486-494

• Although reproductive failure is a rare complaint of the individual cat, it is a common problem in multiple cat households, catteries and breeding colonies.
• Due to a wide range of factors, varying from social and environmental stress to nutritional and infectious disease, cats can be difficult to propagate under intensive conditions.
• Reproductive failure, whether it be a problem in an individual cat or a widespread problem of the cattery, is best handled by initially defining where in the reproductive cycle the problem lies.

• Failure of a queen to exhibit estrus must first be differentiated from inadequate estrus detection. The signs of estrus (increased vocalization, rubbing, lordosis, and treading of the hind legs when exposed to a male) should be reviewed with the client to establish that estrus can be detected when it occurs.
• Ovarian activity should then be investigated in the queen who genuinely fails to exhibit estrus. It should be verified that general conditions necessary for ovarian activity are met. The cat should be of at least pubertal age, sexually intact, healthy, and exposed to adequate light. Since cats can show pubertal estrus from 4 to 21 months of age, failure to show pubertal estrus by 24 months is necessary to diagnose primary anestrus.
• Ovarian activity can be most conveniently detected by demonstrating the effects of circulating estrogen on vaginal cytology. Since the follicular phase lasts about a week in the cat, vaginal smears twice a week can detect cyclic changes in vaginal cytology.
• If the cat fails to exhibit estrus but vaginal cytologic changes suggest normal ovarian activity, the inhibition of behavioral estrus may be due to social or psychological factors. Inexperienced queens or queens low in a social hierarchy of other females may not exhibit estrus. While some queens show distinct male preferences, others will be inhibited in unfamiliar breeding surroundings or in the presence of people.
• To promote behavioral estrus, the queen should be kept at home until she is obviously cycling before introducing her to the male's territory. She should be periodically introduced to the breeding area by herself to familiarize her with the surroundings. If possible a gentle but experienced male should be used for breeding. If the female cannot be induced to exhibit estrus behavior, and the client insists on breeding, then artificial insemination can be attempted during cytologic estrus.
• Absence of ovarian activity can be detected by an absence of cyclic changes in vaginal cytology. To be convincing, vaginal cytology should be performed twice a week for an extended period of time (say three months).
• An alternative, and perhaps more convenient approach would be to test for the presence of functioning ovaries by pharmacologic induction of estrus.
• Normal ovarian activity may be inhibited in cases of environmental stress, chronic disease, cystic ovarian degeneration, pharmacologic agents, or abnormal gonadal development. A minimum data base should be assembled including a complete medical history and physical examination, complete blood count, serum chemistry, urinalysis, abdominal and thoracic radiographs, and FeLV status. T4 levels should be assessed if the cat is underweight.
• Environmental stresses include poor nutrition, over crowding, temperature, subclinical disease, extensive showing and traveling.
• The stress of any chronic infectious, metabolic, or neoplastic condition can disrupt normal ovarian function. Commonly administered steroids such as progestogens and glucocorticoids may also inhibit gonadotropin release. Failure to exhibit pubertal estrus by 2 years indicates primary anestrus and premature gonadal failure discussed in detail in the section on abnormal sexual development. Diagnostic evaluation of the patient suspected of abnormal sexual development should include determination of karyotype, levels of plasma LH and FSH, gonadal histology, and gross appearance of the reproductive tract at laparotomy. While XO monosomy will cause premature gonadal failure and primary anestrus, other cases of abnormal phenotypic or genetic sex may be accompanied by normal cyclic activity and even normal fertility.
• One can attempt to induce fertile estrus in the anestrus queen pharmacologically, or by housing the anestrus queen with cycling queens or changing light exposure to 8 hours of daylight for one week and then increasing to 14 hours of daylight for several weeks.

• Persistent or prolonged estrus (greater than a week) may be due to individual variations of cyclic activity, or hormonally active pathologic conditions of the ovary
• Individual variations of cyclic activity in cats include cats with persistent behavioral estrus during an endocrinologically normal estrous cycle, cats with slightly elevated estrogen levels during the interestrous period due to overlapping follicular waves, and cats which show estrous behavior during diestrus. These conditions are characterized by a cyclic and seasonal pattern to the periods of estrus. In the first two cases ovulation might bring the cat into diestrus and eliminate estrous behavior. This could be attempted by repeated vaginal and cervical stimulation during the estrous periods, or by pharmacologic induction of ovulation as described above.

• Estrus which is non seasonally prolonged or persistent is commonly due to cystic ovarian follicles, or rarely due to neoplasia of the ovary.
• Cystic ovarian follicles are commonly found at routine ovariohysterectomy, and tend to occur in older, nulliparous queens, many of which have concurrent cystic endometrial hyperplasia.
• Queens with cystic ovarian follicles may exhibit signs of hyperestrogenism such as persistent estrous behavior, nymphomania, and aggression to the point of becoming unsuitable as pets.
• The treatment of choice is ovariohysterectomy.
• In those queens required for breeding purposes, prognosis for fertility is low. Medical rupture of the follicles can be attempted using 250 IU of HCG IM once daily for 2 days, although its efficacy is controversial. Alternatively, laparotomy and manual rupture of the cystic follicles may be attempted. On the subsequent estrus after either treatment, the queen should be bred to an aggressive tom to prevent recurrence of the problem. Not all cystic structures of the ovary are follicular cysts, however.
• Cysts of the rete ovarii may be found at routine ovariohysterectomy without any particular clinical signs observed prior to surgery. The clinical and functional significance of these cysts is not yet known. Parovarian cysts may also be incidental findings in the mesovarium at routine ovariohysterectomy.

• Tumors of the feline ovaries occur rarely, and are unlikely causes of persistent estrus in cats. However, granulosa cell tumors are frequently accompanied by signs of hyperestrogenism, and account for half of all feline ovarian tumors.
• A Sertoli-Leydig like tumor has been associated with what appeared to be estrogen induced endometrial hyperplasia in a cat.
• Estrus like behavior was reported in a Siamese cat with a dysgerminoma, although this tumor is otherwise considered to have minimal endocrine activity.
• Malignancy is reported in both granulosa cell tumors and a proportion (16%) of dysgerminomas, metastasis being to other abdominal viscera.
• Ovariohysterectomy should be considered in intact females which show persistent, non seasonal estrus. Such females are predisposed to cystic endometrial hyperplasia and pyometra due to the prolonged effect of estrogen on the endometrium.

• At the time of introducing the estrous female to the male for breeding, copulation may not occur or it may be unsuccessful.
• Hallmarks of successful coitus in the domestic cat are the copulatory cry and the characteristic post coital reaction.
• Failure to copulate, or failure to achieve successful coitus may be due to behavioral or physical reasons.

Behavioral Failure

• Behavioral failure of copulation may result primarily from an inappropriate social setting.
• Breeding should take place in territory where the male is dominant.
• Copulation may fail when a shy male is introduced to a domineering female, or if the pair are members of the same household where the female maintains a higher social position.
• Additionally, previous breeding experience encourages successful coitus. An experienced male may be required to achieve coitus in an inexperienced female and vice versa.
• Finally, the female needs to exhibit adequate behavioral estrus. The queen in proestrus usually will not accept the male, and sexually receptive behavior during estrus may be suppressed due to shyness, social stress, or male preferences.

• Physical incompatibility or abnormalities in both the male and female can prevent successful coitus.
• Male problems may include dental problems which prevent the male from establishing an adequate grip on the female, hair rings around the penis, or penile injury or abnormality preventing extension and intromission.
• Body size differences between male and female may also prevent normal intromission.
• The female with stricture, aplasia, inflammation, infection or neoplasia of the vagina or vestibule may not allow breeding. Vaginal speculum examination can be achieved to a limited degree under sedation using an otoscope with a sterile cone and may allow detection of mechanical obstructions.
• High numbers of neutrophils in vaginal cytology can indicate a vaginitis, but the possibility of purulent endometritis or pyometra should not be ignored. Due to the likelihood of contamination, positive vaginal cultures by themselves do not indicate vaginitis, but must be interpreted in conjunction with cytology and otoscopic examination to confirm inflammation.

• A queen that continues to show heat every 2-3 weeks despite repeated breeding is probably failing to ovulate.
• Failure to ovulate can be diagnosed by progesterone levels less than 2 ng/ml from day 7 post estrus to day.
• Ovulation can fail if coital stimulation is inadequate, mistimed, or a primary dysfunction of the neuroendocrine reflex exists.
• Infectious infertility is unlikely to be a cause of repeated breeding in the cat, unlike other domestic species, because of the cat's unique estrous cycle with its requirement for induced ovulation.

• Inadequate coital stimulation may occur when coitus is unsuccessful, or occurs too few times. Unsuccessful coitus is characterized by absence of both a copulatory cry and post coital reaction and if documented should be analyzed as a failure to copulate. An insufficient number of mountings may also result in a failure of the LH spike necessary for ovulation. Ideally, the female should be left with the male until at least 3 or 4 breeding have taken place and be bred on more than one day during estrus. Some females may ovulate after only one mount, however, if the follicles are mature.

• Coitus that occurs too early or too late in estrus may not result in ovulation.
• If too early, the follicles are not yet mature, if too late the follicles may have undergone regression. Before day 2 of estrus, breeding may fail to result in ovulation.
• Optimal response to vaginal stimulation usually occurs on day 3 of estrus and shortly after.
• Failure of the neuroendocrine reflex is most likely associated with the development of cystic follicles. Possible treatment may be 250 IU HCG IM daily for 2 days, at the time she is bred, however, success of this treatment controversial.

• Additionally, any number of neurologic, endocrine, or developmental abnormalities could potentially lead to a failure of the neuroendocrine reflex.
• A cat with spinal neurologic disease might be expected to have difficulty transmitting sensory information to the hypothalamus.
• Neuroendocrine disease may prevent GnRH or LH release.
• Gonadal abnormality may prevent ovulation. An apparently normal queen which showed cyclic estrous behavior, but upon ovariohysterectomy revealed enlarged gonads with testicular morphology, would not have been expected to undergo normal ovulation post coitus.

• When a cat is found open at pregnancy exam a minimum data base should be assembled to determine if the cat is healthy, if appropriate breeding practices were followed using a fertile male, whether the queen ovulated post breeding, and if primary reproductive disease is present.
• Possible causes of infertility in the queen who ovulates when bred to a fertile male are failure of sperm to reach the egg, failure of fertilization, or undetected death of the developing embryo.

• The minimum data base for the queen who is non pregnant at pregnancy exam should include history, physical, serum progesterone, abdominal radiographs, complete blood count, chemistry panel, urinalysis, FeLV antigen test (Elisa or IFA) and, depending on the presence of a vaginal discharge, vaginal cytology, culture, and vaginoscopy.
• T4 levels should be run if the cat is thin.
• The history taker should attempt to detect abnormalities in the queen's cycling behavior that may indicate a failure to exhibit normal estrus (frequency and duration of estrus periods), or a failure to ovulate (success, number and timing of copulations; repeated breeding every 2-3 weeks).
• Inquiries should be made into the general hygiene, nutrition, and environment in the cattery.
• The male should be ruled out as a possible cause of infertility by confirming siring of recent litters of kittens, or results of recent semen evaluations.

• The physical examination should include determining presence of a vaginal discharge, abdominal palpation to detect uterine or ovarian enlargement, and ophthalmic examination to detect retinal degeneration due to taurine deficiency.
• Routine blood work and urinalysis are performed to detect any chronic underlying disease which may prevent normal cycling or predispose to reproductive failure.
• A progesterone level greater than 2 ng/ml before day 40 of gestation indicates ovulation occurred.
• A uterus visible on abdominal X ray suggests abnormal uterine enlargement and requires further investigation (see below).
• Vaginal cytology, culture, and vaginoscopy will help determine the nature and source (uterus or vagina) of a vaginal discharge.
• Failure of sperm to reach the egg would be due to blockage of the cervix, uterus or oviducts. Assessing the patency of these structures can be attempted at laparotomy by infusing sterile saline into the uterine horn using a small gauge needle, and milking fluid through the oviducts, both horns, or retrograde through the cervix. Due to the risk of developing a peritonitis, this procedure would probably be contraindicated if the uterus appeared infected, or if free fluid was detected in the uterine lumen prior to infusion. Since semen traverses the oviduct during estrus, this would be the appropriate time to attempt this procedure.
• Failure of fertilization is not yet commonly evaluated in practice. However, new technical developments in feline oocyte collection, in vitro fertilization, and embryo transfer show that the ability to evaluate a queen's oocytes may soon be possible perhaps even clinically. It is currently possible to obtain oocytes by laparoscopic aspiration of follicles for use in vitro fertilization studies. Fertilized embryos and unfertilized oocytes have been obtained 7 days after the first breeding from the uterine lumen by placing a flanged tomcat catheter in the caudal terminus of the uterine lumen, 2-3 cm cranial to the uterine bifurcation, and flushing 25-30 ml of culture media cranial to caudal through a 17-gauge catheter placed near the utero tubular junction. The fluid is collected into gridded petri dishes and searched with a stereomicroscope. If fertilized embryos can be collected from the queen which consistently fails to become pregnant, one can establish that the reproductive tract is patent through its entire length, that fertilization took place, and that infertility is likely due to loss of the undetected pregnancy.

• Likely causes for undetected pregnancy loss would be cystic endometrial hyperplasia and endometritis. (Infectious agents, nutrition, genetic defects, and hypoluteoidism might also be responsible, but are discussed in the following section.)
• Cystic endometrial hyperplasia and endometritis are presumptively diagnosed by detecting a radiographically visible uterus. Definitive diagnosis would require exploratory surgery accompanied by uterine biopsy and culture of the uterine lumen. Cystic endometrial hyperplasia is thought to result from prolonged exposure to estrogen in an aged, non pregnant queen, or in one who develops cystic follicles. Pregnancy protects the uterus from the harmful effects of estrogen that can lead to cystic endometrial hyperplasia. The treatment of choice for cystic endometrial hyperplasia is ovariohysterectomy.
• Endometritis can result from cystic endometrial hyperplasia aggravated by bacterial contamination, persistence of mummified or incompletely resorbed fetuses, retained fetal membranes, or from postpartum metritis of a previous pregnancy. If culture of the endometritic uterus is successful one can institute specific antibiotic therapy. Vaginal cultures are of value if the queen has an endometritis of sufficient magnitude to cause a vaginal discharge, and surgical culture is not an option. Prostaglandin therapy at a dose of 0.2 mg/kg subcutaneously once daily for two days followed by 0.5 mg/kg for three days, in conjunction with broad spectrum antibiotics has been successful in treating pyometra (see section titled Pyometra) with good subsequent fertility. A similar protocol may be appropriate in cases of presumptively or definitively diagnosed endometritis in the cat. Prostaglandin has been used successfully to treat endometritis in the dog. If abdominal radiography suggests that fetal remnants are present in the uterus, surgical removal of fetal remains may be necessary.

• When a confirmed pregnancy is lost, either by observed abortion or failure to queen following positive pregnancy diagnosis, a minimum data base should include clinical evaluation of the queen and submission of fetus and placenta, if available, for post mortem examination.
• Likely causes for loss of a detected pregnancy include systemic viral or bacterial disease, ascending bacterial infection, nutritional deficiency, exposure to fetotoxic or abortogenic agents, hypoluteoidism, or lethal genetic defects.
• Clinical evaluation of the queen should include a history to detect signs of concurrent illness, particularly upper respiratory disease.
• Physical examination should include abdominal palpation, and fundoscopic examination of the retina. Abdominal radiography should be performed to detect retained fetuses, ectopic pregnancies, or evidence of uterine rupture. CBC, chemistry panel, urinalysis, FeLV antigen test (ELISA or IFA) and acute serum to be paired with convalescent serum two weeks later should be submitted If the queen is showing signs of upper respiratory infection, ocular, nasal, and oropharyngeal swabs should be submitted for viral, chlamydial, and mycoplasmal isolation, and impression smears of the conjunctiva submitted for detection of chlamydia. Chilled fetus, frozen and formalin fixed samples of placenta should also be submitted if available. The receiving diagnostic laboratory should be contacted for preferred methods of collecting and transporting specimens.

• Systemic infectious agents which are considered potential causative agents of abortion include feline leukemia virus (FeLV), feline panleukopenia virus (FPV), feline infectious peritonitis virus (FIP), feline herpes virus (FHV), chlamydia, mycoplasma, ureaplasma, and toxoplasma.

• The effect of feline leukemia virus on reproduction depends on whether the queen is viremic or not.
• In viremic queens (positive ELISA or IFA) FeLV appears to cause pregnancy loss.
• In a report describing 10 IFA positive cats, 4 underwent unsuccessful breeding, 2 became pregnant but resorbed the fetus, 3 aborted, and 1 developed purulent endometritis with several degenerating fetuses.
• A pregnant cat with lymphosarcoma was also reported to resorb fetuses at 5 weeks of gestation.
• Another author reports a pattern of fetal resorption in FeLV infected queens, and isolation of the virus from litters of unborn fetuses, newborn kittens, and the uterus of viremic, pregnant queens.
• While it appears that pregnancy loss is due to direct fetal infection, it has also been suggested that the virus disrupts the endometrium at the sites of placental attachment. However, further study is necessary to accurately define the occurrence and pathogenesis of abortion in FeLV viremic queens.
• Nonviremic queens (ELISA or IFA negative), who have overcome the initial infection but are latently infected in the bone marrow can reproduce normally and do not appear to be at significantly increased risk for pregnancy loss.
• However, the virus may be passed to the occasional kitten, who may then infect his or her litter mates. In a study of 6 latently infected queens (identified by reactivation of the virus from bone marrow aspirates) none of the queens experienced any reproductive problems over multiple pregnancies, never did they revert to viremia during pregnancy or lactation.
• A single kitten of 30 kittens was viremic at two weeks of birth and nonviremic litter mates subsequently developed viremia at ten weeks post partum. Possible routes of infection in the viremic kitten may have been transplacental or via milk. Latent infection was not detected in any kittens borne to these latently infected queens. Evidence for milk borne transmission was presented in another study in which transmission of virus from a supposedly latently infected queen to a suckling kitten occurred, and the milk cultured positive for the virus. This queen was periodically viremic however. Although direct infection of fetuses with FeLV has been achieved in latently infected queens, the queens were reinoculated with live virus intraperitoneally during gestation. Consequently, this particular model of fetal infection does not apply to the latently infected queen.
• Control of feline leukemia virus in the cattery is achieved by removing all ELISA positive animals from the cattery, and retesting all negative animals in 90 days. Feline immunodeficiency virus, a virus similar to FeLV, has not yet been associated with reproductive failure.

• Feline panleukopenia virus is a hardy parvovirus with a predilection for mitotic tissue. It has been shown to cause in utero infection, leading to cerebellar hypoplasia and ataxia in kittens. The cerebellar external granule cell layer is highly mitotic in the perinatal period and ataxia is manifested when the infected kittens first become mobile. However, earlier in gestation, tissues located in the kidney and gut are mitotically active and serve as sites of viral replication. Consequently, although neonatal ataxia indicates in utero infection late in gestation, infection earlier in gestation can lead to abortion or fetal resorbtion. Similar mitogenic viruses have been shown to cause abortion and fetal resorption in rats. Although dams infected during gestation seroconvert, they usually do not show clinical signs. Diagnosis of fetal infection due to feline panleukopenia virus is by isolation of virus from fetuses or neonates submitted to necropsy, by documenting a seroconversion in the dam, or clinically by characteristic ataxia observed in the neonates.
• Interestingly, cerebellar dysfunction can also occur in kittens borne to queens fed taurine deficient diets.
• Vaccination of queens against panleukopenia virus prior to breeding is recommended.

• Feline infectious peritonitis virus (FIP), once believed to be a major cause of pregnancy loss and kitten mortality in catteries, is currently an unproven cause of abortion.
• FIP does cause fatal neonatal infection, however.
• The initial association of FIP with poor reproductive performance came from observations of high coronavirus titters in catteries with reproductive problems. With the discovery of the widespread nature of feline enteric coronavirus, which cross reacts with FIP in serological tests, and similar reproductive problems occurring in SPF catteries free of coronavirus, the role of FIP virus as a cause of pregnancy loss became unclear.
• It is established, however, that FIP causes disease in the neonate, and that kittens borne to infected mothers are at particular risk. While milk borne transmission is a possibility, transplacental transmission cannot be ruled out. Lesions which could only have been caused in utero have been attributed to a feline coronavirus and the possibility of dual infection of FIP and feline panleukopenia virus has been suggested.
• Since FeLV is a major potentiator of FIP, control of FIP is commonly achieved by elimination of FeLV viremic animals from the cattery.
• A recently licensed vaccine for FIP is now commercially available in the Primucell FIPTM, SmithKline Beecham Animal Health. In clinical trials using a highly virulent challenging strain of FIP, 100% of non vaccinated controls became ill, 83% of which died. Among the vaccinated animals 85% survived the challenge, and exhibited substantially reduced clinical signs compared to the surviving non vaccinates. The vaccine is comprised of a temperature sensitive mutant virus which grows at 31^oC but is inhibited at 37^oC. When administered intranasally the virus replicates in the respiratory tract at the reduced temperature and provides protective cell mediated and local immunity. Temperature sensitivity prevents systemic spread. Because it is a modified live preparation, its use in pregnant queens is contraindicated. A serologic test by which FIP latently infected animals can be removed from the cattery does not currently exist.

• Feline herpes virus appears to cause abortion due to the debilitating effect of upper respiratory infection in queens, and infects kittens in the neonatal period.
• In utero transmission of the disease has not been shown except under certain experimental conditions. In one study, pregnant queens infected intranasally aborted following severe upper respiratory disease. However, no virus was isolated from the uterus, fetus or placenta, nor were any histologic lesions seen.
• When pregnant cats were infected intravenously, pregnant queens aborted after showing minimal signs of illness, and virus was isolated from uterus and placenta, both of which showed histologic lesions. This intravenous inoculation of the virus probably does not represent a true clinical picture of an upper respiratory pathogen.
• Because approximately 80% of cats infected with the virus become latently infected, and shed virus during periods of stress, the neonatal kitten is susceptible to infection from the queen who sheds virus during lactation.
• Although shedders can be detected by isolation of the virus from cats treated with corticosteroids, control of the disease focuses on protecting the neonatal kitten through ensuring adequate colostral protection and vaccination as maternal antibody wanes at 6-12 weeks.

• Chlamydia psittaci, a causative agent of upper respiratory infection and feline pneumonitis has been implicated as a cause of reproductive failure and in utero infection.
• Two queens from a cattery in the UK had kittens which experienced upper respiratory infection due to chlamydia. Both queens had experienced problems with abortions and failure to conceive. One queen, treated with tetracycline, subsequently had two healthy litters.
• Another report describes a condition of fatal pneumonitis in a litter of kittens infected from birth, the survivors afflicted with mucopurulent ocular discharge. Chlamydia psittaci was isolated from the lung of a dead kitten. Abortions were also reported in this cattery.
• Diagnosis of chlamydial infection is by demonstration of organisms in conjunctival scrapings or by culture of ocular or nasal swabs.

• Mycoplasma and ureaplasma have been suggested to be causative agents of abortion among cats. Diagnosis is also by isolation of the organisms from ocular or nasal swabs.
• Tetracycline is the treatment of choice for mycoplasma, ureaplasma and chlamydia and may be warranted when outbreaks occur among non pregnant animals housed with pregnant queens. It should not be administered to pregnant animals, however, since it causes bone and teeth malformation in the developing fetus. Further research is necessary to elucidate the role of these intracellular bacteria in feline abortion and infertility.

• Protozoal infections are unlikely causes of reproductive failure.
• Attempts to transmit Toxoplasma gondii from pregnant queens to their fetuses have not been successful. However, one case of neonatal infection characterized by pneumonitis, myocarditis, encephalitis, and retinitis in a two week old kitten is thought to have originated in utero since encysted organisms which were found would have normally taken four weeks to develop.

• Ascending bacterial agents which may cause abortion include Coliform, Staphylococci, Streptococci, Salmonella, and Mycobacteria.
• It is felt that bacteria rarely cause abortion unless unhygienic conditions prevail in the cattery. Bacteria are thought to migrate from the heavily contaminated vagina into the uterus where infection leads to fetal infection and death.
• Bacterial contamination commonly occurs at parturition but abortion is more likely to result from contamination at breeding.
• The cat aborting due to bacterial causes may show signs of systemic illness including fever, malaise, anorexia, abdominal straining and vaginal discharge.
• Recommended treatment includes appropriate supportive and antibiotic therapy continued for two to three weeks post abortion. In addition, uterine evacuation can be attempted using prostaglandin F2".

• Nutritional deficiency is an unlikely cause of pregnancy loss since most cat are fed commercial, balanced diets, and other signs would be apparent. Nevertheless, special attention should be paid to vitamin A and taurine.
• Vitamin A has been associated with reproductive failure such as anestrus, failure to conceive, early embryonic death, abortion and congenital defects.
• Queens fed a taurine deficient diet can appear clinically normal, yet suffer from reproductive failure. Of 18 queens fed a taurine deficient diet, only 6 carried pregnancy to full term. Clinical findings included abortions, early embryonic death and malformations in the neonates. Mothers were clinically normal except for retinal degeneration detected by fundoscopic examination. Interestingly, affected neonates suffered from cerebellar dysfunction due to a persistence of mitotic activity in the external granule cell layer of the cerebellum. While the histopathologic lesions were thus different from those seen with panleukopenia virus infection, the clinical signs were similarly indicative of cerebellar dysfunction. Hindlegs were abnormally developed, The kittens tended to be paretic in the hind legs, which frequently splayed out.

Hypoluteoidism

• Hypoluteoidism, failure of the corpus luteum or placenta to secrete sufficient progesterone to maintain pregnancy, has not been definitively documented as a cause of pregnancy loss in the cat, although it is suspected in those cats which habitually abort around day 50 - 58 of pregnancy.
• The suggested treatment is to administer injections of progesterone in oil to cats at a dose of 1-2 mg/kg weekly beginning a week prior to the anticipated abortion date, and to discontinue treatment a week prior to parturition.
• There is concern that administration of sex steroids during pregnancy can lead to gonadal dysgenesis of the fetus in utero.

Fetotoxic Drugs

• Fetal injury due to administration of fetotoxic drugs during pregnancy should also be considered as a potential source of fetal death.
• The specific drugs below are known to cause fetal injury and should not be administered during pregnancy: antibiotics (quinolones and tetracyclines), antifungals (griseofulvin), antiinflammatories (dimethyl sulfoxide), anesthetics (pentobarbital), gastrointestinal drugs (misoprostol), anticonvulsants (phenytoin), steroids (testosterone and estrogen analogues), vitamin A analogues (isotretinoin) and mitotane (o,p'-DDD). Organophosphate insecticides, anticancer drugs, corticosteroids, and vaccination with modified live vaccines (eg feline panleukopenia vaccine) should be avoided in pregnant queens.
• Care should be taken to avoid excessive levels of vitamin A during pregnancy (eg from feeding raw liver), since this can be embryo toxic.

• Genetic defects tend to occur when close inbreeding takes place.
• While cats may have many genetic abnormalities, the Manx syndrome is of interest. Breeders of Manx cats find that genetic fetal defects associated with incomplete formation of the spinal cord and fetal death occurs in some litters. Some cats are born with a tendency to acquire megacolon or urinary incontinence due to incomplete innervation of the pelvic viscera. Analysis of aborted fetuses or stillborns for genetic defects such as spina bifida or sacral dysgenesis should be considered when one or both parents are of Manx breeding.

• Failure of normal development of the gonads is termed premature gonadal failure. A common clinical sign is absence of pubertal estrus by two years of age.
• Diagnostic evaluation of the patient suspected of abnormal gonadal development should include determination of karyotype, levels of plasma LH, and FSH, gonadal histology, and gross appearance of the reproductive tract at laparotomy. In the cat, the XO chromosomal abnormality, while uncommon, causes gonadal dysgenesis.
• Clinical signs reported include a cat smaller than its litter mates and lack of pubertal estrus by 2.5 years of age, but otherwise outwardly normal appearance. The reproductive tract is apparently normal early in life but undergoes ovarian atresia as the animal matures.
• The XO condition can be predicted in some situations if one knows the coat color of the parents. The alleles for orange and black are carried on the X chromosome. Females born to a black female (homozygous for the black allele) by a ginger tom (single orange allele on the single X chromosome) should carry a black gene from the mother and a orange gene from the father. Such a female kitten would be tortoiseshell (heterozygous for orange and black). If black, however, she would probably have failed to receive the X chromosome with its orange gene from the father, and would carry only the X chromosome with its black gene from the mother, making her XO. Similar reasoning is used to predict the likelihood of Kleinfelter's syndrome (XXY) and hence sterility in tortoiseshell toms.
• Presence of abnormal sexual development, however, does not rule out the possibility of cyclic estrus behavior or even normal pregnancy. At routine ovariohysterectomy of an outwardly normal female with normal cyclic behavior, abdominal testes have been reported in the place of ovaries. This male pseudohermaphrodite (male because she had testes, pseudohermaphrodite because gonads of only one sex were present) had essentially normal external genitalia, except that the vulva was slightly smaller than usual, and the clitoris somewhat enlarged. Normal pregnancies have been reported in two cats with unilateral ovarian dysgenesis, also detected at routine ovariohysterectomy. Both cats exhibited sex chromosome mosaicism in cultured lymphocytes, (one X/XXY, the other X/XX), and both cats were pregnant with fetuses of normal gonadal development and genetic sex, occupying both horns of the uterus. While each had a small nodule in place of one ovary, the contralateral ovary was normal.
• A condition equivalent to Kleinfelter's syndrome (XXY) has been described in male blue cream burmese, tortoiseshell or calico cats. Such cats can be recognized as unusual since a normal male (XY) has only one X chromosome. Blue cream, tortoiseshell, and calico indicate heterozygosity (two X chromosomes) at the sexlinked locus for coat color, indicating the XXY genotype in males or a mosaic consisting of two cell populations with different X chromosomes. XXY males have slower than average development of external genitalia and libido, but are still within the normal range. No pregnancies have been reported, however, after apparently normal matings using strictly XXY males although mosaics and chimeras at this locus (eg XY/XXY, XX/XY) have been reported to be fertile, as have X chromosome mosaic females.