Reproductive failure in cats

Veterinary surgeons in practice spend most of their time in preventing rather than promoting breeding in cats. However, cats, and particularly pedigree cats, are becoming more popular as pets, so the demands on the veterinary profession for advice on breeding and its problems are likely to increase.

It is a subject which has received scant attention in the veterinary literature in the past, in fact their has been little information available about normal reproduction. For example, until recently, normal hormonal patterns throughout oestrus and pregnancy in the cat were not known. Over the past few years, however, a number of studies into feline reproduction have begun.

Reproductive failure can arise at a number of different stages throughout the reproductive process. Firstly, a queen may fail to ever call or display oestrus. Even if she does call, she may refuse to mate - mating failure. Failure of ovulation, fertilisation and pregnancy may all occur, and finally there may be difficulty at the time of kittening. In addition, problems may occur in either queens or toms.

In the limited space available it is not possible to cover all aspects of this wide subject. Instead, we intend to concentrate on failure of ovulation, fertilisation and pregnancy. In other words, any problem that arises in queens from the time of a successful mating to parturition. These seem to be the stages at which most difficulties are encountered and are the problems veterinary surgeons in practice are most frequently called upon to diagnose.

One of the most interesting features of the reproductive process of cats is the phenomenon of induced ovulation. This has a number of important consequences:

• Vaginal cytology may not be suitable for investigation of reproductive function in cats

The eggs are fertilised in the oviduct and arrive in the uterus 4-5 days after mating. For the first 10 days the blastocysts are nourished by the uterine milk secreted by the endometrial glands. The process of implantation begins 14 days after mating. By 20 days the conceptual swellings are approximately 'pea-size' and it is at this stage that pregnancy can first be confirmed by abdominal palpation. However, the optimum time at which to carry out pregnancy diagnosis by abdominal palpation is 4-6 weeks when the conceptual swellings vary from 'walnut-size' to 'bantam-egg-size'. 3-4 weeks following mating most queens, particularly maidens, show marked reddening of the teats. This phenomenon is referred to as 'pinking-up' by breeders and is used as an indication of pregnancy. However, this will also be seen in pseudopregnant queens and cannot be relied upon to confirm pregnancy. Indeed, as already explained, pseudopregnancy involves formation of corpora lutea and production of progesterone in just the same way as pregnancy.

Other actions of progesterone may cause pseudopregnancy to mimic the changes of pregnancy. For example, it leads to fat deposition and changes in water balance and will cause considerable abdominal enlargement. Therefore, confirmation of pregnancy by abdominal palpation is required to differentiate between pseudopregnancy and pregnancy. Pseudopregnancy in the cat rarely involves pseudo-lactation as is so commonly seen in the bitch. The lifespan of pseudopregnant corpora lutea is very variable and pseudopregnancy may last from 3-7 weeks. Therefore, in some cases a pseudopregnant queen may return to call at the same expected date as if unmated, whilst in other cases there may be an extended period of inactivity before onset of the next oestrus.

After 6 weeks the conceptual swellings begin to merge and cannot be identified individually again until the last two weeks of pregnancy, particularly if the queen is carrying a large litter. However, by this time the abdominal distension will usually be obvious.

Calcification of the foetal skeletons cannot be recognised radiographically until the last week or so of pregnancy.

The corpora lutea are essential for the maintenance of pregnancy during the early stages. There is some disagreement concerning the stage of pregnancy after which ovariectomy, and hence removal of luteal progesterone, will not induce abortion. It is presumed that after this stage the placentae and/or foetuses produce sufficient progesterone to maintain pregnancy. A rapid increase in progesterone occurs soon after mating, followed by a gradual decline which becomes precipitous during the last week of pregnancy until the levels have returned to basal values at the time of parturition. The high oestrogen values of oestrus soon fall away after mating. There is a peak in oestrogens during the sixth to eighth weeks of pregnancy, the magnitude of which may be related to litter size, followed by a rapid fall during the last week.

Gestational failure can occur at various stages of pregnancy and may take several forms:

EED involves death of the blastocysts between the time of fertilisation and implantation. A certain level of EED can be considered normal and is considered to represent foetal wastage resulting from natural selection. Because of its phenomenon of induced ovulation, the cat is ideally suited to a study of EED. It does seem that "normal" EED rate is low in cats.

Resorption by the uterus of the conceptual tissues may occur after either foetal or placental death. Once calcification of the foetal skeletons is well established resorption is not possible. The distinction between resorption and abortion is not always clear cut. Passage of partially resorbed "liver-like" tissue by queens during pregnancy is a common occurrence. On some occasions the tissue may consist purely of resorbed placenta, whilst on others, a partially resorbed foetus may be attached. It is common for resorbed placentae and foetuses to be passed at parturition together with live kittens in cases of large litters, particularly from Oriental queens. These deaths possibly result from "over-crowding" and are not considered to represent reproductive failure.

Recognition of abortion is self-evident. Resorption occurs after implantation and can therefore be identified by failure to produce kittens after pregnancy has been confirmed by abdominal palpation. EED must be differentiated from both fertilisation and ovulation failure.

Assessments of the inter-oestrual period cannot be relied upon to identify the latter due to the variability in the duration of the pseudopregnancy mentioned previously. It is necessary either to examine the ovaries at laparotomy or measure plasma progesterone, as described earlier, after mating to determine whether or not ovulation has occurred.

Investigation of EED requires specialised techniques and is not feasible in general veterinary practice. I shall therefore only briefly discuss EED.

A laparotomy is performed four to ten days after mating and collection of the eggs from the oviducts or uterus is attempted. Microscopic examination enables determination of fertilisation status, morphological abnormalities, or degeneration possibly indicative of an unfavourable uterine environment. If healthy eggs are present these are cultured and subsequently evaluated cytogenetically. It is unlikely, however, that chromosomal abnormalities will account for complete reproductive failure. It is much more likely merely to cause a reduction in litter size. At laparotomy it is also possible to evaluate the ovaries for adhesions and the oviducts for any blockage which might impede the passage of eggs.

Resorption is more common than abortion, and indeed seems to be the most common manifestation of reproductive failure in pedigree queens. The causes can be divided into three main groups.

Undoubtedly environmental and managemental factors influence reproduction in the cat. For example there is, in many groups of cats, a definite breeding season.

Daylight length seems to influence seasonality more than temperature, and constant lighting of 14 hours per day will abolish anoestrus periods. Social stimuli also appear to be important. However, it is not known whether phenomena such as the Bruce effect can operate in the cat to induce resorption. (The Bruce effect involves the resorption of foetuses when a pregnant female mouse is exposed to the pheromones of any male mouse other than the sire of the litter).

The importance of nutritional problems as a cause of reproductive failure in pedigree cats is overemphasised. Deficiencies of Vitamin A, Calcium and Iodine have been shown experimentally to impair reproduction but only when grossly imbalanced diets have been fed. Most pedigree queens receive sensible diets and such marked deficiencies are unlikely to occur in practice.

Hormonal imbalances, too, have probably been overplayed in the past as a cause of resorption and abortion and many undiagnosed cases have been mistakenly ascribed to such problems. Ignorance of the normal hormonal patterns in cats, until only recently, has prevented substantiation of endocrinological imbalances. Cysts are a potential source of abnormal levels of hormones and are common in the cat. Parovarian cysts are often encountered at routine spaying of immature queens. They appear as thin walled, fluid filled structures, of variable size, often quite large, attached to the oviduct, uterus or broad ligament. They do not appear to be of any clinical significance.

True ovarian cysts are usually encountered as incidental findings on examination of tracts from queens with satisfactory breeding performance records. They do not, therefore, seem to be a significant cause of reproductive failure in cats.

Progesterone deficiency has also been suggested as a cause of habitual resorption/abortion in cats. Such queens will supposedly carry their litters to term if injected with progesterone during pregnancy. However, progesterone has, as in other species, a relatively short half life in the cat and a single injection is likely to be of little value.

A number of queens with histories of habitual resorption purportedly resulting from this problem have been studied at Langford. However, only in one case has there been any evidence to substantiate a diagnosis of progesterone deficiency, and from all others FeLV has been isolated. It has been suggested that this condition is analogous to luteal phase inadequacy in man and results from premature regression of the corpora lutea before the foeto-placental unit can produce sufficient progesterone to maintain pregnancy. The progesterone levels from these cases attained normal peak values and have then followed the pattern for pseudopregnancy. The conceptual swellings appear to decrease in size at the same time as the progesterone levels begin to fall, but laparotomy at this time has indicated that the foetuses die at an earlier stage and that the size of the conceptual swellings does not provide an accurate assessment of foetal well being. In the only case of probable luteal deficiency, the peak values of progesterone were much lower than normal. A progesterone implant inserted early in pregnancy enabled the pregnancy to proceed normally.

If progesterone deficiency is of any practical significance it is more likely to result from foeto-placental insufficiency. Single foetuses may not produce enough progesterone to maintain pregnancy and are therefore resorbed. This might explain why the occurrence of litters of a single kitten is unusual. Non-hormonal placental insufficiency may also contribute to reproductive failure. At the present time a lack of suitable tests for monitoring foeto-placental function prevents verification of this possibility.

Just as viruses are the most significant cause of the major infectious feline diseases, so they are important in causing reproductive failure.

a) Feline Leukaemia Virus An association between FeLV and reproductive failure has been suspected for some time. It now seems that FeLV is probably the most important cause of resorption in the pedigree cat, particularly in the cattery where more than one queen is affected at the same time. Indeed reproductive failure is usually the first indication of FeLV infection in entire queens who subsequently develop lymphosarcoma or some other FeLV related disease. The exact manner in which FeLV causes reproductive failure is not known. Possibilities include:

Foetal death as a direct result of infection.
Placental damage.
Development of endometritis due to immunosuppression leading to an unfavourable uterine environment.

Congenital or prenatal infection has been demonstrated but it is not known whether this results from genetic, epigenetic or transplacental infection.

In view of the strong association between FeLV and reproductive failure, all infertile cats should be screened for the virus.

b) Feline Infectious Enteritis The affinity of the panleucopaenia virus for rapidly dividing cells and the subsequent cerebellar damage to kittens born of queens infected during pregnancy are well recognised. It seems likely that this virus could cause foetal death at other stages of pregnancy. However, FIE is probably not a significant problem in practice due to the efficiency and widespread use of vaccines.

c) Respiratory Virus FVR infection by abnormal routes of entry has been shown experimentally to cause placentitis and abortion. Certainly pregnant cats with acute respiratory virus infection may subsequently resorb or abort their foetuses although it is not certain whether this is the result of placentitis or non-specific pyrexia and illness. There is no convincing evidence to suggest that sub-clinical infection in carrier animals is a significant cause of reproductive failure.

d) Feline Infectious Peritonitis Until recently FIP infection could only be recognised by the presence of associated clinical signs. Since the prognosis, once signs have developed, is hopeless and it is primarily a disease of young cats, little opportunity has been afforded for any associated reproductive problems to become evident. However, now that the recently developed serological tests have indicated that FIP infection is more common than was originally thought and epigenetic transmission has been demonstrated, it is likely that efforts will be concentrated on clarifying the apparent association with reproductive failure. There is some evidence of such a link but this could result from the association between FIP and FeLV rather than any action of FIP itself.

No specific bacterial infectious causes of reproductive failure nor venereally transmitted infections are recognised in cats. This species seems naturally immune to brucellosis and leptospirosis. However, a number of bacteria - particularly staphylococci, streptococci and coliforms - may be associated with reproductive failure. The findings of Dr. Povey and myself indicate that the assessment of the significance of any bacteria isolated from infertile cats is difficult for a number of reasons:-

The vaginal flora of the cat is not representative of the picture in the uterus - which is usually sterile.
The bacterial flora varies at different stages throughout the reproductive cycle. It is therefore vital to take serial swabs and not to rely on the results of a single sample. At oestrus the cervix is open and therefore swabs do provide a more representative picture of the uterine flora. However, the high levels of oestrogens at oestrus facilitate control of infections and the results of swabs taken at this time may be misleading.
Staphylococci, streptococci, coliforms, etc. are isolated with the same frequency from both infertile and "normal" queens.
Even if bacteria are isolated they may only be secondary to some other problem, such as FeLV or chronic endometritis.

This is a common cause of reproductive failure in the cat, probably secondary only to FeLV in importance. Various grades of severity are seen. In mild cases the placentae may function efficiently until approaching the terminal stages of pregnancy and the condition may be manifested by the birth of stillborn kittens. In other cases, the uterus may initially support the growth of foetuses, but these subsequently die and are resorbed. If changes are severe the blastocysts will not survive the hostile environment and eventually frank pyometra may develop.

Chronic endometritis probably results from a number of factors - primarily hormonal creation of a uterine environment suitable for the development of secondary bacterial infection. Vaginal swabs may not be useful in diagnosing this condition for reasons discussed earlier and the only satisfactory method of confirming chronic endometritis, particularly in mild cases, may be by direct examination of the uterus, possibly with endometrial biopsy, at laparotomy.

Cats with severe endometritis will not breed again, but in mild cases there may be a return to normal fertility. Antibiotics seem of little help, the most valuable approach is to leave the queen unmated for at least two calls in the hope that she will be able to clear herself of infection naturally.

The progesterone dominated uterus is particularly susceptible to infection and progestagens may exacerbate endometritis. Therefore, in view of the frequency of this condition, empirical use of progestational agents in cases of reproductive failure of uncertain aetiology is positively contra-indicated.

Although the cat is the primary host of Toxoplasma gondii , experimental studies have failed to demonstrate either reproductive failure or congenital infection associated with infection. This organism is therefore thought to be of little practical importance as a cause of reproductive failure in cats.

In conclusion, reproductive failure and reproduction in the cat have only received serious attention during the past few years. Our knowledge of even the normal reproductive process of the cat is scant at present and many questions about reproductive failure are unanswered.

Until recently, very little attention has been paid to the problems of fertility in the tom cat. The impression gained from reading the textbooks is that male fertility is almost inevitably above suspicion and that it is the poor female who fails in her duty. However, we are now beginning to realise that the tom does have his problems too and that these require some attention.

Factors affecting fertility in male animals can be divided arbitrarily into three:

In the first group, anatomical factors can again be sub-divided into developmental and acquired abnormalities.

• Cryptorchidism : This is a failure of the testes to descend from the abdomen into the scrotum. During foetal life the testes lie within the abdomen, close to the kidneys. Normally, as the animal develops, the testes migrate posteriorly through the inguinal ring and finally come to lie outside the body. The testes are normally descended at birth but may not be palpable until the animal is four to twelve weeks old. If they have not descended by six months of age, they probably will not do so. When the condition is bilateral the animal is sterile because the deep body temperature is too high to allow normal spermatogenesis. If the condition is unilateral, one testis is normally descended. (The animal is not a mon-orchid since this implies that he has one gonad. He has two, but only one is visible). Unilateral cryptorchids are fertile because the normally descended testis will produce spermatozoa. However, it is not recommended that such animals are used for breeding since cryptorchidism is probably genetic in origin. Furthermore, because of the danger of tumour development in the abdominal gonad, both testes are usually removed.

• Persistent frenulum : During its development the penis is attached to the wall of the prepuce by a fold of tissue called the frenulum. This normally breaks down as the animal matures. However, in rare cases this fold of tissue persists and the animal is unable to protrude the penis and complete intromission. The condition can easily be rectified by a simple surgical operation.

• Chromosomal abnormalities : It is now well recognised that male tortoiseshell cats are almost always infertile. The infertility is due to abnormalities in the development of the seminiferous tubules and spermatogenesis. Some of these males lack the normal secondary sexual characteristics and show no libido. Cytogenic analysis of the chromosomes of these animals have shown them to have an extra (X) chromosome and a karyotype of 39XXY. Other male tortoiseshell cats have been more male looking and these had multiple cell lines, some of which were quite complex. Although such chromosomal abnormalities have only been found in tortoiseshell toms, there is no reason to suppose that other breeds of cats should not occasionally have similar abnormalities. Although nothing can be done to treat such animals, recognition of the condition would save the animal from being subjected to numerous, ineffectual remedies.

• Infections : Some foetal or neonatal infections can lead to a maldevelopment of the reproductive system. For example, testicular hypoplasia may be a consequence of an early infection of panleucopaenia.

• Trauma : Such things as scrotal bite wounds will lead to local inflammation, heat and hence disruption of spermatogenesis. The effects on fertility may last longer than the visible effects of the wound. There is a time lag of a number of days before the effects on the developing spermatozoa are seen in ejaculated semen. Trauma resulting in a penile haematoma may be a sequel to urethral obstruction.

Another problem said to be associated with long-haired cats is penile hair rings. These develop because of the friction of the penile spines against the perineal and dorsal hair of the female. Usually, any such hair accumulation is removed by the tom during grooming but if it is allowed to persist it may prohibit intromission. When recognised, the problem can easily be rectified by removing the hair ring.

• Malnutrition : This is often secondary to a prolonged illness and results inter alia in marked reduction of spermatogenesis. The effect is usually reversible.

• Obesity : At the other extreme, fat cats often have poor libido although spermatogenesis is usually normal. Cats fed on a high liver diet may develop testicular degeneration because of hypervitaminosis A. The process can be halted, although not reversed, by reducing the liver intake.

• Overuse : In these cases there is no real abnormality, it is just that the tom is being asked to use up the semen faster than he can produce it. In such cases libido will be maintained even after spermatozoa in the ejaculate have fallen below levels adequate for conception.

• Immature toms : Males reared in isolation often do not mature until over a year old. Examination of testosterone levels in such animals have shown them still to be low. Furthermore, even mature toms, removed from the stimulus of other animals, may suffer a temporary loss of libido.

• Debilitating diseases : Any chronic disease will affect steroid production and secretion and hence reduce spermatogenesis.

• Hypothyroidism : This condition produces a generalised reduction on metabolic rate and all bodily processes are retarded. However, this is reversible with suitable treatment.

• Environment : Young males may be disturbed by changes in environment or routine. This may be sufficient to inhibit them making advances to queens even when they are well in oestrus.

• Queen : Aggressive behaviour on the part of the female may discourage an inexperienced male. memories of such behaviour may persist and the tom may be reluctant to mount even a receptive female.

In conclusion, fertility problems in the male usually present either as a lack of libido or as a failure of conception, but both can be caused by a number of factors.