THE BREEDING SEASON

Ruminants

Clinical Signs and Diagnosis

Approximately 70% to 80% of cows affected by CFD are anestrus, whereas 20% to 30% display frequent or intense estrus (nymphomania). Cystic ovarian disease affects 10% to 30% of dairy cows. The condition is rare in commercial beef cows because of rigid culling for reproductive failure.

The physical appearance of cows with CFD depends on the duration of the condition. No changes are apparent after a short time, but in long-standing cases relaxation of the pelvic ligaments may result in prominence of the tailhead and masculine characteristics such as a crested neck.

The diagnosis of CFD is based on an accurate history and clinical examination. A history of constant or frequent estrus, short interestrous intervals, or anestrus may suggest CFD. Examination of the ovaries by palpation per rectum reveals the presence of enlarged fluid-filled structures raised above the surface of the ovary that greatly increase total ovarian size. Ovarian cysts are larger (>25 mm) than preovulatory follicles (15 to 25 mm). Differentiation between a single large cyst and several smaller cysts on the same ovary may not be possible, nor may be recognition of the presence of partially luteinized cysts (based on peripheral progesterone concentrations) unless ultrasonography is used. Ovarian cysts appear to be dynamic structures; those that develop early in the postpartum period may regress without treatment, and a normal estrous cycle may follow, or another cystic structure may develop.

During palpation of the ovaries, several normal structures may complicate the diagnosis of CFD. Normal preovulatory follicles may approach 25 mm in diameter and have palpable characteristics similar to those of small cysts. During the follicular phase of the estrous cycle, however, the uterus responds to palpation by becoming more turgid, whereas the uterus of a cow with CFD is typically flaccid and unresponsive. In neglected cases of CFD, mucometra may develop and must be differentiated from pregnancy. During the first 5 to 7 days of the estrous cycle, the developing CL may be smooth and soft and is commonly mistaken for an ovarian cyst. More mature CLs are solid and liver-like in consistency, often feature a palpable ovulatory papilla at the apex, and are more easily differentiated from ovarian cysts. However, 10% to 20% of mature CLs may lack an ovulatory papilla, making them more easily confused with ovarian cysts. Ultrasonography is generally more accurate in identifying subtle structural differences than transrectal palpation. Salpingitis, hydrosalpinx, oophoritis, ovarian abscesses, ovarian neoplasms, and cysts of the fimbria are other causes of enlargement of the ovary and surrounding structures that must be differentiated from ovarian cysts.¹¹

Histories that may erroneously suggest CFD include apparently short interestrous intervals because of inaccurate detection of estrus.¹² Oxytocin administered to stimulate milk letdown may result in short interestrous intervals and suggest CFD. The estrous cycle may be shortened by administering 100 IU of oxytocin per day on days 2 through 6¹³ or on days 3 through 7 or 8.¹⁴ Heifers treated with 100 IU of oxytocin per day returned to estrus in an average of 12.9 days versus 20.3 days in untreated controls.

Clinical Pathology

Plasma progesterone concentrations are low in cows with follicular cysts. Partial luteinization may occur, and progesterone concentrations may increase over time but remain lower than those of cows with normal CLs. Estrogen concentrations in the plasma of cows with CFD are variable.

Treatment and Prognosis

The goal in treating CFD is to induce luteinization of the cyst and reestablish normal estrous cycles. Several methods have been recommended.

ARTIFICIAL LIGHTING

The vernal transition can be moved but not shortened beyond its physiologic length of 6 to 8 weeks by exposure of mares to artificial light. A common artificial lighting regimen is to expose the mares to 16 hours of light and 8 hours of dark by extending the photoperiod in the evening starting in late November to initiate ovulation by February (in the Northern Hemisphere). Light should be added to the end of the day, or split between the beginning and end of the day, as opposed to adding light only at the beginning of the day.⁶ An alternative regimen is to expose mares to 1 hour of artificial light 9.5 to 10.5 hours after the onset of darkness.²⁴ Use of one 200-watt incandescent bulb or two 40-watt fluorescent tubes at a height of 7 to 8 feet in a 12- by 12-ft box stall has been recommended.²⁵ Paddock lighting has been described.⁵

GONADOTROPIN-RELEASING HORMONE

Treatment with GnRH or a GnRH analogue for mares in anestrus or spring transition has been shown to induce ovulation.^26-30 Twice-daily injections of a GnRH agonist induced ovulation in a majority of mares within 2 to 3 weeks.³⁰ Mares that are in deep anestrus (January and February, Northern Hemisphere) can be expected to return to anestrus after treatment.

DOPAMINE ANTAGONISTS

Domperidone and sulpiride have been reported to stimulate follicular activity and advance the first ovulation of the year in seasonally anestrous mares.^31,32 However, the efficacy of dopamine antagonists in advancing follicular growth and ovulation in anestrous mares has recently been questioned, and it has been suggested that adjustments in light and climactic conditions may influence the efficacy of the treatment.^33,34

STEROIDS

Exogenous progestins suppress the release of LH from the anterior pituitary and may be used for estrous regulation during the vernal transition. After treatment of mares for 10 to 14 days, withdrawal of progestin may result in LH release from the pituitary and estrus beginning in 4 to 5 days, with ovulation within 10 days after cessation of treatment. Mares should be in mid to late transition and have a follicle at least 25 mm in size to respond to treatment. Progestins will not induce estrus or ovulation in anestrous mares.³⁵ The recommended dose of progesterone in oil is 150 to 300 mg daily by intramuscular injection. The synthetic progestin, altrenogest, is administered orally (PO) at 0.044 mg/kg daily. Progestins may be used in combination with extended photoperiod and gonadotropins. Products that are ineffective or unavailable include repositol progesterone, melengestrol acetate, chlormadinone acetate, proligestone, medroxyprogesterone acetate, hydroxyprogesterone acetate, and norgestomet implants.

Synchronization of the first ovulation (or any ovulation during the cyclic season) can be accomplished by the administration of a combination of progesterone in oil (150 mg/day IM) and estradiol-17β (10 mg/day IM) once daily for 10 days.³⁶ Treatment is most effective if given after mares have been under lights for 45 to 60 days. PGF_2α should be given on the last day of steroid treatment. Treated mares will ovulate within 8 to 10 days after the last treatment.

GONADOTROPINS

At a dose of 2500 to 3000 IU, hCG may induce ovulation within 48 hours when administered to a mare with a follicle larger than 35 mm in diameter³⁷ and may reduce time to first ovulaton in transitional mares, particularly when used in combination with lights and/or progesterone treatment. Ovulation response here is less predictable than that induced with hCG during the breeding season.

FOLLICULAR ASPIRATION

Ultrasound-guided transvaginal follicular aspiration of follicles <35 mm has been shown to hasten the onset of cyclicity in transitional mares.³⁸ Follicular aspiration resulted in the formation of an active CL, and subsequent treatment with PGF_2α resulted in estrous behavior and ovulation of a dominant follicle.

Cow

Failure of a cow to display, or a manager to observe, the signs of estrus contributes significantly to reproductive inefficiency. When the presenting history suggests anestrus (failure to have a normal estrous cycle), the clinician must determine if the cause is failure of the manager to detect estrus in normal cows or failure of the cow to cycle because of some abnormal process. In dairy herds approximately 90% of cows presented for examination because of a history of anestrus have evidence of normal cyclic ovarian changes, whereas only approximately 10% are affected by an abnormality that suspends the estrous cycle (i.e., only approximately 10% are in true anestrus).

Nearly 90% of well-managed dairy cows have initiated normal-length estrous cycles by 60 days after calving, but only approximately 60% are detected correctly to be in estrus by that time.⁴⁵ Rates of estrous detection by twice-daily observation range from 50% to 73% depending on the skill of the observer.

Mounting activity and estrous behavior are reduced by hot and cold ambient temperatures and during the times of milking and feeding. More mounts are observed when cows are kept on dirt than on concrete. Estrous behavior varies with the time of day and may be an inverse reflection of extraneous activity interfering with cow behavior. In one study, 43% of cows showed heat between midnight and 6 AM; 22% between 6 AM and noon; 10% between noon and 6 PM; and 25% between 6 PM and midnight.⁴⁶

Estrus in dairy cows averages 7 to 16 hours in length but ranges from 0.5 to 36 hours. Sixty-five percent of cows are in estrus for less than 16 hours, and 25% are in estrus for less than 8 hours.⁴⁷ The number of mounts per hour ranges from 2 to 8, and the total number of mounts during estrus ranges from 11 to 56. Total number of mounts per estrus increases with the number of cows simultaneously in estrus.

Clinical Signs and Diagnosis

Dairy herds in which infertility is caused by inaccurate estrous detection are usually characterized by prolonged intervals from calving to first breeding and between services; insemination intervals of 10 to 15 days and 30 to 35 days; records of examinations that confirm cyclic ovarian changes, but in which observation of estrus is not recorded; and finding more than 15% of cows presented for pregnancy examination to be nonpregnant. Insemination during the luteal phase of the estrous cycle may occur in 10% to 20% of cows and is not likely to result in conception; insemination of pregnant cows may be followed by abortion.

The diagnosis of unobserved estrus requires sequential examination of affected cows and accurate records. Other causes of anestrus are eliminated. Conditions such as CFD, pyometra, mummified fetuses, granulosa-theca cell tumors, and segmental aplasia that cause anestrus affect individual animals. Anestrus caused by undernutrition is characterized by depressed milk production and low body condition score.

Treatment and Prognosis

PGF is widely used in clinical management of unobserved estrus. Mature CLs (approximately day 6 through day 18 of the estrous cycle) are responsive to PGF-induced luteolysis. Estrus occurs an average of 3 days (range 2 to 5 days) after administration of PGF, depending on the follicular status of the ovaries at the time of injection. The endocrine events surrounding the controlled estrus are indistinguishable from those surrounding spontaneous estrus and ovulation. Treatment with PGF shortens the intervals from treatment to first breeding and from treatment to conception but has no effect on fertility. The benefits of PGF treatment are limited by inaccurate palpation of the temporary ovarian structures, injection during the wrong phase of the cycle, and failure of the manager to observe estrus in treated cows (timed AI can be used to overcome this problem).

Measurement of progesterone concentrations in milk samples taken on the day of breeding is useful in herds with a history of reduced fertility to confirm that cows being inseminated are not in the luteal phase of the estrous cycle. If more than an occasional cow presented for insemination has an elevated concentration of progesterone, the methods of estrous detection should be reviewed. Enzyme immunoassay kits for measuring concentrations of progesterone in milk and plasma of cows and other female animals have been described and are commercially available.

Various heat detection aids have been developed. Several use devices mounted on the tailhead to record that a cow has stood to be ridden. Pressure-sensitive devices that are glued to the tailhead and change color after sustained pressure by the weight of a mounting cow are commonly used. Similarly, pressure-sensitive devices glued to the tailhead can send a record of riding events directly to a computer. Chalk, cattle crayon marker, or paint applied to the tailhead are inexpensive aids that are rubbed off when the animal is mounted when she is in heat. These methods require daily maintenance and twice daily evaluation to function effectively. Detection aids that measure changes in activity (pedometers), mucous conductivity, or body temperature can be used successfully. Accuracy is enhanced when measurements are related to previous estrous activity and progesterone concentrations.⁴⁸

Prevention and Control

Because unobserved estrus is primarily a problem of management, efforts to reduce time lost from delayed breeding are directed at improving efficiency of heat detection. Accurate records are required to identify cows that have not been observed in estrus by 40 days after calving. Cows not observed in estrus by 40 days after calving should be examined, and abnormalities of the reproductive organs that cause anestrus treated as indicated. The time of estrus can be predicted by palpation of the temporary ovarian structures, or estrus can be controlled with PGF. The most significant benefit of a planned herd health program is stimulation of improvements in management that decrease the interval from calving to conception as a result of improved estrous detection.

Anestrus after insemination is frequently interpreted as a clinical sign of pregnancy. However, unobserved estrus in cows that have failed to conceive or have experienced early embryonic death (postservice anestrus) contributes significantly to increased calving intervals. Clinical management of postservice anestrus depends on diligent observation of cows 18 to 24 days after breeding and identification of nonpregnant cows as early as possible after the infertile service so they may be reinseminated with minimum delay. Nonpregnant cows may be accurately identified by ovarian palpation or ultrasonography for absence of a mature CL, by low milk or plasma progesterone at the time of the first expected postservice estrus (approximately 21 days after breeding), or by palpation of the uterus per rectum before the second expected postservice estrus (30 to 42 days after breeding).

Monosomy X (XO)

Monosomy X is also known as Turner’s syndrome., Owing to the lack of a Y chromosome and the consequent Sry, gene, but the presence of the Dax1, gene on the present X chromosome, the phenotype is female. Monosomy X is the most commonly reported chromosomal abnormality in mares.⁴⁹ Animals with this syndrome often have a history of poor performance and lack of or sporadic reproductive cyclicity. Ovaries are typically inactive, small, smooth, and firm. The uterus and cervix are usually hypoplastic. Externally the mare’s genitalia may appear normal or underdeveloped.

XXY Syndrome

The genotype for XXY syndrome is part of Klinefelter’s syndrome. Because of the presence of a Y chromosome and the consequent Sry, gene, affected individuals are phenotypically male; but probably owing to the presence of two copies of the Dax1, gene on the two X chromosomes, they generally have hypoplastic genitalia and reproductive organs. It is thought that some factor (Dax1, or some other) on the X chromosome must escape the inactivation process, which happens very early in development (around day 7 or 8 in the horse). Testicular development and spermatogenesis are inhibited, resulting in small, flaccid testes and azoospermia. The testes may be retained or descended, but they are often small and soft. The penis may be normal or smaller than usual. Affected males often show normal libido and sexual behavior. Low testosterone concentrations may be noted. Infertility always accompanies this syndrome. Reports have been made in numerous species, including the horse.^50,51

XXX

More is not better. A report of an infertile mare with the 65,XXX genotype confirms this.⁵² The mare had bilaterally small, inactive ovaries, and a hypoplastic uterus and cervix.

Mosaics

Mosaics are individuals that have at least two cell lines with different karyotypes arising from the same zygote (Fig. 43-2).

Fig. 43-2 Process of how a mosaic may occur. The haploid sperm and egg form a diploid zygote. Through the process of mitosis, diploid cells are replicated to always produce the same number of chromosomes. If, however, a chromosome pair does not separate during anaphase, called a nondisjunction event, cell lines that do not reflect a correct representation of the genome will be created and potentially propagated. If this happens with the sex chromosomes in the germ cell line, fertility of the individual or its offspring may be affected.

Phenotypes vary in accordance with the degree of mosaicism. Varying degrees of hermaphroditism and pseudohermaphroditism have been reported in many domestic species. Mosaics often have mixed gonadal dysgenesis, with an ovary and a testis, or ovotestes, owing to sex chromosome mosaic cell lines.^53,54 These are true hermaphrodites.

Chimeras

Chimeras are individuals having cell lines from two different embryonic sources. This can occur experimentally or from the natural fusion of blastocysts in utero. The possibility has been reported from a suspected double ovulation and fertilization followed by blastomere fusion in the horse (64,XX/64,XY and 63,XO/64,XY genotypes reported). Freemartinism is a common occurrence in ruminants resulting in chimeric twins.

Freemartins

Freemartinism is a phenomenon in ruminants in which an infertile female is twin to a male. The dizygotic occurrence happens when the blastodermic vesicles of the two zygotes fuse early in development (day 18 to 20 in cattle) and share embryonic tissue. The placentas fuse (day 30 to 50 in bovines), and they share blood throughout gestation. This occurs before gonadal differentiation at day 40 to 50. Both individuals are XX/XY chimeras. The Sry, gene of the male twin causes the freemartin gonads to develop at least partially toward the male testis. The degree of differentiation varies with each freemartin, and many freemartin gonads remain undifferentiated. The shared circulation allows testosterone and antimüllerian hormone (AMH; discussed later) from the male twin, and possibly from the chimeric freemartin, to affect the freemartin genitalia, and so she lacks a cervix, uterus, uterine tubules, and cranial vagina. The vulva is fairly normal. The yearling freemartin fails to exhibit estrus, the udder and teats remain small, and the freemartin externally resembles a steer (only with a vulva). Diagnosis can be made by establishing a blind end to the vagina (no cranial vagina, no cervix). Of heifers born co-twin to a male, 92% will be freemartins.⁵⁵

The male twin may develop into a fertile adult, but these individuals show a higher incidence of infertility than bulls with a 60,XY genotype. Most male twins to freemartins become steers.

Freemartinism is less common in sheep than in cattle, but it does occur. It has also been reported in goats and pigs. With increased fecundity in modern animals, we observe the phenomenon more often than was reported in the past. This is because ovine freemartinism is rare with twins or triplets but much more common with quadruplets or quintuplets. A notable difference between ovine and bovine freemartinism is the marked masculinity of the ovine freemartin. Gonads within the inguinal canal resemble normal prepubertal testes, and those within the abdomen resemble cryptorchid testes from rams of normal XY gonadal sex. Many ovine freemartins also have epididymides, vasa deferentia, vesicular glands, and even cremaster muscles.

TESTICULAR FEMINIZATION

Testicular feminization is reported in domestic species, including the horse.⁶⁰ Patients have external genitalia that are either female or ambiguous in appearance. The vagina may be blind-ending, or the uterus hypoplastic. The gonads are testicles, although they are usually abdominal or inguinal. Male behavior may be reported in horses. The problem lies in the gene for the androgen receptor, located on the X chromosome received from the dam. This X-linked recessive inheritance has been demonstrated in both humans and horses. Affected individuals are male pseudohermaphrodites; the condition has been diagnosed in multiple horse breeds. Serum testosterone is often elevated as a baseline because of loss of negative feedback, or at least in response to an hCG test.

ABNORMALLY SMALL OVARIES

The most common causes of bilaterally small ovaries in the mare are (1) seasonal anestrus, (2) immaturity, (3) advanced age, (4) use of anabolic steroids, (5) gonadal dysgenesis, (6) hypothalamopituitary dysfunction, and (7) severe malnutrition. Clinical signs and treatment of malnutrition, hypothalamopituitary dysfunction, and seasonal anestrus are discussed elsewhere in this chapter. The average age at which fillies reach puberty is 18 months, with a wide range of 10 to 24 months. Many older mares (>20 years of age) are still reproductively active, but some mares reach ovarian senescence when they grow older.^61,62 In addition, infertility in aged mares may be a result of defects inherent in ovulated oocytes that result in embryos of lowered viability.⁶³ Anabolic steroids are derivatives from androgens that have been altered to provide high anabolic activity with minimal androgenic side effects. A suppression of gonadotropin secretion has been documented when mares have been treated with these drugs.⁶⁴ Aberrations of meiosis involving the X and Y chromosomes may lead to genotype abnormalities accompanied by gonadal dysgenesis. Abnormal genotype is most commonly 63X0; but 63X/64XX, 63X/64XY, 65XXX, and 64XY sex reversed have been reported.⁶⁵

EXOGENOUS HORMONE TREATMENT

Anabolic steroid administration may affect both estrous behavior and ovarian function. The treatment of mares with low doses of anabolic steroids can cause aggressive or stallion-like behavior, whereas high doses can inhibit ovarian activity and result in failure of follicular development and ovulation.⁶⁴ Prolonged treatment of prepubertal mares with anabolic steroids results in hypertrophy of the clitoris.⁷⁰

Progestins are commonly given to cycling mares for the suppression of estrus or synchronization of ovulation. Mares may continue to ovulate during progestin administration, especially if treatment is started late in the luteal phase. A high incidence of persistent CL formation has been observed in mares that ovulate during progestin treatment.⁷¹ Administration of the potent GnRH agonist deslorelin acetate (Ovuplant, Ft. Dodge) to induce ovulation has been associated with delayed follicular development and a prolonged interovulatory interval.^72,73 Deslorelin acetate is very effective in inducing ovulation, but treatment appears to cause a temporary downregulation of follicle stimulating hormone (FSH) secretion. The low FSH concentrations have been associated with a prolonged period of decreased follicular growth. Administration of PGF_2α7 to 8 days after ovulation appears to increase the risk of delayed follicular development. It has been suggested that PGF_2αadministration “resets” the timing of the estrous cycle during a period when limited follicular activity is present.

GONADAL DYSGENESIS

Chromosomal abnormalities occur in all breeds of horses. Mares are usually small and phenotypically female. The ovaries are small, firm, smooth, and inactive. The tubular tract is thin and flaccid. Endometrial hypoplasia is a common finding. Diagnosis is confirmed by physical findings and karyotype.

EQUINE CUSHING’S DISEASE

Mares with hypertrophy, hyperplasia, or adenoma formation in the pars intermedia of the pituitary (equine Cushing’s disease [ECD]) have been reported to have abnormal estrous cycles, infertility, or both.^74,75 The mechanisms by which ECD causes reproductive abnormalities have not been determined. Potential cause(s) may be destruction of the gonadotrophs of the anterior pituitary owing to compression by the enlarged pars intermedia⁷⁶ or suppression of gonadotropin secretion owing to elevated levels of glucocorticoids or androgens produced by the adrenal cortex.⁷⁶ In support of the glucocorticoid hypothesis, administration of dexamethasone to intact mares results in reduced estrous behavior, LH concentrations, follicular growth, and incidence of ovulation.⁷⁷ In addition, administration of dexamethasone to ovariectomized mares results in suppression of pituitary LH and FSH secretion,⁷⁸ and treatment of pony mares with dexamethasone during the winter eliminates estrous behavior.⁷⁹ A majority of horses diagnosed with ECD are older, with the average age being approximately 20 years. Consequently the decrease in reproductive efficiency in mares with ECD may be partly a result of advanced age.

Clinical signs of ECD include hirsutism and abnormal hair-coat shedding patterns, polyuria, polydipsia, and hyperhidrosis.⁸⁰ Diagnostic tests for ECD include measurements of serum glucose, insulin, adrenocorticotropic hormone (ACTH) cortisol levels, dexamethasone suppression, ACTH stimulation, and thyrotropin-releasing hormone response tests.⁸¹ The measurement of single samples for basal cortisol or ACTH concentrations is of limited value in the diagnosis of ECD.

IMMATURITY AND ADVANCED AGE

No treatment is available for age-related ovarian inactivity. Because aged mares often experience a delayed seasonal onset of ovarian activity, they benefit from an artificial light regimen starting 60 to 90 days before the breeding season. GnRH has been used to stimulate follicular growth in mares with poor follicular development attributable to anestrus or transition. Several studies (reviewed by Ginther²³) have examined the effects of GnRH administered at different doses and intervals to stimulate follicular development in mares. In general, the number of mares responding to GnRH therapy increased as the size of follicle or time of year at the onset of therapy increased.

EXOGENOUS HORMONE TREATMENT

Ovarian inactivity in mares treated with anabolic steroids is reversible, and pituitary and ovarian function eventually return to normal in most mares after withdrawal of the treatment. Mares intended for breeding should not be treated with anabolic steroids.

Removal of the deslorelin implant after ovulation has been detected will decrease the incidence of prolonged interovulatory intervals.⁸²

GONADAL DYSGENESIS

Mares diagnosed with gonadal dysgenesis are sterile, and there is no treatment.

EQUINE CUSHING’S DISEASE

The medical management of ECD includes the administration of pergolide mesylate, a dopamine receptor agonist, at a dose of 0.5 to 2 mg every 24 hours in an adult horse. The serotonin antagonist cyproheptadine has also been used, but it may not be as efficacious as pergolide. The dose of cyproheptadine is 0.25 mg/kg every 24 hours, given once in the morning.

GRANULOSA-THECA CELL TUMORS

The granulosa-theca cell (GCT) tumor is the most common ovarian tumor in the mare (Fig. 43-4). It is usually slow growing, unilateral, and benign. It occurs in mares of all ages and is occasionally found in pregnant mares. The tumor arises from the steroidogenic cells of the follicle, resulting in abnormal secretion of inhibin and testosterone.

Fig. 43-4 Granulosa cell tumor removed from a mare.

Clinical Signs and Diagnosis

Ovarian enlargement is commonly bilateral. Pregnant mares may show stallion-like behavior associated with increased testosterone production from the fetus during midgestation. Pregnancy should always be considered in a mare with stallion-like behavior, elevated serum testosterone concentrations, and enlarged ovaries. Pregnancy is diagnosed by rectal palpation and ultrasonographic examination.

Cow

Spontaneous prolongation of luteal function in the presence of a normal, nongravid uterus does not occur in cows. But several conditions affecting the uterus do suspend the luteolytic mechanism, resulting in prolonged luteal function, persistently elevated progesterone concentrations, and anestrus. Common causes of prolonged luteal function in cows include pregnancy, pyometra, mummified fetus, and segmental aplasia, including uterus unicornis.

Cow

A freemartin is a phenotypic female, born co-twin to a male, that is sterile because of arrested development of the reproductive tract. The term “freemartin” is said to have originated in England, where it referred to a heifer that was not pregnant after the summer breeding season and therefore “free” for fattening and slaughter at Martinmas, a fall festival in honor of St. Martin.¹¹ Freemartinism arises as a result of anastomoses between the placental circulations of twin fetuses of opposite sexes. Sexual differentiation of the male embryo occurs earlier than that of the female; therefore the male twin may sterilize the female by transfer of HY antigen, which inhibits development of the female gonad. The ovaries of a freemartin are underdeveloped and contain seminiferous tubules. Abnormalities of the tubular genital organs vary in severity, and the structures range from cordlike bands to near-normal uterine horns. In most freemartins there is no cervix; therefore no communication exists between the uterus and vagina. The latter is a short blind pouch. Frequently, seminal vesicular glands of varying size are present.

As many as 92% of phenotypic females born co-twins to males are freemartins⁵⁵; the history suggests a diagnosis in most cases. Singleton freemartins are possible if male and female twins are conceived and the male is lost after 30 days of gestation. Palpation per rectum of breeding age freemartins reveals aplasia or hypoplasia of the tubular genital organs and hypoplastic ovaries. If animals too small for palpation per rectum are presented, examination of the vagina with a small glass speculum (or test tube) reveals that the vagina of a freemartin is short (6 to 7 cm in freemartins versus nearly double that length in normal heifers). A definitive diagnosis may be made by karyotyping the suspected individual; varying percentages of male cells are found in freemartins.¹⁰² More details on freemartinism are discussed elsewhere in this chapter.

Ewe

Although freemartinism is possible in sheep, the condition is rare, despite the high incidence of multiple births. The condition can be confirmed by determination of blood cell chimerism.

Doe

Twinning is also common in goats, but vascular anastomosis is either uncommon or occurs after the critical period for sexual differentiation. Caprine freemartins comprise approximately 6% of intersexes.⁵

Doe

Intersexes are common among Saanen, Toggenburg, and Alpine goats. The fetal testes appear to be unable to fully masculinize the duct system or external genitalia. Parts of both the mesonephric and paramesonephric ducts persist; therefore the phenotype of affected individuals may approach that of either sex. Intersexes are most frequent among polled goats, and the condition is thought to be caused by a recessive gene linked to that for polledness; however, intersexuality may rarely be seen in horned goats. Diagnosis is based on a history of abnormal sexual behavior, and identification of abnormal genital development is by physical examination. There is no satisfactory treatment, but the prevalence of the condition may be reduced by preventing mating between two polled animals.⁵ More detailed information can be found elsewhere in this chapter.

Granulosa Cell Tumor

Cow

Ovulation tags develop after ovulation, resulting from blood loss associated with rupture of the follicle.¹¹ Fine adhesions may develop between the ovarian surface and surrounding structures. Most ovulation tags resolve spontaneously and have no effect on fertility. Severe ovarian hemorrhage may follow attempts to manually enucleate the CL. Adhesions between the ovary and its bursa interfere with their normal function. Enucleation of CLs for treatment of anestrus and pyometra has been superseded by treatment with PGF products.

Cow

Inflammation of the ovary may follow traumatic manipulations, such as enucleation of CLs and attempts to drain fluid from ovarian cysts, and ascending infections from the uterus. Oophoritis may also accompany brucellosis, mycoplasmosis, and tuberculosis.

Clinical Signs and Diagnosis

The usual history associated with diseases of the uterine tubes is one of infertility. Additional history may include uterine infection or traumatic therapy such as uterine irrigation, enucleation of CLs, or administration of exogenous estrogen during CL function. Salpingitis is an uncommon clinical finding in the mare. However in one study, up to 88% of mares were found to have macroscopic lesions in the oviduct, including adhesions, fibrous bands, and parovarian cysts, which may or may not have affected fertility.¹⁰³ Accumulations of cells and debris may form intraluminal masses; however, their role in infertility has not been adequately tested.¹⁰⁴ The pathology of the oviduct has been reviewed.¹⁰⁵ Similarly, moderate lesions of uterine tube disease may escape diagnosis by physical examination in cows, but the results of abattoir studies suggest that lesions of the oviducts are not uncommon.¹¹ In cows, lesions involving adhesions among the ovary, ovarian bursa, oviduct, and surrounding tissues may be identified per rectum by inserting two or three fingers into the ovarian bursa and rolling the oviduct between the fingers and thumb. Easy identification of the oviduct by palpation per rectum is sometimes considered indicative of abnormalities. Diagnosis of diseases of the oviducts in ewes and does is impossible by physical examination. Although a history of infertility after one of the predisposing causes might suggest oviductal lesions, diagnosis is made by exploratory laparotomy, peritoneoscopy, or necropsy.

Lesions of the oviductal or perisalpingial tissues must be differentiated from other causes of abnormal enlargements such as ovarian neoplasia, parovarian cysts, cystic ovarian disease, and ovarian hematomas. Neoplasia of the oviducts in domestic animals is extremely rare.

Clinical Pathology

Several tests that determine oviductal patency of mares¹⁰⁶ and cows¹⁰⁷ have been described, but neither the starch test nor the phenolsulfonphthalein dye test is very reliable or consistently diagnostic. For suspected unilateral blockage,¹⁰⁸ each uterine horn may be catheterized individually with a Foley catheter placed at the base of the horn on different days.

Embryo Recovery

Embryo recovery after either a single ovulation or superovulation is objective evidence that one or both uterine tubes are patent and functional. Improved reproductive performance of cows may follow uterine lavage; therefore embryo recovery as a diagnostic test may have therapeutic benefits as well.¹⁰⁹

Treatment and Prognosis

Treatment of diseases of the oviducts is not likely to be successful. Appropriate treatment for concurrent uterine infections should be instituted. A period of sexual rest may be beneficial and is indicated in valuable animals. The prognosis for reproduction in cases of bilateral obstruction of the oviducts is poor. In vitro fertilization of ova harvested from affected females is a therapeutic option. Affected females can also serve as embryo recipients.

Prevention and Control

Traumatic manipulation of the ovaries, irrigation of the endometrial cavity with large volumes of fluid (over 100 mL in heifers or 150 mL in cows) or irritating chemicals, and administration of estrogenic hormones to luteal phase females should be avoided.¹⁰² Because abnormalities of the oviducts are frequently associated with uterine infections, reduction of the prevalence of uterine infections results in fewer tubal infections as well.

Retained Fetal Membranes

Camelids

The placenta is usually passed within 1 to 2 hours of parturition. Camelid placentas resemble equine placentas (diffuse, microcotyledonary, epitheliochorial), with the exception that the left horn is almost always the pregnant horn. RFMs in camelids are most commonly seen as sequelae to dystocia or other disorders of parturition.⁹ Treatment is similar to that described for the mare.

Endometritis

A failure of the uterine defense mechanisms to effectively eliminate an antigen (bacteria or spermatozoa) and inflammatory products from the uterus results in persistent endometritis, which is a major cause of reduced fertility in broodmares.¹²³ In the normal mare the uterus is well protected from external contamination by physical barriers consisting of the vulva, the vestibule, the vagina, and the cervix, and any compromise of these barriers may predispose the mare to a chronic uterine infection.¹²⁴ Breeding is another source of uterine contamination. Intrauterine deposition of semen causes an inflammatory reaction resulting from bacterial contamination of the ejaculate or from spermatozoa.¹²⁵ Approximately 15% of a normal population of thoroughbred broodmares developed persistent endometritis after breeding.¹²⁶ Natural resistance to experimentally induced bacterial contamination has been demonstrated in young mares, whereas a population of multiparous and barren mares developed persistent endometritis after bacterial contamination of the uterus.^127,128 Based on these studies, mares have been classified as either susceptible or resistant to persistent uterine infection.¹²⁷ Endometritis has severe effects on the fertility of affected mares. A persistent inflammation may interfere directly with the survival of an embryo or may cause premature luteolysis and embryonic loss because of increased PGF concentrations.¹²⁹

Several classes of immunoglobulins have been isolated from the equine uterus. Although antibody-mediated uterine defense may be important for effective elimination of bacterial contaminants from the uterus in susceptible mares, concentrations of immunoglobulins in uterine secretion are similar or even elevated compared with those of resistant mares.^130-134 Polymorphonuclear neutrophils (PMNs) are the first inflammatory cells to enter an inflamed site.¹³⁵ Chemoattractive properties of uterine fluid have been described in vitro in horses, and the uterus responds quickly to an antigen with release of PMN-chemotactic mediators, which results in a rapid migration of PMNs into the uterine lumen.¹³⁶ Complement products and leukotriene B₄ (LTB₄), PGE, and PGF may all serve as chemoattractants for PMNs in the uterus.^136-140 Studies on the role of local uterine factors in PMN function suggested that an impaired phagocytosis by uterine PMNs in susceptible mares is the result of insufficient opsonization in uterine secretion rather than a primary dysfunction of the PMNs.¹⁴¹

Mechanical aspects of the uterine defense system are currently believed to be a major contributor in uterine clearance of bacteria and inflammatory products.^142-144 Through use of intrauterine inoculations of a combination of radioactive-labeled microspheres and bacteria, impaired uterine clearance was demonstrated in susceptible but not in resistant mares.¹⁴² Studies using scintigraphic measurements of intrauterine clearance of radioactive colloids further defined a delayed physical clearance in susceptible mares.¹⁴³ Through use of electromyography (EMG) to register myometrial activity, it was observed that the impaired uterine clearance in susceptible mares was caused by reduced myometrial activity in response to the inflammation (Fig. 43-6).¹⁴⁴ The dependent position of the mare’s uterus may also interfere with effective clearance.

Fig. 43-6 Myoelectrical activity before and after uterine inoculation of Streptococcus zooepidemicus, in mares susceptible () and resistant () to persistent endometritis. Time 0 indicate time of inoculation. Susceptible mares had impaired myoelectrical activity after inoculation.

Modified from Troedsson MH, Liu IK, Ing M, et al: Multiple site electromyography recordings of uterine activity following an intrauterine bacterial challenge in mares susceptible and resistant to chronic uterine infection, J Reprod Fertil, 99:307, 1993.

Based on pathogenesis, persistent endometritis can be divided into (1) sexually transmitted diseases (STDs), (2) persistent uterine infection, (3) persistent breeding-induced endometritis, and (4) chronic degenerative endometritis (endometrosis).

SEXUALLY TRANSMITTED DISEASES

Few true STDs are known in the horse. Contagious equine metritis (CEM) is an example of a true STD.^145,146 The disease is caused by Taylorella equigenitalis, a highly contagious and pathogenic microorganism. Although the present status of a mare’s uterine defense mechanism is important for the manifestation of the disease, this bacterium is highly resistant and capable of overcoming the mare’s normal disease barriers.

PERSISTENT UTERINE INFECTION

Bacteria most commonly isolated from the uterus of the mare are beta-hemolytic streptococci (Streptococcus zooepidemicus, and Streptococcus equisimilis,), Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae., Other aerobic bacteria isolated from reproductive tracts of mares include alpha-hemolytic streptococci, Corynebacterium, species, Staphylococcus, species, Enterobacter, species, Actinobacter, species, Proteus, species. Citrobacter, species, Candida, species, and Aspergillus, species are the organisms most commonly associated with yeast or fungal endometritis. The role of viruses, mycoplasmas, ureaplasma, and anaerobic bacteria in endometritis is poorly understood. P. aeruginosa, K. pneumoniae, and possibly S. zooepidemicus, and E. coli, can be sexually transmitted in horses, but the consequences of exposure to these microorganisms are determined by the particular strain involved and active participation of all facets of the mare’s uterine defense mechanisms. In contrast to a true STD, persistent infectious endometritis is often the result of contamination of the uterus by the mare’s fecal and genital flora in combination with compromised uterine defense.^147,148

PERSISTENT BREEDING-INDUCED ENDOMETRITIS

CHRONIC DEGENERATIVE ENDOMETRITIS (ENDOMETRIOSIS)

Degenerative changes of the endometrium such as periglandular fibrosis and glandular dilation are often seen in older multiparous mares. The condition is associated with susceptibility to persistent endometritis¹⁶¹ and may result from repeated uterine inflammation. However, the condition has also been observed in older mares without any known history of endometritis, suggesting that degenerative fibrosis of the endometrium can be a process of aging rather than inflammation.¹⁶² Based on the possibility of a noninfectious cause of the disease, it was suggested that the condition should be called endometrosis, rather than degenerative endometritis.,¹⁶² It is not clear why mares with fibrotic degenerative changes to the endometrium have an impaired physical uterine clearance mechanism. Sclerotic changes in the uterine vascular bed impair blood flow to both the endometrium and the myometrium.¹⁶³

Diagnostic Approach

History compatible with endometritis includes infertility after breeding to a fertile stallion. Mares with severe endometritis may have shortened interestrous intervals and may show vaginal discharge. Physical and speculum examination may show anatomic defects of the vulva or cervix. Excessively easy passage of a vaginal speculum may indicate loss of integrity of the vestibulovaginal sphincter. Discharge from the cervix and vaginal inflammation may be apparent. Transrectal palpation and ultrasonography may reveal accumulations of luminal fluid (Fig. 43-7). Diagnostically, it may be difficult to identify susceptibility to breeding-induced endometritis before breeding. Some mares have free fluid present in the uterine lumen before breeding, but most mares are not diagnosed until after they have been bred. If susceptibility to persistent breeding-induced endometritis is suspected, the mare should be monitored closely by ultrasonography per rectum at 6 to 12 hours after breeding, if possible, and at a minimum within 24 hours after breeding. If free fluid is present in the uterine lumen, the mare should be considered to have persistent mating-induced endometritis. Clearance of charcoal particles from the uterus within 48 hours of inoculation and the use of scintigraphy to measure uterine clearance have been suggested to be useful in identification of mares that are susceptible to persistent breeding-induced endometritis.^143,164 However, these methods may not be practical under field conditions.

Fig. 43-7 Transrectal ultrasonographic image of uterine intraluminal fluid accumulation in a mare with endometritis.

MICROBIOLOGY

Quantitative aerobic bacterial culture of the uterine lumen is necessary to identify potential pathogens and for antibiotic sensitivity testing. Samples should be taken during estrus, and the swab plated immediately on a solid medium or transported in a nonnutritive medium to the laboratory. Inadvertent contamination of cultures with bacteria from the lower reproductive tract is common, so the culture instrument should be guarded until it is within the uterus.¹⁶⁵ A false-positive bacterial sample result may be obtained as the result of contamination (even when double-guarded swabs are used), and culture results should always be interpreted together with results from endometrial cytology. Culture alone is not diagnostic. False-negative swab sample results are frequently obtained even under optimal circumstances, and laboratory results should always be interpreted in light of clinical findings. Use of culture and histologic interpretation of an endometrial biopsy appears to be the most accurate method to diagnose persistent infectious endometritis.¹⁶⁶ Cultures may also be performed on endometrial biopsy samples. Culture samples for T. equigenitalis, should be taken from the endometrium, cervix, clitoral fossa, and sinuses. Samples should be placed in Amies medium with charcoal or Steward’s medium and be kept refrigerated until delivered to the laboratory.

ENDOMETRIAL CYTOLOGY

PMNs migrate into the uterine lumen in response to inflammation, so endometritis is rapidly and accurately diagnosed by examination of exfoliated endometrial cells. A sample may be taken with a guarded swab, a cytology brush, or by infusion and aspiration of a small amount of fluid. Air-dried smears are stained with new methylene blue or modified Wright-Giemsa stain. Epithelial cells may be shed singly or in rafts. Arbitrary definitions of endometritis have been established on the basis of relative numbers of PMNs. Using these criteria, more than one PMN per 10 epithelial cells is consistent with endometritis. Endometrial cytology from normal mares may contain PMNs and spermatozoa for several days after breeding. It has been suggested that eosinophils are associated with fungal endometritis and pneumovagina. Urine crystals indicate urovagina.

ENDOMETRIAL BIOPSY

Endometrial biopsy is an accurate diagnostic and prognostic tool for endometritis. The biopsy sample should be taken during the breeding season, should be of adequate size, and should be fixed in Bouin’s solution for 24 hours and then transferred to 10% formalin. Chronic endometritis is characterized by infiltration of the endometrium with mononuclear cells and deposition of layers of fibrosis around endometrial glands. Fibrosis of the endometrium is a degenerative change and is permanent. The severity of endometrial changes is inversely related to reproductive performance. A system to classify histologic changes has been described and is widely used⁵ (Table 43-5). Special stains such as periodic acid—Schiff and Gomori’s methenamine silver may be used to identify the presence of fungi in endometrial biopsies.

Table 43-5 Endometrial Biopsy Grade and Fertility Prognosis (Kenney and Doig)

TRANSRECTAL ULTRASONOGRAPHY

The presence of free intraluminal fluid before breeding strongly suggests susceptibility to persistent endometritis.¹⁶⁷ Ultrasonographic examination of the uterus is helpful to assess both the quantity and quality of accumulated fluid in the uterine lumen. Normal mares may retain fluid up to 6 to 12 hours after mating. If fluid is present at 12 hours or more after breeding, the mare should be considered to have a persistent mating-induced endometritis.¹⁶⁸ Increased echogenicity of the fluid is associated with the presence of inflammatory cells and debris.

Treatment and Prognosis

Clinical Signs and Diagnosis

Metritis is characterized by uterine accumulation of postpartum secretions, bacteria, and the products of inflammation, with discharge from the cervix and possibly the vulva. Discharge is usually fluid and red-brown and may be fetid. Systemic signs of depression accompanied by neutropenia and leukopenia are apparent with development of endotoxemia. Differential diagnoses include normal lochia and causes of profound depression in the postpartum period as a result of uterine tears and abdominal catastrophes.

Treatment and Prognosis

Treatment is directed toward removing contamination and microorganisms from the uterus while providing systemic treatment for endotoxemia. Broad-spectrum systemic antibiotics, antiinflammatory drugs, and fluid therapy are indicated. Uterine contamination may be removed by gentle intraluminal infusion of warm water or saline and siphoning off of uterine contents. Vigorous lavage should be avoided, particularly during acute systemic disease. Prognosis depends on severity of clinical signs. If metritis is diagnosed quickly and treatment is instituted, prognosis for fertility and systemic health is good. Prognosis is guarded once endotoxemia and laminitis develop.

Clinical Signs and Diagnosis

Lochia is normally expelled during the first 2 weeks after calving and may range from dark red or brown to white to clear. If uterine involution is delayed, discharge of lochia may continue until 30 days after calving. Discharge of lochia is not abnormal unless the fluid is fetid or the cow develops other abnormal clinical signs. Abnormalities of uterine involution cannot be diagnosed by palpation per rectum during the first several days after calving when both normal and abnormal uteri are out of reach and cannot be safely retracted. By 10 to 15 days after calving the entire uterus can be palpated if involution is normal. Fluid should not be palpable within the uterine lumen by 14 to 18 days after calving. Gross reduction in size and histologic repair of the endometrium are complete in dairy cows by 40 to 50 days after calving.

Postpartum metritis in cows is characterized by the presence of variable amounts of lochia within the uterine lumen that may be discerned by palpation per rectum. A vaginal discharge is usually present, but it may become obvious during palpation. Septic metritis is characterized by clinical signs of toxemia that may include fever, depression, partial or complete anorexia, and laminitis. Milk yield is depressed, and cows may be unwilling or unable to rise. Some cases may be complicated by tenesmus. Vaginitis and cervicitis may accompany metritis. Discharges associated with septic metritis vary from scanty white mucus to copious amounts of red to red-black, watery, malodorous fluid. In some cases inflammation may spread through the uterine wall and cause perimetritis and peritonitis.¹⁸¹ Septic metritis in ewes and does is characterized by fever, depression, anorexia, and tenesmus.

Endometritis in cattle is usually observed between 2 and 8 weeks after calving. Discharge can range from white pus to estrual mucus. Purulent exudate may be observed only with palpation or may be found in the cranial vagina and cervical canal on examination with a speculum. The history may indicate that the cow has failed to conceive after several services but the patient is otherwise healthy.

Culture of endometrial fluid is not usually done in individual cases of bovine uterine infection but may be indicated to determine the antibiotic susceptibility of microorganisms on a particular farm or as a part of the diagnostic plan when the incidence of postpartum metritis or endometritis increases suddenly.

Endometrial biopsies are rarely used in cows but have been recommended when complete evaluation is required of the reproductive tract of cows that do not conceive or that conceive but do not complete their pregnancies.⁵

Treatment and Prognosis

To be useful in treating uterine infections in cows, an antibiotic must be active against the primary uterine pathogens (A. pyogenes, and gram-negative anaerobes), in the presence of organic debris, and in the anaerobic environment of the postpartum bovine uterus.¹⁸² Organisms infecting the uteri of cows are usually susceptible to penicillin, but during the first month after calving, contaminating microorganisms may produce penicillinase. Therefore penicillin is not likely to be effective if given locally during the early postpartum period. By 30 days after calving, organisms that produce penicillinase are usually eliminated from the uterus, and intrauterine treatment with penicillin may be beneficial. The daily intrauterine dose of penicillin required to reach the minimum inhibitory concentration of common bacteria such as A. pyogenes, is 1 × 10⁶ IU.¹⁸² Oxytetracycline is active against many of the microorganisms that infect the bovine uterus, and its activity is only slightly reduced by organic debris and absence of oxygen. Intrauterine treatment with administration of 4 to 6 g of oxytetracycline per day has been recommended. Some preparations of oxytetracycline irritate the endometrium, cervix, and vagina. Intrauterine antibiotic treatment of dairy cows results in residues in their milk.¹⁸³ For example, oxytetracycline has been found in milk from 44¹⁸⁴ to 96¹⁸⁵ hours after intrauterine administration.

Penicillin by systemic administration is effective for treatment of some uterine infections in cows. Daily doses of penicillin required to reach the minimum inhibitory concentration of A. pyogenes, are 10,000 to 20,000 IU/kg/day. Minimum inhibitory concentration of oxytetracycline for A. pyogenes, in the uterus is usually higher than the concentration that can be achieved by systemic administration of the drug.

Treatment of septic metritis should be directed toward controlling septicemia. Large doses of broad-spectrum systemic antibiotics are indicated, along with fluids and other supportive therapy. Attempts to remove RFMs or irrigate the uterus are contraindicated during the acute phase of the disease. After the patient has recovered from acute septicemia, intrauterine therapy may be considered.

Clinical Signs and Diagnosis

The clinical signs of perimetritis are those of peritonitis and may include fever, depression, partial or complete anorexia, stasis of the gastrointestinal tract, and evidence of abdominal pain. Abdominal pain is typified by colic in mares and by grinding the teeth (odontoprisis) in cows. In cows the condition should be differentiated from traumatic reticuloperitonitis, displacements of parts of the digestive tract, abomasal ulcers, postpartum metritis, and abdominal fat necrosis. Perimetritis in mares must be differentiated from other causes of severe abdominal pain. Antemortem diagnosis of perimetritis is difficult in sheep and goats that are presented mainly with fever, depression, anorexia, and odontoprisis.

Clinical Pathology

Cases of acute perimetritis are accompanied by leukopenia, neutropenia, and a degenerative left shift. Further evidence of peritonitis is obtained when peritoneal fluid is obtained by paracentesis and examined for its cellular and microbiologic content.

Treatment and Prognosis

The cause of perimetritis should be treated if possible. Cases of severe metritis should be treated appropriately and uterine ruptures sutured if possible. Repair of uterine ruptures inaccessible by flank incisions may be facilitated by intentional prolapse of the uterus after administration of epinephrine, provided the tear is not too close to the cervix (see next section). Treatment with broad-spectrum systemic antibiotics is indicated. Lavage to remove peritoneal exudate has been recommended but is difficult to accomplish, especially in cows in which the rumen, abomasum, and greater omentum make ventral drainage almost impossible and in which fibrinous peritonitis with loculation of infection occurs rapidly. Other supportive treatments such as intravenous fluids and antiinflammatory drugs should be administered as indicated.

The prognosis depends on the severity of lesions. Fatalities can occur in spite of prompt treatment, and surviving animals may be infertile because of mechanical interference with gamete transport caused by adhesions between the genital organs and other pelvic and abdominal tissues. In general, the prognosis for fertility in affected animals is fair at best.

Prevention and Control

Perimetritis occurs sporadically in individual animals; therefore prevention depends on avoiding the causes. Immature females, especially heifers and fillies, should not be allowed at pasture with adult males, to prevent undesired mating complicated by penetration of the vagina. Traumatic obstetric, insemination, and uterine lavage procedures must be avoided. Uterine tears that occur at parturition must be sutured immediately. Postpartum metritis must be treated promptly and appropriately before it progresses to perimetritis.

Clinical Signs and Diagnosis

Endometrial cysts can be visualized by ultrasonography or by hysteroscopy. Cysts may mimic pregnancy when mares are examined per rectum by palpation or ultrasonography.¹⁹³ Sequential examination reveals that size of endometrial cysts remains static, whereas amniotic vesicles enlarge. Large, discrete, fluid-filled cysts may be identified by palpation of the uterus per rectum. Smaller cysts and lacunae may be observed in endometrial biopsy sections. Uteri affected by lymphatic lacunae are enlarged and have a thicker wall than normal.

Treatment and Prognosis

Endometrial cysts do not require treatment unless they are suspected to interfere with pregnancy. Endometrial cysts have been suggested to cause embryonic death and abortion if large or numerous. However, one study failed to find an association between the presence or number of cysts and fertility.¹⁹² Obliteration of endometrial cysts using endoscopic guided laser surgery removes the cysts permanently, but the long-term effect on fertility has not been critically evaluated. Needle aspiration, mechanical rupture of the cyst, uterine curettage, or intrauterine infusion of hypertonic saline solution have all been suggested to effectively remove endometrial cysts. However, the cysts often recur after treatment.

Treatment and Prognosis

The prolapsed uterus should be washed with clean saline and replaced manually in the standing mare as rapidly as possible. Replacement is aided by sedating the mare and administering epidural anesthesia. The uterus should be supported on a clean sheet held at the level of the pelvis. The uterus should be replaced, beginning with the uterine body and working gradually, replacing the tip of the horns last. Correct positioning of the uterus is important to prevent the prolapse from recurring. Replacement should be followed by treatment with broad-spectrum antibiotics, antiinflammatory drugs, and intravenous isotonic fluids. Treatment with oxytocin (10 to 20 IU IM) facilitates uterine involution. Prognosis is related to development of sequelae such as uterine tears, metritis, and endometrial damage.¹⁹⁴

Clinical Signs and Diagnosis

Clinical signs of uterine prolapse are obvious. The membranes may remain attached. Immediately after prolapse occurs the tissues are nearly normal, but within a few hours they become enlarged and edematous. The endometrium is usually contaminated with feces and bedding material. In some cases the prolapsed tissue may be lacerated or severely traumatized and may contain loops of intestines.

Clinical signs that may accompany uterine prolapse include straining, abdominal pain, restlessness, anorexia, and increased pulse and respiratory rates.¹⁰² Parturient paresis is common in affected dairy cows. In most patients these signs are transitory, but shock may complicate some cases.

Clinical Pathology

Uterine prolapse in cows is frequently accompanied by hypocalcemia and a significant increase in the packed cell volume.¹⁹⁵

Treatment and Prognosis

The prolapsed tissue should be protected from further damage by wrapping it in wet towels or covering it with a plastic bag. Beef cows should be restrained where they are found, to prevent trauma to the uterus or rupture of the large uterine vessels should an animal try to escape on arrival of the clinician. Treatment of hypocalcemia is usually indicated before replacement of the uterus if the cow is recumbent and semicomatose; otherwise calcium gluconate is administered after replacement. Epidural anesthesia is frequently (but not always) required.

The prolapsed tissue is washed with a mild presurgical scrub. The membranes are removed if they can be easily separated from the endometrium but are left in place if removal is difficult. Some clinicians recommend that cows stand during replacement, whereas others have found that the organ can be replaced in recumbent cows if the patient is placed on her sternum with the hind legs drawn straight out behind. The prolapse is placed between the extended limbs.¹⁹⁶ In fresh cases, replacement is relatively easy and is begun at the cervical pole of the organ; the dorsal and ventral parts are massaged alternately back into their normal position. After the ovarian pole has been replaced, the previously prolapsed horn must be straightened, and eversion of the uterus corrected. Administration of clenbuterol is reported to relax the uterus, facilitate replacement, and reduce the need for epidural anesthesia, but its use is illegal in the United States.¹⁹⁷ If the patient has been neglected, accumulated fluid must be reduced by lubricating the tissue with an emollient ointment then carefully but vigorously massaging the tissue from the ovarian pole toward the cervical pole. The hygroscopic action of sugar when applied liberally to prolapsed uteri is of limited value and vastly overrated.

Oxytocin is frequently administered to stimulate myometrial contractions after the uterus has been replaced. Metritis is a frequent sequela, and appropriate antibiotic treatment is indicated in most cases. Temporary closure of the vulva with heavy sutures after replacement is not necessary¹⁰² but is practiced by many clinicians.⁵ If replacement of the prolapsed uterus is impossible or the tissue is severely traumatized, amputation may be indicated; in this case it is important that the uterine arteries be double ligated.¹⁹⁸

The prognosis varies but is generally favorable if there has been no serious damage to the uterus.^5,196 Fatalities can occur in cases complicated by shock or by rupture of large uterine vessels. The culling rate from infertility of cows with uterine prolapse is higher than that of their herdmates, and the calving interval is prolonged in affected cows. Barring hypocalcemia, the risk of uterine prolapse at a subsequent calving is no greater than for other cows in the herd.

Prevention and Control

Because the condition is associated with hypocalcemia in cows, provision of a properly balanced ration before calving is indicated. Although uterine prolapse can occur after an apparently normal delivery, it is more commonly associated with dystocia and forced extraction; therefore prolapse should be anticipated, and the dam observed so affected patients may receive prompt treatment.