6/7. Infertility Flashcards
Non-infectious causes of infertility
◦ Poor bitch breeding management
◦ Irregularities of the estrous cycle
◦ Structural anomalies of reproductive tract
◦ Disorders of sexual development (DSDs)
◦ Ovarian disease
◦ Uterine disease
◦ Hypothyroidism
◦ Systemic disease
◦ Nutrition
◦ Stress
most common cause of infertility/subfertility
Poor bitch breeding management (poor/no ovulation timing)
Irregularities of the estrous cycle that contribute to infertility
◦ Anestrus
◦ Anovulation
◦ “Slow rise” in pre-ovulatory progesterone levels
◦ Split heat
◦ Persistent estrus
◦ Insufficient luteal phase
if split heat is suspected as a cause of infertility, what do we need to distinguish between?
Need to distinguish between true split heat & shortened diestral/anestrus phase (4 months inter-estrus interval)
important to distinguish persistent estrus from what?
vaginitis
how does persistent estrus relate to vaginal cytology and progesterone? what does a bitch with this condition likely have?
◦ If have cornified vaginal cytology for >30 days without rise in progesterone
◦ Likely have repro tract pathology > secreting hormones
common congenital vaginal structural abnormalities
Vaginal structural abnormalities are common
◦ Vaginal septum
◦ Vaginal circumferential stricture
◦ Hymenal remnants
vaginal structural abnormalities can cause:
◦ Vaginitis
◦ Infertility/subfertility
> Male cannot penetrate (painful or completely unable)
=> Bitch reactive to natural breeding
> Can block sperm transport
◦ UTIs, urinary incontinence
how to diagnose vaginal structural abnormalities
*digital palpation
-also, history, vaginoscopy
how to treat vaginal septum?
◦ If small and can place finger around – can use spay hook with sedation + lidocaine gel
◦ Sometimes too large – has to be done under GA
◦ Want to incise the tissue as cranially as possible
◦ If left inside > issues at whelping > dystocia
vaginal hyperplasia occurs in response to what hormone? when, generally?
Occurs in response to estrogen (during proestrus & estrus)
breeds predisposed to vaginal hyperplasia
Brachycephalic bitches = predisposed
vaginal hyperplasia always originates from where?
ALWAYS originates from vaginal floor just cranial to urethral papilla
possible sequelae from lots of vaginal hyperplasia
circumferential vaginal prolapse
Sequelae
◦ 2nd infections
◦ Self mutilation
◦ Interference with urination
◦ Inability to be bred naturally
possible sequelae from lots of vaginal hyperplasia
circumferential vaginal prolapse
Sequelae
◦ 2nd infections
◦ Self mutilation
◦ Interference with urination
◦ Inability to be bred naturally
will vaginal hyperplasia resolve on its own? when?when might it recur and what is a result?
Subsides on its own post-ovulation as estrogen levels decrease
Can reoccur just prior to whelping as estrogen levels rise again > obstructive dystocia?
Reoccur at each subsequent heat, usually gets worse at each cycle
Vaginal hyperplasia treatment
◦ Keep mucosa moist – lubricant with panties
◦ Can AI around it (genetics; parturition?)
◦ Surgical removal > reoccurrence
◦ Can induce ovulation if really bad to remove estrogen earlier – can’t breed if this is done
vaginal growth other than hyperplasia
Vaginal polyps
Vaginal tumors
◦ Occasionally hormone dependent
◦ Leiomyomas, leiomyosarcomas
are disorders of sexual development common in dogs?
yes
types of disorders of sexual development in dogs
-Can have both ovaries + testes,
-both uterine tubes + vas deferens,
-ovaries + external male genitalia,
-testis + external female genitalia + ambiguous external genitalia + any other combinations of the above
Examples include: os clitoris, Persistent Mullerian Duct Syndrome (PMDS), segmental aplasia of uterus, hypoplastic ovaries, etc.
how do disorders of sexual development usually arise?
Often hereditary
◦ Miniature Schnauzers ◦ Cocker Spaniels
bitches affected by disorders of sexual development are usually
infertile
ovarian diseases contributing to infertility
ovarian cysts
follicular cysts
neoplasia
symptoms of follicular cysts
◦ Can secrete estrogen
◦ Persistent estrus
◦ Vulvar swelling, discharge
◦ Other signs of hyperestrogenism
◦ Cornification on estrus smear
how do we diagnose ovarian disease
ultrasound
how can we treat ovarian or follicular cysts
OHE, or induce ovulation in valuable breeding bitch – may reoccur
are ovarian neoplasias common in dogs?
no
most common type of ovarian neoplasia in dogs and what it does/signs
Granulosa cell tumor
◦ Often secretes estrogen
◦ Signs of persistent estrus, as in follicular cysts
◦ Can also secrete progesterone
◦ Can metastasize
how do we diagnose ovarian neoplasia
History & clinical signs
◦ Cornified vaginal epithelium
◦ Ultrasound
how can we treat ovarian neoplasia
◦ OHE
◦ Chemotherapy if metastatic
◦ Histopathology
what is ovarian remnant syndome and what are clinical signs? how does it arise and what do we need to distinguish it from?
Signs of functional ovarian tissue being present in a dog that had OHE previously
◦ Ovarian tissue “left behind” re-vascularizes
◦ Anomalous reproductive anatomy
◦ Surgeon error
◦ Abnormal accessory ovarian tissue
Clinical signs
◦ Estrous signs
◦ Pseudopregnancy signs
Important to distinguish from exogenous hormone exposure
how to diagnose ovarian remnant syndome
◦ Estrogen detection > vaginal cytology
◦ Progesterone
◦ LH test
◦ AMH
◦ Abdominal ultrasound
how to treat ovarian remnant syndrome
surgery
uterine diseases that can lead to infertility
◦ Endometritis
◦ Cystic Endometrial Hyperplasia
◦ Pyometra
endometritis clinical signs
Does not cause overt clinical disease
Can cause infertility/subfertility
diagnosis of endometritis
◦ Vaginal cytology
◦ Endometrial culture, biopsy & cytology
◦ Ultrasound?
how can we treat endometritis
◦ Antibiotics at breeding – controversial – currently debated topic
what is cystic endometrial hyperplasia? what does it lead to and what type of bitches is it more common in? why does it occur?
Progressive disease
◦ Non pregnant cycles
◦ More common in older bitches
Abnormal response to uterine stimulants (estrogen, progesterone, irritants)
Endometrium is cystic
◦ Hyperplasia of endometrial glands
Causes fluid accumulation within the uterine lumen
cystic endometrial hyperplasia predisposes a bitch to what?
infection and pyometra
what hormone is pyometra associated with? what part of the cycle?
progesterone dependent disease
>occurs in diestrus
important part of history for considering pyometra
was in heat 3-10 weeks ago
pyometra can occur with concurrent ____? why?
Can occur with or without concurrent CEH
CEH helps with infection by providing a nice home for bacteria
is pyometra serious?
yes, medical emergency
presentation of pyometra and types
◦ Can present as lethargic, anorexic, vomiting, PU/PD, +/-vaginal discharge (purulent, red tinged)
vaginal discharge = open
no discharge = closed
what do we see on CBC with pyometra
leukocytosis with degenerative left shift
diagnostics for pyometra
CBC
ultrasound
radiographs
vaginal cytology
differential for pyometra
pregnancy
how to treat pyometra
need to get rid of progesterone
>need to cause luteolysis
>PGF2a causes uterine contractions, luteolysis (also can have some side effects)
Surgical
◦ Stabilization with IV fluids, antibiotics
◦ OHE
Medical
◦ Usually only reserved for cases where bitch is not too clinically ill or in cases of open pyometras
>valuable breeding bitches
◦ Aglepristone (EDR) –progesterone receptor blocker
>once cervix is open; if closed give PFF2a
◦ Antibiotics
◦ Stabilization (IV fluids, hospitalization)
difficulties/considerations that arise when treating pyometra and what we can do about them
◦ Risk of uterine rupture if give PGF2⍺ if cervix is closed
◦ Requires rechecks > bloodwork, serial ultrasounds to ensure fluid is draining, progesterone assay
◦ Need to breed next cycle – likely to happen again –antibiotics during next breeding?
CASE:
CBC/Biochemistry :
◦ Leukocytosis with neutrophilia & monocytosis
◦ Elevated total protein & albumin
Vaginal cytology
◦ Marked degenerative neutrophils noted
Progesterone level = 7.98ng/ml
Diagnosis?
think about pyometra
infectious causes of infertility have a lot of overlap with:
Lots of overlap with infectious causes of pregnancy loss
◦ Hard discern, if at all, infertility from early embryonic death (EED)
◦ Too early to diagnose pregnancy
common pathogens that are infectious causes of infertility
◦ Brucella canis
◦ Canine Herpes Virus
◦ Mycoplasma & Ureoplasma
brucellosis transmission
- Aerosol
- Nose to nose
- Venereal/transplacental
- Contact with any tissues/fluids containing Brucella
brucella canis is especially important because:
it is zoonotic
brucella canis causes what in females?
brucellosis
◦ Infertility
◦ EED
◦ Abortion
> Late term
> Classic time frame = 2 weeks prior to whelping
◦ Metritis
◦ Neonatal deaths
◦ Prolonged vaginal discharge (post-heat or post- whelp)
brucellosis causes what in males?
In males:
* Orchitis
* Epididymitis
* Scrotal dermatitis
* Prostatitis
general zymptoms of brucellosis
- Generalized lymphadenopathy
- Discospondylitis
- Uveitis
how to diagnose brucellosis
◦ Serology
> Rapid slide agglutination test (RSAT)
>low Sp, high Sn
◦ Culture
how do we treat brucellosis?
◦ Difficult
◦ Life-long infection with intermittent shedding
◦ Neuter/spay + long term antibiotics
◦ In kennel situations > euthanasia of all affected animals is often recommended
how can we prevent brucellosis
Screening of breeding animals is recommended
◦ Quarantine all new dogs coming into kennel situation while awaiting test results
causes of canine herpes virus
◦ EED
◦ Abortions
◦ Stillbirths
◦ Neonatal death > usually acute, largest puppies affected
is canine herpes virus common? why?
Most dogs are exposed at some point in their life
◦ Latent infections – shed in the environment
when does canine herpes virus cause the most problems
Problem arises when naïve bitches are exposed during pregnancy
◦ Typically once bitch develops immunity
> subsequent litters are not affected
how do we diagnose canine herpes virus?
◦ Post mortem, histology of tissues, serology, PCR
how do we treat canine herpes virus?
◦ Typically not rewarding once clinical signs are present
how can we prevent canine herpes virus?
◦ Isolation of infected animals
◦ Do not expose 1st time bitches to unknown animals
◦ Optimal hygiene
◦ Warming ambient temperature to over 380C
> Virus does not replicate well at high temperatures
commensals of the canine reproductive tract that may cause infectious infertility
◦ Mycoplasma, Ureoplasma, E. coli, Enterobacter spp., Streptoccus, Pasteurella, etc.
good way to look for infectious cause of infertility
vaginal swab, culture
◦ Should be based on clinical signs (malodorous vaginal discharge, vaginal cytology indicative of inflammation, history of infertility)
good way to look for infectious cause of infertility
vaginal swab, culture
◦ Should be based on clinical signs (malodorous vaginal discharge, vaginal cytology indicative of inflammation, history of infertility)
when should we treat an infectious cause of infertility, after a culture?
Only treat when suspect what you cultured as the cause of infertility
Benefits of spay prior to 1st heat, and drawbacks
◦ Reduced risk of mammary neoplasia (high rate of metastasis)
◦ Removes risk of pyometra (spay in general)
Adverse effects reported
◦ Cancer
◦ Orthopedic disease
◦ Obesity
◦ Urethral sphincter mechanism incontinence
benefits and adverse effects of neuter
Benefits of neuter
◦ Removes risk for testicular disease
◦ Reduced risk for prostatic disease
◦ Reduces roaming risk
◦ Reduces undesired behaviors (sometimes)
Testicular & prostatic disease won’t be impacted by neutering prepubertal vs at 1-2 years of age
Adverse effects reported
◦ Cancer
◦ Orthopedic disease
◦ Obesity
generally, desexing is recommended at what age? important considerations to tell owner about?
6 months, unless large breed
female - communicate increased risk of mammary cancer if spayed later/ not spayed
male - can wait for skeletal maturity, but dog must be watched
contraceptive options and considerations. What are their main uses?
◦ Steroid hormones
◦ Protein hormones
◦ Contraceptive vaccines
Efficacy is variable
Reversal is variable
Can be used for breeding animals that come into heat before owners want them to, or for those that cannot undergo surgery for medical reasons, or if owners want a trial of if spay/neuter will change their behavior.
use of estrogen as a contraceptive. Side efffects? Is it reccomedned?
- Used for mismating
- Serious side effects: pyometra, bone marrow suppression
- Not recommended
how do progestins work as contraceptives? when should they be given? how fast is reversal?
Progestins (megestrol acetate, medroxyprogesterone acetate, proligesterone)
- Believed to work by negative feedback loop (decrease gonadotropin concentrations)
- Should only be given during anestrus (when estrogen levels are low)
- Return to estrus expected in 9-12 months, but sometimes can take up to 2-3 years
side effects of progestins as contraceptives? how can we mitigate risk?
- Side effects: uterine pathology, mammary tumors, diabetes mellitus, acromegaly, immunosuppression, increased appetite, weight gain, lethargy, restlessness, alopecia, etc.
- Using a low dose, and appropriate timing = potentially less side effects
how do androgens work as contraceptives? when will reversal occur? side effects?
- Negative feedback loop on LH (suppression of LH surge)
- Return to estrus 1-7 months; used up to 5 years but no studies on return to reproductive function
- Side effects: clitoral hypertrophy, vaginal discharge, vaginitis, male-type behaviors
types of protein hormones that can be used as contraceptives?
Gonadotropin-releasing hormone agonists
Gonadotropin-releasing hormone antagonists
types of steroid hormones that can be used as contraeptives:
estrogen
progestins
androgens
Gonadotropin-releasing hormone agonists mechanism of action as contraceptive
- Initially stimulates gonadotropins (LH & FSH)
> estrus induction = “flare” effect
=> Makes it less desirable as a contraception method - Continuous usage: down-regulation of LH & FSH
> down-regulation of estrogen, progesterone, testosterone
variable duration of effect (6 or 12 months)
- Side effects similar to spay/neuter
Gonadotropin-releasing hormone antagonists pros and cons vs agonsits for contraception
- Get immediate suppression: no “flare” effect
- Injections, high doses are required.
- Not long lasting, $$$
available contraceptive vaccines
Porcine zona pellucida vaccines
Gonadotropin-Releasing Hormone vaccines
◦ Both appear to work better in horses than in dogs
when might we want to induce estrus? when is it most successful?
Need to shorten the interestrus interval (IEI)
Most successful when bitches are at least 120 days from previous proestrus
Indications:
◦ Prolonged IEI
◦ Breeding around particular time (stud availability, dog sports/shows)
methods of induction of estrus
◦ *Dopamine agonists (cabergoline, bromocriptine)
◦ GnRH agonists (Deslorelin)
◦ Gonadotropins (FSH & LH)
◦ GnRH agonists & gonadotropins = associated with premature luteal failure
Most common reason for infertility/subfertility
poor breeding mgmt
always do what as part of bitch breeding management exam
digital palpation
what hormone do we need to remove for pyometra treatment
progesterone
check brucella canis status how often?
every 6 months
most useful option for contraception
GnRH agonists
most useful option for estrus induction
dopamine agonists
