Reference Point - UF Animal Science - University of Florida

39 downloads 121 Views 3MB Size Report
Sciences, University of Florida, Gainesville, FL 32611 (Bartolome,. Thatcher); and the Department of Large Animal Clinical Sciences,. College of Veterinary ...
1101refpoint.qxp

10/13/2005

10:02 AM

Page 1409

Reference Point Strategies for the diagnosis and treatment of ovarian cysts in dairy cattle Julian A. Bartolome, MV, PhD, DACT; William W. Thatcher, PhD, DACT; Pedro Melendez, MV, PhD; Carlos A. Risco, DVM, DACT; Louis F. Archbald, DVM, PhD, DACT

C

ystic ovarian degeneration is a pathologic condition of dairy cows that results in formation of ovarian cysts secondary to anovulation of preovulatory follicles.1 The incidence of cystic ovarian degeneration is approximately 15%2-6 and ranges from 9.5% to 25%.3 The condition can occur at any time during the lactation period, but the incidence reportedly is higher between 40 and 150 days after parturition7,8 or between 31 and 60 days and between 120 and 210 days after parturition.5 Factors such as metabolic disorders, stress,9,10 uterine infection,11 and lameness12 are associated with a high incidence of cystic ovarian degeneration. In addition, a genetic predisposition may be involved.13,14 It has been reported that in cows with ovarian cysts, the positive feedback of estradiol on release of gonadotropin-releasing hormone (GnRH) is compromised.15-19 Therefore, although the pituitary gland is able to release luteinizing hormone (LH) in cows with ovarian cysts,20,21 function of the hypothalamic-pituitary-ovarian axis is altered.1 After a preovulatory follicle fails to ovulate, a transient increase in follicle-stimulating hormone (FSH) concentration stimulates a new wave of follicular development, which occurs under conditions of low progesterone concentration and high LH concentration, and this causes excessive growth of dominant follicles. These follicles produce large amounts of estradiol and inhibin, which are responsible for a delay in follicular turnover.22,23 Several reports1,24,25 have described the etiology, dynamics, and pathogenesis of ovarian cysts in dairy cattle. The present review focuses on strategies for the diagnosis and treatment of ovarian cysts that develop in lactating dairy cows after a voluntary waiting period. Diagnosis On the basis of results of palpation per rectum, ovarian cysts have been defined as follicles > 25 mm in diameter that persist in the ovaries for at least 10 days in the absence of a corpus luteum and are classified as follicular or luteal according to the degree of luteinization and progesterone secretion.26 Although cows with

From the Facultad de Ciencias Veterinarias, Universidad Nacional de La Pampa, Argentina (Bartolome); the Department of Animal Sciences, University of Florida, Gainesville, FL 32611 (Bartolome, Thatcher); and the Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610 (Melendez, Risco, Archbald). Address correspondence to Dr. Archbald. JAVMA, Vol 227, No. 9, November 1, 2005

ovarian cysts may have nymphomania and irregular estrous cycles,26 anestrus is a common clinical sign.1,7,8 It has been shown that ovarian cysts are not static structures since they may persist, luteinize, or become atretic.1 Similar to cows with normal estrous cycles, cows with ovarian cysts have ovarian follicular waves that may result in spontaneous ovulation or in the formation of another cyst.27 Follicular turnover in cows with ovarian cysts takes 1322 to 1923 days, whereas in clinically normal cows, it occurs every 8.5 days.28 Because preovulatory follicles range from 14 to 16 mm in diameter following 3 or 2 follicular waves, respectively,29 a follicle > 17 mm in diameter could be classified as a cyst.30 In addition, ovarian cysts have been defined as a single follicular structure > 20 mm in diameter or multiple follicles > 15 mm in diameter that persist for 7 days in the presence of low progesterone concentrations.31 Therefore, on the basis of information obtained concerning follicular waves and results of ovarian ultrasonography and assays of endocrine hormone concentrations in cows with ovarian cysts, we define this condition as the presence of multiple ovarian follicles approximately 18 to 20 mm in diameter, the absence of a corpus luteum, and a lack of uterine tonicity. After spontaneous or induced ovulation of a dominant follicle in a cow with ovarian cysts, a corpus luteum is formed and the cow could become pregnant, even though other cysts may remain in the ovaries. Follicular and luteal ovarian cysts must be differentiated from cystic corpora lutea, preovulatory follicles, postpartum and nutritional anestrus, cysts of the fimbria, cysts of the ovarian bursa, and granulosa cell tumors. Differentiating between follicular and luteal ovarian cysts—The sensitivity and specificity of using rectal palpation to differentiate follicular from luteal ovarian cysts are low. Ultrasonography is effective in detecting luteal cysts but has a low specificity for follicular cysts.32 The accuracy of diagnosing ovarian cysts and differentiating follicular and luteal cysts can be increased by combining per rectum palpation of the genital tract to determine that a corpus luteum is absent and the uterus lacks tone7,33; ultrasonography to confirm that a corpus luteum is absent, to determine the size of follicles that are present, and to check for luteinization32,34,35; and measurement of plasma progesterone concentration to determine the degree of luteinization.36,37 For therapeutic purposes, differentiation of follicular and luteal cysts may not be necessary Vet Med Today: Reference Point

1409

1101refpoint.qxp

10/13/2005

10:02 AM

Page 1410

because most of the recommended treatment regimens include administration of a dose of GnRH followed by administration of a dose of prostaglandin F2αα (PGF2αα) and are effective for both conditions. Differentiating between luteal cysts and cystic corpora lutea—Luteal cysts are pathologic and originate from follicles that fail to ovulate and subsequently luteinize. In contrast, cystic corpora lutea are physiologic and originate from follicles that have ovulated and formed a cavity during corpus luteum development.26 A luteal cyst can be differentiated from a cystic corpus luteum by palpation per rectum to determine whether the structure has the typical characteristics of a corpus luteum. These include detection of a line of demarcation and distortion in the shape of the ovary. These palpable characteristics are observed with a corpus luteum but not with a luteal cyst.33 Sensitivity and specificity of using palpation per rectum to detect luteinization of follicles are low; therefore, ovarian ultrasonography is also often used to detect luteal cysts.34,38,39 However, during ultrasonography, a corpus luteum can still be observed 2 days after regression, when it is already nonfunctional.40 Therefore, results of palpation per rectum and ultrasonography of the ovaries should be combined to differentiate luteal cysts from cystic corpora lutea. Differentiating between ovarian cysts and normal preovulatory follicles—Ovarian cysts and normal preovulatory follicles are differentiated on the basis of number and size but mainly on the basis of uterine tonicity.7,33 During palpation per rectum, ovarian cysts are identified as multiple follicles that are typically larger-than-normal Graafian follicles with a flaccid uterus in the absence of a corpus luteum. In contrast, cows in proestrus have an erect, turgid uterus.7,33 In cows without ovarian cysts that are in proestrus or estrus, luteal oxytocin secreted at the time of luteolysis41 contributes to the tone of the uterus, with maximal binding to oxytocin receptors in the myometrium at the time of estrus.42 In contrast, cows with ovarian cysts are typically examined after they fail to ovulate, at which time the uterus is flaccid.33,43 The number and size of ovarian follicles can be determined by means of ultrasonography. Even though uterine hyperechogenicity is common during proestrus, uterine tonicity should be determined by means of palpation per rectum. Therefore, differentiating ovarian cysts from normal preovulatory follicles involves both palpation of the uterus per rectum and ultrasonography of the ovaries. Differentiating between ovarian cysts and postpartum nutritional anestrus—The terms noncyclic, anovular, and anestrus have been used to describe anovulatory conditions in postpartum, lactating dairy cows. However, several physiologic (eg, pregnancy), pathophysiologic (eg, postpartum and nutritional anestrus and ovarian cysts), and pathologic (eg, pyometra, hydrometra, ovarian hypoplasia, and granulosa cell tumor) 1410

Vet Med Today: Reference Point

conditions result in a lack of cyclic activity, anovulation, or anestrus. Therefore, we use the term deep postpartum nutritional anestrus to describe a condition that occurs mainly during the early postpartum period under conditions of extreme negative energy balance, lack of gonadotropin support, and nearly complete suppression of follicular development.44,45 Similarly, we use the term shallow postpartum nutritional anestrus to describe an anovulatory condition that occurs during the early postpartum period and is characterized by recurring follicular waves yet insufficient basal secretion of LH and insulinlike growth factor I (IGF-I) to support full follicular development and insufficient estradiol secretion to trigger ovulation.46-48 In contrast, the term cystic ovarian degeneration is used to describe a condition that occurs at any time during lactation, usually under conditions of positive energy balance in which follicular development is pronounced but positive feedback of estradiol on GnRH release is altered.15 During postpartum resumption of ovarian cyclicity, cows may experience deep or shallow anestrus and then resume cyclicity or develop ovarian cysts (Figure 1).45,46 Depending on nutritional status and energy balance, cows may alternate between periods of normal cyclicity and shallow or deep anestrus. In addition, cows with normal cyclicity may develop ovarian cysts in response to various conditions that cause stress49 or low plasma progesterone concentrations50 because stress blocks the estradiol-induced preovulatory surge in LH concentration. Cows with ovarian cysts can return to normal cyclicity following treatment or spontaneous ovulation.1 Differentiating ovarian cysts from deep postpartum nutritional anestrus is not difficult because cows in deep anestrus have low FSH secretion and small ovaries with minimal follicular development.51 Ovarian cysts are differentiated from shallow anestrus on the basis of the number and size of the follicles, occurrence of follicular waves, body condition score (BCS), and stage of lactation. Shallow postpartum nutritional anestrus is associated

Figure 1—Dynamics of postpartum nutritional anestrus and ovarian cysts in lactating dairy cows. P4 = Progesterone. JAVMA, Vol 227, No. 9, November 1, 2005

1101refpoint.qxp

10/13/2005

10:02 AM

Page 1411

with a condition of negative energy balance and is characterized by a low BCS (< 3 on a scale from 1 to 5); low concentrations of IGF-I, LH, and estradiol47; and, typically, a single nonestrogenic follicle (≤ 18 mm in diameter) and a few small follicles (≤ 8 mm in diameter) in the ovaries. Shallow anestrus is more common in the early postpartum period, when incidence is approximately 20%,48 and less common late in lactation, when incidence is approximately 3%.52 In contrast, ovarian cysts can occur during any stage of lactation, are not necessarily associated with conditions of negative energy balance, and typically occur in cows with a BCS > 3. Cows with ovarian cysts have more pronounced follicular development because of normal FSH concentrations, higher basal concentrations of LH, and follicular waves with a longer turnover period than in cows without ovarian cysts.22,23 In summary, the diagnosis of ovarian cysts can be made on the basis of detection of multiple follicles approximately 18 to 20 mm in diameter, the absence of a corpus luteum, and a lack of uterine tonicity. These characteristics can be identified by combining results of palpation per rectum and ultrasonography.7,33,43,53,54 In addition, cows with ovarian cysts will usually have a BCS ≥ 3. Confirmation of the diagnosis 7 to 10 days later may not be necessary because the lack of palpable uterine tonicity indicates that luteolysis had occurred at least 7 days ago, the uterus is no longer under the effect of oxytocin, and the follicles have been growing in the absence of progesterone. Moreover, because ovarian cysts and ovarian follicles are dynamic structures, a delay of 7 to 10 days may yield a different stage of ovarian follicular development. During ultrasonography, cows in the follicular phase of the estrous cycle (proestrus and estrus) have high uterine tone with 1 or more large ovarian follicles. However, cows with ovarian cysts or in shallow nutritional postpartum anestrus have a flaccid uterus. Cows with ovarian cysts have pronounced follicular growth and an acceptable BCS. In contrast, cows in shallow anestrus have poor follicular development and low BCSs (Figure 2). Treatment Spontaneous recovery (ie, ovulation of a dominant follicle) has been reported in cows with experimentally induced and naturally occurring ovarian cysts,22,27,55 with the rate of spontaneous recovery seemingly higher during the early postpartum period than during the late lactation period.2,3 Even with spontaneous recovery, development of ovarian cysts, without treatment at the time of diagnosis, can extend the interval from calving to conception by 64 days and cause economic losses of $55 to $160/lactation.5 Treatment of ovarian cysts originally consisted of administration of exogenous compounds with LH activity.56 Similarly, administration of compounds that induce LH release may stimulate luteinization of the cysts and ovulation of mature follicles, resolving the cystic condition.57 Manual rupture of the cysts is not recommended because there is a risk of hemorrhage and formation of adhesions to the mesovarium, which can compromise fertility.26 Administration of human chorionic gonadotropin (3,000 units) and GnRH analogues and agonists (gonadorelin diacetate [100 µg] or JAVMA, Vol 227, No. 9, November 1, 2005

buserelin acetate [10 µg]) has been used for the treatment of ovarian cysts,58-60 but GnRH is preferred because it is a small, stable molecule and does not generate any adverse effects or immune response.58 A dose of GnRH induces LH release within 30 minutes, with concentration of LH peaking after 2 hours,61 and this causes luteinization of the cysts or ovulation of a mature follicle.57,58 The increase in progesterone concentration results in negative feedback on the hypothalamic-pituitary axis, inhibiting LH pulsatility and contributing to follicular atresia. Moreover, the GnRH-induced increase in FSH concentration causes recruitment of a follicular wave that may restore normal cyclicity.1 In 1 study,61 for instance, cyclicity resumed within 20 days in 72% of cows with ovarian cysts treated with GnRH, compared with 16% of control cows. Administration of PGF2α 9 days after GnRH treatment induced expression of estrus in 2 to 3 days.57 In cows without ovarian cysts, an interval of 7 days between doses of GnRH and PGF2α synchronizes follicular wave development and induces estrus within 2 to 3 days.62 In cows with ovarian cysts, plasma progesterone concentration is high 5 days after GnRH treatment.63 Therefore, an interval of 7 days can be used in cows with ovarian cysts to obtain high fertility after insemination at estrus.54 However, this approach requires a high estrus detection rate.53 Alternatively, timed insemination may be used to increase pregnancy rate in cows with ovarian cysts.54 Administration of exogenous progesterone has also been successfully used in the treatment of cows

Figure 2—Ultrasonograms of the ovaries and uterus of 4 cows. A—Ultrasonograms obtained during proestrus or estrus. A single dominant follicle can be seen in the left ovary (thin arrow); the uterine horn has high echogenicity (thick arrow). B—Ultrasonograms obtained during presumed shallow nutritional anestrus. Notice the poor echogenicity of the uterine horn (thick arrow); 2 follicles (14 and 8 mm in diameter) can be seen in the ovary (thin arrow). C—Ultrasonograms obtained during proestrus or estrus. High echogenicity of the uterine horns can be seen. D—Ultrasonograms of a cow with ovarian cysts. Notice that several cysts can be seen in both ovaries (arrows). Vet Med Today: Reference Point

1411

1101refpoint.qxp

10/13/2005

10:02 AM

Page 1412

ination were treated with the ovulation synchronization with follicular cysts.64 Similarly, various progesteroneprotocol with or without pretreatment with GnRH 8 releasing intravaginal devices, such as the progesdays earlier. Pregnancy rate was higher for cows that terone-releasing intravaginal device (PRID)31,65-67 and received the GnRH pretreatment than for cows that did the controlled internal drug-releasing insert (CIDR),68 not. Pretreatment with GnRH may have induced formahave been used. The CIDR is approved for use in laction of a corpus luteum or a follicular wave that pertating dairy cows in the United States, but the PRID mitted induction of a corpus luteum when the first dose and norgestomet are not approved for use or available of GnRH was given with the ovulation synchronization in the United States. protocol. A method for synchronizing ovulation (ovsynch) Finally, in a study73 in which cows with ovarian in dairy cows has also been advocated for treatment of cysts and cows in proestrus were treated with GnRH, cows with ovarian cysts. With this method, a dose of a CIDR, or both, followed by administration of PGF2α GnRH is given, followed by a dose of PGF2α 7 days 7 days later, administration of GnRH 2 days after that, later. A second dose of GnRH is given 2 days after the and artificial insemination 16 hours after administradose of PGF2α, and the cow is artificially inseminated tion of GnRH, pretreatment with GnRH significantly at a predetermined time (typically, 16 to 20 hours increased the number of cows with ovarian cysts that later), regardless of whether signs of estrus are seen. had a corpus luteum 7 days later but did not have any In a study54 of whether this ovulation synchronizaeffect on the number of cows in proestrus. Use of the tion protocol could be used to treat cows with ovarian CIDR increased pregnancy rate in cows with ovarian cysts, the pregnancy rate for cows with ovarian cysts cysts but not in cows in proestrus. Approximately 25% treated with this protocol (18/76 [24%]) was not sigof the cows with ovarian cysts had a BCS < 3, and nificantly different from the pregnancy rate for cows cows with a BCS < 3 had a lower pregnancy rate than with ovarian cysts that received a single dose of GnRH did cows with a BCS ≥ 3, despite use of the CIDR. and then a dose of PGF2α 7 days later and were artifiThus, it was assumed that cows with a BCS < 3 were cially inseminated when signs of estrus were seen. in shallow nutritional anestrus. This is in agreement Separate studies in Florida68 and Wisconsin69 also with findings of a previous study74 in which cows in found acceptable pregnancy rates following use of the early lactation with low BCSs were more likely to be ovulation synchronization protocol to treat cows with anovulatory, to have smaller follicles, and to have a ovarian cysts. lower pregnancy rate following use of the ovulation A follow-up study70 of dairy cows with ovarian synchronization protocol, compared with cows that cysts that were routinely given bovine somatotropin were cycling. Moreover, previous studies75,76 in which (bST) every 14 days evaluated whether administration plasma progesterone concentration was used to deterof a dose of bST, GnRH, or both at the time ovarian mine cyclicity during the early postpartum period (ie, cysts were identified, followed by the ovulation synday 50) reported low pregnancy rates in cows with chronization protocol 7 days later, would affect preglow BCSs subjected to the ovulation synchronization nancy rates. In that study, there was no effect of preprotocol. treatment with GnRH, but pretreatment with bST Taken together, results of these studies suggest that reduced the pregnancy rate,70 possibly because the the ovulation synchronization protocol is more effective additional dose of bST created an excess of growth horthan the estrus synchronization protocol for treating mone or IGF-1, as reported for nonlactating dairy cows with ovarian cysts, that administration of bST to cows,71,72 which reduced fertility. cows with ovarian cysts that are routinely (ie, every 14 Another study52 evaluated whether synchronization days) treated with bST reduced the pregnancy rate assoof estrus was as effective as synchronization of ovulation ciated with the ovulation synchronization protocol, that in the treatment of cows with ovarian cysts. In that study, pretreatment with GnRH 8 days prior to use of the ovucows with ovarian cysts were randomly assigned to treatlation synchronization protocol increased pregnancy ment with the ovulation synchronization protocol or rate in cows with ovarian cysts, that cows with ovarian with an estrus synchronization protocol in which GnRH was given followed, 7 days later, by PGF2α, but estradiol cypionate was given 24 hours after the dose of PGF2α and the cow was artificially inseminated 48 hours later. The pregnancy rate 45 days later for cows treated with the ovulation synchronization protocol was significantly higher than the rate for cows treated with the estrus synchronization protocol. The lower pregnancy rate in cows that received estradiol was likely attributable to the fact that positive feedback of estradiol on GnRH release is compromised in cows with ovarian cysts.15-19 Also, estradiol cypionate is no longer available for use in dairy Figure 3—Alternative protocols for synchronization of estrus and ovulation in cows cows in the United States. with ovarian cysts. PGF2α = Prostaglandin F2α. GnRH = Gonadotropin-releasing horIn a fourth study,6 cows in which ovar- mone. TAI = Timed artificial insemination. D = Day. CIDR = Controlled internal drugian cysts were detected 30 days after insem- releasing insert. RP = Rectal palpation. US = Ultrasonography. CL = Corpus luteum. 1412

Vet Med Today: Reference Point

JAVMA, Vol 227, No. 9, November 1, 2005

1101refpoint.qxp

10/13/2005

10:02 AM

Page 1413

cysts treated with GnRH at the time of diagnosis are more likely to have a corpus luteum 7 days later, that insertion of a CIDR on the day of diagnosis and removal 7 days later increased pregnancy rate in cows with ovarian cysts treated with the ovulation synchronization protocol, and that cows with ovarian cysts that had low (< 3) BCSs had low pregnancy rates when treated with the ovulation synchronization protocol, compared with cows with higher (≥ 3) BCSs. Conclusions Previous research has shown that 2 approaches could be considered in the diagnosis of cystic ovarian degeneration. First, the diagnosis could be made on the basis of detection of multiple follicles approximately 18 to 20 mm in diameter, the absence of corpora lutea, and a lack of uterine tonicity, as determined during a single clinical examination by means of per rectum palpation and ultrasonography of the genital tract. This approach could be used in clinical trials evaluating pharmacologic treatments or in clinical practice. Second, a more specific diagnosis could be made by means of detection of multiple ovarian follicles ≥ 18 to 20 mm in diameter and ovarian follicular waves during a period of 7 to 10 days in the absence of ovulation, corpora lutea, and uterine tonicity. Determining the presence of ovarian follicular waves during a 7- to 10-day period with follicles that reach ovulatory size (12 mm) could be used to retrospectively differentiate ovarian cysts from shallow nutritional anestrus in cows with low BCSs. Strategies for treatment of ovarian cysts (Figure 3) should include induction of ovarian follicular turnover and an increase in progesterone concentration, which can be achieved by use of an ovulation synchronization protocol. However, cows should be evaluated at the time of PGF2α injection to determine the presence of a corpus luteum. If a corpus luteum is present, cows can be treated with PGF2α and inseminated when estrus is detected, if the estrus detection rate is high, or be treated with a second dose of GnRH to synchronize ovulation for timed insemination. However, if a corpus luteum is not present, cows should be retreated with GnRH. Use of a CIDR may eliminate the need for evaluation of the presence of a corpus luteum at the time of PGF2α treatment. References 1. Garverick HA. Ovarian follicular cyst in dairy cows. J Dairy Sci 1997;80:995–1004. 2. Morrow DA, Roberts SJ, McEntee K, et al. Postpartum ovarian activity and uterine involution in dairy cattle. J Am Vet Med Assoc 1966;149:1596–1609. 3. Whitmore HL, Tyler WJ, Casida LE. Incidence of cystic ovaries in Holstein-Friesian cows. J Am Vet Med Assoc 1974;165:693–694. 4. Erb HN, White ME. Incidence rates of cystic follicles in Holstein cows according to 15-day and 30-day intervals. Cornell Vet 1981;71:326–331. 5. Bartlett PC, Ngategize PK, Kaneene JB, et al. Cystic follicular disease in Michigan Holstein-Friesian cattle: incidence, descriptive epidemiology and economic impact. Prev Vet Med 1986;4:15–33. 6. Bartolome JA, Sozzi A, McHale J, et al. Resynchronization of ovulation and timed insemination in lactating dairy cows. II. Assigning protocols according to stages of the estrous cycle, or presence of ovarian cysts or anestrus. Theriogenology 2005;63:1628–1642. 7. Bierschwal CJ. A clinical study of cystic conditions of the bovine ovary. J Am Vet Med Assoc 1966;149:1591–1595. JAVMA, Vol 227, No. 9, November 1, 2005

8. Romaniuk J. The incidence and treatment of ovarian cysts in cows. Bull Vet Inst Pulawy 1972;16:98–108. 9. Dobson H. Effect of transport stress on luteinizing hormone release by GnRH in dairy cows. Acta Endocrinol 1987;115:60–63. 10. Day N. The diagnosis, differentiation, and pathogenesis of cystic ovarian disease. Vet Med 1991;86:753–760. 11. Peter AT, Bosu WTK. Relationship of uterine infections and folliculogenesis in dairy cows during early puerperium. Theriogenology 1988;30:1045–1051. 12. Melendez P, Bartolome J, Archbald LF, et al. The association between lameness, ovarian cysts and fertility in lactating dairy cows. Theriogenology 2003;59:927–937. 13. Casida LE, Chapman AB. Factors affecting the incidence of cystic ovaries in a herd of Holstein cows. J Dairy Sci 1951;34:1200–1205. 14. Kirk JH, Huffman EM, Lane M. Bovine cystic ovarian disease: hereditary relationships and case study. J Am Vet Med Assoc 1982;181:474–476. 15. Dobson H, Alam MG. Preliminary investigations into the endocrine systems of subfertile cattle: location of a common lesion (rate-limiting step). J Endocrinol 1987;113:167–171. 16. Refsal KR, Jarrin-Maldonado JH, Nachreiner RF. Basal and estradiol-induced release of gonadotropins in dairy cows with naturally occurring ovarian cysts. Theriogenology 1988;30:679–693. 17. De Silva M, Reeves JJ. Hypothalamic-pituitary function in chronically cystic and regularly cycling dairy cows. Biol Reprod 1988; 38:264–269. 18. Kaneko H, Todoroki J, Noguchi J, et al. Perturbation of estradiol-feedback control of luteinizing hormone secretion by immunoneutralization induces development of follicular cysts in cattle. Biol Reprod 2002;67:1840–1845. 19. Gumen A, Wiltbank MC. An alteration in the hypothalamic action of estradiol due to lack of progesterone exposure can cause follicular cysts in cattle. Biol Reprod 2002;66:1689–1695. 20. Kittok RJ, Britt JH, Convey EM. Endocrine response after GnRH in luteal phase cows and cows with ovarian follicular cysts. J Anim Sci 1973;37:985–989. 21. Kawate N, Yamada H, Suga T, et al. Induction of luteinizing hormone surge by pulsatile administration of gonadotropin-releasing hormone analogue in cows with follicular cysts. J Vet Med Sci 1997; 59:463–466. 22. Hamilton SA, Garverick HA, Keisler DH, et al. Characterization of ovarian follicular cysts and associated endocrine profiles in dairy cows. Biol Reprod 1995;53:890–898. 23. Todoroki J, Noguchi J, Kikuchi K, et al. Plasma concentrations of inhibin A in cattle with follicular cysts: relationships with turnover of follicular waves and plasma levels of gonadotropins and steroid hormones. Domest Anim Endocrinol 2004;27:333–344. 24. Silvia WJ, Hatler TB, Nugent AM, et al. Ovarian follicular cysts in dairy cows: an abnormality in folliculogenesis. Domest Anim Endocrinol 2002;23:167–177. 25. Peter AT. An update on cystic ovarian degeneration in cattle. Reprod Domest Anim 2004;39:1–7. 26. Roberts SJ. Veterinary obstetrics and genital diseases (theriogenology). 2nd ed. Ann Arbor, Mich: Edwards Brothers Inc, 1971; 421–435. 27. Cook DL, Smith CA, Parfet JR, et al. Fate and turnover rate of ovarian follicular cysts in dairy cattle. J Reprod Fertil 1990;90: 37–46. 28. Sirois J, Fortune JE. Ovarian follicular dynamics during the estrous cycle in heifers monitored by real-time ultrasonography. Biol Reprod 1988;39:308–317. 29. Ginther OJ, Knopft L, Kastelic JP. Temporal association among ovarian events in cattle during oestrus cycle with two and three follicular waves. J Reprod Fertil 1989;87:223–230. 30. Hatler TB, Hayes SH, Laranja da Fonseca LF, et al. Relationship between endogenous progesterone and follicular dynamics in lactating dairy cows with ovarian follicular cysts. Biol Reprod 2003;69:218–223. 31. Calder MD, Salfen BE, Bao B, et al. Administration of progesterone to cows with ovarian follicular cysts results in a reduction in mean LH and LH pulse frequency and initiates ovulatory follicular growth. J Anim Sci 1999;77:3037–3042. 32. Farin PW, Youngquist RS, Parfet JR, et al. Diagnosis of luteal Vet Med Today: Reference Point

1413

1101refpoint.qxp

10/13/2005

10:02 AM

Page 1414

and follicular ovarian cysts in dairy cows by sector scan ultrasonography. Theriogenology 1990;34:633–642. 33. Zemjanis R. Diagnostic and therapeutic techniques in animal reproduction. 2nd ed. Baltimore: The Williams & Wilkins Co, 1970; 3–62. 34. Ribadu AY, Ward WR, Dobson H. Comparative evaluation of ovarian structures in cattle by palpation per rectum, ultrasonography and plasma progesterone concentration. Vet Rec 1994;135:452–457. 35. Pierson RA, Ginther OJ. Ultrasonography for detection of pregnancy and study of embryonic development in heifers. Theriogenology 1984;22:225–233. 36. Dobson H, Rankin JEF, Ward WR. Bovine cystic ovarian disease: plasma hormone concentrations and treatment. Vet Rec 1977; 101:459–461. 37. Nakao T, Sigihashi A, Saga N, et al. Use of milk progesterone enzyme immunoassay for differential diagnosis of follicular cyst, luteal cyst, and cystic corpus luteum in cows. Am J Vet Res 1983;44:888–890. 38. Farin PW, Youngquist RS, Parfet JR, et al. Diagnosis of luteal and follicular ovarian cysts by palpation per rectum and linear-array ultrasonography in dairy cows. J Am Vet Med Assoc 1992;8: 1085–1089. 39. Hanzen CH, Pieterse M, Scenczi O, et al. Relative accuracy of the identification of ovarian structures in the cow by ultrasonography and palpation per rectum. Vet J 2000;159:161–170. 40. Kastelic JP, Pierson RA, Ginther OJ. Ultrasonic morphology of corpora lutea and central luteal cavities during the estrous cycle and early pregnancy in heifers. Theriogenology 1990;34:487–498. 41. Fields MJ, Barros CM, Watkins WB, et al. Characterization of large luteal cells and their secretory granules during the estrous cycle of the cow. Biol Reprod 1992;46:535–545. 42. Soloff MS, Fields MJ. Changes in uterine oxytocin receptor concentrations throughout the estrous cycle of the cow. Biol Reprod 1989;40:283–287. 43. Archbald LF, Thatcher WW. Ovarian follicular dynamics and management of ovarian cysts. In: Van Horn HH, Wilcox CJ, eds. Large dairy herd management. Champaign, Ill: American Dairy Science Association, 1992;199–208. 44. Hanzen C. Endocrine regulation of postpartum ovarian activity in cattle: a review. Reprod Nutr Dev 1986;26:1219–1239. 45. Jolly PD, McDougall S, Fitzpatrick LA, et al. Physiological effects of undernutrition on postpartum anoestrus in cows. J Reprod Fertil Suppl 1995;49:477–492. 46. Beam SW, Butler WR. Energy balance and ovarian follicle development prior to the first ovulation postpartum in dairy cows receiving three levels of dietary fat. Biol Reprod 1997;56:133–142. 47. Beam SW, Butler WR. Energy balance metabolic hormones and early postpartum follicular development in dairy cows fed prilled lipid. J Dairy Sci 1998;81:121–131. 48. Roche JF, Mackey D, Diskin MD. Reproductive management of postpartum cows. Anim Rep Sci 2000;60–61:703–712. 49. Dobson H, Smith RF. Stress and reproduction in farm animals. J Reprod Fertil Suppl 1995;49:451–461. 50. Wiltbank MC, Gümen A, Sartori R. Physiological classification of anovulatory conditions in cattle. Theriogenology 2002;57:21–52. 51. Roche JF, Crowe MA, Boland MP. Postpartum anoestrus in dairy and beef cows. Anim Rep Sci 1992;28:371–378. 52. Bartolome JA, Silvestre FT, Kamimura S, et al. Resynchronization of ovulation and timed insemination in lactating dairy cows. I: use of the Ovsynch and Heatsynch protocols after nonpregnancy diagnosis by ultrasonography. Theriogenology 2005;63:1617–1627. 53. Archbald LF, Norman SN, Tran T, et al. Does GnRH work as well as GnRH and PGF2α in the treatment of ovarian follicular cysts? Vet Med 1991;86:1037–1040. 54. Bartolome JA, Archbald LF, Morresey P, et al. Comparison of synchronization of ovulation and induction of estrus as therapeutic strategies for bovine ovarian cysts in the dairy cow. Theriogenology 2000;53:815–825. 55. Carroll DJ, Pierson RA, Hauser ER, et al. Variability of ovarian structures and plasma progesterone profiles in dairy cows with ovarian cysts. Theriogenology 1990;34:349–370. 56. Casida LE, McShan WH, Meyer RK. Effects of an unfrac-

1414

Vet Med Today: Reference Point

tioned pituitary extract upon cystic ovaries and nymphomania cows. J Anim Sci 1944;3:273–282. 57. Kesler DJ, Garverick HA. Ovarian cysts in dairy cattle: a review. J Anim Sci 1982;55:1147–1159. 58. Bierschwal CJ, Garverick AH, Martin CE, et al. Clinical response of dairy cows with ovarian cysts to GnRH. J Anim Sci 1975; 41:1660–1665. 59. Britt JH, Harrison DS, Morrow DA. Frequency of ovarian follicular cysts, reasons for culling, and fertility in Holstein-Friesian cows given gonadotropin-releasing hormone at two weeks after parturition. Am J Vet Res 1977;38:749–751. 60. Whitmore HL, Hurtgen JP, Mather EC, et al. Clinical response of dairy cattle with ovarian cysts to single or repeated treatments of gonadotropin-releasing hormone. J Am Vet Med Assoc 1979; 174:1113–1115. 61. Cantley TC, Garverick HA, Bierschwal CJ, et al. Hormonal response of dairy cows with ovarian cysts to GnRH. J Anim Sci 1975; 41:1666–1673. 62. Thatcher WW, Macmillan KL, Hansen PJ, et al. Concepts for regulation of corpus luteum function by the conceptus and ovarian follicles to improve fertility. Theriogenology 1989;31:149–164. 63. Garverick HA, Kesler DJ, Cantley TC, et al. Hormone response of dairy cows with ovarian cysts after treatment with hCG or GnRH. Theriogenology 1976;6:413–425. 64. Johnson AD, Ulberg LC. Influence of exogenous progesterone on follicular cysts in dairy cattle. J Dairy Sci 1967;50: 758–761. 65. Douthwaite R, Dobson H. Comparison of different methods of diagnosis of cystic ovarian disease in cattle and an assessment of its treatment with a progesterone-releasing intravaginal device. Vet Rec 2000;147:355–359. 66. Nanda AS, Ward WR, Dobson H. Treatment of cystic ovarian disease in cattle—an update. Vet Bull 1989;59:537–556. 67. Zulu VC, Nakao T, Yamada K, et al. Clinical responses of ovarian cysts in dairy cows after PRID treatment. J Vet Med Sci 2003; 65:57–62. 68. Ambrose DJ, Schmitt EJ-P, Lopes FL, et al. Ovarian and endocrine responses associated with the treatment of cystic ovarian follicles in dairy cows with gonadotropin releasing hormone and prostaglandin F2α, with or without exogenous progesterone. Can Vet J 2004;45:931–937. 69. Fricke PM, Wiltbank MC. Effect of milk production on the incidence of double ovulation in dairy cows. Theriogenology 1999; 52:1133–1143. 70. Bartolome JA, Hernandez J, Sheerin P, et al. Effect of pretreatment with bovine somatotropin (bST) and/or gonadotropin releasing hormone (GnRH) on conception rate of dairy cows with ovarian cysts subjected to synchronization of ovulation and timed insemination. Theriogenology 2003;59:1991–1997. 71. Bilby TR, Guzeloglu A, Kamimura S, et al. Pregnancy and bovine somatotropin in nonlactating dairy cows: I. Ovarian, conceptus, and insulin-like growth factor system responses. J Dairy Sci 2004;87:3256–3267. 72. Guzeloglu A, Bilby TR, Meikle A, et al. Pregnancy and bovine somatotropin in nonlactating dairy cows: II. Endometrial gene expression related to maintenance of pregnancy. J Dairy Sci 2004;87:3268–3279. 73. Bartolome JA, Sozzi A, McHale J, et al. Resynchronization of ovulation and timed insemination in lactating dairy cows. III. Administration of GnRH 23 days post AI and ultrasonography for nonpregnancy diagnosis on day 30. Theriogenology 2005;63: 1643–1658. 74. Gumen A, Guenther JN, Wiltbank MC. Follicular size and response to Ovsynch versus detection of estrus in anovular and ovular lactating dairy cows. J Dairy Sci 2003;86:3184–3194. 75. Moreira F, Orlandi C, Risco CA, et al. Effects of presynchronization and bovine somatotropin on pregnancy rates to a timed artificial insemination protocol in lactating dairy cows. J Dairy Sci 2001;84:1646–1659. 76. Santos JE, Juchem SO, Cerri RL, et al. Effect of bST and reproductive management on reproductive performance of Holstein dairy cows. J Dairy Sci 2004;87:868–881.

JAVMA, Vol 227, No. 9, November 1, 2005