Irregularities of the Estrous Cycle and Ovulation in Mares (Including Seasonal Transition)

CHAPTER 18 Irregularities of the Estrous Cycle and Ovulation in Mares (Including Seasonal Transition)



Irregularities of the estrous cycle may be associated with pathology of the ovary (granulosa cell tumor, gonadal dysgenesis) or uterus (shortened luteal activity due to endometritis) or, rarely, may be due to apparent functional abnormalities of the ovarian/hypophysial axis (anovulation with hematoma formation). However, wide variations in cycle length and ovarian characteristics are associated with normal fertility. Abnormalities of endocrinology, cyclicity, and ovulation are uncommon in mares with normal reproductive tracts, and thus other causes of infertility should be ruled out before implicating abnormal cyclicity as a cause of infertility.


Apparent estrous cycle irregularities that are not associated with pathology include prolonged estrus without ovulation during the seasonal transition period, “silent heat” (apparent failure to show estrous behavior), prolonged luteal activity, and anestrus or constant estrus during pregnancy. Additionally, aging of mares is associated with changes in cyclicity.


Abnormal behavior may be related to ovarian pathology, most commonly granulosa cell tumors, in mares. Because this link is known, many other behavioral changes may be attributed to the ovaries by mare owners when in fact they have no association with reproduction. For this reason, mares with abnormal behavior may be presented for examination of the reproductive tract, and it becomes a diagnostic challenge on the part of the theriogenologist to determine the cause of the change in behavior.


Diagnosis of the cause of estrous cycle irregularities in mares is based on history, teasing records, findings on palpation and ultrasonography per rectum, and determination of hormone concentrations, when indicated.



ASSESSMENT OF THE ESTROUS CYCLE AND OVULATION



The Estrous Cycle


A complete review of mare endocrinology is given in Chapter 7. An important factor to remember when evaluating apparent cycle abnormalities is the normal variation in length of estrus. Estrus length in normal cycling mares can vary at least from 2 to 12 days. Estrus length is generally repeatable within mares, and is longer at the beginning and end of the breeding season (the peak of the breeding season being the first day of summer, June 21 in the Northern Hemisphere). In some mares, estrus becomes so short in midseason that it may be missed if teasing is only performed sporadically. Owners may report that their mare was showing good heat in April and May but that they haven’t seen her in heat in June.


Teasing is a major determinant of apparent cyclicity. Individual teasing of mares with an active stallion is the best method of heat detection. To adequately detect cyclical changes in behavior, teasing should be performed thoroughly at least three times weekly, and the mare’s behavior scored by a knowledgeable individual. “Silent heat” may occur in mares that have normal ovarian function. The meaning of this term is relative, indicating only that the observer did not recognize estrous behavior. Knowledge of the estrous and diestrous reactions of each individual mare is crucial in heat detection; one mare in heat may be less demonstrative than another mare in diestrus. Some mares may show signs of estrus immediately on contact with the stallion; others—especially young or timid mares—may require teasing for 3 to 4 minutes before they respond. A mare that shows no change in behavior at all during her cycle, as assessed by an experienced observer using good heat detection methods, may present a challenge. Such a mare may need to have the reproductive tract examined regularly by transrectal palpation and ultrasonography to detect estrus (see later discussion). However, assessing the willingness of the mare to allow mounting by a stallion may reveal that she is receptive to him, even though teasing evoked no signs of estrus. Mares that do not show good signs of estrus to a stallion may begin to show estrous behavior if they are bred by natural cover, during estrus, on a few occasions.


Estrous behavior in mares does not necessarily indicate follicular activity. Estrous behavior can be seen in mares in seasonal anestrus, in mares that have been ovariectomized, and in mares with gonadal dysgenesis. This is because sexual behavior in the mare is largely regulated by progesterone; that is, estrous behavior is suppressed by progesterone. In the absence of progesterone, even the small amount of estrogen produced by the adrenals is sufficient to cause the mare to show some signs of estrus. Further stimulation with estrogen does, however, increase the intensity of estrous behavior. This is reflected in the finding that mares in true estrus (during the follicular phase of the cycle) have fewer negative reactions to mounting or intromission than do seasonally anestrous or ovariectomized mares.1


The length of diestrus is more repeatable among mares than is the length of estrus, at 15 ± 2 days.1 When evaluating heat detection records, repeated diestrus intervals of normal length, interspersed with estrous intervals, are a good indication that corpora lutea are forming and being lysed normally. The formation of corpora lutea in turn suggests that normal follicle growth and ovulation are occurring.


Hormone analysis can also be helpful in defining the pattern of cyclicity in a mare; progesterone concentrations are of most value. Reflecting teasing records, a pattern of high progesterone (increasing to >4 ng/ml) for approximately 14 days followed by low progesterone (<1 ng/ml) for 3 or more days is strongly indicative of normal cyclicity.



Ovarian and Uterine Characteristics of Normal Cyclicity


In assessing the normality of follicle growth and ovulation, the large variation in follicle size at ovulation should be recognized. The size of the follicle the day before ovulation is detected is commonly 35 to 45 mm in diameter, but mares can ovulate much smaller follicles (less than 30 mm), or larger follicles, with normal fertility. Follicle size at ovulation is often repeatable for a given mare. Small follicle size at ovulation may be a cause of apparent infertility because, unless this tendency is known, the mare may not be bred at the appropriate time. When double ovulations occur, the follicles ovulate at a smaller size than for single ovulations. Follicle size at ovulation also decreases toward the middle of the breeding season (July and August). Numerous large follicles and corpora lutea are normally present on the ovaries of pregnant mares, especially between 30 and 120 days. These are sometimes mistaken for ovarian pathology.


Transrectal palpation and ultrasonography are indispensable tools in the evaluation of the estrous cycle. Familiarity with the normal appearance of the ovary and uterus on ultrasonographic examination throughout the cycle is a great help when assessing possible abnormalities.2 Multiple follicles may be present on the ovaries at any stage of the cycle. During estrus, the dominant preovulatory follicle is usually identifiable at approximately 25 mm diameter, when it is about 5 mm larger than other follicles on the ovary. In some mares, however, multiple follicles appear to grow to a large size (>30 mm) from which one or two ovulate; this is associated with normal fertility. On ultrasonographic examination, follicles usually are round and should be echolucent (black) in appearance. In the day or so before ovulation, infrequent small echodensities may be seen within the follicle, and the follicle may become less round, reflecting a palpable loss of tone. Immediately before ovulation, follicles may appear pointed on ultrasound examination, as they apparently protrude toward the ovulation fossa.


On the first day after ovulation, the collapsed follicle may be difficult to define ultrasonographically. The only finding may be that the follicle seen previously is gone; however, a thick echodense line or mass is usually visible within the ovary. At this time, a depression may be palpable on the ovary, and the ovary may be sensitive to palpation. The normally developing corpus luteum (CL) has two major forms on ultrasonographic examination.2 Over the first few days after ovulation, the CL may become more and more apparent as an echodense structure within the ovary; then, after about 7 days, it may become less dense and less easily delineated. Alternatively, the ovulated follicle may fill with clotted blood over 1 to 2 days. This corpus hemorrhagicum has a typical ultrasonographic appearance of a round structure with an echodense rim and an echolucent interior, crossed with a lattice of echodense fibers. The echolucent area decreases in size over the next few days as the echodense rim thickens; after 5 or more days this structure is indistinguishable from the CL that did not have an interior clot. A normal corpus hemorrhagicum is typically no larger than was the original follicle; a larger structure with similar appearance on ultrasonography may be a hematoma (see later discussion).


Uterine changes detectable on ultrasonographic examination are also helpful in staging the cycle in mares with questionable estrous behavior. The uterus in estrus becomes edematous. This is characterized on palpation as a heaviness and lack of tone, and ultrasonographically by presence of echolucent areas of fluid within the uterine folds, giving a “wagon wheel” or “orange slice” effect to the cross-sectional uterine image. In diestrus, the uterus is homogenous in appearance on ultrasonographic examination and tends to be more tightly circular in cross section, reflecting increased tone. Changes in palpable cervical tone reflect those of the uterus but may be more influenced by individual variation between mares; cyclical ultrasonographic changes in the cervix are not obvious.



PHYSIOLOGIC ESTROUS IRREGULARITY—THE TRANSITIONAL PERIOD


The mare is a seasonal, long-day breeder, and the majority of mares enter anestrus in the winter. Ten to 25% of mares may cycle through the winter, this percentage being higher in mares having good nutrition and housing. In anestrus, gonadotropin-releasing hormone (GnRH) and gonadotropin secretion is low; follicles reach a maximum diameter of 10 to 15 mm and then regress. The period between anestrus and the first ovulation of the year is termed the transitional period. During this time, pituitary gonadotropin output is sufficient to cause follicular growth, but insufficient to stimulate normal follicle maturation and ovulation. The follicles produced at this time are indistinguishable from normal follicles on palpation and ultrasonographic examination; however, they may be structurally and hormonally abnormal. For this reason, transition follicles will not ovulate in response to one-time administration of gonadotropins or GnRH analogues.


During the transitional period, mares may be presented for examination because of constant or irregular estrus, as they respond to rising and falling estrogen from waves of nonovulatory follicles. Owners may become frustrated at this time with breeding mares over periods of weeks as the mares remain in heat. When estrous behavior does subside, it may recur within days; there is no normal diestrus interval. Unless the mare is bred immediately before the first ovulation of the year, the breedings will not result in pregnancy.


On palpation and ultrasonographic examination, the ovaries have multiple small (in early transition) to large (in late transition) follicles. Extreme cases may have many (5–10) follicles greater than 30 mm in diameter on each ovary. No corpora lutea are present on the ovaries; however, corpus hemorrhagicum–like structures may be present, as these anovulatory follicles sometimes become filled with blood. The structures do not luteinize and so do not progress over time to the normal CL appearance on ultrasonography as described previously. The lack of luteal progesterone (<1 ng/ml in peripheral blood throughout this period) is reflected in poor uterine tone. Some practitioners feel that the presence of uterine edema signals the presence of a functional preovulatory follicle; however, recent studies have not supported this relationship. As gonadotropin secretion reaches functional levels, one of the follicles on the ovary will grow and ovulate; this signals the end of transition and the mare will cycle normally through the season from this point.


Irregular estrous behavior and multiple anovulatory follicles are a normal aspect of the transition period and do not represent an abnormality. Diagnosis of seasonal transition is based on the season of the year (usually February through April in the Northern Hemisphere), lack of evidence of ovulation (no diestrous periods; no corpora lutea; poor uterine tone; low progesterone on assay), and multiple small to large follicles present on both ovaries.



MANAGEMENT OF SEASONAL TRANSITION


Because of the January 1 birthdate imposed by many breed registries, foals born in a given year compete with one another. This has resulted in a demand for foals to be born early in the year. To have a foal born in January, the mare must conceive the previous February, during the period of seasonal transition. Many management methods have been developed to shorten the transitional period or move it to an earlier time of year (December to January). Currently no method is both commercially feasible on a large scale and highly predictable; however, it is likely that in the future this may be achieved using some combination of the treatments currently under investigation.


The most widely used method for management of seasonal transition is increasing perceived day length. This may be done by housing mares under artificial light (100 lux, or equivalent of a 200-watt bulb 12 ft from the ground in a 12 ft by 12 ft stall) starting approximately December 15. Mares should be exposed to 14.5 to 16 hours of light per day; there is no benefit to increasing the apparent day length slowly, and lengths of light greater than 20 hours may actually reduce effectiveness. Alternatively, it has been shown that a short (1- to 2-hour) burst of light timed to occur at 9.5 to 10.5 hours after dusk is equally effective as having light on constantly for 16 hours. Although this technique saves electricity and may allow large groups of horses to be treated, application is more difficult because the time of the light burst must be correlated with changing day length. Recent studies have shown that reduced lux and reduced treatment periods may be equally as effective as is the traditional regimen.3 Mares typically ovulate and resume normal cyclicity 6 to 10 weeks after the onset of increased day length.


Use of GnRH administration to induce cyclicity in anestrous or seasonal transition mares has been studied extensively.4 Infusion of pulses of GnRH (25 to 250 μg/hour) at hourly intervals results in ovulation in essentially all anestrous mares within 11 days. This ovulation may be fertile, but mares may not continue to cycle if not pregnant. Although native GnRH is commercially available, this application requires the attachment and use of a pump. Constant infusion of GnRH or its analogues may also be effective, but responsiveness appears to be greater when the mare has entered transition. Constant infusion of GnRH using an osmotic minipump (an implant that releases drug as it accumulates fluid osmotically), delivering 100 to 200 ng GnRH per kg body weight per hour, induced ovulation in 60 to 70% of mares within 30 days. Injection of long-acting GnRH analogues (e.g., 40 μg buserelin twice daily) induced ovulation in 50% of anestrous mares in 10 to 25 days; however, this compound is not available commercially in the United States. Use of the commercially available implant containing 2.2 mg of the GnRH analogue, deslorelin, administered every other day has been shown to induce ovulation in about 50% of transitional mares. However, recent reports that deslorelin implants suppress pituitary responsiveness to native GnRH after administration suggest that repeated use of the implant may not be advisable. Indeed, when deslorelin was used to induce cyclicity, ovarian suppression was noted in the treated mares that did not ovulate.


Injection of equine pituitary extract (once daily for 14–20 days; dosage is dependent on strength of the preparation) is effective for induction of follicular growth and ovulation in anestrous mares, but this compound is not currently commercially available.


Progesterone and its analogues (e.g., altrenogest) have been used in an attempt to induce early cyclicity with the thought of suppressing luteinizing hormone (LH) release from the pituitary and then having a “rebound” when the progesterone is withdrawn. Progestins are effective in suppressing estrous behavior in transition mares and for this reason may be used simply to reduce the client’s concern about whether to breed the mare. The progestin is typically given for 10 to 15 days. Mares return to estrus approximately 3 days after the progestin is withdrawn, because the suppressive action of progesterone on estrous behavior is lost. Administration of progestin is not effective in hastening ovulation if given to mares in anestrus or early transition. In late transition, the first ovulation of the year in mares treated with progestin (e.g., 0.44 mg/kg altrenogest for 12 days) may be hastened by about 10 days.


Other methods for inducing cyclicity during seasonal transition are currently under study. Dopamine antagonists, such as sulpiride (0.5 mg/kg, IM) or domperidone (1.1 ng/kg PO) daily for 10 to 60 days have been shown to induce cyclic activity in seasonally anestrous and transition mares.3 However, a repeatable method for use of these compounds has not yet been developed, and the response seems to depend on mare, environmental conditions, and stage of transition at the time of treatment. The variability in effect may be due to the mechanism of action of dopamine antagonists in the mare. In contrast to its action in ewes, dopamine antagonists do not appear to directly increase gonadotropin secretion in mares. Dopamine antagonists may work via increasing prolactin concentrations, which sensitize the ovary to circulating gonadotropins;3 therefore, there must be some native gonadotropin activity for ovarian response to occur.

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Sep 3, 2016 | Posted by in SUGERY, ORTHOPEDICS & ANESTHESIA | Comments Off on Irregularities of the Estrous Cycle and Ovulation in Mares (Including Seasonal Transition)

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