Approach to infertility (Proceedings)


An accurate history is critical to the evaluation of a female animal suspected to be infertile.

An accurate history is critical to the evaluation of a female animal suspected to be infertile. The history-taking should investigate the details of previous cycles, including the dates of onset of each cycle, the female's behavior during estrus, the dates and methods of previous inseminations, the fertility of the studs used, and the events following breeding. A complete physical examination should be performed to identify (1) potential causes of infertility outside the reproductive tract; (2) other abnormalities that might adversely affect the health of the female or the pregnancy itself should conception occur; and (3) congenital and heritable defects that should exclude this female from a breeding program.

The reproductive tract is then examined. Mammary glands are carefully palpated to assess their size and consistency and the character of any secretions. The vulva is inspected to determine if there are structural abnormalities or any discharge. The labia are separated so that the vestibular mucosa and clitoris (in bitches) can be visualized. The uterus is palpated transabdominally. A vulvar discharge may be more apparent after abdominal palpation. The vestibule and posterior vagina should be palpated with a gloved finger in bitches of adequate size. Rectal palpation may help determine the extent of abnormal structures within the vestibule and caudal vagina.

The history and physical examination findings determine the nature of any additional diagnostic tests performed. Historic or physical abnormalities outside the reproductive tract should be investigated. All dogs should be tested for Brucella canis before breeding and before infertility is evaluated further. The reproductive history often dictates the nature of the diagnostic approach. Perhaps most important are characterizing proestrus-estrus and the interestrous interval of the female, identifying the criteria used to determine when the female is bred, and determining the female's behavior during mating. Typically one of the following four descriptions applies: failure to cycle, abnormal interestrous interval, abnormal proestrus-estrus, or normal cycles.

Failure To Cycle

There are two subcategories of animals with persistent anestrus. Primary anestrus refers to females 24 months of age or older that have never cycled. Secondary anestrus applies to females that have previously cycled but no longer are. An animal that has never cycled may be a normal prepubertal animal less than 24 months of age, may be experiencing "silent" heats, may have a congenital gonadal or chromosomal anomaly, or may have a concurrent disorder that is preventing estrous cycles. Exposure to light may be inadequate to initiate and maintain cyclicity in queens with persistent anestrus. Gonadal dysfunction, concurrent metabolic disorders or medications, and advancing age should be considered in females with secondary anestrus.

Diagnostic tests for persistent anestrus are usually delayed until a female is 2 years of age because of the probability that she is a normal prepubertal animal. Some veterinarians believe that an initial undetected or "silent" first heat cycle is common in bitches. If so, this could explain why some young bitches appear to have persistent anestrus. Unobserved or silent heats may be detected retrospectively by measuring the serum progesterone concentration. If the concentration is greater than basal anestrus levels (> 2 ng/ml; or > 6.4 nmol/L) in a bitch, a cycle has occurred within the last 60 to 90 days. The finding of high serum concentrations of progesterone in a supposedly anestrous queen indicates that unobserved estrus has occurred and also that either unobserved mating or spontaneous ovulation occurred within the past 30 to 40 days. Clinical signs of false pregnancy would also indicate that an undetected cycle occurred approximately 60 days earlier. Silent cycles could be detected prospectively by examining vaginal cytology every 1 to 2 weeks. Non-cycling females should be housed with cycling females whenever possible because the pheromones from cycling females may induce non-cycling females to cycle. Queens should be exposed to at least 12 hours of light for at least 2 months before further testing is done.

Persistent anestrus may result from suppression of function of the hypothalamic-pituitary-ovarian axis. Hypothyroidism and concurrent metabolic disease are commonly reported but rarely confirmed causes in bitches. Exogenous glucocorticoids are commonly administered to animals and cause many alterations in reproductive function, including prolonged anestrus and abortion. The presence of other concurrent metabolic disease is determined with a CBC, serum biochemistry panel, urinalysis, and a thyroid panel in bitches.

Persistent anestrus may also result from a primary abnormality anywhere within the hypothalamic-pituitary-gonadal axis, including intersex conditions, ovarian dysgenesis, progesterone-secreting luteal cysts or ovarian tumor. It may also result from previous ovariohysterectomy. Females with ovarian dysgenesis or that have undergone oophorectomy are expected to have chronically increased serum concentrations of LH, which can be measured. Serum progesterone concentrations can be determined to assess functional luteal cysts. Measuring serum LH and progesterone concentrations before and after GnRH administration can evaluate the functional status of the hypothalamic-pituitary-ovarian axis. Ultrasonographic evaluation of the ovaries may identify ovarian abnormalities such as cysts or neoplasia. On close inspection, many apparently female intersex animals have detectable anatomic abnormalities of the clitoris, vestibule, and/or vagina that result from exposure to androgens. A GnRH stimulation or human chorionic gonadotropin (hCG) test, done to assess the serum concentrations of testosterone, could be used to demonstrate the presence of testicular tissue. Karyotyping can also be performed.

Induction of estrus may be tried in otherwise normal, healthy females if other diagnostic tests have failed to identify the cause of persistent anestrus. Exploratory celiotomy or laparoscopy, done to assess the gross appearance of the reproductive tract and to obtain biopsy specimens of the internal genitalia, should be considered only after all noninvasive diagnostic methods have been tried.

Prolonged Interestrous Interval

Interestrous intervals of greater than 12 months in bitches and greater than 1 month in cycling queens are usually considered abnormal, although long interestrous intervals may also be a normal breed variation, as seen in the Basenji, Tibetan Mastiff, and Dingo dogs, which often cycle only once a year. Many of the causes of persistent anestrus, such as glucocorticoid administration in bitches and inadequate photoperiods in queens, may also cause a prolonged interestrous interval. Pregnancy, pseudopregnancy and early embryonic death are causes of prolonged interestrous intervals in queens, but not in bitches. This difference is because the CL life span in bitches is 60-70 days, irrespective of pregnancy status. Lack of hiding places and irregular feeding times have been shown to disrupt normal cycles in colony cats. Prolonged interestrous intervals may also occur with increasing age or may signify an underlying disorder. Silent or unobserved heats should also be considered. The diagnostic workup in animals with prolonged interestrous intervals should include a thorough review of the estrus identification techniques used by the owner, identification of medications being administered to the animal, and assessment of the overall metabolic health of the animal.

Short Interestrous Interval

Abnormally short interestrous intervals of less than 4 months are occasionally seen in bitches and are usually associated with infertility. Infertility in these animals presumably results from implantation failure because the endometrium has not recovered from the previous cycle, a process that takes 120 to 150 days. In some breeds, most notably the German Shepherd, and in some individual animals, an interestrous interval of 4 to 4.5 months may be normal and may not interfere with fertility. Cystic ovarian follicles might cause frequent cycling (ie, short interestrous interval), but most commonly are associated with persistent estrus. The administration of drugs such as gonadotropins, prostaglandin F2α, prolactin antagonists, or estrogen can artificially shorten the interestrous interval. In most bitches, however, the cause of short interestrous intervals is not discovered.

A short interestrous interval must be differentiated from a split heat cycle in bitches. Split heats are characterized by normal proestrus that stops abruptly before progressing to estrus. Two to 4 weeks later, proestrus begins again and progresses through normal, fertile estrus. Split heats are a normal phenomenon that can occur in any bitch during any estrus, but they are seen most often in pubertal bitches that have normal proestrus and estrus during subsequent cycles. Rarely do split heats occur repeatedly in an individual bitch. Split heats do not cause infertility, except in the sense that the initial proestrus frustrates breeding management.

Additional diagnostic tests are often not performed in bitches with confirmed short interestrous intervals, although ovarian ultrasound would be reasonable. Another diagnostic consideration would be to monitor the changes in serum progesterone concentrations during estrus and diestrus to assess whether the short cycles may be related to ovulation failure. In which case, induction of ovulation should be attempted during the next cycle. Empirical treatment of short interestrous intervals with an androgen such as mibolerone or methyltestosterone to prevent estrus for at least 6 months has been considered, but there is little published evidence of efficacy. Interrupting the short cycle by administering a progestin during proestrus has recently been shown to be helpful. Treatment with megestrol acetate (2 mg/kg, orally) or clormadinone acetate (0.5 mg/kg, orally) for 8 days, beginning within the first 3 days of proestrus, stops the cycle before ovulation. Progesterone concentrations remain at basal levels. The next cycles occur 1.5-3.5 months (mean 2.7 months) after treatment. In other words, the interestrous interval is prolonged by an average of 2.7 months. Breeding on the first estrus occurring after the discontinuation of therapy is recommended, because short interestrous intervals frequently resume. The role of genetics in this problem is not known.

Abnormal Proestrus And Estrus

The most common abnormalities of proestrus and estrus are refusal to allow mating, prolonged estrus, and abnormally short estrus. Females that are not in estrus refuse mating. An occasional bitch or queen exhibits partner preference by refusing to mate with one male but readily mating with another. Inexperienced and timid females may also be reluctant to breed. In bitches, physical abnormalities of the vulva or vagina are common causes of refusal to mate. Physical abnormalities include vaginal strictures, congenital defects in the vulva and vagina, vaginal hyperplasia/prolapse, and rarely, vaginal neoplasia.

Vaginal cytology should be performed to confirm the present stage of the cycle because females that are not in estrus will not accept mating. Digital palpation of the vulva, vestibule, and vagina in animals of adequate size can identify vaginal prolapse and most vaginal strictures and congenital defects. Vaginoscopy should be performed if digital palpation fails to identify a cause for the refusal to allow mating. Artificial insemination can be used to breed otherwise normal estrual females that refuse to mate, as well as those with vaginal hyperplasia/prolapse. With the exception of vaginal hyperplasia/prolapse, physical abnormalities should be surgically corrected if the female is to remain in the breeding program. Surgery is best performed during anestrus. The heritability of congenital vaginal and vulvar anomalies is unknown.

Prolonged or Persistent Estrus

Although proestrus and estrus each last an average of 9 days, proestrus lasting as long as 17 days and estrus lasting 21 days have been observed in normal, fertile bitches. A season is not considered abnormally long in bitches until it reaches 35 to 40 days. In queens, estrus lasting longer than 16 days is considered abnormal. This must not be confused with the normal, multiple cycles that occur in queens.

Prolonged proestrus/estrus is usually caused by functional follicular cysts, which occur in intact ovaries and also in ovarian remnants in spayed bitches and queens. Ovarian neoplasia and exogenous estrogen administration may also cause persistent signs of estrus. Vaginal cytology should be performed to confirm that estrogenic stimulation is present and thus could reasonably be considered the cause of the behavioral and physical signs. Usually the diagnosis of ovarian follicular cysts is based on the historic, physical, vaginal cytologic and ultrasound findings. Serum concentrations of estrogen could also be determined. Because spontaneous regression of follicular cysts may occur, watchful waiting for 2 to 4 weeks is often the initial therapeutic approach. If clinical signs do not promptly resolve, treatment is indicated. Induction of ovulation can be attempted using GnRH (Cystorelin®; 2.2 microgram/kg IM, once daily for 3 days); however, the results have been variable. If mature follicles are present and induced to ovulate, signs of estrus should resolve in 5 to 7 days. The cysts can be manually ruptured via laparoscopy or celiotomy. In cases of unilateral ovarian cysts, unilateral oophorectomy can be performed. Ovariohysterectomy should be considered for those females that fail to respond promptly to medical management for cystic ovaries, because the prognosis for fertility is guarded and continued estrogenic stimulation may be harmful to the uterus and bone marrow. Ovarian neoplasia is uncommon in bitches and queens. Surgical excision is the treatment of choice. If exposure to exogenous estrogenic drugs is the cause of persistent signs of estrus, it should be discontinued.

Short Estrus

Abnormally short estrus of less than 3 days in bitches or less than 1 day in queens is most often the result of an error in observation or recognition of estrus. Females older than 6 to 8 years of age may experience erratic cycles, including short estrus. A split heat cycle should also be considered in bitches with an apparently short estrus. Short estrus may be normal in some animals. Methods of proestrus and estrus detection should be changed in females with a truly short estrus so that they can be bred at the appropriate time. This would usually entail beginning vaginal cytologic studies or teasing with a stud well before the expected onset of the next estrus and continuing this until the first day of estrus is identified. Combining this with ovulation timing, as determined by serum progesterone or LH concentrations, may be helpful in identifying the optimal time for insemination.

Normal Cycles

Infertility in a female otherwise normal in all aspects of the reproductive cycle may result from improper breeding management; infertility in the male; abnormalities in the ovary, uterine tubes, uterus, or vagina; early embryonic death; or advancing age. A history of false pregnancy occurring after previous cycles strongly suggests that the hypothalamic-pituitary-gonadal axis was intact during those cycles. Therefore the investigation should initially focus elsewhere. Conception rates and litter size are greatest, and neonatal mortality is lowest, in bitches (Beagles) between 2 and 3.5 years of age. Reproductive performance in queens is best between 1 and 6 years of age. After 5 years of age in Beagles and 6 years of age in queens, conception rates and litter size decline and neonatal mortality begins to increase. Because of this age-related decrease in fertility, an extensive diagnostic evaluation of older females may not be warranted.

The most common causes of infertility in females with normal estrous cycles are improper timing of insemination and poor semen quality. Because male fertility can be so easily evaluated, the male should be evaluated before an extensive diagnostic evaluation of the female is undertaken. A solid history that the male sired litters that were born shortly before and shortly after mating with the bitch in question would provide good circumstantial evidence against male infertility. Semen evaluation would provide information about the male's current status. The process of freezing and thawing canine semen substantially decreases its quality. Because the post-thaw life span may be only 24 hours, and because its ability to transverse cervical mucus is so diminished, pregnancy rates using frozen semen are very poor unless ovulation timing and intrauterine, not intravaginal, insemination are used. Although the effects of chilling semen are far less deleterious, freshly ejaculated semen retains the best quality.

In well-managed colonies of normal dogs, pregnancy rates of better than 90% are expected. A thorough history concerning breeding management, particularly how the owner determines when to breed, is imperative. See paper on Optimizing Pregnancy Rates elsewhere in these Proceedings for breeding management.

After the female has been bred using optimal protocols and semen of excellent quality, she should be examined 20 to 30 days later to determine whether she is pregnant. Pregnancy can be diagnosed on the basis of abdominal palpation, ultrasonographic findings, or by finding high serum concentrations of relaxin. Ultrasonography should be performed in animals found not pregnant because the ovary and uterus can be evaluated for a potential cause. If the female is not pregnant, the serum progesterone concentration should be measured to determine if ovulation occurred. Low serum progesterone concentrations (less than 2 to 5 ng/ml or approximately 6.4 to 16 nmol/L) suggest ovulation failure or premature luteolysis. The cause of ovulation failure may be an ovarian abnormality or, in the case of queens, inadequate coital stimulation. Premature luteolysis, or failure of the corpora lutea to maintain progesterone production, results in fetal resorption with no outward clinical signs when it occurs before day 35 of gestation. Premature luteolysis is rarely documented in bitches or queens; however, to differentiate ovulation failure from premature luteolysis, serum progesterone concentrations are serially determined using quantitative methods (e.g., RIA) from the time of proestrus through diestrus. Progesterone concentrations that never exceed 8 ng/ml (approximately 25 nmol/L) suggest ovulation failure, whereas premature luteolysis is reflected by a more rapid or earlier decline than normal from high postovulatory concentrations of progesterone. Hypothalamic or pituitary dysfunction would be unlikely causes of ovulation failure in the female that is otherwise cycling normally. More likely, hypothalamic or pituitary malfunction would be manifest as abnormal cycles.

When a female with normal cycles is known to have been bred appropriately during estrus to a male that is known to be fertile, and when ovulation has been confirmed by the finding of elevated serum progesterone concentrations during diestrus, the hypothalamic-pituitary-gonadal axis is considered intact. Abnormalities in the vagina, uterus, uterine tubes, placenta, or the conceptus itself are then likely to be the source of the infertility. The diagnostic approach should begin with a review of the history to identify potential causes of early embryonic death. Special attention should be paid to infectious disease and medications administered to the female. Early embryonic death is difficult to confirm in bitches and queens, but in queens a prolonged interestrous interval provides a clue. Attempts to confirm pregnancy by ultrasound or measuring serum concentrations of relaxin can be done as early as day 14-20; however, false negative results are understandably common at that stage.

Infectious agents are an important cause of early embryonic death. Although many agents are capable of causing placentitis or fetal death, B. canis in bitches, and calici and herpes viruses in queens are the foremost such agents. In lieu of cultures of specimens from the uterine lumen, cultures of the cranial vagina should be performed. Some authors recommend that cultures be obtained during estrus because the cervix is open at that time and fluid in the cranial vagina may have originated from the uterus. Bacterial infections should be treated appropriately prior to breeding. The uterus may be incapable to supporting implantation or pregnancy because of disorders such as bacterial endometritis or cystic endometrial hyperplasia. Ultrasound of the reproductive tract is indicated. Vaginal lesions can easily be excluded as the cause of infertility by vaginoscopy and vaginal cytology. The potential teratogenic or abortifacient effects of medications should always be considered. Many commonly used medications such as glucocorticoids and certain antibiotics also cause embryonic death. In addition, some congenital fetal anomalies cause early embryonic death because they are incompatible with continued survival.

The presence of antisperm antibodies in the female has not yet been documented as a cause of infertility in dogs or cats. However, were they to occur, breeding with a different male could circumvent the problem. Finally, exploratory celiotomy can be performed during anestrus to visualize the reproductive tract, to assess the patency of the uterus and uterine tubes, to obtain uterine specimens for culture, and to obtain full-thickness uterine biopsy specimens for histologic assessment.

Normal seminal quality, normal desire to breed (libido), and normal ability to mate all are necessary for normal fertility in males. Therefore the diagnostic approach to infertility must investigate all three of these factors. The diagnostic approach begins with a complete history and physical examination. The history should assess the male's past breeding performance, breeding management, fertility of the females to which he has been bred, and current or previous health problems. Dogs achieving pregnancy rates of less than 75% when bred to apparently normal females using proper breeding management should probably be evaluated for subfertility.

Assessment of the male's libido and mating ability can help narrow the differential diagnoses. A normal male may appear to lack libido if he is not in his established territory; if he is less dominant than the female or another male in the immediate vicinity; if he is inexperienced or frightened; or if he prefers a different partner. Some normal males show no interest until the female is actually in estrus, as opposed to proestrus. Dogs that are accustomed to semen collection may no longer be interested in natural service despite normal arousal and a willingness to ejaculate. Daily ejaculation, especially over a week or two, and ejaculation more often than once a day are other factors that can diminish the libido of normal male dogs. Such frequent ejaculation does not diminish libido in tomcats. Excessive endogenous or exogenous glucocorticoids, stress, and pain can also cause decreased libido in dogs. Libido also appears to decrease with advancing age.

Some animals may exhibit normal arousal and mount, only to dismount before attempting intromission. It is often difficult to determine whether this behavior is caused by inadequate libido or by inadequate mating ability. This behavior is often exhibited when a vaginal abnormality is encountered and also in some males accustomed to semen collection. Painful conditions often diminish libido, as well as interfere with mating ability. Generally, mating ability is determined by physical, mechanical, and neurologic factors governing mounting, erection, intromission, and ejaculation. Orthopedic disorders of the rear legs, spine and, less commonly, the front legs may prevent mounting or intromission but do not usually affect libido and ejaculatory ability. Semen collection and artificial insemination could be used in such animals.

A complete physical examination should be performed to assess the animal's overall health and identify congenital or heritable abnormalities that should be grounds for excluding the male from the breeding program. Many metabolic and physical abnormalities can adversely affect spermatogenesis, libido, and mating ability. The testes and epididymides are palpated to determine their size, shape, consistency, and location. In situations of unilateral disease, there is urgency to establish and correct the cause before the condition affects the contralateral testis. This can occur by direct extension of the disease process itself or as a result of local swelling, pressure, and hyperthermia, all of which are deleterious. The canine prostate is palpated per rectum and transabdominally. The penis and prepuce are palpated and inspected.

Anatomic abnormalities reported to cause difficulty in mating include phimosis, a persistent penile frenulum, an abnormally short os penis in dogs, and entanglement of the penis in preputial hair in cats. Male cats that fail to grasp the female's neck in the proper location may not be in the correct position for intromission. This is seen in some inexperienced males and in mating pairs with disparate body lengths. Male dogs are often reluctant to breed bitches with anatomic abnormalities of the vulva or vagina. Usually neither shows outward signs of discomfort other than failure to mate; thus it may be difficult to discern whether intromission does not occur because of a female or a male problem.

A thorough neurologic and orthopedic examination, especially of the rear limbs, should be performed. Motor nerve dysfunction can cause difficulty with mounting and intromission. Semen collection for artificial insemination may be possible in such animals. Sensory or autonomic disturbances can cause difficulty with erection (and therefore with intromission in cats) and ejaculation. Semen collection by electrical stimulation may or may not be possible in such animals, depending on the location of the lesion.

The semen of infertile males should be submitted for semen evaluation (see paper on Semen Quality and Artificial Insemination in these proceedings) and bacterial culture, and B. canis testing should be performed in dogs. Males with a history of infertility but that currently have normal semen, normal libido, and normal mating ability are now normal. Such males may have recovered from their previous infertility, the breeding management (e.g., timing of insemination) could have been inappropriate, or the females may have been infertile. Normal males should be bred again to fertile females using optimal breeding management. If the semen is abnormal, further evaluation of the reproductive tract is indicated.

Abnormal motility and morphology are often the first indicators of gonadal damage, irrespective of the cause. Morphologically abnormal sperm often do not have normal motility. Causes include primary testicular disease, metabolic disorders, transient insults (e.g., fever), incomplete ejaculation, and iatrogenic causes. Sperm in semen from young dogs and from dogs that have not mated for a long time may show poor motility, and the semen may contain more than the usual number of morphologically abnormal sperm. Iatrogenic causes of abnormal motility and/or morphology include temperature shock, exposure of the semen sample to a stain of improper pH and osmolality, and exposure of the sample to latex rubber, plastics, and other spermicidal agents.

The semen should be reevaluated in the next 4 to 7 days (or sooner if an iatrogenic cause is suspected); care should be taken at that time to ensure that the entire sperm-rich fraction is ejaculated and collected and that the sample is not damaged during handling. If abnormalities persist, semen culture and a metabolic evaluation are indicated. If a cause is not identified, semen should be reevaluated in 2 to 3 months before additional testing is done because that is the length of the spermatogenic cycle.

A decrease in the total number of sperm per ejaculate may occur with or without abnormalities in sperm morphology or motility. Sperm numbers may be less than normal (oligozoospermia), or sperm may be completely absent (azoospermia). Frequent copulation, as often as five times per hour for the first 2 hours of exposure to an estrual queen, is normal in cats. Unlike dogs, such frequent copulation is not associated with diminishing libido or decreased pregnancy rates in tomcats. In the absence of equipment to collect semen from cats, the presence of spermatozoa in the ejaculate can be confirmed by examining a vaginal cytology specimen obtained from the queen after copulation. A possible cause for low sperm count is that the entire sperm-rich fraction was not collected; therefore, more than one collection should be done.

Spermatogenesis is a complex process that can be affected by environmental factors such as scrotal temperature; metabolic disorders, especially endocrinopathies; toxins and drugs; and infection. A thorough history and physical examination, standard laboratory tests, and semen culture help to identify these possibilities. In addition, oligozoospermia and azoospermia may result from primary testicular failure, bilateral obstruction of the vas deferens or epididymides, or retrograde ejaculation. Because a bilateral obstruction could occur at the level of the prostate gland, the prostate should be carefully evaluated. Measuring the seminal alkaline phosphatase activity should help determine whether epididymal fluid is present in the ejaculate. If the seminal alkaline phosphatase activity is high, this shows that epididymal fluid, which should have high numbers of sperm, has been collected. Obstruction to flow from the epididymides is apparently not the cause of the low sperm count.

Retrograde ejaculation of semen into the urinary bladder rather than out the urethra is thought to be neurogenic in origin, perhaps resulting from inadequate pressure in the proximal urethra or neck of the bladder. Some spermatozoa normally pass retrograde during ejaculation but substantially more do so during electroejaculation than during natural copulation. In the event of pathologic retrograde ejaculation, the volume of semen or the number of spermatozoa discharged is lower than normal. Retrograde ejaculation is diagnosed on the basis of the finding of excessive numbers of sperm in the urinary bladder after ejaculation. This is likely to be easiest to assess when an animal has an empty bladder before ejaculation. Some sperm are normally found in urine, but large numbers, especially approaching those in discharged semen, are considered abnormal. Treatment with a-adrenergic drugs (e.g., pseudoephedrine, 4 to 5 mg/kg PO q8h or twice, 3 hours and 1 hour, before breeding) to increase urethral tone in dogs with retrograde ejaculation has been recommended, but experience with this treatment is limited.

The treatment of oligozoospermia and azoospermia depends on finding and eliminating the cause. Unfortunately this is not always possible. As a general rule, azoospermic males tend to remain azoospermic, especially if testicular size is also less than normal. The finding of small testes in an infertile male suggests the presence of congenital hypoplasia or of acquired testicular atrophy or fibrosis, none of which is likely to be reversible. Oligozoospermia may or may not progress to azoospermia, depending on the cause. Because recovery from a testicular insult is slow and because canine spermatogenesis takes 62 days, the animal could reasonably be evaluated every 2 months for a year to determine the trend in the numbers of sperm per ejaculate before pronouncing him irreversibly sterile.

Oligozoospermic males may be subfertile rather than infertile. It is assumed that sperm reserves and spermatogenesis are poor in oligozoospermic males, therefore they should be bred judiciously. This means adequate time between breedings to allow sperm reserves to be replenished, infrequent ejaculation during estrus, insemination at the optimal time on the basis of vaginal cytology and ovulation in the female, and breeding only to healthy, fertile females. Dogs with as few as 20 x 106 to 100 x 106 sperm per ejaculate have been reported to successfully impregnate normal, fertile bitches when ejaculation has been limited to twice, done at a 2-day interval late in estrus. Intrauterine, rather than intravaginal, insemination may also be considered.

If excessive numbers of WBCs (leukozoospermia) are found in the semen, the site of contamination (urine, preputial cavity) or of the inflammatory process must be determined (e.g., testes, epididymides, prostate). The third fraction of the canine ejaculate should be submitted separately for cytologic and microbiologic examination. B. canis should be excluded by appropriate cultures and serologic tests. Ultrasonography with or without fine-needle aspiration of the testis or prostate may be helpful in localizing the lesion.

The semen should be cultured for aerobic and anaerobic bacteria and Mycoplasma. Bacterial infection of the testes, epididymides, or scrotum causes alterations in spermatogenesis as a result of the destructive properties of the organisms themselves and as a result of local swelling and hyperthermia. The role of bacterial prostatitis in canine infertility is unclear, but most theriogenologists consider bacterial prostatitis to be a common, potentially reversible, cause of infertility. Appropriate antibiotic therapy should be initiated if the semen culture is positive for pathologic numbers of bacteria. Appropriate antimicrobial therapy should continue for a minimum of 2 to 4 weeks, or longer in the case of chronic bacterial prostatitis.

If the history, physical examination, semen evaluation, and semen culture findings fail to establish the diagnosis, a thorough metabolic and endocrine evaluation should be done. Testicular aspiration or biopsy can be considered if other, noninvasive diagnostic tests have failed to identify the cause and the abnormalities in sperm morphology or concentrations have not diminished after several months. Seminiferous tubule architecture, spermatogenesis, interstitial cell numbers, and the presence or absence of inflammation and etiologic agents within the testicular parenchyma can be assessed in testicular biopsy specimens. A portion of the biopsy specimen should also be submitted for bacterial culture. The following histologic lesions have been identified in dog testes: neoplasia, suppurative and nonsuppurative inflammation, mycotic orchitis, lymphocytic orchitis, granulomatous orchitis, spermatogenic arrest, and testicular degeneration. There is limited information available on cats other than information on the testicular changes associated with aging.

From: Johnson CA, Reproductive System Disorders. In: Nelson RW and Couto CG (eds) Small Animal Internal Medicine 4th edition. St. Louis, Elsevier.

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