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.
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.
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.
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.
Ovarian and Uterine Characteristics of Normal Cyclicity
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).
MANAGEMENT OF SEASONAL TRANSITION
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.
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.