Female cats: Normal Reproduction, and Reproductive Diseases and Conditions

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Female cats: Normal Reproduction, and Reproductive Diseases and Conditions

Susan E. Little

Abstract

The pedigreed cat fancy has developed and grown in popularity around the world during the last 100 years. The widespread appeal of pedigreed cats and cat breeding means that veterinarians need to be familiar with the unique characteristics of feline reproduction and breeding management. In the past 35 years, considerable progress has been made in understanding the behavioral, gonadal, and endocrine factors involved in successful feline reproduction. This chapter focuses on the most common situations likely to be encountered in general practice.

Keywords

Puberty; estrous cycle; estrus; proestrus; interestrus; anestrus; diestrus; follicle-stimulating hormone; ovulation; luteinizing hormone; pseudopregnancy; corpus luteum; spontaneous ovulation; ovarian remnant syndrome; mammary hyperplasia; segmental uterine aplasia; pregnancy; relaxin; gestational age; parturition; dystocia; uterine torsion; uterine prolapse; eclampsia; mastitis; metritis; retained placenta; postpartum intussusception; infertility; vaginal cytology; estrus induction; ovary; cystic endometrial hyperplasia; endometritis; pyometra; prostaglandins; cabergoline; aglepristone; pregnancy loss; assisted reproduction

INTRODUCTION

The pedigreed cat fancy has developed and grown in popularity around the world during the last 100 years. The widespread appeal of pedigreed cats and cat breeding means that veterinarians need to be familiar with the unique characteristics of feline reproduction and breeding management. In the past 35 years, considerable progress has been made in understanding the behavioral, gonadal, and endocrine factors involved in ­successful feline reproduction. This chapter focuses on the most common situations likely to be encountered in general practice. More information is available in image e-Box 45.1.

ANATOMY

The anatomy of the female reproductive tract is composed of the ovaries (paired), oviducts (paired), uterine horns (paired), uterine body, cervix, vagina, and vulva. The anatomy of the female cat (queen) differs in several ways from the anatomy of the female dog (bitch). The vulvar labia of the queen are nonresponsive to estrogen and remain small and covered with hair during proestrus and estrus in contrast to the increase in size seen in bitches. Another difference is the relatively straight horizontal anatomy of the vestibule, the vagina, and the cervix in the queen. The junction between the vestibule and vagina is narrow and inelastic. The shape of the uterus in the queen is similar to that in bitches – bicornuate, with two long horns and a small body.

NORMAL REPRODUCTION

Puberty

The first estrus typically occurs between 5 and 9 months of age, but age at onset may be highly variable (3.5 to 18 months). In a survey of breeders of four breeds (Norwegian Forest cat, Maine Coon, Persian, Bengal) in Italy, the average age at puberty was 12 ± 7 months.1 Puberty was earliest for the Norwegian Forest cat, Bengal, and Maine Coon (10 months) and was latest for the Persian (17 months). The time of the first estrus is influenced by several factors; for example, breed (shorthair breeds often reach puberty earlier than longhair breeds), season (which determines the length of daylight), and the queen’s body condition. Persians and related breeds may not have the first estrus until 18 months of age or older and may not be sexually mature until 2 to 3 years of age. The average body weight at puberty is 2.3 to 3.2 kg (5 to 7 pounds) or 80% of adult body weight. Shorthair breeds, such as the Siamese and Burmese, are more precocious and may reach puberty at a lower body weight.

Seasonality

The cat is seasonally polyestrous and a long-day breeder. Queens undergo estrous cycles repeatedly during a breeding season unless interrupted by pregnancy, pseudopregnancy, or illness. Estrous cycles will occur at variable intervals but typically occur every 14 to 21 days. The link between photoperiod and reproduction is the hormone melatonin. In response to a seasonal decrease in the length of daylight, the pineal gland increases production of its only hormone, melatonin. As melatonin levels increase, gonadotropin-releasing hormone (GnRH) production in the hypothalamus decreases, so ovarian activity also decreases.

In the northern hemisphere, increasing daylight length in January and February promotes the onset of estrous activity. In the survey of cat breeders in Italy, queens were reported in estrus every month of the year, but 67% of estrous cycles occurred between January and June.1 Regular estrous activity will continue until as late as October or November, depending on the geographic distance from the equator (and therefore the length of daylight) as the effect of seasonality diminishes or disappears near the equator. Most cats housed indoors in North America will experience winter anestrus because of the short length of daylight. However, the effect of daylight length on cats housed indoors is complicated as they are exposed to natural and artificial light, which sometimes leads to unpredictable ovarian cycles. In addition, queens housed together may have synchronized estrous cycles (the “dormitory effect”).

Longhair breeds seem to be more sensitive to the amount of daylight than shorthair breeds. Although many longhair queens (such as Persians) will not exhibit regular estrous cycles even during periods of long daylight, many shorthair queens (such as Siamese and related breeds) exhibit estrous cycles year-round, regardless of daylight length. Inadequate intensity or duration of light is an important cause of infrequent estrous cycles in cats housed indoors. Breeding catteries should provide 12 to 14 hours of daylight or artificial light per day to encourage regular estrous cycles.

Estrous Cycle

The feline estrous cycle is divided into proestrus, estrus, interestrus, anestrus, and diestrus (Fig. 45.1). Proestrus is considerably more difficult to detect in the queen than in the bitch. This part of the estrous cycle may last only 1 or 2 days and the signs may be subtle. Some queens will rub their head and neck against convenient objects and display affectionate behavior. Occasionally, queens in proestrus have a slight mucoid vulvar discharge and pollakiuria. During proestrus, tom cats may be attracted to the queen, but the queen will not be receptive to breeding.

Estrus is defined as behavioral receptivity to mating. This stage may last from 2 to 19 days, with the average duration being 5.8 ± 3.3 days.2 A queen in estrus will crouch with her front legs pressed to the ground, her back in lordosis, and her tail turned to one side to present the vulva (Fig. 45.2). The queen may roll or thrash about on the floor. Queens in estrus often vocalize to attract the attention of males. They may be restless, have a poor appetite, and show increased affection to their caretakers. It is not uncommon for inexperienced owners to interpret estrus behavior as a sign of injury or illness.

Occasionally, queens have prolonged estrus (>7 days). This may be due to maturation of overlapping waves of follicles with resulting prolonged high estradiol levels. This type of prolonged estrus is most commonly seen in Siamese and related breeds. Other queens with prolonged behavioral estrus have normal distinct patterns of follicular growth. Why these queens show prolonged estrus rather than distinct estrus periods is not understood. Prolonged estrus can also be associated with cystic ovarian follicles. Functional cystic follicles can produce persistent increases in plasma estradiol levels (>20 pg/mL [>73.4 pmol/L]). Cystic ovarian structures may be identified with abdominal ultrasonography. Another infrequent variation is the split heat, most often associated with young queens. The proestrus signs occur but then subside, only to be followed a few days later by a normal proestrus and estrus. This phenomenon tends to disappear with maturity.

The period between one estrus and the next in queens that have not ovulated is the interestrus. During this time, plasma estradiol is low (<15 pg/mL [<55.1 pmol/L]) and no sexual behaviors are seen. In research colonies, the duration of interestrus can range from 2 to 19 days but on average is 7 days. However, data for pedigreed breeds may be different. In the survey of cat breeders in Italy, the average interestrus interval was 39 ± 17 days, with no difference among breeds (Bengal, Maine Coon, Norwegian Forest cat, Persian).1

Anestrus is the absence of cycling activity that may occur naturally in periods of short daylight, but individual variation is common. During this time, progesterone and estrogen are at baseline concentrations (progesterone <1 ng/mL [<3.2 nmol/L], estrogen 8 to 12 pg/mL [29.4 to 44.0 pmol/L]).

The luteal phase (diestrus) of the queen’s estrous cycle is the period after ovulation when the dominant hormone is progesterone. Unlike the bitch, the queen does not experience a pre-ovulatory rise in progesterone. After ovulation, fertilization of oocytes occurs in the oviducts, and the embryos enter a uterine horn 4 to 5 days after ovulation. The embryos then space out along the uterine horns and may even migrate from one horn to another before implantation.3 Some embryos may be lost in this process. Implantation occurs about 12 to 13 days after breeding, and the implantation rate is estimated to be about 84%.3 The feline placenta is endotheliochorial in structure and zonary in shape. The average duration of gestation is 65 to 67 days (Table 45.1).2,4,5

Table 45.1

Gestation Length and Average Litter Size for Selected Cat Breeds from Various Sources.
Gestation Length (days) Average Litter size
Persian 651,4
Maine Coon
Bengal 641
Ragdoll  
Siamese 664
Norwegian Forest cat 661
Multiple breeds 655 45

If the oocytes are not fertilized after ovulation, a pseudopregnancy will occur that lasts 40 to 50 days. Pseudopregnancy may also result if early embryonic loss occurs. Pseudopregnancy in cats is not usually associated with maternal behaviors or lactation.

Estrus may resume about 10 days after the end of the luteal phase, but nursing queens often experience a lactational anestrus that can last for up to 8 weeks after weaning. Most queens will return to estrus about 4 weeks after weaning kittens if this occurs during the breeding season. However, it is entirely possible for a queen to return to estrus while still nursing. The first estrus after a pregnancy may be shorter and less fertile. Estrus behavior during gestation has also been reported in the queen, although serum estradiol is not increased and no luteinizing hormone (LH) surge occurs, even if the queen allows copulation.6 Superfetation—kittens of different gestational ages in one litter—has never been proven to occur in the cat. The presence of poorly developed fetuses along with kittens of normal gestational age in a litter is most likely a problem of arrested development.

Hormonal Events of Estrus and Pregnancy

Although little data about follicle-stimulating hormone (FSH) concentrations or activity in the queen exist, it is believed to be similar to that in other species. The pituitary gland produces FSH which initiates development of ovarian follicles. Three to seven follicles develop and start producing estradiol-17β. As the follicular activity peaks, plasma estradiol levels increase and may vary widely but usually are >20 pg/mL (>73.4 pmol/L).7 Estradiol levels stay high for 3 or 4 days during estrus and then abruptly fall. The high estradiol levels produce two important effects: overt estrous behavior and priming of the gonadotropin surge necessary to cause ovulation. Estradiol concentrations rise again at about day 58 of gestation and decline just before parturition.

Ovulation requires the release of LH from the anterior pituitary gland. During intromission, the penis probably causes distention of the posterior vagina and induces release of GnRH from the medioventral hypothalamus via neuroendocrine reflexes. Sufficient stimulus is required to provoke the release of GnRH. A surge of LH occurs within minutes of copulation. With multiple copulations, the LH surge is higher in amplitude and lasts longer than when only one breeding occurs, thus increasing the chances that ovulation will occur.

Several days of estradiol priming are required before LH release sufficient to cause ovulation occurs. This is typically reached by the third or fourth day of estrus. There also appears to be a stimulus threshold individual to each queen that must be exceeded for adequate LH release to occur. Unlike the rabbit, where a single mating is sufficient to induce ovulation, queens vary considerably in the number of copulations required to induce sufficient LH release and ovulation although most queens will ovulate after four or more copulations.

Ovulation occurs 48 hours or more following the LH surge.8 All oocytes are released at the same time. The granulosa cells of the ovarian follicles undergo luteinization and begin to produce progesterone almost immediately. Progesterone concentrations rise within 24 hours and may reach highs of 60 to 90 ng/mL (190.8 to 286.2 nmol/L) by 20 to 25 days postovulation.9,10 Throughout pregnancy, progesterone is maintained at high concentrations until the last few days of gestation, when the level falls to about 2 ng/mL (6.4 nmol/L) and to <1 ng/mL (<3.2 nmol/L) immediately following parturition.10 A minimum progesterone concentration of 1 ng/mL (3.2 nmol/L) appears to be necessary to sustain pregnancy in the queen. Although progesterone declines at term, unlike the bitch, baseline concentrations are not required for onset of parturition in the queen.

As for other induced ovulators, the corpus luteum (CL) may be the primary source of progesterone throughout pregnancy in the cat.9 Two other hormones are important in feline pregnancy. Relaxin is produced primarily by the placenta in carnivores and facilitates parturition by softening the connective tissue of the pelvis, softening the cervix, and relaxing uterine musculature. Relaxin concentrations increase as early as day 20 of gestation.6 Prolactin is produced by the anterior pituitary and has various effects, including regulation of lactation. Prolactin concentrations increase from about day 35 of gestation, plateau at about day 50, and then increase abruptly just before parturition.6 Prolactin appears to be necessary for maintenance of pregnancy by supporting the CL, as suppression of prolactin with a dopamine agonist results in abortion.

Pseudopregnancy may result if a mating is infertile. High progesterone concentrations are maintained by a centrally mediated blockage of GnRH secretion during both pregnancy and pseudopregnancy. This prevents the queen from returning to estrus until the luteal phase has ended. During pseudopregnancy, progesterone concentrations start to decline by day 25 to 30 and are <1 to 2 ng/mL (<3.2 to 6.4 nmol/L) by day 40 to 50.9 The feline CL may be preprogrammed to atrophy after 25 to 30 days unless luteotrophic factors are present. These luteotrophic factors may originate from the fetoplacental unit and/or from the pituitary. The two most likely luteotrophic factors in the queen are relaxin and prolactin.

Spontaneous Ovulation

Traditionally, queens are described as reflex-mediated induced ovulators. Ovulation should not occur unless mating or a similar stimulus induces it. However, pyometra and mucometra can occur in middle-aged, intact, virgin queens. Studies have found evidence that spontaneous ovulation not only occurs in cats but occurs with some frequency. A study of 44 female cats with uterine disease classified them based on ovarian status (active or cystic follicles versus luteal phase ovaries).11 Of the 44 queens, 35 had no recent exposure to male cats. However, 20 of these 35 queens had luteal phase ovaries, established by histologic examination. In another study, 20 domestic shorthair queens ranging from 2.5 to 11 years old were evaluated.12 These cats were housed individually, but they could see and hear other cats, including males. Seven of the 20 queens had evidence for spontaneous ovulation, and some queens experienced it repeatedly. A study designed to approximate conditions in multicat homes and catteries group-housed 15 young, nulliparous, female cats.13 After 3 months, a male cat was housed in the same room but caged separately so there was no physical contact with the queens. Of the 15 queens, 87% showed evidence of at least one instance of ovulation and pseudopregnancy without mating during the 4.5 months of the study. As well, 67% of the queens had evidence of spontaneous ovulation during the 3 months before the male cat entered the room. Finally, in a study of 89 queens presented for ovariectomy (OE), approximately one-third showed evidence of spontaneous ovulation.14

These studies indicate that non-copulatory ovulation may be possible in response to a variety of tactile, visual, auditory, or olfactory cues in queens. Thus, it is more appropriate to consider the queen to be an induced and spontaneous ovulator. Unrecognized spontaneous ovulation and subsequent pseudopregnancy is one important cause for infrequent estrous cycles that must be ruled out in cases of suspected infertility.

FERTILITY AND BREEDING MANAGEMENT

The ancient Egyptian goddess of fertility, Bastet, was portrayed as a cat for good reason. Queens are most fertile between the ages of about 18 months and 8 years, although examples of successful production of kittens in aged queens have been reported. Queens more than 8 years of age tend to have irregular estrous cycles, smaller litters, more spontaneous abortions, and more kittens with congenital defects compared with younger queens.

The average litter size is four kittens, but there is wide variability, especially among pedigreed breeds (Table 45.1).5,15 Queens are not monogamous and may accept several toms during an estrous cycle, allowing some litters to have multiple sires (superfecundity). Multiple paternity litters may occur more than 70% of the time in free-roaming cats in population-dense urban environments compared with less than 22% of the time in sparsely populated rural environments.16 Also, queens may use partner selection to control inbreeding. One study of eight queens in a feral colony concluded that queens avoided breeding with closely related toms but not distant relatives.17

Breeders of pedigreed cats attempt to exert control over reproduction and plan pairings based on many factors, such as the qualities (e.g., health, color, conformation) desired in the offspring. Breeders also control the timing of litters based on the health of the queen, demand for kittens, show schedules, and other factors. Breeders should be educated about maintaining proper breeding records (Box 45.1) as part of a sound cattery management plan. In a survey of 110 cat breeders in Italy, only 24% kept accurate records.1

Under optimum conditions, many pedigreed queens can successfully rear two litters per year or three litters over 2 years. Litters may be born any time in the year, although most studies show there are slightly more litters born to pedigreed cats in the spring. Queens should be fully mature and in good body condition before they are first bred to ensure successful breeding, a healthy pregnancy, and good maternal care of the kittens. Queens younger than 1 year of age may have irregular estrous cycles and may not display mature maternal behavior.

Queens selected for a breeding program should also meet certain health criteria. Breeding queens should be healthy, in good body condition, and up to date with vaccinations. All cats in a cattery should be tested for feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) and any new cats should be tested and confirmed free of infection before joining the cattery. Before breeding, queens should be free of internal and external parasites. In addition, testing for inherited diseases (e.g., polycystic kidney disease, hip dysplasia, hypertrophic cardiomyopathy) may be desirable for certain breeds and should be performed before a queen or tom has reproduced. Queens of breeds with a high prevalence of blood type B should be blood typed before breeding to prevent neonatal isoerythrolysis (see Chapter 46: Pediatrics).

Introducing young or inexperienced cats into a breeding program can sometimes result in shyness or a refusal to mate. Ideally, two inexperienced cats should not be matched. A shy queen is best exposed to an experienced mate gradually, preferably daily for short periods (e.g., about 15 minutes), before mating. Inexperienced queens should be placed with experienced, but calm and nonaggressive males.

It is preferable to bring the queen to the tom cat, as many tom cats will not breed successfully when in unfamiliar territory. Environmental factors can interrupt mating behavior, especially in tom cats. Tom cats spend considerable time marking their territory. If the area is cleaned too thoroughly, especially if a scented cleaner is used, some tom cats will ignore or even attack a visiting queen until they have re-marked their territory. It may take up to 14 days before the tom cat is comfortable again. Travel stress can adversely affect the female, temporarily upsetting pituitary and ovarian function. If the queen must travel for breeding, it is best to transport the queen to the tom cat several weeks in advance to allow adaptation to the new surroundings and to the tom cat before attempting breeding.

The queen in estrus will signal willingness to breed by displaying interest in the tom cat and vocalizing or purring. The queen will assume a lordosis position low to the ground with her tail to one side (Fig. 45.2). The tom cat will mount the queen, grasp the skin on the back of her neck, and position her body for copulation. Intromission and ejaculation occur in a matter of seconds. Immediately after successful copulation, the queen will vocalize (coital cry) and may swat at the tom cat. The tom cat should have an avenue of escape; the breeding area should be roomy or should have usable vertical space. For the next several minutes the queen will roll and thrash on the ground, stretching and licking at her perineum. Most breeding pairs will copulate several times in a day although the female may not accept every breeding attempt by the male.

Cats may have partner preferences so that a queen that accepts one tom cat may not accept another. A queen may have had a previous adverse experience that makes it reluctant to accept a tom cat. Although it is possible to physically restrain a reluctant queen for a tom cat to breed, this is not without considerable risk to the handler.

One efficient breeding protocol involves allowing the tom cat and queen to copulate three times daily (at 4-hour intervals) on the second and third days of estrus. It has been shown to induce ovulation in greater than 90% of queens.18 Another successful breeding scheme allows the pair of cats to breed ad libitum for short periods during the first 3 days of estrus. However, ovulation and pregnancy rates quoted in the literature are usually derived from random-bred or colony-bred cats and may not always be achieved with pedigreed cats. Simply housing queen and tom cat together for the duration of the queen’s estrus may be more practical often results in pregnancy.

CLINICAL PROBLEMS

Even the practitioner that does not have pedigreed cat breeders as clients will be presented with some reproductive system problems in cats. Knowledge of the clinical appearance, diagnosis, and treatment options for these conditions is an essential part of feline practice.

Ovarian Remnant Syndrome

Ovarian remnant syndrome (ORS) is the presence of functional ovarian tissue with signs of estrus in a queen that has had an ovariohysterectomy (OVH) or OE. Neoplasia in ovarian remnants, such as granulosa cell tumors, is a rare cause of ORS. Signs of estrus may occur weeks to many years after OVH/OE and include lordosis, vocalizing, rolling on the ground, and receptivity to intact males.19 Age at the time of surgery and breed of cat do not appear to influence the risk of ORS, although one report did not find any cases in queens spayed before 4 months of age.19 The most common causes of ORS are failure to remove all or part of an ovary at surgery and revascularization of ovarian tissue inadvertently left or dropped in the abdomen during OVH or OE.20,21

There are various methods for confirming a diagnosis of ORS (Box 45.2). Once ORS is confirmed, the ovarian tissue should be surgically removed. Queens with ovarian remnants may be at increased risk of mammary and ovarian neoplasia. Many owners will not be tolerant of the estrus behavior. During exploratory laparotomy, a thorough search of the peritoneal cavity is necessary, starting at the most common location for remnants, the ovarian pedicles. Other common sites for ovarian remnants are the omentum and the peritoneal walls. Remnants may be unilateral or bilateral. Surgery is most rewarding if performed when the cat is in diestrus or has been induced to ovulate as the corpora lutea will be visible as yellow–orange structures against the red background of ovarian tissue. Laparoscopy has also been used successfully to find and excise ovarian tissue, although the surgeon should always be prepared to convert to laparotomy if necessary.22,23 Excised tissue should be submitted for histopathology to confirm ovarian tissue has been removed.

It should be noted that occasionally parovarian nodules located proximal to the ovary (near or within the vasculature) are identified in queens. They are typically 2 to 3 mm in diameter and white to tan in color. They may be mistaken for ectopic or accessory ovaries, which have not been documented in the cat. Histologic studies confirm that most parovarian nodules are ectopic adrenocortical tissue and are not clinically significant.24,25 The second most common histologic diagnosis for parovarian nodules is residual mesonephric structures.

An interesting case report involved an 11-year-old spayed female domestic shorthair cat evaluated for a 4-month history of weight loss, aggression, urine spraying, and behaviors suggestive of estrus.26 Diagnostic investigation included an adrenocorticotropic hormone stimulation test and adrenal hormone panel that revealed elevated androstenedione and testosterone pre- and ­post-stimulation, mildly decreased cortisol pre- and post-stimulation, and decreased resting aldosterone. On ultrasound examination, a 6-mm hypoechoic nodule was detected in the left cranial abdomen. At exploratory laparotomy, a cystic, nodular mass was found in the region of the left ovary. Histopathology confirmed an ovarian remnant with an intact CL and non-neoplastic parovarian cysts. Clinical signs resolved within 2 weeks of surgery and follow-up testing 6 weeks later revealed normal androstenedione, testosterone, and cortisol concentrations.

Mammary Hyperplasia

Approximately 80% of feline mammary masses are neoplastic, most commonly adenocarcinomas. The remaining 20% are benign and are predominately mammary hyperplasia (MH; also called fibroepithelial hyperplasia or mammary fibroadenomatous hyperplasia). Mammary hyperplasia is most commonly seen in young cycling queens but may also be seen in pregnant queens and in male or female cats treated with progestins (e.g., megestrol acetate, medroxyprogesterone acetate). There is one published case report of a male cat with MH that had no history of progestin treatment.27 Typically, most or all mammary glands are affected. The hyperplasia can be severe, leading to tissue necrosis, ulceration, and infection (Fig. 45.3). It is often mistaken for neoplasia on gross appearance. Histologically, the lesions consist of benign, unencapsulated, fibroglandular proliferation. Progesterone receptors have been commonly found in MH samples, while estrogen receptors have been found in only about 50% of cases.28 The etiology is suspected to be an exaggerated response to natural progesterone or synthetic progestins, but the disease is also rarely reported in surgically sterilized male and female cats with no history of progestin therapy. In spayed queens, ORS should also be ruled out.

The diagnosis is made by clinical signs, patient signalment, and history. Biopsy of affected tissue and histopathology will confirm the diagnosis of MH. However, surgical biopsy of markedly swollen mammary glands may create incisions that are difficult to heal due to wound tension. Treatment varies with the underlying cause. If the cat is being treated with an oral progestin, treatment should be stopped. Intact queens not intended for breeding should undergo OVH or OE, and a flank approach may be most appropriate (Fig. 45.4).

Drug therapy can be used as the sole treatment for MH, especially if the queen is intended for breeding, or as an adjunct to OVH/OE. The drug of choice is the competitive progesterone receptor antagonist aglepristone (10 to 15 mg/kg/day, SC, days 1, 2, and 7). One study monitored 14 queens with MH for 12 months following treatment with aglepristone.29 Remission of clinical signs occurred in an average of 4 weeks. cats that had been treated with long-acting medroxyprogesterone acetate required treatment for 5 weeks. Six of the queens were subsequently bred, and four delivered normal litters. Another study found that cats with MH that had received long-acting progestin therapy (e.g., medroxyprogesterone acetate) were more difficult to resolve and had a higher risk of persistent mammary growth after OVH/OE than cats that had not received progestins.30 In those cases, the authors recommend concurrent treatment with aglepristone; more than one treatment may be necessary.

Other drug choices include dopamine agonists that reduce prolactin levels, such as cabergoline (5 µg/kg, PO, once daily for 5 to 7 days) or bromocriptine (250 µg, PO, 5 to 7 days). In most countries, these drugs are not licensed in the cat. Infections should be treated with broad-spectrum antibiotics and analgesics should be used. Occasionally, MH will resolve spontaneously, but it typically takes several weeks to several months to resolve even with treatment.

Spayed or Not?

It may be difficult to determine if an adult queen with unknown history has been spayed. Traditional methods to determine reproductive status include observing for signs of estrus and examining the ventral abdomen (or flank) for a surgical scar. However, hormonal assays are now available that represent a more practical diagnostic tool.

Luteinizing hormone is released from the anterior pituitary gland in response to copulation and stimulates ovulation and luteinization of mature ovarian follicles. In intact queens, serum LH is maintained at basal levels through negative feedback provided by ovarian estradiol secretion. Following OVH/OE, negative feedback is lost, and serum LH levels are persistently elevated.31 Patient-side and referral laboratory assays for LH are available. A single negative test is highly likely to indicate a sexually intact queen. A single positive test suggests a spayed queen, although false positives may occur if an episodic LH surge is sampled, or the queen is in estrus. One study evaluated a point-of-care LH assay in female cats that were intact and surgically sterilized.32 Test sensitivity was 90.8%, specificity was 92.3%, and accuracy was 91.7%. Ten intact queens were unexpectedly positive for LH; two of these cats were in estrus. The authors recommend repeat testing in 24 hours for cats with signs of estrus and positive results. In another study, LH tests were performed on 236 female cats presented for OVH in adoption centers in the United Kingdom.33 In this group of cats, sensitivity was 69%, specificity was 100%, positive predictive value was 1.0, and negative predictive value was 0.77. The authors suggest the use of LH assays in shelters may provide a lower risk, faster, and less traumatic alternative to OVH/OE which may decrease costs and facilitate more rapid adoption.

Anti-Müllerian hormone (AMH; also known as Müllerian inhibitory substance) can also be used to determine reproductive status. This hormone is produced by the fetal testes and inhibits Müllerian (paramesonephric) duct development in males. After birth, AMH is produced by granulosa cells in ovaries and by Sertoli cells in testes. Studies have shown that a negative or below reference range value for AMH in serum is highly likely to indicate the cat has undergone OVH or OE.34,35

Congenital Anomalies

Congenital anomalies of the female reproductive tract in cats are not common and are poorly described in the literature. Segmental uterine aplasia is the anomaly most often reported. In this condition, portions of the tubular genital tract (uterus, cervix, vagina) are poorly developed or absent. There are a variety of aplasia/hypoplasia abnormalities that likely depend on the timing of the disruption in development. Disruptions early in development may lead to abnormalities that start in the proximal part of the tract and halt normal development of the remainder. Disruption later in development is likely to affect a smaller portion of the tract. In one case report, multiple reproductive tract abnormalities were documented in an 8-year-old queen presented for routine OVH.36 The cat had bilaterally hypoplastic uterine horns that were mildly distended with fluid and aplasia of the cervix and vagina that resulted in a blind dilation of the cranial vagina that had formed a cystic structure. The urethra and ureters were normal.

Segmental aplasia or hypoplasia of a uterine horn (also called uterus unicornis) is encountered occasionally and can present difficulties for veterinarians when found incidentally during OVH/OE. In a report on uterine abnormalities in cats and dogs presented for OVH, 49 of 53,258 cats (0.09%) had a suspected congenital uterine abnormality compared with 15 of 32,660 (0.05%) of female dogs.37 The most common types in cats were unicornuate uterus and segmental agenesis or hypoplasia of one uterine horn. In affected cats, ipsilateral renal agenesis was common. Other studies have documented cases where one uterine horn is missing or reduced to a thread-like remnant, and the ipsilateral kidney is absent.3841 However, both ovaries are typically present, and the surgeon must ensure the ipsilateral ovary is found and removed during OVH/OE (Fig. 45.5). Failure to remove the ipsilateral ovary is likely to result in ORS. When one normal uterine horn and ovary are present, the queen may have normal estrous cycles and may even become pregnant.38 However, segmental aplasia may also cause failure to conceive associated with fluid accumulation in the uterine lumen, depending on the location of the occlusion.3941 Segmental uterine aplasia/hypoplasia with ipsilateral renal agenesis may be more common in the Ragdoll breed than other cats.42,43 In an ultrasound study designed to assess the prevalence of renal abnormalities in Ragdoll cats in Belgium, 2 of 244 (0.8%) had only one visible kidney.44

The urogenital tract arises from interactions between two cell populations in the developing embryo. The urinary tract and tubular uterine structures develop from cells in the intermediate mesoderm and the ovaries develop from the gonadal ridge. This common ancestry explains why renal and uterine abnormalities often occur together while the ovaries are not affected. In humans, a similar condition called Mayer–Rokitansky–Küster–Hauser syndrome type 2 is inherited as an autosomal dominant mutation with incomplete penetrance and variable expressivity.45 To date, inheritance patterns or specific mutations have not been identified in cats.

NORMAL GESTATION AND PARTURITION

Occasionally, practitioners may be called upon to evaluate a pregnant queen or a queen during parturition. Although many pedigreed cat breeders are knowledgeable about these aspects of feline reproduction, the general public often is not. Accurate evaluation of these patients depends on understanding the normal processes of gestation and parturition.

Pregnancy Diagnosis

There are several methods to diagnose pregnancy in queens (Box 45.3). The failure of a queen to come back into estrus after breeding is one of the most obvious signs of pregnancy, but pseudopregnancy will produce the same effect. However, queens experiencing a pseudopregnancy will return to estrus in about 40 to 50 days. One of the first physical indications of pregnancy is “pinking” of the nipples, which occurs around day 15 to 18 after ovulation. This change in the nipples, which become noticeably pinker and easier to see as the hair around them recedes somewhat and the nipples increase in size, is most obvious in maiden queens. With experience, it can be recognized in queens that have had several litters.

The developing fetuses can be palpated in the abdomen as early as 14 to 15 days, but more easily at about 21 to 25 days after breeding. They remain distinctly palpable up to about 35 days, when the fetuses and placentas become large enough that they cannot easily be distinguished individually. Toward the end of pregnancy, the heads of fetuses may be easy to palpate.

Radiography may be used to detect pregnancy once fetal bones begin to mineralize (Table 45.2). Until this time, only uterine enlargement may be detected, which could be consistent with pregnancy or uterine disease (e.g., pyometra). Radiography is useful for determining the number of fetuses by counting the number of skulls present, but this can only be done in late pregnancy (Fig. 45.6).

Table 45.2

Number of days Prior to Parturition for First Radiographic Detection of Fetal Skeletal Mineralization of Various Bones and Teeth in 17 Pregnant cats.
First day of Visible Mineralization
Structure Mean ± SD Range
General mineralization 26 ± 1 25–29
Vertebral column 24 ± 1 22–27
Skull 22 ± 1 21–27
Ribs 22 ± 2 20–25
Scapula 20 ± 2 17–24
Humerus 20 ± 1 20–24
Femur 21 ± 1 19–23
Radius 19 ± 2 15–22
Tibia 19 ± 1 15–21
Ulna 17 ± 2 5–21
Pelvis 19 ± 1 8–20
Fibula 13 ± 3 0–17
Tail 15 ± 2 8–16
Metacarpals and metatarsals 8 ± 3 3–14
Phalanges 6 ± 3 0–11
Calcaneus 6 ± 3 0–10
Teeth 2 ± 1 1–6

SD, Standard deviation.

Reprinted with permission from Haney D, Levy J, Newell S, et al. Use of fetal skeletal mineralization for prediction of parturition date in cats. J Am Vet Med Assoc. 2003;223(11):1614-1616.

Ultrasonography can detect pregnancy earlier than radiography. The gestational sac, a spherical anechoic structure slightly compressed at the pole, can be detected at 11 to 14 days and the embryo at 15 to 17 days post breeding. From day 30, it is possible to identify fetal organs. Details on the time of ultrasound appearance of various fetal and extra-fetal structures in the cat have been published (Table 45.3).46,47

Table 45.3

Time of Ultrasound Appearance of Selected Fetal and Extra-Fetal Structures in the First 30 days of Pregnancy.
Structure Details Days after Mating
Gestational sac Spherical shape 10–11
Lemon shape 19–21
Embryo position On the wall of the gestational sac 13–16
In the center of the gestational sac 19–21
Fetus Heartbeat 16–18
Definitive form 24–27
Hyperechoic long bones, thoracic limbs, head 30–33
Fetal movements 30–34

Adapted from: Zambelli D, Caneppele B, Bassi S, et al. Ultrasound aspects of fetal and extrafetal structures in pregnant cats. J Feline Med Surg. 2002;4(2):95-106.

A benefit of ultrasonography is the ability to determine fetal viability by detecting a beating heart (as early as 16 days) and fetal movement (as early as 32 days). Unlike the dog, fetal heart rate remains stable during gestation in the cat. Fetal sex determination is possible at about days 38 to 43 post breeding.48 However, ultrasonography may not be as good as radiography for determining the number of fetuses. Ultrasonography views each fetus individually, and movement of the queen or the uterus makes identification of individual fetuses confusing.

Many sonographers prefer to shave the hair coat to improve image quality. If the hair coat is not shaved, alcohol or another wetting agent can be used in addition to the acoustic coupling gel to decrease the amount of air between the transducer and the skin. The queen ideally should have a full bladder at the time of examination to move the bowel out of the way and move the uterine body out of the pelvic canal so that it is more readily imaged. It also helps to fast the queen for 12 hours before the ultrasound examination so that intestinal gas is less likely to obscure views, especially in early pregnancy.

Traditionally, there has been no blood test available in the cat to detect pregnancy. cats do not produce a placental hormone similar to human chorionic gonadotropin (hCG), which is the basis for some human pregnancy tests. However, the hormone relaxin is produced primarily by the placenta and is therefore a useful marker for pregnancy. Relaxin levels increase in pregnancy but not in pseudopregnancy. Test kits (e.g., Witness Relaxin, Zoetis) are available in some countries for pregnancy detection in cats and dogs. In a study designed to evaluate the Witness Relaxin test, pregnant, nonpregnant, and ovariohysterectomized queens were tested.49 The test was able to detect pregnancy as early day 20. From day 29 of pregnancy, test sensitivity was 100% and specificity was 96%. Three queens had false positive tests; two of these queens had large ovarian cysts, which suggests another source of relaxin.

Estimating Gestational Age and Fetal Sex

The mean length of pregnancy in the queen is 65 to 67 days, but it can be variable. It is influenced by breed (the longest gestations are in the Siamese and Oriental breeds) and litter size (larger litters are associated with shorter gestations).1,4,5,50 Pregnancy length can also be influenced by the queen’s body weight (positive correlation) and age (negative correlation).51 Normal pregnancies lasting <60 days or >70 days are uncommon and may be associated with high neonatal mortality. During their breeding life, most queens will establish a predictable pattern for length of gestation. If the breeding date is unknown, it may be helpful to have an alternate method of estimating gestational age in some circumstances, such as preparing for parturition, scheduling a cesarean section (CS), and managing kittens at risk for neonatal isoerythrolysis. Two useful methods are assessment of maternal serum progesterone and imaging.

As mentioned earlier, maternal progesterone levels decrease near the end of gestation. In one study, levels declined from 4 to 5 ng/mL in late gestation to 2.99 ± 1.29 ng/mL 1 day before parturition and were about 2.2 ng/mL on the day of parturition.10 In another study, progesterone declined to 3.18 ± 1.68 ng/mL on the day of parturition.52

Guidelines for estimating gestation age using radiography to detect fetal skeletal mineralization have been developed for cats. There is a predictable sequence of bone mineralization in the feline, similar to that in the canine, but beginning about 1 week earlier. Prediction of the date of parturition within 3 days was possible for 75% of 32 cats (and within 7 days in all cats) using a schedule for bone mineralization developed in one study (Table 45.2).53 However, not all bones are reliable for prediction of parturition. Mineralization of the humerus and femur occurs over the narrowest range, while the ulna, fibula, and pelvic bones have more variable mineralization times. The fibula, calcaneus, and phalanges may not become visibly mineralized before parturition.

Prediction of gestational age and date of parturition can also be estimated using ultrasound measurements of the gestational sac (up to day 25) and the fetus (e.g., biparietal diameter, body diameter, crown–rump length), and by evaluating fetal organ development (Table 45.3). Use of a 7.5 to 12.5 mHz probe is recommended for this purpose. Crown–rump length is a simple assessment that can be used after day 38 but is difficult to perform near term when the fetuses are in a flexed position (Table 45.4). Formulas have been developed based on measurement of fetal structures (Fig. 45.7, Box 45.4).10,46,52,54 In one study, the date of parturition was estimated ±2 days about 75% of the time.54 A detailed review of gestational aging and prediction of parturition date in the bitch and queen has been published and should be consulted for more information.55 Most of the research on parturition prediction using ultrasound has been performed with non-pedigreed cats. In a study of 23 pregnant Maine Coons aged 1 to 6 years and weighing 4.5 to 7.6 kg (9.9 to 16.7 pounds), serial ultrasound examinations with fetal measurements were performed and a breed-specific formula for predicting parturition date was developed.56

Table 45.4

Use of Crown-Rump Length to Estimate Gestational Age.
Crown-Rump Length (mm) Days from Conception
58 38
75 41
84 44
94 47
106 50
114 53
121 56
130 58
136 60
145 65 (full term)

Adapted from: Lopate C. Gestational aging and determination of parturition date in the bitch and queen using ultrasonography and radiography. Vet Clin North Am Small Anim Pract. 2018;48(4):617-638.

With all methods, accuracy can decrease near parturition. In addition, the aforementioned factors influencing gestation length are difficult to incorporate into assessments. One study suggested that in the last 5 days of gestation, combining fetal head measurement by ultrasound with maternal serum progesterone level is the best approach.52

Fetal sex can be evaluated with ultrasound between days 38 and 43 using a midsagittal view under the tail base.55 In the male, the bulge of the scrotum dorsally and the prepuce ventrally will be seen. In the female, a single triangular bulge representing the vulva is seen distant to the tail base.

Care of the Pregnant Queen

The nutritional requirements for reproducing queens are different from adult maintenance needs. Lactation is the most demanding phase of reproduction so queens should be in good body condition to meet the demands of nursing kittens. Unlike most species, the queen gains weight linearly from conception to parturition.57 Energy intake also increases linearly. Mean weight gain for queens during pregnancy is approximately 40% of prebreeding weight.57 At parturition, only 40% of the weight gained during pregnancy is lost; the remaining weight is consumed by the demands of lactation.57 High-quality diets designed for growth or reproduction are appropriate for the pregnant queen and obesity should be avoided.

During pregnancy, the queen should not be exposed to new cats or to sick cats. There is no need to restrict activity, although most queens become less active and eat smaller meals more frequently during the last trimester because of rapid abdominal enlargement. “Morning sickness” has not been documented in the queen, nor have diet cravings. During the last 2 weeks of gestation, the queen should be isolated from other cats and provided with a safe, quiet maternity area. Stress should be avoided because it may have detrimental effects on parturition and on maternal behavior. A birthing box should be provided that is lined with absorbent material that can be laundered (e.g., towels or blankets) or that is disposable (e.g., disposable diapers or pads). Some queens will change birthing sites as do feral queens, especially if they have access to the entire home or cattery.

The decision to use medications in a pregnant or lactating cat must be carefully considered, weighing potential benefits against risks. Most medications have not been tested in pregnant or lactating queens so information may be scant about the safety of a given drug. More information is available in Chapter 4: Guidelines and Precautions for Drug Therapy in cats.

Normal Parturition

About 1 week before delivery, most queens will exhibit nesting behavior and will spend time in the birthing box that has been provided or a site of their own choosing. Most queens wish to be secluded during parturition, but a few will want to be near a familiar caregiver.

In dogs, the fetal heart rate shows a significant decrease in the 5 days before whelping, and this can be used to predict onset of parturition. However, the fetal heart rate of kittens is stable throughout gestation. Although not always reliable, rectal temperature may be used to monitor for impending parturition. The temperature can be monitored twice daily starting at about day 61. Once the temperature has dropped one full degree (usually to about 99 °F [37.5°C] or less), obvious signs of labor should appear in 12 to 24 hours. Another sign that active labor will begin within 24 to 48 hours is the presence of milk in the mammary glands, although in some queens, milk comes in up to 8 days before parturition.

The first stage of labor may pass largely unnoticed. During this stage, the cervix dilates, and the uterus starts contracting. Stage 1 labor may last for a few hours or for as long as 24 hours. Queens may be restless, exhibit overgrooming, pacing, panting, or even vomiting during this stage. Queens may not eat for up to 24 hours before active labor, although some queens eat normally through stage 1 labor. No visible contractions are seen, although there may be a clear mucoid discharge from the vagina. As the end of stage 1 labor approaches, most queens will settle in the birthing box, purr loudly, and scratch around to prepare the birthing box. The location where the queen will give birth should be warm enough for neonatal kittens (27°C to 32°C [80 °F to 90 °F]).

During stage 2 labor, the kittens are delivered, and during stage 3 labor, the placentas are delivered. Therefore, the delivery of a litter is a series of stage 2 and stage 3 labors. Strong, visible uterine contractions deliver each kitten from its uterine horn into the uterine body, and through the cervix and vagina. The queen can be seen bearing down but crying out is uncommon. Both headfirst (two-thirds of births) and hindquarters first (one-third of births) presentations are normal in the cat. Presentation of the tail and rump before the hind legs is less common and may represent a more difficult delivery.

The time from the start of active labor to the birth of the first kitten is usually less than 60 minutes. A queen that is in active labor for more than 2 hours without delivering a kitten may need veterinary attention. Once delivery begins, kittens are generally born every 30 to 60 minutes, although they may be delivered more rapidly. In one survey of research colony cats, the average delivery time for the entire litter was 16 hours (range, 4 to 42 hours).2 In a large survey of pedigreed queens, the time from delivery of the first kitten to delivery of the last kitten was less than 6 hours in the majority of cases, but it was more than 24 hours in 1.6% of queens.4 In another survey of 197 queens, the median time between kittens was 30 min (range, 2 to 343 min) and 95% were born within 100 min after birth of the preceding kitten.5

In extended deliveries, the queen may nurse the ­kittens that are already born, giving the appearance that delivery is finished. Queens may interrupt parturition if something disturbing occurs in the environment. In general, the queen in labor should be monitored but interfered with as little as possible.

Kittens are typically born within the amniotic sac, and the queen will bite through the amniotic membranes and the umbilical cord and lick the kitten to stimulate breathing. Since stage 2 and 3 labor happen concurrently, delivery of kittens is interspersed with delivery of placentas. The queen may or may not ingest the placentas; there is no evidence that it is necessary.

If kittens are born in rapid succession, the queen may not be able to clear membranes from each kitten or sever the umbilical cords promptly. This may also be a problem for inexperienced queens delivering the first litter. Occasionally, kittens may be found dead inside the amniotic sac, or several kittens may become entwined by their umbilical cords as they crawl around the birthing box (Fig. 45.8). Entrapment of an umbilical cord around a distal limb may result in significant injury. Gentle, calm intervention by the caregiver is necessary to ensure survival and prevention of injury in these situations. The amniotic membranes should be removed, and each kitten should be carefully cleaned and dried. The umbilical cord may be clamped, ligated, and transected about 1 inch from the body wall. Kittens should be kept warm and safe until the queen can attend to them.

Once delivery of the litter is complete, the queen will lie down on her side, curled around the kittens to protect and warm them, and will encourage them to nurse. Normal kittens have a strong suckle reflex and will knead the mammary gland while nursing to promote milk letdown. Kittens tend to develop a preference for a specific nipple.

Cannibalism of kittens is uncommon. Potential causes include pain (e.g., from mastitis, metritis, or postsurgical pain), stressful conditions, and overcrowding. Poor maternal behavior may account for queens that repeatedly cannibalize kittens without apparent reason. Queens may reject kittens that are unhealthy or unresponsive. Such kittens should be presented for veterinary examination. If the entire litter is rejected, the cause is more likely to be illness in the queen (e.g., mastitis, metritis, eclampsia) than in the kittens. Stressful environmental conditions may also lead some queens to reject an entire litter. A queen that is a poor mother for the first litter may well raise subsequent litters without problems if conditions improve.

Most queens begin eating within 24 hours of delivery. Fresh water should be provided ad libitum. Many queens are reluctant to leave the birthing box for more than a few minutes at a time during the first week. The caregiver should ensure the queen has easy access to a litter box as well as food and water, and the queen should be monitored for adequate nutritional intake. By the time the kittens are about 4 weeks of age, the queen spends less time with them and often stands when they attempt to nurse.

Postpartum discharge (lochia) is typically scant in the queen. Because the queen cleans the vulva frequently, it may not even be noticed. Ultrasonographically, uterine involution is virtually complete by 28 days postpartum, much earlier than in the bitch.58 The queen should be monitored for signs of abnormal vulvar or mammary discharge, fever, anorexia, or neglect of the kittens. Indications for caregivers to seek veterinary assistance in the postpartum period are found in Box 45.5. It is normal to be unable to express milk from the queen’s mammary glands provided the kittens are gaining weight.

PROBLEMS WITH PARTURITION AND THE POSTPARTUM PERIOD

Most queens deliver their kittens uneventfully, without the need of human intervention. On occasions when the practitioner is presented with an apparent dystocia, it is important to understand the characteristics of dystocia in the queen, along with causes and effective treatments.

Dystocia

Dystocia (from the Greek “dys” meaning difficult or abnormal and “tokos” meaning birth) is defined as a painful, slow, or difficult delivery. It is not always easy to differentiate normal parturition from dystocia in the queen because prolonged time between the births of kittens can be normal. Most commonly, birth of the kittens is difficult from the start in a dystocia, but it is possible for some kittens to be delivered without incident before difficulties are encountered. Indications for caregivers to seek veterinary assistance during parturition are found in Box 45.6.

Mar 30, 2025 | Posted by in GENERAL | Comments Off on Female cats: Normal Reproduction, and Reproductive Diseases and Conditions

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