

• • Late gestation radiograph

  • Signs of fetal death include gas within or around fetus, collapse of the axial skeleton, overlap of cranial bones and/or failure of skeleton to calcify or fetus to grow; lack of signs of fetal death does not imply viability.

  • * Ultrasound - Fetal vesicles are first visible routinely day 24 to 28, and fetal heartbeats are easily visible after day 30. Fetal heart rate and movement can be used to assess fetal viability.

Mid-gestation pregnancy on ultrasound

* Relaxin - A commercial assay is available (Witness - Synbiotics). Accuracy is good after about 28 days of gestation.

* Miscellaneous - Acute phase proteins (fibrinogen), measurement of serum prolactin after challenge with naloxone

Parturition / Dystocia

• Parturition

1. Endocrine induction of parturition

2. The fetus induces parturition. The hypothesized scheme is : Fetal ACTH causes release of fetal and maternal cortisol with subsequent decrease in progesterone secretion and increase in production and release of estrogen and prostaglandin. Dead or abnormal fetuses, or small litter size, may be insufficient to initiate labor.

3. Progesterone is thermogenic. As the serum progesterone concentration declines at the time of parturition, you will see a transient decrease in body temperature until other thermoregulatory systems take over. Most bitches begin labor within 24 hours of a rectal temperature drop to less than 99 degrees F.

4. Normal parturition

5. * Stage I = cervical dilation. This occurs secondary to increased estrogen and prostaglandins, and decreased progesterone, uterine contractions and the pressure of the fetus at the cervix. Contractions are not visible. The bitch is restless, pants and may vomit. Signs should increase in frequency and severity.

6. * Stage II = expulsion of fetuses. The cervix should be fully dilated. The length of this stage is variable, 6 to 12 hours on average. Abdominal contractions are strong and coordinated. The chorioallantoic sac may be seen first, then the pup with or without the covering of the amniotic sac. Puppies may present cranially or caudally. You ordinarily see passage of a neonate every 30 to 60 minutes. You should see passing of the first pup within 4 hours of labor onset, and the bitch should deliver pups at least every 2 hours thereafter. The bitch should tear away the amniotic sac and lick the neonate to stimulate respiration. If the bitch ignores the pup, tear away the sac and rub briskly with a towel. You may need to aspirate fluid from the pup's respiratory tract.

7. * Stage III = expulsion of placentas. Placentas usually pass 5 to 15 minutes after each pup is born. The bitch may eat them; they have no known physiological value, and may cause vomiting and diarrhea.

8. Post-partum period

9. * Uterine involution

10. Normal uterine involution is slow and may take up to 12 weeks; placental sites are visible histologically for up to 84 days post-partum. Administration of oxytocin to promote uterine contraction post-partum is only necessary if the pups are stillborn or not nursing.

11. * Lochia

12. Lochia = normal vaginal discharge present for up to 3 weeks after whelping. Lochia should be sero-mucoid and odorless, ranging in color from pale brown to pale green. Lochia may be slightly hemorrhagic.

13. * Rectal temperature

14. Slight elevation in body temperature is normal for the several days following parturition.

15. * Care of the neonates

16.      Warmth - Leave with bitch or provide an external heat source. Pups are incapable of thermoregulation until 2 to 3 weeks of age. Be careful with heating pads or heating lamps; pups are easily burned.

17.      Colostrum - All pups should nurse within the first 12 hours of life. Pups receive 75 to 80% of maternally derived antibodies from colostrum.

18.      Weight - The pups should double their birth weight by 10 to 14 days of age.

19.      Tails and dewclaws

• Dystocia

• "dys" = difficult, "tokos" = birth

1. Causes

2.      Maternal

3.           * Obstruction of passage

4.                - Pelvis - congenital or acquired

5.                - Vagina - hypertrophy, neoplasia, developmental

6.                - Vulva - "infantile"

7.           * Abnormality of uterine function

8.                - Obese, debilitated, poorly exercised

9.                - Primary inertia = no second stage of labor seen, requires C-section

10.                - Secondary inertia = second stage starts but does not progress as uterine muscle fatigues. May be obstructive so be cautious with ecbolic agents.

11.           * Abnormality of pregnancy

12.                - Fetal fluid disorder

13.                - Herniation or torsion of uterus

14.      Fetal

15.           * Obstruction of passage

16.                - Relative oversize = birth canal too small

17.                - Absolute oversize = pup too big, birth canal normal

18.           * Developmental abnormality

19.                - e.g. fetal monster, hydrocephalus

20.           * Abnormal presentation, position, posture

21.                - Presentation = relation of long axis of pup to birth canal. Cranial and caudal are normal.

22.                - Position = relation of fetal vertebral column to birth canal

23.                - Posture = disposition of head and limbs

24. Determination of dystocia

25.       Questions to ask:

26. * Obvious malpresentation?

27. * First stage > 12 hours, second stage weak and intermittent > 2 to 3 hours, second stage hard > 30 minutes, > 2 hours between pups?

28. * Abnormal vulvar discharge? Pus, frank hemorrhage, green fluid (denotes placental separation)

29. * Rectal temperature decline > 24 hours ago?

30. * Signs of labor not progressing?

31. * Systemic illness in bitch?

32. * Prolonged gestation? Be aware that pups cannot be born prematurely and survive. Significant surfactant production occurs late in gestation, from 57 to 60 days of pregnancy. If there appears to be premature labor, treatment with betamethasone (0.5 mg/kg of maternal body weight) may enhance surfactant production in late gestation. Gestational age can be determined using ovulation data, radiographs, or serum progesterone concentrations.

33. * High risk pregnancy? (Previous pelvic trauma or dystocia)

34.       Presentation:

35. * History

36. - Previous disease or trauma

37. - Breeding dates

38. - History of previous whelpings

39. - Pups and progress at this whelping

40. - Temperature drop data

41. - Treatment thus far

42. * Physical examination

43. - General examination

44. - Abdominal palpation

45. - Digital vaginal examination

46. - Lateral abdominal radiographs

47. - Uterine monitors (WhelpWise)

Treatment of dystocia

     Manipulative

          * Feathering

          * Digital manipulation

          * Instruments

     Pharmacologic agents

          * Oxytocin - Oxytocin acts as an ecbolic (causes uterine contraction). It may cause premature placental separation and should not be used in obstructive dystocia. Dose = 2 to 5 IU at 20 to 30 minute intervals, for no more than 3 to 4 doses if not effective. Suggested initial doses are 0.25 IU for dogs weighing less than 11 pounds (5 kg); 0.5 to 1 IU for dogs weighing 11 to 22 pounds (5 to 10 kg); 1 to 3 IU for dogs weighing 22-66 pounds (10 to 30 kg); and 3-5 IU for dogs weighing more than 66 pounds (30 kg). If there is no response to the initial oxytocin injection, progressively higher doses may be used, with an upper limit of 5 IU.

          * Calcium - Calcium increases strength of uterine contractions; oxytocin increases frequency of uterine contractions. Use of calcium is described in the dystocia flow-chart.

          * Glucose

DYSTOCIA FLOW-CHART

SHOULD THE BITCH BE SEEN BY THE VETERINARIAN?

Dystocia most likely is occurring if any of the following are present. The bitch should be seen if there is:

" Obvious malpresentation of a pup

" First stage labor (panting, restlessness, inappetance, vomiting) for more than 12 hours

" Second stage labor with weak and intermittent contractions for more than 4 hours before birth of the first pup

" Second stage labor with weak and intermittent contractions for more than 2 hours between pups

" Second stage labor with hard or continuous contractions for more than 30 minutes before the birth of the first pup or between pups

" Green vulvar discharge before the birth of the first pup

" Purulent or frankly hemorrhagic vulvar discharge

" A history of decline in rectal temperature more than 24 hours ago

" Clinical evidence of systemic illness in the bitch

" A history suggesting high risk pregnancy (previous pelvic trauma or dystocia)

SHOULD THE BITCH BE TREATED MEDICALLY OR SURGICALLY?

If elective Cesarean section has been requested by the client and okayed by the therio clinician, this scheme should not be followed and Cesarean section should be performed if onset of labor is confirmed.

This scheme should be abandoned and Cesarean section performed if green vulvar discharge is evident prior to the birth of any pups, if fetal heart rate (by ultrasound) is less than 150 bpm, or if the bitch appears systemically ill.

Key for dystocia management:

1. The puppy is present in the birth canal and can be manipulated for delivery ----- 2

1'. The puppy is not present in the birth canal or cannot be manipulated for delivery ------ 3

2. Attempt delivery with lubrication and gentle traction. After that pup is passed or if other pups are present in utero ------ 3

2'. Attempt delivery with lubrication and gentle traction. If the pup cannot be delivered ----- 4

3. Fetal heart rate is less than 150 beats per minute ----- 4

3'. Fetal heart rate is 150 beats per minute or more ------ 5

4. Perform Cesarean section.

5. Abdominal radiographs have been taken ------ 6

5'. Abdominal radiographs have not been taken ----- 7

6. Pups are too large to pass or are malpositioned ----- 4

6'. Pups are not too large to pass and are not malpositioned ----- 8

7. Take abdominal radiographs and go to ----- 6

8. Four or fewer pups are present ----- 9

8'. More than four pups are present ----- 4

9. Oxytocin therapy may be attempted as follows: Give 2-5 IU IM, watch for effect for 20 minutes. If no effect is seen, give 2-5 IU oxytocin IM plus a 5 ml bolus of 10% calcium gluconate SQ and watch for effect for 20 minutes. If no effect seen ----- 4

     Cesarean section - Anesthesia and surgical technique for C-section will not be described (see link to information about anesthesia below). One study reported that 195 of 352 bitches presenting for dystocia (55.4%) required C-section after unsuccessful attempts at medical management. If a given bitch has a C-section, that does not automatically mean she must have C-sections at future whelpings. Some breeds appear to be at increased risk for C-section; this may be biased by requests for elective C-section. These breeds include Boston terriers, bulldogs (English and French), mastiffs, and Scottish terriers.

Abnormalities of...

• Puerperium

• I will only discuss eclampsia at this point but be aware that metritis, mastitis, and subinvolution of placental sites are also puerperal conditions.

1. Eclampsia

2. = Puerperal tetany = hypocalcemia. This is seen primarily in small breed dogs nursing large litters during the first 2 to 4 weeks of lactation, when the bitch is under the heaviest metabolic stress due to lactation. It may also be seen at or near parturition.

3. Serum calcium concentrations fall to about 4 to 7 mg/dl (normal 9 to 11 mg/dl). The initial presentation is trembling and weakness. As the condition progresses, dilation of the pupils, elevated pulse rate, elevated body temperature and eventually convulsions occur.

4. Treatment includes removal of pups from the bitch for 12 to 24 hours, administration of 5 to 10 ml 10% calcium gluconate solution slowly IV while ausculting the heart (give to effect - too rapid infusion can cause bradycardia, cardiac arrhythmias and/or cardiac arrest). Follow-up therapy includes administration of 5 to 10 ml 10% calcium gluconate SQ, and discharge of the dog with 1 - 3 gm calcium lactate or calcium gluconate to be given PO SID with 10,000 to 25,000 IU Vit D. Oral calcium gels also exist. Recurrence in the same or a subsequent lactation is common. Wean pups only if more than one clinical episode occurs within a lactation.

5. Some people feel that post-parturient hysteria (savaging of pups) may be a manifestation of eclampsia. Insure the bitch is on a well-balanced ration.

6. Metritis (see Uterine disorders)

7. Mastitis (see Mammary gland disorders)

8. Subinvolution of placental sites (SIPS)(see Uterine disorders)

• Ovaries

1. Cysts

2. Bitches present with a history of irregular cycles or, more commonly, with a history of prolonged proestrus and/or estrus. Ascertain whether the bitch is truly in a prolonged heat cycle. You may need to perform serial vaginal cytology and progesterone assays over 2 to 3 weeks to verify this.

3. Diagnosis is based on a true history of persistent estrus, and physical examination and vaginal cytology signs indicative of estrogen secretion (swollen vulva, cornified vaginal epithelial cells). Similar signs may occur secondary to functional ovarian tumors. Differentiate by abdominal palpation, abdominal radiography or ultrasound, exploratory laparotomy, and response to treatment.

Gross image of a follicular cyst

Ultrasound image of a follicular cyst

Treat with induction of ovulation using gonadotropin releasing hormone (GnRH; 50 mcg IM) or human chorionic gonadotropin (hCG; 1000 IU, half IV, half IM). The bitch should be monitored for signs of uterine disease, as she may develop cystic endometrial hyperplasia / pyometra after ovulation induction. For bitches not intended for breeding, and for those bitches that do not respond to medical treatment in 7 to 10 days, OHE is the treatment of choice.

1. Neoplasia

2. Primary ovarian neoplasia is uncommon in the dog. Some may be productive tumors, with excessive and/or persistent levels of progesterone and estrogen causing paraneoplastic syndromes referable to actions of the hormone present.

3. Most ovarian tumors are palpable as masses in the mid- to cranial abdomen. Radiographs verify tissue location of the mass and are used to assess for metastasis.

4. i) Sex cord/Stromal tumor = Granulosa cell tumor. This is the most common primary ovarian neoplasm in the dog. These usually occur in older bitches, and may be more prevalent in nulliparous bitches. Clinical presentation includes a history of progressive abdominal distension. Functional granulosa cell tumors may produce estrogen causing vulvar enlargement, serosanguinous vulvar discharge, persistent estrus and occasionally pancytopenia, progesterone causing CEH/pyometra, or both. Eighty percent of these tumors do not metastasize so surgical removal usually is curative.

5. ii) Germ cell tumors = teratoma (benign) and dysgerminoma (malignant)

Gross image of a teratoma (interoperative)

Gross image of a teratoma cut open

Treatment - Complete OHE. Tumors are often bilateral, direct extension to the uterus may occur, and older bitches with ovarian disease may be even more predisposed to uterine disease.

• Uterus

1. Metritis

2. Metritis does not equal pyometra!

3. Metritis occurs postpartum. It is caused by ascending infection following normal parturition or abortion, fetal infection, dystocia, and/or retention of placentas. Clinical presentation includes fever, anorexia, depression, neglect of pups and exudation of foul-smelling purulent vulvar discharge.

4. Diagnose by demonstration of leukocytosis with left shift on CBC, demonstration of purulence of vulvar discharge by cytology, and/or culture of bacteria from vulvar discharge. Abdominal radiographs and/or ultrasound can be used to diagnose retention of placentas and/or feti.

5. Treat by promoting evacuation of uterine contents with oxytocin at a dose of 1 IU/kg IM or PGF-2a at a dose of 0.25 mg/kg SQ, and treatment of infection with an antibiotic chosen via culture and sensitivity. While awaiting culture results, start on a broad spectrum antibiotic; as metritis is most commonly caused by Gram negative enterobacters, ampicillin is a common choice (20 mg/kg PO TID). As long as the bitch does not show evidence of toxemia, pups can be allowed to nurse.

6. Subinvolution of placental sites (SIPS)

7. This is a disorder that most commonly occurs in young bitches after whelping their first litter. They will present with excessive or prolonged sanguinous vulvar discharge postpartum (remember the normal exudation of lochia for 3 weeks post-whelping). The discharge is cytologically non-purulent and the bitch is normal in all other respects.

8. Diagnostic tests to be run include cytology and culture of vaginal discharge (to assess for presence of infection), careful abdominal palpation +/- radiography and/or ultrasound (to rule out metritis, retained placentas or feti), CBC (to rule out metritis and monitor PCV in bitch with chronic hemorrhage), and testing for brucellosis. Definitive diagnosis rarely is performed as it requires histologic examination of placental sites; on gross examination, affected sites are larger than involuted sites and contain nodular protrusions of endometrium. Histologically, these nodules are made up of eosinophilic tissue with necrosis and hemorrhage. The persistent hemorrhage is due to failure of the normal thrombosis and occlusion of endometrial blood vessels which occurs as part of the involution process.

9. Treat by OHE in bitches not intended for breeding in the future, and supportive care for those left intact. Monitor the PCV and transfuse if necessary, and give antibiotics if secondary reproductive tract infection develops.

10. Cystic endometrial hyperplasia (CEH) / Pyometra

11. Pyometra does not equal metritis!

12. The initial insult is development of CEH. CEH develops due to repeated prolonged exposure of the estrogen-primed uterus to progesterone (estrogen increases the number of progesterone receptors in the endometrium). Bitches are prone to uterine disease due to the unique nature of cycling in the dog. Most bitches older than 5 to 6 years of age have some degree of CEH. Exogenously administered estrogens and progestogens can induce CEH and subsequent pyometra. Pyometra develops when ascending infection overlies CEH. E coli is the organism most commonly isolated.

Gross image of CEH

Presenting history is of a bitch usually older than 5 to 6 years of age who was in heat 1 to 12 weeks ago, and who is currently exhibiting anorexia, depression, PU/PD, abdominal distension, and possibly purulent vulvar discharge (variable, depending on patency of cervix). Signs of septic shock, vomiting and diarrhea may also be present, especially late in the course of the disease. On physical examination, vulvar discharge may or may not be present and the uterus will be palpably enlarged. Be cautious with abdominal palpation; overly aggressive palpation of the friable, distended uterus may induce uterine rupture.

Diagnosis involves demonstration of uterine enlargement and non-pregnancy (remember, we're in diestrus) by radiography and/or ultrasound. Immature neutrophilia will be present, with higher WBC number if the cervix is closed. Changes on a serum chemistry profile include increased BUN and increased total plasma protein (globulins). Urine will be normal to dilute and proteinuria may or may not be present. The vaginal discharge is cytologically purulent.

CEH on ultrasound

Microscopic image of purulent vulvar discharge

Gross image of pyometra in a bitch

Treatment is dependent on cervical patency. Students often ask about placing drains through the cervix to bypass the problem of cervical patency. There are few such reports in the literature, with most using catheters as a path by which intrauterine fluid can drain along the catheters rather than through them. Success has been variable and most reports have included medical therapy (prostaglandin) along with the catheter placement for success. Successful treatment of this type has been described in big cats but their vaginal and cervical anatomy differs significantly from that of bitches. I have not tried these techniques nor do I know of anyone who considers them a likely alternative for the treatments listed below. One medical therapy not described here is the combination of antibiotics and aglepristone, a progesterone receptor blocker. This is a preferred therapy in other countries; aglepristone is not available in the United States.

* Closed cervix

- OHE + fluids + antibiotics

1) Correct fluid deficit

2) Culture cranial vagina, start bitch on

ampicillin (20 mg/kg PO TID)

3) OHE as soon as stable

* Open cervix

- OHE + fluids + antibiotics

As above - OHE is always the best treatment

since the bitch with pyometra has underlying

CEH which will probably always be present.

Pyometra is an acute manifestation of a

chronic disease process.

- PGF-2a

Four criteria required for medical treatment of pyometra are an open cervix (evidenced by vulvar discharge), the bitch is still of breeding age (generally less than about 6 years of age) and is valuable in a breeding program and the bitch is not azotemic.

1) Determine uterine size (to follow progress)

2) Culture and sensitivity of vaginal discharge

3) Start bitch on ampicillin (20 mg/kg PO TID).

Change antibiotic if necessary based

on sensitivity. Continue antibiotic for

1 month.

4) PGF-2a (Lutalyse - Upjohn) at dose of

250 mcg/kg SQ SID x 2 to 7 days,

until uterine size nears normal. If the

bitch is still in diestrus, administer BID

to lyse CL and decrease progesterone.

5) Recheck bitch 2 to 4 weeks after therapy is

concluded. Vulvar discharge may

persist for up to 1 month. If vulvar

discharge is increasing in volume or

uterine size has increased, consider

repeat of PGF-2a therapy or OHE.

6) At next proestrus, collect an anterior vaginal

culture and treat with an appropriate

antibiotic for 3 weeks. Breed at that

season. If she does not conceive,

consider luteolysis with PGF-2a to de-

crease progesterone effect and

recurrence of pyometra. OHE as

soon as breeding life over!

• Vagina

1. Vaginitis

2. * Prepuberal = puppy vaginitis. This appears prior to the first estrus. The dog presents with a history of small amounts of clear to cloudy sticky vulvar discharge with occasional vulvar licking, and rarely presents with systemic signs.

3. * Adult vaginitis. This appears after the first estrus and in spayed females. Signs are similar to those above. Vulvar discharge may be copious and the bitch may attract male dogs.

4. Physical examination findings are all normal except in the genital system. Perform a digital vaginal examination to assess for presence of anatomic abnormalities predisposing to infection. Perform vaginoscopy to evaluate for inflammation of the vaginal mucosa.

Normal narrowing of the vagina just cranial to the urethral papilla (the cingulum)

Radiographic image of a vaginal septum

Endoscopic image of a vaginal septum

Radiographic image of a vaginal stricture

Endoscopic image of vaginitis

Lymphoid follicles (a non-specific indicator of long-term inflammation)

Diagnose by anterior vaginal culture and sensitivity (remember that the vagina is not a sterile environment). Perform vaginal cytology; vulvar discharge may be a normal indication of estrus in an intact dog. Check for brucellosis. Make sure to differentiate from urinary tract disease.

Treatment - Puppy vaginitis often resolves spontaneously, and may be more likely to resolve spontaneously if the bitch is allowed to go through one estrous cycle. Treat with a 4 week course of a specific antibiotic only after ruling out or treating all underlying problems (e.g. vaginal strictures, urinary incontinence, pyometra). Some dogs may respond to topical therapy with triple-antibiotic ophthalmic ointment. Spayed dogs may benefit from low-dose estrogen therapy. Veterinarians at Colorado State University recommend a therapeutic trial with phenylpropanolamine as used for urinary incontinence in bitches with idiopathic vaginitis, assuming subclinical urine leakage into the vaginal vault through an incompetent urethral sphincter. Some dogs respond well to therapy for atopy, using either diphenhydramine (2-4 mg/kg per os TID) or hydroxyzine (1-2 mg/kg per os BID-TID).

1. Vaginal prolapse

2. Signalment - This occurs in intact, young, large breed dogs. It almost always occurs during proestrus or estrus, occasionally at parturition. Estrogen stimulus causes edematous enlargement of the vagina with subsequent protrusion of the vaginal mucosa through the vulvar lips.

3. Three stages: Stage I = perineal swelling, Stage II = eversion of vaginal floor (hyperplastic change originates just cranial to urethral papilla), Stage III = eversion of entire vaginal circumference.

Stage II vaginal prolapse

Stage III vaginal prolapse

Treatment - If the bitch can be spayed, OHE! If the bitch is to be left intact, treat with topical soothing lubricants and an Elizabethan collar and consider administration of GnRH to induce ovulation. Surgical resection may be necessary. Recurrence is common in dogs without surgical resection (2/3), but may even recur after surgery. Purse-string sutures and pexy- procedures are not recommended as secondary infection may occur.

* Differentiation of vaginal prolapse and vaginal neoplasia *

1. Neoplasia

2. Leiomyoma and TVT most common.

3. Patients with vaginal neoplasia present with clinical signs of bulging of the perineal region, dysuria or pollakiuria, and/or bulging of tumor tissue through the vulva. Diagnose by exfoliative cytology or histopath after core or excision biopsy. Treatment of vaginal tumors consists of surgical removal.

Vaginal leiomyoma

TVT = transmissible venereal tumor = naturally occurring neoplasm with unique chromosome complement (2n = 59), transmitted by transplantation to external genitalia at mating. It appears as single or multiple nodules or pedunculated cauliflower-like friable masses on the genitalia. Transplantation to nasal mucosa and other tissues can occur. Tumor behavior varies depending on host's immune status. Treat with surgical debulking and chemotherapy with vincristine.

Vaginal TVT

• Mammary glands

1. False pregnancy

2. This is a normal phenomenon in which the dog exhibits nesting behavior, lactation and possibly maternal protection of inanimate objects as a response to the normal decline in serum progesterone at the end of diestrus. This can be mimicked by withdrawal of exogenous progestogen therapy or OHE during diestrus.

3. Pyometra does not predispose a bitch to false pregnancy or vice versa. Belgian researchers have some evidence that false pregnancy may be associated with mammary neoplasia, presumably secondary to distension of the mammae with milk and subsequent hypoxia and free radical formation.

4. Treatment - Spontaneous remission - Light sedation with hot and/or cold compresses of mammary glands may help very uncomfortable animals. Do not treat with phenothiazine tranquilizers (e.g. acepromazine), which may inhibit dopamine and potentiate prolactin secretion. Mibolerone at 18 mcg/LB PO x 5 days is reported to alleviate signs of false pregnancy (not approved). Testosterone cypionate (0.5 to 1.0 mg/kg IM once) decreases milk production in dogs (not approved). Pseudopregnancy can also be treated with prolactin inhibitors (bromocriptine, cabergoline). Do not use progestogens; the dog will relapse after therapy is discontinued. OHE is not curative.  

5. Mastitis

6. Mastitis is most commonly due to ascending or hematogenous infection with coliforms, Staph or Strep sp. in the first week of lactation.

7. Infected mammary glands are enlarged, hot and painful. The bitch exhibits pyrexia and neglect of pups. The CBC shows immature neutrophilia. Abscessation and gangrene of mammary tissue may be present.

Gross image of mastitis in a bitch

Gross image of mastitis in a bitch

Expression of normal milk from the mammary gland

Expression of mastitic milk from the mammary gland

Treatment - Start on broad spectrum antibiotics until culture and sensitivity results are back. If abscessation or necrotic tissues are present, the areas should be surgically drained and debrided, leaving them open to heal by second intention. Warm soaks or hot packing may be beneficial. Aspirin can be given for its antipyretic and analgesic effects. Pups need not be weaned unless abscessation is present.

1. Agalactia

2. Agalactia is poorly documented in the bitch. Treat with oxytocin therapy (Syntocinon). Oxytocin aids in milk letdown only, not in milk production. Anxious bitches may benefit from use of DAP spray. Acupuncture also can be used to stimulate lactation in bitches as can treatment with the dopamine antagonist, metoclopramide (0.5-1.0 mg/kg per os BID-TID - watch for behavior changes; causes depression in women) or domperidone (2.2 mg/kg per os BID). With any drug therapy, several days of treatment are required before significant change in milk production will be seen.

3. Mammary neoplasia

4. This is the most common neoplasm in female dogs.

5. Signalment - Mammary neoplasia is most common in bitches over 6 years of age, those left intact (bitches spayed before 2.5 years of age or 4 estrous cycles have decreased risk of developing mammary neoplasia with greatest benefit if spayed before puberal estrus), and in purebreds (compared to crossbreds) with tumors most often arising in the caudal pair of mammae.

6. Many types of tumors may arise in mammary tissue with many patterns of metastasis possible. In the dog, 50% of mammary tumors are benign fibroadenomas (=mixed mammary tumor) and 50% are malignant adenocarcinomas. The most common sites of metastasis for adenocarcinoma are the regional lymph nodes (axillary LN drain 3 cranial mammae, superficial inguinal LN drain 2 caudal mammae) and lungs. Many of these tumors contain receptors for estrogen and progesterone. The mammary gland of dogs is more sensitive to neoplastic transformation due to progesterone than is mammary tissue in other species. This effect may be mediated by growth hormone.

7. Diagnose by palpation of masses in 1 or more glands. More than one mass is present in the majority of cases. Systemic signs vary with pattern of metastasis. Needle aspirate, scraping of ulcerated lesions or cytology of fluid from affected glands may yield useful information in diagnosis of malignancy, but lack of neoplastic cells does not imply that malignancy is not present. Definitive diagnosis requires histopath on an excision biopsy sample.

8. Treatment - Surgical removal +/- OHE - If OHE is performed at the same time as tumor removal, do the OHE first to prevent seeding of the abdomen with neoplastic cells. Surgical removal is strongly recommended.

9. * Lumpectomy = removal of mass only

10. * Simple mastectomy = removal of gland containing mass

11. * En bloc dissection = removal of mass, gland, intervening lymphatics, and regional LN

12. * Unilateral mastectomy = removal of entire chain of glands +/- regional LN

13. No definitive studies have been done that determine which technique is associated with best survival time. In women, studies suggest that more radical therapy is not necessarily correlated with improved survival time. Chemotherapy, radiation therapy, and immunotherapy are possible, but are not well characterized in the dog.

14. Prognosis - Prognosis is very good with benign masses, and poor to good with malignant masses with poorest prognosis associated with tumors greater than 2 to 3 cm is diameter or the presence of metastasis (75% survive < 2 years after surgical removal of primary tumor).

15.  

CANINE - MALE

Anatomy and physiology

• Puberty, defined as presence of spermatozoa in the ejaculate and normal breeding behaviors, occurs from 6 to 24 months of age, with an average of 10 to 12 months of age. Male domesticated dogs do not show a change in testicular size or androgen production with season. Wolf-crosses may show these changes; wolves breed in mid- to late winter.

• Anatomy:

• The two testicles should be completely descended by 6 months of age. The two testicles should be completely descended by 6 months of age. Testicular size varies with size of the dog. and can be evaluted by measurement of total scrotal width (Woodall PG, Johnstone IP. J Sm Anim Prac 1988;29:543). The prostate is the only accessory sex gland. The penis of canids contains a bone, the os penis.

Normal excised testis and associated epididymis

Techniques

• Semen collection and evaluation

1. Semen collection

2. i) Equipment - Teaser bitch (may increase number of sperm in ejaculate), collection vessel (AV, syringe case, cup or plastic bag)

Semen collection equipment

ii) Technique

The dog is manually stimulated through the prepuce. As erection begins, the prepuce is pushed caudal to the bulbus glandis and the artificial vagina (AV) introduced. The fingers encircle the penis caudal to the bulbus glandis tightly, simulating contraction of the constrictor vestibulae muscles during the copulatory lock (=tie). Three fractions of semen are ejaculated; the clear pre-sperm, cloudy sperm-rich (thrusting behavior) and clear prostatic fluid fractions (rhythmic anal contractions and urethral pulsations). When you are done collecting semen, release the grip caudal to the bulbus and gently peel off the AV. Ensure detumescence and replacement of penis within the prepuce prior to kenneling the dog.

Semen collection in the dog 

1. Semen evaluation

2. i) Color - Normal = milky, red or brown = blood, yellow = urine, green = pus

3. ii) Volume (ml/ejaculate) - Normal = 1 to 30 ml, extremely variable. Dogs with virtually no sperm volume (minimal prostatic fraction) still are fertile. Prostatic fluid may prevent premature capacitation of spermatozoa and helps propel spermatozoa forward in the female repro tract.

4. iii) pH - prostatic fraction only. Normal 6.5 to 7.0

5. iv) Progressive motility - Look at one drop of semen on a warmed glass slide with or without extender. Normal = > 70%

6. v) Concentration (sperm/ml) - Hemacytometer and WBC Unopette system. Count center square to get number of million sperm per milliliter. The normal number is variable as it is dependent on the volume of prostatic fluid collected.

7. vi) Total sperm number (sperm/ejaculate) = volume x concentration. Normal = 300 to 2000 million. Larger dogs make more sperm as they possess a larger mass of spermatogenic tissue. For small breed dogs, normal total number may be calculated as 10 million spermatozoa per kilogram.

8. vii) Morphology - Stain with eosin-nigrosin (SFT Morphology stain) or DiffQuik stains. Normal = > 80% morphologically normal sperm. Examine at least 100 individual sperm under the oil immersion objective. Primary defects are those that occur during spermatogenesis (abnormally shaped heads, any portion of the spermatozoon doubled, bent midpiece, proximal cytoplasmic droplets) and secondary defects are those that occur during maturation or sample preparation (bent tails, detached heads, distal cytoplasmic droplets). Correlation of defects with fertility is unknown in the dog.

Canine spermatozoa on phase contrast microscopy

Canine spermatozoa stained with DiffQuik

Canine spermatozoa stained with eosin-nigrosin (SFT) stain

viii) Cytology - Examine the sample for abnormal cells, bacteria, and/or inflammatory cells.

ix) Microbial culture - Aerobes, anaerobes, Mycoplasma. Perform a quantitative culture with > 10,000 bacteria (CFU) per ml indicative of significant overgrowth of an organism.

The correlation between inflammatory cytology and presence of infection is not 100%. Perform a culture even if the cytology is normal if you are suspicious of reproductive tract infection (e.g. recurrent prostatitis or cystitis, infertility).

• Prostatic palpation and massage

• The normal prostate is palpable on rectal examination as a bilobed symmetrical organ 2 to 3 cm caudal to the pelvic brim. As the animal ages, the prostate enlarges (see BPH), and may be pulled cranially to the point where it may be palpable per abdomen. The prostate secretes fluid constitutively; this prostatic fluid normally drips down into the bladder and out the penile urethra.

• Prostatic massage is used for collection of prostatic fluid from dogs that cannot or will not ejaculate. The dog is sedated if necessary, and placed in lateral recumbency. A sterile polypropylene urinary catheter is used to empty the urinary bladder which is then flushed with 3 to 5 ml sterile saline. A gloved finger is inserted into the rectum and the urinary catheter withdrawn until its tip is palpable in the post-prostatic urethra. The catheter is then advanced until it is judged to be within the prostatic urethra. A volume of 1 to 2 ml sterile saline is flushed in while the prostate is massaged vigorously for 1 minute. Fluid and cells are aspirated and submitted for culture and cytology.

Abnormalities of ...

• Penis/Prepuce

1. Congenital defects

2. Balanoposthitis

3. = inflammation of penile and preputial mucosa. The condition is usually caused by opportunistic invasion of normal flora. Affected dogs may show preputial discharge and/or excessive licking. Diagnose by physicalsigns and culture; treat with local and systemic specific antibiotic therapy.

4. Phimosis / Paraphimosis

5. Phimosis = inability to extrude penis. This may be due to congenital or induced stenosis of the preputial orifice.

Phimosis

Paraphimosis = extruded penis cannot be withdrawn into prepuce. Paraphimosis may follow normal copulation or may be due to presence of a hair ring decreasing vascular outflow or physical movement of the penis. Treat by lubrication. If recurrent, this condition may respond to therapy with progestogens (megestrol acetate 0.5 mg/kg once daily per os for a maximum of 30 days) or may require surgical enlargement of the preputial orifice.

Paraphimosis

1. Neoplasia

2. TVT, skin tumors

• Testicles/Epididymes

1. Cryptorchidism

2. = lack of descent of one or both testicles into the scrotum by 6 months of age. The retained testicle(s) may be found at the inguinal ring, in the inguinal canal, or in the abdomen. Descent of both testes is complete in 99.4% of dogs by 12 to 14 weeks of age but because the inguinal ring does not close until 6 months of age, on average, definitive diagnosis of cryptorchidism is not made until that time.

3. Normal testicular descent - The testes develop initially caudal to the kidneys, attached to the superficial inguinal ring by the gubernaculum testis. The gubernaculum grows, pulling the testicle through the abdomen and inguinal canal, and then shrinks, pulling the testicle into the scrotum. The process is dependent on physical presence of the testis, elongation of the abdominal cavity, testosterone, and non-androgenic factors secreted from the testes. Testosterone is not necessary for normal movement of testes through the inguinal canal deep into the scrotum. Factors controlling gubernacular outgrowth are unknown (Amann RP, Veeranachaneni DNR. Cryptorchidism in eutherian mammals. Reproduction 2007;133:541-561).

4. Cryptorchidism is due to hormonal, genetic and/or physical-environmental factors altering gubernacular outgrowth and movement of the testis. In rats, cryptorchidism is associated wtih decreased androgen secretion, decreased smooth muscle content in the gubernaculum or decreased sympathetic tone in the gubernaculum. Canine cryptorchidism is believed to be a sex-limited hereditary trait with transmission due to a single autosomal recessive gene. The genetic predisposition may be carried by males or females, although it will only be manifested in males.

5. Incidence - This is a common disorder with purebred dogs more susceptible than crossbreds (perhaps due to inbreeding), with toy breeds predisposed, and unilateral cryptorchidism more common than bilateral with the right side more commonly retained.

6. The risk of testicular neoplasia and torsion is increased in retained testicles.

7. The unilateral cryptorchid is fertile. Retained testicles are incapable of spermatogenesis due to elevated abdominal temperature destroying spermatogenic tissues, but are capable of steroidogenesis.

8. Breeding of unilateral cryptorchids should be discouraged. Neuter them! This condition is hereditary, and the dog is at increased risk of testicular torsion and neoplasia. Cryptorchid dogs cannot be shown in AKC sanctioned dog shows.

9. Orchitis/Epididymitis

10. = inflammation of the testicular and/or epididymal tissue due to infection by bacteria, introduced by puncture or hematogenously, trauma, or autoimmune disease. Brucella canis infection in male dogs is associated with epididymitis. The dog will be painful, the scrotum reddened and the testicles palpably enlarged. Diagnose by physical examination findings, needle aspirate of the affected testicle, CBC (immature neutrophilia) and/or serology for brucellosis. Treat with specific antibiotics and/or castration. Prognosis for future fertility is guarded as inflammation = increased temperature within the scrotum = decreased spermatogenesis.

11. Neoplasia

12. Testicular neoplasia is the second most common type of neoplasia in male dogs (skin #1).

13. Three types exist; all are equally common in scrotal testicles. Incidence of testicular neoplasia is increased in animals over age 8. It may be uni- or bilateral and more than 1 tumor type may be present. Bilateral castration is the treatment of choice for all types.

14. * Sertoli cell tumor - Arises from Sertoli cells - Large - This is the type most likely to produce a paraneoplastic syndrome due to production of estrogen, with gynecomastia, attraction of male dogs, pendulous penile sheath, alopecia and blood dyscrasias. The non-neoplastic testicle atrophies due to increased scrotal temperature and negative feedback of excessive gonadal steroids from the neoplastic testicle. Sertoli cell tumors are the most common type in abdominally retained testicles.

15. * Seminoma - Arises from germ cells. Paraneoplastic syndromes are uncommon. These are the most common type in inguinally retained testicles.

16. * Interstitial cell tumor - Arises from interstitial (Leydig) cells - Small - These occasionally produce paraneoplastic syndromes.

Testicular neoplasia in the scrotum

Comparative testicular neoplasia and atrophy of the contralateral testis

Neoplasia in an excised testis

Treatment = castration. You can do a unilateral orchiectomy in a valuable breeding dog but be aware that fertility may be reduced due to atrophy or undetected neoplasia in the testicle left behind. Signs of paraneoplastic syndromes regress with tumor removal. Prognosis is good; while the occurrence of metastasis varies greatly, it is generally <10%. Prognosis is worse if pancytopenia is present.

• Prostate

1. Benign prostatic hypertrophy (BPH)

2. = enlargement of the prostate, unassociated with infection

3. BPH occurs in intact dogs. It occurs to some degree in all intact dogs > 5 years of age. Prostate growth is mediated by estradiol and a testosterone metabolite, 5-alpha-dihydrotestosterone (DHT). Early in life, prostate growth is balanced by apoptosis (programmed cell death). As the animal ages, the rate of cell growth becomes greater than the rate of cell death, leading to an overall increase in prostate size.

4. The dog may be asymptomatic or show clinical signs consisting of dripping bloody fluid from the penis unassociated with urination, blood in the semen, or hematuria. Usually no systemic signs are present.

5. Palpation - The prostate is symmetrically enlarged and non-painful.

6. Diagnosis - This list of diagnostic tests is applicable for all prostatic

7. disease conditions.

8. * Cytology and culture of prostatic fluid, collected by ejaculate or prostatic massage

9. * Survey radiographs of the caudal abdomen

10. * Retrograde cystourethrography

11. * Prostatic ultrasound

12. * Prostatic aspirate or biopsy

13. In BPH, no significant changes besides prostatic enlargement are noted. The diagnosis can be verified by prostatic biopsy or aspirate but these tests only define the condition in the part of the prostate that was sampled.

BPH on ultrasound

Treatment:

      * Surgical = castration

     * Medical - In breeding dogs, you may treat with progestogens (e.g. Ovaban at 1 mg/lb for up to 2 weeks) or 5-alpha reductase inhibitors (Finasteride [Proscar™] at 0.1 - 0.5 mg/kg/day). Progestogens act by exerting negative feedback to the pituitary, decreasing release of LH and testostesterone and have not been demonstrated to be detrimental to spermatogenesis. Finasteride causes a decrease in prostate size within one month of therapy and does not appear to affect semen quality or libido. Other treatments used in men (e.g. nutritional supplements, doxazosin mesylate [Cardura™]) have not been evaluated in the dog. Herbal therapy (saw palmetto) is not effective in dogs. If the male with BPH is to continue breeding, you may see adequate reproductive performance, even with blood in the semen. Monitor with quantitative semen cultures every 4 to 6 months to catch early onset of prostatitis, which will decrease fertility. The long range plan = castration as soon as the dog's breeding life is over.

1. Prostatitis

2. = prostatic inflammation associated with infection

3. Prostatitis occurs in intact dogs. Ascending infection is often superimposed on BPH. The clinical presentation varies. In acute prostatitis, the dog will be painful, will have a stilted gait in the rear limbs, may be febrile and anorectic, and will be painful when ejaculating. In chronic prostatitis, the dog may be asymptomatic or show intermittent signs of urinary tract disease.

4. Palpation - The prostate may be asymmetrical. If cysts or abscesses are present, the prostate may be greatly enlarged.

5. Diagnosis - See the list of diagnostic tests under BPH. Cytology of prostatic fluid will be inflammatory, and cultures of prostatic fluid positive (> 10,000 CFU per ml, most common organisms E. coli, Staph and Strep sp.). On retrograde cystourethrography, the contrast medium will move out into the honeycomb of prostatic tissue and may fill cystic spaces. On ultrasound, the prostatic tissue may appear mottled. If an abscess is present, it will be visible as a round, fluid-filled structure within the parenchyma.

Abnormal prostatic fluid

Ultrasound image of prostatitis

Treatment - Appropriate antibiotic therapy is the treatment of choice. The antibiotic used must diffuse into prostatic tissue. Trimethoprim sulfa, chloramphenicol, and fluoroquinolones (enrofloxacin, ciprofloxacin, marbofloxacin) are known to diffuse well into prostatic tissue. Treat for 3 to 4 weeks, recheck cultures at 7 days and 3 to 4 weeks post-treatment if necessary. Castration will decrease prostatic size and increase the chance of clearing prostatitis but do not perform castration in the presence of uncontrolled reproductive tract infection. Treatment of prostatic abscesses may involve surgical resection of the abscess (some research suggests marsupialization of the abscess or packing of the cavity with omentum hastens recovery and decreases recurrence) or ultrasound-guided aspiration of purulent material. Appropriate antibiotic therapy is paramount prior to these procedures.

1. Neoplasia

2. The most common prostatic neoplasm is malignant adenocarcinoma.

3. Prostatic neoplasia occurs in intact or neutered dogs. One study suggested that neutered dogs may have 2X more risk of developing this tumor than intact dogs. There is no known hormonal influence. It is most common in older dogs. Dogs may present with a wide array of clinical signs, varying with the pattern of metastasis. These include stilted gait, tenesmus, dysuria, emaciation, rear limb weakness, and lumbar pain. Metastasis occurs most often in iliac LN, lungs, urinary bladder, periprostatic tissue, rectum, bone, and kidney.

4. Palpation - The neoplastic prostate is usually enlarged, firm and nodular and may be asymmetrical. You may be able to palpate enlarged sublumbar LN.

5. Diagnosis - See the list of diagnostic tests under BPH. You rarely will see exfoliated neoplastic cells on cytology. Retrograde cystourethrography reveals prostatic enlargement, disruption of the smooth mural surface of the urethra, and/or excessive movement of contrast medium into the gland. On ultrasound, the gland will appear mottled with hyperechoic areas suggestive of calcification. Definitive diagnosis is based on cytologic samples of prostatic fluid, or biopsy or aspirate samples of prostatic parenchyma.

Ultrasound image of prostatic carcinoma

Treatment - Prostatectomy is not the treatment of choice. No hormonal therapy is known to be effective. The prognosis is grave as metastasis usually already has occurred when the dog is diagnosed.

CANINE - GENERAL

Artificial insemination

• Fresh semen

• Semen collection: Routine

• Semen handling: None

• Storage: None

• Shipment: None

• Insemination: Vaginal

• Fresh chilled semen

• Semen collection: Routine

• Semen handling: The semen is mixed with extender which serves to increase semen volume, protect against changes in temperature and pH, provide nutrients and decrease bacterial growth.

• Storage: None

• Shipment: Must reach destination within 24 hours

• Insemination: Vaginal

• Frozen semen

• Semen collection: Routine - Recommend a breeding soundness examination beforehand.

• Semen handling: The semen is mixed with extender and cryoprotectant, then frozen in straws or pellets.

• Storage: Liquid nitrogen

• Shipment: No time limit, must be maintained in liquid nitrogen canister

• Insemination: Intrauterine

• Insemination volume

•      Vaginal

•           1.5 to 3 ml for bitches weighing less than 10 pounds

•           3 to 5 ml for bitches weighing 10 to 50 pounds

•           5 to 8 ml for bitches weighing more than 50 pounds

•      Intrauterine

•           Even very small volumes will distend the uterine body and both uterine horns. Excessive volume (more than 4 to 5 ml) will leak through the cervix readily.

Vaginal insemination

The cervix as seen endoscopically in transcervical insemination

Surgical insemination

Conception rates

Natural service > Fresh AI > Fresh chilled > Frozen

Brucellosis

The etiologic agent is Brucella canis. Canine brucellosis is a zoonotic disease.

Transmission occurs primarily via ingestion, secondarily by venereal or congenital routes. The prepatent period is 1 to 3 months. Bacteremia with no fever may persist for 6 to 12 months. This bacterium eludes the immune system by persisting inside macrophages and PMNs.

Clinical history:

Both genders: Asymptomatic, occasional cause of vertebral discospondylitis

Females: Abortion late in gestation, persistent vaginal discharge, infertility

Males: Orchitis, epididymitis, scrotal irritation, poor semen quality, infertility

Diagnosis:

- Serologic tests - Dog must be off antibiotics for 4 weeks prior to testing. Chronically infected animals are intermittently bacteremic, and show an intermittent decrease in titres. Chronically infected animals may therefore test negative falsely with any test. If you are unsure, 3 negative tests at monthly intervals are required to call a suspicious animal truly negative.

* Rapid slide agglutination test (RSAT) - This test is sensitive but not specific. False positives are due to cross-reaction with Bordetella, Pseudomonas, Staph sp., etc. The RSAT becomes positive earliest of all serologic tests in a true infection. All positives should be rechecked!

* Tube agglutination test (TAT) - Gives a titre instead of just a yes/no answer. The same problem with false positives exists as described above.

* Agar gel immunodiffusion test (AGID) - This test is performed at Cornell University. It identifies cytoplasmic antigens (very specific) and cell wall antigens (less specific). This test remains positive longer after the animal becomes abacteremic.

* Polymerase chain reaction (PCR) - These tests have been demonstrated to be very sensitive and specific when used to assay serum, semen, or vaginal swabs. PCR tests for canine brucellosis are commercially available in the United States as of this writing but are not considered the gold standard by the CDC, suggesting more evidence of accuracy is required.

- Culture - This is definitive but difficult. Consider blood, LN aspirates, and obvious samples such as aborted tissues and vaginal or preputial discharge for culture. Blood culture requires submission of at least three samples, in sodium citrate or heparin tubes.

Treatment: OHE or castration should be performed as gonadectomized animals shed fewer organisms. Consider euthanasia, especially in kennel situations. Antibiotic therapy may decrease titres but is not curative.

Herpesvirus

Canine herpesvirus is a ubiquitous organism that is readily destroyed outside the body with common disinfecting agents. The virus apparently is transmitted via ingestion or inhalation. Transplacental transmission also may occur. Signs of disease are most common in bitches and neonates from 3 weeks prior to 3 weeks post-whelping. Both male and female dogs may become latently infected, with localization of virus in the lumbosacral ganglia, tonsils, parotid salivary glands and liver. Latently infected animals are asymptomatic. Recrudescence of virus may be induced by immunosuppression. Clinical signs of herpesvirus infection in male dogs are uncommon. Papulovesicular lesions of the genitalia and oral mucosa may be seen. Affected males may shed virus in semen for an undetermined length of time post-infection.In bitches infected in late gestation, placentitis will lead to fetal death and clinical signs including abortion, decreased litter size and birth of mummified or stillborn pups. Normal and affected pups may be born in the same litter.Neonates infected in utero or at birth will exhibit signs of viremia at about 3 weeks of age, with anorexia, hypothermia and death occurring within 48 hours of onset of signs. On necropsy, petechia will be evident on the kidneys, liver, lungs and intestinal mucosa, and pleural and abdominal effusion may be present. Inclusion bodies in affected tissues are diagnostic for the disease.There is no effective treatment for adult animals infected with herpesvirus. Puppies should be removed from the bitch, treated supportively, and placed in an area with elevated environmental temperature such that core body temperature is greater than 98.6F, the temperature above which the virus cannot replicate. Treatment with hyperimmune serum may help prevent or decrease signs of clinical disease, but will not protect pups from latent infection.

Control of herpesvirus infection is problematic. Antigenicity of the virus is poor and infected bitches will often have normal litters after having an affected litter, precluding regular measurement of antibody titres or observation for clinical signs of disease as ways to monitor presence of herpesvirus in a kennel.A polymerase chain reaction (PCR) test for canine herpesvirus is available in some areas. No vaccines are currently available, but use of a killed vaccine in early gestation may someday be feasible as a means of controlling clinical manifestations of the disease peri-partum.

FELINE - FEMALE

Anatomy

Estrous cycle

Cats are seasonally polyestrous. In natural light, queens will cycle from January to mid-October. They can be induced to cycle year-round with artificially increased daylength (14 to 16 hours light daily).

• Puberty

• Queens enter puberty at 4 to 12 months of age or when they reach 2.3 to 2.5 kg in weight. Puberty onset is dependent on season. Long-haired breeds and Manx cats show later puberty onset.

• Stages

1. Proestrus

2. Rarely observed in cats

3. Estrus

4. Length = 6 to 10 days, range 12 hours to 19 days, +/- effect of breeding

5. Clinical appearance - Signs of heat include lordosis, vocalization, increased affection, positive stimulation and allowing the male to mount. Very rarely, estrous queens will exude clear vulvar discharge.

6. Vaginal cytology - Vaginal epithelial cells become cornified, but not to the same degree as in canine samples.

Lordosis in a cat

1. Postestrus

2. = period after an estrus during which the queen was not induced to ovulate. Length = 13 to 18 days.

3. Diestrus

4. = period after an estrus during which the queen was induced to ovulate. The CL persists and progesterone is produced. Length if a fertile mating occurred (= gestation length) is about 65 to 66 days with range of 63 to 71. If a non-fertile mating occurred, pseudopregnancy will follow, with a length of 40 to 50 days.

5. Anestrus

6. Seasonal

• Induced ovulation

• Induced ovulators include the domestic cat, ferret, rabbit, mink, skunk, 13-lined ground squirrel, camel, llama, short-tailed shrew and giant fruit bat, and possibly the tiger, cheetah and jaguar.

• An external trigger, usually coitus, is required for stimulation of GnRH release and the subsequent LH surge inducing ovulation. The amount of LH released is dependent on the timing and number of copulations; 50% of queens bred only once showed progesterones indicative of ovulation, while 100% of those mated at least 4 times apparently ovulated.

FELINE - MALE

Anatomy

Accessory sex glands = prostate and bulbourethral glands

Penis - Penile "spines" = cornified papillae which encircle the penis. These spines appear at puberty and disappear with castration (androgen-dependent).

Penile spines

FELINE - GENERAL

Breeding/Artificial insemination

• Breeding

• - Mount

• - Intromission and ejaculation

• - Dismount and "after reaction"

• - Remount

• Semen is deposited into the posterior vagina; the erect penis of the tomcat is too short and too large to reach the queen's cervix.

Normal cat breeding behavior

• Artificial insemination - Rarely performed

• - Semen collection by artificial vagina or electroejaculation

• - Semen deposited vaginally

Pregnancy/Parturition

• Gestation length = 65 to 66 days with wide normal range. The literature reports 100% incidence of stillbirth or early postnatal deaths in litters with gestation length of < 61 days. Gestational age can be guesstimated by amount of mineralization visible on a lateral projection radiograph, as in the dog.

• Placentation = endotheliochorial, zonary as in dog

• Pregnancy diagnosis - Abdominal palpation can be performed at 21 to 25 days, ultrasound is not commonly used and radiography can be used after about day 38 to 40. Radiographic measurement of fetal crown-rump length can be used to estimate fetal age as can degree of mineralization.

• Parturition - The stages are the same as in the dog. Dystocia is uncommon (incidence 0.22%) and is treated the same as in the bitch. Normal parturition can take > 24 hours; in our colony, median parturition length was 8 hours, with a range of 4 to 42 hours.

Abnormalities of ...

• Sexual differentiation

• Male calico and tortoiseshell cats - White coat color is on an autosome while black and orange are on the X chromosome. A male, with 1 X, should therefore only be able to exhibit orange or black, not both. If he exhibits both, he probably has an abnormal karyotype (e.g. XXY, XX/XY chimera). These cats usually are sterile.

• Female cats

1. Ovarian remnant syndrome

2. = presence of functional ovarian tissue in a previously ovariohysterectomized queen

3. Causes:

4. * Surgeon error - Improper placement of clamps or ligatures, inadvertent deposition of ovarian tissue in abdomen. One study found that < 50% of cases evaluated had been spayed by new graduates :)

5. * Congenital anomaly? - Presence of completely or partially separated piece of normal ovary near the main ovary or in the broad ligament

6. * Drugs?

7. Presentation:

8. Post-surgical onset is variable but once cycles are resumed, they assume normal periodicity. The cat exhibits normal signs of estrus and attracts tomcats.

9. Diagnosis:

10. * Vaginal cytology - Cytology will be cornified when the cat is showing signs of behavioral estrus.

Non-cornified feline vaginal cytology

Cornified feline vaginal cytology

* Hormone assays

Resting:

- Estradiol - Not accurate. Cytology is more accurate as a bioassay.

- Progesterone - Will be low as cats are induced ovulators

Challenge:

- Give GnRH (25 mcg/cat IM) while the cat is in estrus. Recheck progesterone in 2 to 3 weeks. If the serum progesterone concentration is high (> 2 ng/ml), you have proven that luteinized ovarian tissue is present.

* Exploratory laparotomy

Treatment:

* Medical - Estrus-suppressing drugs. None are approved for use in cats, and this would have to be life-long therapy.

* Surgical - Perform an exploratory laparotomy when the cat is exhibiting signs of estrus (follicular structures on remnant) or after induction of luteinization of tissue (luteal structures on remnant). Most ovarian remnants are found at one or both ovarian pedicles. It is recommended that if no remnants are obvious, scar tissue at the pedicles should be removed and submitted for histopath.

1. Mammary hypertrophy

2. This condition is usually seen in young intact females following estrus, and in male and female cats receiving long-term therapy with progestogens. It is a progesterone-dependent condition.

3. Diffuse or localized non-painful firm swellings of one or more mammary glands will be present. No necrosis or inflammation is present histologically. As hypertrophy mimics mammary neoplasia which is usually malignant, biopsy is indicated.

Mammary hypertrophy

Treat by removing the progesterone source, with OHE in diestrus animals and cessation of exogenous progestogen therapy in other animals. The mammary glands usually regress spontaneously if left untreated. Testosterone cypionate (0.5 to 1.0 mg/kg IM once) causes a decrease in milk production and may hasten regression of mammary hypertrophy (not approved).

1. Mammary neoplasia

2. This is the third most common tumor of the cat (skin #1, lymphatics #2). Malignant adenocarcinoma is the most common type.

3. Presentation - This is seen in older cats. They will present with firm nodular masses in one or more mammae, unrelated to the time of last estrus. Tumor incidence is equally common in all mammary glands.

Gross pathologic image of feline mammary neoplasia

Metastasis to regional LN may or may not be palpable. Metastasis to many tissues may occur; the most common cause of death is respiratory dysfunction secondary to pulmonary metastases.

Due to its highly malignant character, biopsy always is indicated. Needle aspirates may not be diagnostic. It is usually best to submit tissue after surgical excision of the mass. Radical surgery, compared to lumpectomy, has not been shown to increase overall survival time, but will decrease incidence of local recurrence. Prognosis is associated with tumor size; following surgery, the median survival for cats with tumors > 3 cm in diameter is 6 months, for cats with tumors 2 to 3 cm in diameter 2 years, and for cats with tumors < 2 cm in diameter approximately 3 years. Patients with pulmonary metastatic disease rarely survive longer than 2 months after diagnosis.

1. Pyometra

2. Pyometra is most common in cats > 6 years of age.

3. The underlying lesion is CEH, which develops secondary to repeated exposure of the endometrium to progesterone. Pyometra develops due to ascending infection with normal flora of the vagina (most common are E. coli, b-hemolytic Strep sp.). Pyometra may occur in cats receiving exogenous progestogens.

4. Diagnosis - Pyometra is easily diagnosed by identification of an enlarged uterus in a non-pregnant animal. You may or may not see purulent to sanguinous vulvar discharge. Systemic signs (e.g. PU/PD) are less common than in the dog.

Radiograph of a cat with pyometra  

Treatment :

* OHE + fluids + antibiotics - This is the best option!

* PGF-2a + fluids + antibiotics. As in the bitch, treatment may not promote endometrial repair to a significant extent. Queens with CEH will always be predisposed to pyometra.

• Male cats

•      Cryptorchidism - Cryptorchidism is less common in the cat than in the dog. Heritability is unknown in the cat, as is predisposition to torsion and neoplasia.

Reproduction control in dogs and cats

REPRODUCTIVE PHYSIOLOGY OF THE FEMALE

The ovaries contain thousands of follicles, each of which contains an egg or ovum. As each estrous cycle begins, a cohort of follicles is selected to begin development. Development is promoted by release of hormones from the hypothalamus (gonadotropin releasing hormone [GnRH]) and pituitary (follicle stimulating hormone [FSH] and luteinizing hormone [LH]). As the follicle develops, it secretes estrogen, which causes the physical and behavioral signs of early heat, or proestrus. Estrogen levels fall about 9 days after the onset of proestrus; at this time, the bitch will stand to be bred (standing heat or estrus) and a surge of LH is released, causing ovulation. Queens are induced ovulators. Copulation is the most common trigger for release of GnRH and subsequent ovulation. The eggs are released from the follicles into the uterine tube, where fertilization occurs.

The egg ovulated into the oviduct is surrounded by a thick capsule, the zona pellucida, and by a layer of cells from the follicle. Spermatozoa introduced into the reproductive tract of the bitch undergo capacitation, a process involving the acrosome reaction on the head of the spermatozoon and achievement of hypermotility. Capacitated spermatozoa digest the layer of cells surrounding the egg and invade the zona pellucida. As soon as one spermatozoon gets to the inner layer of the zona pellucida, entry of other spermatozoa is blocked by an electrochemical reaction so only one spermatozoon fertilizes each egg. Cell division begins immediately. The developing embryo moves into the uterus within days but does not implant in the uterine wall and develop a placenta until about 12 days after the LH surge in cats and about 16 to 18 days after the LH surge in dogs.

REPRODUCTIVE PHYSIOLOGY OF THE MALE

Testes of male dogs should be descended into the scrotum by 8 weeks of age and must be descended by 6 months of age for the dog to be considered normal. Testes usually are descended at birth in male cats but may not be palpable until 6 to 8 weeks of age. The testes contain spermatogonia, which will divide to form spermatozoa under the influence of the hormone testosterone. Testosterone secretion is stimulated by GnRH and LH release from the hypothalamus and pituitary, respectively. Spermatozoa are manufactured in the testis but are neither motile nor capable of fertilization until after they pass through the epididymis. Spermatozoa ejaculated at the time of semen collection come from the epididymis.

REPRODUCTION CONTROL

STERILIZATION = any procedure that makes an individual incapable of reproduction

Ovariectomy (surgical removal of the ovaries), ovariohysterectomy (surgical removal of the ovaries and uterus) and tubal ligation (tying off the uterine tubes) are the techniques described. Tubal ligation is not commonly used for contraception of bitches or queens anywhere in the world.

Ovariectomy is commonly used in Europe and appears to offer the same benefits and concerns as does ovariohysterectomy (OHE or spay). Ovariectomy is reported to be less time-consuming and less invasive then OHE. In one study of 264 dogs, 126 of which had undergone ovariectomy and 138 of which had undergone OHE, no significant differences were reported in incidence of urogenital problems during a follow-up period of 8 to 11 years after surgery. Urinary incontinence was a reported finding in both groups; difference in incidence between the groups was not statistically significant. In the United States, OHE still is the most common surgical sterilization method.

In male dogs and cats, castration (surgical removal of both testes) and vasectomy (tying off the spermatic cord) are reported sterilization techniques. Castration is the most common surgical sterilization method.

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OPTIMAL AGE FOR SURGICAL STERILIZATION OF DOGS AND CATS

Optimal age at which to perform ovariohysterectomy (OHE) or castration of dogs and cats is not defined by the veterinary literature. In the United States, most veterinarians recommend cats and dogs be spayed or neutered when about 6 months of age, prior to puberty, which is defined as acquisition of normal breeding behavior and semen quality in males and first estrus in females. In other countries, veterinarians recommend that dogs and cats be spayed after their first estrus, or do not recommend elective surgical sterilization be performed at any age. Indeed, in some countries, elective gonadectomy is considered unethical and is either strongly discouraged or illegal. For this discussion, it is assumed that the veterinarian is comfortable with the ethics of elective gonadectomy and practices in a country in which such surgery is considered acceptable by professional associations and the society at large.

Dogs and cats can be considered as part of a larger population of animals or as individuals. Recommendation for age at which to perform elective gonadectomy must take this into account. Animals at humane organizations, who are not yet associated with a responsible owner or guardian, should be evaluated as part of the larger population. Dogs and cats with an owner or guardian may be considered either as part of a larger population or as an individual.

DOGS AND CATS WITH NO OWNER OR GUARDIAN

In the United States, a serious problem with pet overpopulation exists, such that millions of unowned dogs and cats are euthanized yearly. Some of these are feral animals, some are abandoned and brought to the humane association as a stray, and many are relinquished. Intact animals are much more likely to be relinquished than are spayed or neutered animals and animals that are adopted out from the humane association while still intact may either be returned or repopulate that shelter with their offspring. While most intact animals are adopted out with a spay-neuter contract, compliance with such contracts has been demonstrated to be less than 60%. There is a significant lack of knowledge among pet owners regarding normal reproductive physiology among dog and cats owners; studies have demonstrated that up to 57% of bitch owners were unaware that bitches cycle at least twice yearly, up to 83% of queen owners were unaware that queens are polyestrous from spring to early fall, and up to 61% of dog and cat owners were unsure or believed that their animal would somehow be "better" after having had at least one litter. In one survey of dog- and cat-owning households, 56% of 154 canine litters and 68% of 317 feline litters were unplanned, with the majority of those owners reporting that they did not know the female had been in heat. While everyone would like to believe that better education of pet owners would lead to more responsible pet ownership, and while increasing education is a worthy goal that should be pursued, gonadectomy of dogs and cats prior to adoption is one weapon in the fight against overpopulation that should be employed at this time. Multiple studies have been published demonstrating safety of gonadectomy in puppies and kittens as young as 7 weeks of age. To that end, I recommend that all male and female dogs and cats should be spayed or castrated prior to adoption from humane organizations.

DOGS AND CATS WITH AN OWNER OR GUARDIAN

MALE CATS

The normal behavior of most intact male cats is incompatible with their living as housepets. Breeding behavior in cats is aggressive and intact male cats show that behavior readily. Urine from intact male cats is used for territorial marking and has a very distinct, strong odor. There are virtually no health conditions reported to be increased or decreased in association with gonadectomy in male cats. Because of this, I recommend that any male cat not intended for breeding be castrated.

FEMALE CATS

Benefits of OHE in female cats include decreased incidence of mammary neoplasia, ovarian or uterine tumors, and pyometra. Of these, the most significant is mammary neoplasia. Mammary neoplasia is the third most common tumor of female cats, with a reported incidence of 2.5%. Incidence in increased with number of estrous cycles in the cat's life and is increased in the Siamese and domestic Japanese breeds. Greater than 90% of cases are malignant adenocarcinoma.

Detriments of OHE in female cats include possible complications of surgery, obesity, increased incidence of feline lower urinary tract disease (FLUTD), and increased incidence of diabetes mellitus. Reported incidence of post-surgical complications in cats is 2.6%, with most reported complications mild and self-resolving. Incidence of obesity after OHE is high, and is due to decreased metabolic rate in cats after gonadectomy. Obesity can be controlled by proper feeding regimen. Finally, increased incidence of FLUTD and diabetes mellitus has been reported after OHE in queens, with the Burmese breed especially prone to development of diabetes mellitus. Incidence of these two conditions is 0.6% and 0.5%, respectively.

Because the incidence and morbidity of mammary neoplasia are much higher than are the incidences of FLUTD and diabetes mellitus, and because morbidity associated with obesity can be controlled by the owner or guardian of the cat, I believe that female cats not intended for breeding should be spayed as early in their life as possible.

MALE DOGS

Benefits of castration in male dogs include decreased incidence of testicular neoplasia and non-neoplastic prostate disease, and possible increased lifespan. Testicular neoplasia is a common tumor of aged, intact male dogs, with a reported incidence of 0.9%. Morbidity generally is low. Benign prostatic hypertrophy (BPH) is a very common disorder of male dogs, with reported incidence of 75 - 80% in dogs aged 6 years or more. Again, morbidity generally is low. Finally, several studies have documented increased lifespan in castrated male dogs compared to intact males. This may be due to greater care by owners after the "investment" of surgery has been made in that animal, or may be due to a decrease in sexually dimorphic behaviors that put the animal at increased risk, such as roaming.

Detriments of castration in male dogs include complications of surgery, increased incidence of prostatic neoplasia, transitional cell carcinoma, osteosarcoma, and hemangiosarcoma, increased incidence of anterior cruciate ligament (ACL) injury, obesity, and possible increased incidence of diabetes mellitus. Reported incidence of post-surgical complications in dogs is 6.1%, with most reported complications mild and self-resolving. Prostatic neoplasia, transitional cell carcinoma, osteosarcoma, and hemangiosarcoma generally are low in incidence but high in morbidity and mortality. No breed predisposition has been identified for prostatic neoplasia, but does exist for the other cancers noted. Incidence of ACL injury in dogs is relatively high, at 1.8%, and morbidity may be high, although this is generally considered to be a curable condition with surgery. Again, some breeds, most notably large and giant breeds, are predisposed to ACL injury. Obesity is high in incidence but morbidity can be controlled by the owner or guardian.

Appropriate recommendation for castration of male dogs is less readily evident than is that for male cats. While a given male dog can produce many more offspring than can a given bitch, suggesting that castration is necessary for population control, the significant morbidity associated with castration as a possible predisposing cause of the conditions described above suggests that castration is not recommended when considering the animal as an individual. I believe this recommendation must be made on a case-by-case basis, evaluating the breed of the dog, his intended working life or activity level, and the owner's wishes regarding use of that animal for breeding.

FEMALE DOGS

Benefits of OHE in bitches include decreased incidence of mammary neoplasia, with greatest benefit if spayed before the first heat, decreased incidence of ovarian or uterine neoplasia and pyometra, and possible increased lifespan. Mammary neoplasia is the most common tumor of female dogs, with reported incidence of 3.4%. It is the most common malignant tumor in female dogs, with 50.9% of mammary tumors reported to be malignant; metastases are found in about 75% of cases of mammary carcinoma with the lung the most common site of metastasis. Exact cause-and-effect relationship has not been defined, although a hormonal basis for malignant transformation of mammary cells and progression of neoplasia is hypothesized based on the decreasing benefit of OHE with increasing number of estrous cycles in the dog's life prior to surgery. The other very common disorder in female dogs when aged is pyometra, reported to occur in 15.2% of dogs by 4 years of age and in 23 - 24% of dogs by 10 years of age. Morbidity is high, although OHE at the time of clinical presentation is curative; reported mortality ranges from 0 - 17% in dogs. One study of extremely long-lived Rottweilers showed increased longevity in females left intact; it is not clear if intact status was the sole factor involved in their longevity.

Detriments of OHE in female dogs include complications of surgery, increased incidence of transitional cell carcinoma, osteosarcoma and hemangiosarcoma, increased incidence of ACL injury, obesity and diabetes mellitus, a possible increase in aggression in at least one breed, and increased incidence of urethral sphincter mechanism incompetence (estrogen-responsive urinary incontinence). Reported incidence of post-surgical complications in dogs is 6.1%, with most reported complications mild and self-resolving. As in male dogs, incidence of tumors reportedly associated with gonadectomy is low but morbidity with these tumor types is high. Breed predispositions exist for all three tumor types. Incidence of obesity is high after OHE but morbidity can be controlled by the owner. Incidence of ACL injury in dogs is relatively high, at 1.8%, and morbidity may be high, although this is generally considered to be a curable condition with surgery. Again, some breeds, most notably large and giant breeds, are predisposed to ACL injury. Aggression after OHE has been reported in English Springer Spaniels; there is some suggestion that this effect may be more likely in bitches that demonstrated aggressive tendencies prior to surgery. Urethral sphincter mechanism incompetence is a problem of spayed female dogs, especially those weighing more than 20 kg. While morbidity is low and this is a disease easily controlled with medical therapy in most female dogs, evidence exists suggesting incidence can be decreased by spaying bitches when greater than 3 months of age. One study

Appropriate recommendation for OHE of female dogs is less readily evident than is that for female cats. Certainly mammary neoplasia and pyometra are of high incidence and high morbidity, and are greatly decreased in incidence by OHE. However, possible predisposition to very high morbidity tumor types or ACL injury must be evaluated. As with male dogs, I believe this recommendation must be made on a case-by-case basis, evaluating the breed of the dog, her intended working life or activity level, and the owner's wishes regarding use of that animal for breeding.

Much information and misinformation about this topic is available to the owners, guardians, and breeders of dogs and cats. It behooves us, as veterinarians, to be familiar with the current veterinary literature and to base our recommendations on science, rather than on anecdote or tradition.

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CONTRACEPTION = the prevention of conception

PHARMACOLOGIC - Drug therapy affects normal hormone secretion, decreasing estrous cycling. Examples include:

a) Progesterone - Megestrol acetate (Ovaban™). This is the only approved estrus-suppressing drug for dogs in the United States. Ovaban can be given either during anestrus (0.25 mg/lb once daily per os x 30 days), to prolong time until the next proestrus begins, or within the first 3 days of proestrus (1.0 mg/lb once daily per os x 8 days), at which point the bitch will go out of heat in 5 to 6 days and will not ovulate at that cycle. If used properly, Ovaban should not cause uterine disease or impact fertility in bitches. Possible side-effects of treatment with any form of progesterone in dogs include weight gain, predisposition to mammary neoplasia and uterine disease and induction of diabetes mellitus. These same side-effects are seen in queens with administration of progesterone, as is mammary hypertrophy. Current research describes use of progesterone within silastic implants, reported to suppress estrus for up to 2 years in bitches with no side-effects.

b) Estrogen - Estrogen compounds can be used to induce azoospermia (lack of spermatozoa in the ejaculate) in dogs. However, toxic effects of estrogen include induction of squamous metaplasia in the prostate and pancytopenia. I do not recommend the use of estrogens in male dogs.

c) Androgens - The only androgen approved for use in female dogs (Cheque™) is no longer available from the manufacturer. This compound never was approved for use in breeding bitches. Other androgens described for estrus suppression are forms of testosterone, which is effective in a dose-dependent manner and has been reported to be only 66% effective at suppressing estrus in Beagle bitches. Possible side-effects include vaginitis, hypertrophy of the clitoris and liver disease. Androgens cannot safely be used for estrus suppression in queens, in which they are hepatotoxic and thyrotoxic.

d) GnRH agonists - These drugs mimic the action of GnRH, causing release of FSH and LH. Initially this will cause estrus but continued treatment with the drug will shut down the system, with no further estrous cycling. These drugs have been demonstrated to prevent estrus in bitches for up to 27 months and have not been associated with decreased fertility. Similarly, in males initially administration of these drugs will cause increased release of LH and testosterone but will eventually shut down the system, decreasing testosterone secretion and spermatogenesis. GnRH agonists have been demonstrated to suppress fertility for up to 27 months in dogs with subsequent return to normal fertility. These drugs are not approved for use in dogs or cats in the United States.

In queens, GnRH can be used to induce ovulation (GnRH; 25 mcg/cat IM). Luteinized follicles will be maintained an average of 40 to 50 days, giving the owner a respite from estrous cycling in the queen. Ovulation induction by physical means also has been described but in the author's experience is less effective than is pharmacologic induction of ovulation.

IMMUNOLOGIC - Immunologic approaches to contraception work by vaccinating the animal against one of the tissues or hormones described above. When an animal is vaccinated against a tissue, for example, it will create antibodies against that tissue that will either destroy the tissue or prevent its normal function. There is no commercially available contraceptive vaccine for dogs or cats at this time. Because of variable efficacy and likely lack of return on the significant investment required for FDA product approval, contraceptive vaccines are not expected to be available for at least 8 to 10 years. Compounds that are being investigated include:

a) Zona pellucida - Vaccinated animals may or may not continue to cycle and time until re-vaccination is required varies much between individuals. This technique may or may not be reversible; ovarian pathology described after immunization of bitches against porcine zona pellucida proteins include ovarian atrophy and polycystic disease.

b) GnRH - This is a compound against which animals do not develop antibodies readily. Immune response in tested animals has been poor, however, at this time this vaccine may be the best candidate for commercial availability in the near future.

SCLEROSING AGENTS - Sclerosing agents are drugs or compounds that are injected into the testes or epididymes to cause localized inflammation and destroy or scar testicular or epididymal tissue, preventing formation and movement of spermatozoa. Many compounds have been investigated including calcium chloride and zinc gluconate.

In 2002, the FDA approved one compound, Neutersol™, for use in puppies aged 3 to 10 months with testicular width between 10 and 27 mm. The compound (zinc gluconate with arginine) is injected directly into each testis, with dose dependent on testicular width. Sedation may be required but most dogs are reported to tolerate the injection well. Immediate side effects include transient swelling of the testes or scrotum and vomiting. Neutersol™ cannot be used in cryptorchid dogs and should not be used in dogs with scrotal irritation or malformation of the testes or epididymes. In a field study of 224 dogs treated with Neutersol™, 223 were considered to be completely sterilized by 6 to 12 months after injection, based on inability to collect normal semen from these males. Testosterone secretion was decreased but not to as great an extent as with castration. Studies are ongoing for evaluation of safety of the product, efficacy as a contraceptive or sterilant and effect of decreased testosterone concentrations on prostate disease and behavior. Esterisol and Zeuterin, which are similar compounds, also are available.