The objective of this study was to test the efficacy and safety of a short-term progestin treatment administered at two different times to prevent estrous induction in response to the administration of an implant releasing the GnRH agonist, deslorelin acetate (DA), in anestrous bitches. Interestrous intervals (IEI) observed prior to and post DA were compared. Forty-two anestrous bitches, with previous IEI history, were randomly allocated to one of the following treatments: PL: placebo sc (n = 12); MA: megestrol acetate 2mg/kg po for 8 days (n = 4); DA: 10mg sc (n = 8); MA&DA-1: MA beginning the day before DA (n = 8); and MA&DA-4: MA beginning 4 days before DA (n = 10). The dose of MA was identical for each treatment. All bitches were examined daily for 1 month and then every 3 months until the next spontaneous post-treatment estrous cycle. Post-GnRH estrous response occurred in 0, 0, 100, 50, and 10% of the PL, MA, DA, MA&DA-1, MA&DA-4, groups, respectively (<0.01). There was an interaction between the treatment and period for the duration of the IEI (< 0.01). Changes in IEI were different among treatments (p<0.01); the three DA-treated groups (147.5% +/- 10.3, 161.3% +/- 14.1, 148.6% +/- 19.2) differed from both the MA (12.9% +/- 17.6) and PL (8.1% +/- 7.8), but not among themselves. It is concluded that an 8 days megestrol protocol and DA on Day 4 was better than DA on Day 1 to prevent estrous response in anestrous bitches and that both protocols significantly increased the IEI.

In the present study, we tested the effect of treatment with a slow-release implant containing the gonadotrophin-releasing hormone agonist Deslorelin(TM) (Peptech Animal Health Australia, North Ryde, NSW, Australia) on pituitary and testicular function in mature male dogs. Four dogs were treated with Deslorelin (6-mg implant) and four were used as controls (blank implant). In control dogs, there were no significant changes over the 12 months of the study in plasma concentrations of luteinising hormone (LH) or testosterone, or in testicular volume, semen output or semen quality. In Deslorelin-treated dogs, plasma concentrations of LH and testosterone were undetectable after 21 and 27 days, testicular volume fell to 35% of pretreatment values after 14 weeks and no ejaculates could be obtained after 6 weeks. Concentrations returned to the detectable range for testosterone after 44 weeks and for LH after 51 weeks and both were within the normal range after 52 weeks. Semen characteristics had recovered completely by 60 weeks after implantation. At this time, the testes and prostate glands were similar histologically to those of control dogs. We conclude that a single slow-release implant containing 6 mg Deslorelin has potential as a long-term, reversible antifertility agent for male dogs.

After removal of the ovaries approximately 20% of dogs develop urinary incontinence. Removal of the gonads results in estrogen deficiency and chronic elevation in the production and secretion of FSH and LH. The gonadotrophins may directly or indirectly, adversely affect the sphincter function of the urethra. Estrogen replacement therapy and treatment with sympathomimetics, such as ephedrine or phenylpropanolamine (PPA), are effective only in some of the affected dogs, and many of these subsequently become nonresponsive. Since the role of the elevated gonadotrophins has not been elucidated, we used depot preparations of GnRH analogues to down-regulate gonadotrophins once or twice in 13 ovariectomized (ovx), incontinent dogs, which were either refractory to alpha-adrenergics (n=11) or in which alpha-adrenergics were contraindicated (n=2). Dogs were treated with leuprolide, deslorelin, buserelin or triptorelin. In 7 dogs treatments with GnRH analogues alone (n=11) resulted in continence for 50-738 days (mean 247). In all dogs except one, where GnRH treatments did not resolve the incontinence completely, additional treatment with phenylpropanolamine was successful. With additional treatment of phenylpropanolamine complete continence was restored for 21-367 days (mean 159). All treatments caused long-term reduction of circulating FSH and LH concentrations to very low or undetectable levels. No adverse effects of treatments were observed.

Objective To evaluate the potential of an implant of a GnRH-agonist (deslorelin) to create a progesterone free animal suitable for studying progesterone (P4) metabolism in intact cows by measuring blood P4 and faecal P4 metabolites.Methods Experiment 1: Eighteen non-lactating cycling Holstein-Friesian cows, 4 to 7 years old, were allocated to one of three groups to study plasma P4 concentrations preceding an intravaginal insert. These groups comprised: i) a deslorelin group (GnRH-agonist implanted); ii) a PGF group receiving two injections of prostaglandin (PGF(2 alpha)) 12 days apart; and, iii) an ovariectomised (OVX) group. An intravaginal device (CIDR) was inserted into the vagina of each animal and left in place for 11 days. Plasma P4 concentrations were measured during the study period.Experiment 2: Twelve non-lactating cycling Holstein-Friesian cows, 4 to 7 years old, were allocated to two groups: i) a deslorelin group (GnRH-agonist implanted); and ii) an ovariectomised group. Plasma P4 and faecal P4 metabolites (20-oxo-pregnanes, 20 alpha -OH and 20 beta -OH) were monitored for a period of 5 weeks.Results Experiment 1: Average plasma P4 concentration did not differ between the three groups (1.28, 1.43 and 1.55 ng/mL for deslorelin, OVX and PGF cows, respectively, P=0.8) during the period of supplementation.Experiment 2: There was no difference in plasma P4 (mean plasma P4<0.02 ng/mL, P=0.9) and faecal P4 metabolites between deslorelin and OVX cows 2 weeks after the implantation (P=0.7).Conclusions These data showed that a GnRH-agonist (deslorelin) implant may be used as an alternative to ovariectomy to create a progesterone free animal suitable for studying the metabolism of administered P4.

The aim of this study was to develop a method for long-term but reversible inhibition of oestrous cycles in female cats by downregulation of GnRH receptors with deslorelin released from a long-acting implant. In a blind study with mature cats (n = 20), a 6 mg deslorelin implant was administered s.c. to ten cats and a placebo implant was administered to ten cats. Occurrence of oestrus and general health were observed daily, and individual faecal samples were collected at 3 day intervals for 14 months and analysed for oestradiol content. All the placebo-treated queens continued to undergo normal oestrous cycles during the study. Oestrus was accompanied by peaks in oestradiol concentrations of > or = 20 ng g-1 faeces. Treatment with deslorelin initially stimulated oestradiol release, which accompanied treatment-induced ovulations. Thereafter, oestradiol concentrations decreased to 1-10 ng g-1 faeces and remained low for extended periods. Observations of small increases in oestradiol concentrations in one cat led to a second treatment with 6 mg deslorelin in five cats on day 155 after first treatment. Faecal oestradiol concentrations remained < 20 ng g-1 faeces in the five single treatment cats for 8.0, 8.5, 11.0 and 14.0 (two cats) months. Cats receiving two implants had the first oestradiol peak > 20 ng g-1 faeces after treatment at 7.5, 11.0 (two cats), 11.5 and 14.0 months. After 14 months, two cats had returned to normal cyclic activity, two had irregular small oestrogen peaks and six showed no cyclic activity. For months 2-5, 6-10 and 11-14, oestrogen values in treated cats were significantly different from control values (P < 0.001, 0.05 and 0.02, respectively). Differences in oestrogen concentration between control cats and cats that were treated twice were significant (P < 0.001) during months 6-10 only. The general health of treated cats was unchanged throughout the study. These results confirm that deslorelin can effectively suppress ovarian activity in domestic cats, but that the duration of suppression varies among individuals.

Continuous low-dose administration of a GnRH analogue postpones oestrus in bitches and suppresses reproductive function in dogs. A new drug delivery formulation that could enhance the practicality of this approach for the control of reproduction has been developed. The objective of the present study was to determine whether this method of delivery could, by sustained release of the GnRH analogue deslorelin, act as a reversible anti-fertility agent in domestic male and female dogs for periods exceeding 1 year. Several long-term studies were performed, which monitored reproductive function in 30 dogs and 52 bitches. Suppression of reproductive function in male dogs was dose-related. Spermatogenesis was suppressed for more than a year in 14 of 16 dogs that received doses of > 0.25 mg deslorelin kg-1. In females, postponement of oestrus for periods of up to 27 months was observed, but there was no relationship between the stage of the oestrous cycle at the start of treatment and the duration of efficacy. Treatment-induced effects on fertility were reversible in both sexes. In summary, sustained release deslorelin implants were shown to elicit reversible long-term reproductive control in male and female domestic dogs.

Studies were undertaken in Australia and Belgium to determine whether the initial prooestrous-oestrous responses of anoestrous bitches to treatment with deslorelin administered in a s.c. implant were inhibited by progestin treatment. Thirty-nine bitches of mixed breeding were treated daily with 2 mg megestrol acetate kg(-1) body weight for 21 (group 1, n = 5) or 14 days (group 2, n = 10), or with 1 mg megestrol acetate kg(-1) body weight for 14 days (group 3, n = 10). A deslorelin (6 mg) implant was placed s.c. on day 14 (group 1) or day 7 (groups 2 and 3) of treatment. Bitches not treated with progestin also received a deslorelin implant (group 4, n = 9) or were untreated controls (group 5, n = 9). Signs of pro-oestrus-oestrus were not observed in bitches in groups 1, 2 and 5, but were observed in bitches in groups 3 (4/10) and 4 (9/9). Four bitches in group 4 were mated, two of which became pregnant. The pregnancies failed at about day 40 of gestation and were associated with low plasma progesterone concentrations. Treatment with progestin inhibited the pro-oestrous-oestrous responses of bitches to deslorelin.

In two separate controlled clinical trials, the efficacy and safety of 2.2 mg of the GnRH analogue deslorelin, administered subcutaneously as a short-term implant to normally cycling mares in oestrus with a dominant ovarian follicle more than 30 mm in diameter, were evaluated, using a placebo as a negative control. The oestrous cycle of each mare was followed by teasing, palpation per rectum and transrectal ultrasonography. Follicles were monitored every 24 hours by ultrasonography until ovulation occurred. The mares were either mated naturally or inseminated artificially. In trial 1, 174 mares were treated at six locations in Canada, and in trial 2, 98 mares were treated at three locations in the USA. In trial 1, the treatment with deslorelin reduced the mean (sd) time to ovulation from 84.2 (48.4) hours to 50.2 (19.6) hours (P<0.001) and in trial 2 it reduced it from 88.8 (40.3) hours to 54.1 (26.5) hours (P<0.001). In trial 1, the percentage of mares ovulating within 48 hours increased from 37.7 per cent in control mares to 86.1 per cent in treated mares (P<0.001) and in trial 2 the percentage increased from 26.5 to 80.9 per cent (P<0.001). In trial 2, the duration of oestrus in the deslorelin-treated mares was reduced from 6.1 days to 4.3 days and the number of matings or artificial inseminations was reduced from 2.5 to 1.7 (P<0.001). In trial 1, days 12 to 20 pregnancy rates for matings at the treatment oestrus were not different for deslorelin-treated (75.6 per cent) and placebo-treated (66.1 per cent) mares. In trial 2, days 12 to 20 pregnancy rates from matings at the treatment oestrus were lower for deslorelin-treated (58.7 per cent) than for placebo-treated (83.3 per cent) mares (P<0.05), although pregnancy rates were similar for deslorelin-treated (97.1 per cent) and placebo-treated (95.0 per cent) mares after mating at the second oestrus. In both trials, pregnancy losses due to early or late abortions were within the normally expected range and similar for deslorelin-treated (3.6 and 3.7 per cent, respectively) and placebo-treated (13.4 and 7.5 per cent) mares. The treatments did not cause systemic side effects and local reactions at the implantation sites were slight and of short duration.

A more precise characterization of the effects of human chorionic gonadotropin (hCG) treatment on the preovulatory follicle is needed to improve reproductive efficiency in broodmare management. The objectives of this study were (1) to study the effects of different hCG doses within and among three consecutive estrous cycles on ovulatory response, preovulatory follicle dynamics, and endometrial echotexture; (2) to study the temporal relationship among changes in preovulatory follicle diameter, endometrial echotexture, and estradiol levels; and (3) to analyze a system for prediction of ovulation. In experiment 1, mares were treated with 2,500 IU hCG, 1,500 IU hCG, 500 IU hCG, or saline (controls) and examined by ultrasonography every 6 hours across three consecutive preovulatory periods (n = 135). Similar treatment groups were utilized in experiment 2 (n = 177 preovulatory periods) with examinations performed every six, 12, or 24 hours to test the effectiveness of a prediction of ovulation system. Effective hCG doses (2,500 and 1,500 IU) led to cessation of growth rate and reduction of the preovulatory follicle diameter concurrently with a reduction in systemic estradiol concentration and endometrial echotexture score. A system of prediction of ovulation, based on preovulatory follicle ultrasonographic signs of impending ovulation, was highly accurate for the diagnosis of positive and negative outcomes in both hCG-treated and control groups. However, the effectiveness of this prediction system was reduced due to the false-negative diagnoses that were a reflection of a lack of sensitivity for the detection of nonovulation.

An experiment was conducted in which 30 stall-fed dairy cows were fed a basal ration of either good or poor quality pasture (approx. 7 kg DM) and supplemented with varying amounts of either crushed wheat or a pelleted. high energy supplement (0, 4 kg/clay or ad libitum). The cows were in their third month of lactation and were fed their allotted rations for 5 weeks. Where no supplements were fed, the approximate 9% difference in digestibility between pasture types resulted in differences in daily production of 2.4 kg milk/cow, 0.07 kg milk fat/cow and 0.06 kg milk protein/cow, and a difference of 0.4 units of body condition over a 5-week period. Where supplements were fed, responses depended on the interaction between a supplement and basal ration. With good quality pasture as the basal ration, the type of supplement was not important; marginal returns of milk products to extra feeding were similar for both supplements, for example, 1.0 kg milk/cow.day was produced for each additional kg of concentrate consumed. There was a reduction in milk fat production when more than about 5-6 kg DM of supplement was fed. This was due to a depression in the fat content of the milk which was associated with low dietary fibre (<250 g/kg of dietary neutral detergent fibre). However. when pellets were fed to cows offered poor quality pasture. a reduction in milk fat yield did not occur. When wheat supplemented poor quality pasture, on the other hand, deficiencies other than fibre were implicated. While fibre was the most important limitation to productivity when good quality pasture was supplemented with concentrates, protein was the most likely nutrient to limit productivity first when poor quality pasture formed the basal ration. The potential exists for major imbalances of nutrients to occur unless the composition of dietary components is known.

Levels of acceptance of mixtures of rolled oats and predominantly saturated, molten or free-flowing fatty acids were assessed with lactating dairy cows. Twenty cows grazed pasture and were offered rolled oats comprising 0, 2, 4, 8, 15, 25 or 40% (w/w) fatty acids. One kg/cow was offered twice daily to cows following milking. The acceptability of grain-fat mixtures was influenced by level of fatty acids. The fatty acid concentrations above which less than 95% of the supplement was consumed by animals ranged from 22 to 31%. Time spent eating the supplement was reduced by 2.4 s for every percentage unit increase in fatty acid concentration, while high air temperature increased (P<0.05) eating time.

Three groups of 8 cows in their second month of lactation grazed irrigated perennial pasture alone, or grazed and were supplemented with either 3.3 kg/day of a high energy supplement or 3.8 kg of a high energy supplement containing additional long-chain fatty acids. Yields of milk and milk products were generally highest for those cows fed the supplement containing fat. Yield of milk fat was 13% higher in fat supplemented cows than those in the other supplemented treatment because these cows overcame the negative effect of starch supplements on milk fat test. Inclusion of long-chain fatty acids in the diet caused only minor changes in the fatty acid composition of the milk fat and in the various rumen parameters. The immediate marginal increases in daily yields of milk and milk fat per kg of long-chain fatty acids consumed by cows were 1.8 and 0.33 kg/cow. After comparison with data from other experiments, we concluded that the type of basal diet is not an important factor influencing the response of dairy cows to dietary long-chain fatty acids

This experiment studied the effects of feeding a supplement of a blend of unesterified and saturated long-chain fatty acids on the productivity of dairy cows in mid-lactation. Twenty-three cows in their fourth month of lactation were individually fed ad libitum, a mixed balanced ration based on maize silage, lucerne hay and rolled grain. Varying quantities, up to 1020 g cow-1 day-1 of the fatty acid supplement, were mixed into the ration. Yields of milk and milk products were linearly related to total long-chain fatty acid intake. Milk fat content increased linearly while milk protein content averaged 3.59 (s.d. 0.15)%. The marginal returns from feeding 1 kg of the supplement were 3.3 kg milk, 0.33 kg fat and 0.07 kg protein. The proportions of C 10:0, C12:0 and C 14:0 fatty acids in milk were decreased, while those of C 18:0 and C18:1 were increased as the result of feeding long-chain fatty acids. The concentration of lipid in plasma was increased, but acetate and D-(3)-hydroxybutyrate levels in blood remained unchanged with increased levels of dietary long-chain fatty acid. Efficiency of milk production was increased by 11% from feeding 1 kg of the supplement. In vivo digestibilities of dry matter, neutral and acid detergent fibres, and dietary long-chain fatty acids were unaffected by supplement.

Stall-fed dairy cows were fed amounts of pasture ranging from 6.7 to 11.8 kg DM/cow.day and supplemented with either 0, 2.2 or 4.5 kg DM/cow.day of pelleted concentrates. Twenty-eight cows in their third month of lactation and 29 cows in their eighth month of lactation were fed in this manner for about 5 weeks. Stage of lactation had a major influence on responses obtained from feeding a high energy supplement to pasture-fed cows. In early lactation, for cows fed 6.8 kg DM, marginal responses from feeding an additional kg DM of concentrates were 1.85, 0.053 and 0.059 kg milk, milk fat and milk protein, respectively; if they were fed 11.7 kg DM of pasture, marginal responses from concentrates were more than halved (0.58 kg milk, 0.019 kg milk fat and 0.027 kg milk protein per kg DM). The latter response to concentrates, where high levels of pasture were fed to cows in early lactation, were less than those obtained in late lactation at any level of pasture feeding.

Eighty-eight Friesian cows and heifers were fed in two trials on four complete diets based on maize silage and lucerne hay during early lactation. The four diets varied in grain content from 0 to 500 g kg−1 dry matter (DM), but were isonitrogenous at 25 g N kg−1 DM. In the second trial, 46 of these animals were monitored for their entire lactation. Voluntary feed intake, yields of milk and milk solids and changes in liveweight and body condition (the latter in the second trial only) were measured. Digestibility of organic matter, concentrations of rumen ammonia and volatile fatty acids and excretion of whole grains in faeces were also measured during early lactation. The dietary effect was partitioned into that attributable to linear or quadratic influences.

Five experiments were done in which stall-fed dairy cows were provided with a basal ration of pasture (6-7 kg DM) which was supplemented with varying amounts of a pelleted, high energy supplement (0-10 kg DM). Forty-seven cows at various stages of lactation were fed in this manner for up to 5 weeks. Responses to feeding the supplement depended on the stage of lactation at which the supplement was fed, and the amount of the supplement consumed. Marginal responses in milk production fell from 1.6 to 0.7 kg milk per kg supplement as lactation progressed, and as the level of feeding increased. Although responses in milk fat yield also decreased as lactation advanced, there was also a reduction in milk fat production when more than about 6 kg DM of supplement were fed. This was due to a severe depression in the fat content of the milk, which was found to be associated with intakes of diets with less than 250 g kg DM-1 neutral detergent fibre; diets with less than this level of fibre resulted in ratios of lipogenic to glucogenic volatile fatty acids in the rumen below 4:1. This occurred when the supplement constituted 0.4-0.5 of the diet on a dry matter basis. In addition, rumen ammonia levels were low when large amounts of supplement were fed. With all rumen characteristics, stage of lactation had no influence on values.

This experiment examined the effects of level of concentrate feeding and pasture allowance on the productivity of dairy cows in late lactation. Thirty-two cows in their 8th month of lactation were allocated to eight treatments; these were combinations of two pasture allowances (about 15 and 26 kg DM/cow.day) and four levels of concentrates (0,2,4 kg/cow.day and ad libitum). Milk and protein yields increased linearly with level of supplementation but the response of milk fat yield was curvilinear; peak fat yield occurred at 4 to 5 kg DM/cow.day of concentrates fed. The marginal returns from feeding 1 kg of concentrates were 0.57 kg milk, 0.030 kg fat and 0.022 kg protein from feeding up to 5 kg DM/ cow.day. The different pasture allowances significantly influenced only fat yield; the cows at the higher allowance produced 0.044 kg more fat than did the cows at the lower allowance.