Sasser, R. Guardia, B. Alexander, D. Holcombe, DR ...

Norgestomet implants prevent pregnancy in beef heifers on pasture T. W. Geary, J. J. Reeves, D. W. Schafer, R. R. Evans, R. D. Randel, L. M. Rutter, R. G. Sasser, R. Guardia, B. Alexander, D. Holcombe, D. R. Hanks and D. B. Faulkner J ANIM SCI 1997, 75:3089-3093.

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Norgestomet Implants Prevent Pregnancy in Beef Heifers on Pasture T. W. Geary*,1, J. J. Reeves†, D. W. Schafer*, R. R. Evans‡, R. D. Randel§, L. M. Rutter¶, R. G. Sasser#, R. Guardia#, B. Alexander#, D. Holcombe*, D. R. Hanks**, and D. B. Faulkner†† *Colorado State University, Fort Collins 80523; †Washington State University, Pullman 99164; ‡Mississippi State University, Prairie 39756; §Texas A&M University, Overton 75684; ¶University of Florida, Ona 33865; #University of Idaho, Moscow 83844; **University of Nevada, Reno 89501; and ††University of Illinois, Urbana 61801

ABSTRACT: The efficacy of erodible norgestomet implants for preventing pregnancy in postpubertal heifers was evaluated in two experiments at five locations each. Heifers ( n = 896) within each study location were stratified by weight and allotted randomly to receive an ear implant containing either 0, 24, 36, or 48 mg of norgestomet ( d 0). Heifers were exposed to fertile bulls immediately after implantation for 75 d ( d 0 to 74) in Exp. 1 ( n = 476) or for 80 d ( d 75 to 154) in Exp. 2 ( n = 420). Weights were recorded on d 0 and 74 (Exp. 1 and 2 ) and d 154 (Exp. 2). Each heifer was palpated rectally for pregnancy at the end of each experiment. Pregnancy rates were higher ( P < .01) for control heifers ( 0 mg implant) than for heifers that received 24, 36, or 48 mg of norgestomet. In Exp. 1, pregnancy rates were 96, 29, 6, and 4% for heifers that received 0, 24, 36, and 48 mg implants of

norgestomet, respectively. In Exp. 2, pregnancy rates were 85, 36, 19, and 9% for heifers that received 0, 24, 36, and 48 mg implants of norgestomet, respectively. Estrous activity during the first 3 wk of bull exposure was reduced ( P < .05) among heifers that received norgestomet implants compared to control heifers but was not completely abolished at any dosage in Exp. 1. During the first 75 d of Exp. 1 and 2, heifers treated with 36 or 48 mg norgestomet implants gained weight faster ( P < .05) than control heifers. Combined across both experiments, ADG during the first 74 d were .53, .56, .59, and .60 kg/d for heifers treated with 0, 24, 36, and 48 mg implants of norgestomet, respectively. These data indicate that norgestomet implants increased rate of weight gain, reduced estrous activity, and reduced the occurrence of pregnancy in heifers on pasture.

Key Words: Beef Cattle, Progestogens, Heifers, Females, Fertility, Pastures J. Anim. Sci. 1997. 75:3089–3093

Introduction Pregnancy among stocker and feedlot heifers can decrease feed efficiency, weight gain, and carcass dressing percentage (Bennett et al., 1984; Stanton et al., 1988; Walker et al., 1988; Kreikemeier and Unruh, 1993). The incidence of pregnancy among heifers at slaughter ranges from 3.9 to 17% (Bennett, 1985; Laudert, 1988; Kreikemeier and Unruh, 1993). Spaying heifers is uneconomical, requires skilled labor, and increases death losses (Dinusson et al., 1950; Ray et al., 1969; Cameron et al., 1977; Garber et al., 1990). A

1Corresponding Author: Dept. of Anim. Sci., Colorado State Univ., Fort Collins, CO 80523−1171, phone: 970−491−6244, fax: 970−491−5326. Received August 23, 1996. Accepted July 25, 1997.

practical method of preventing pregnancy while increasing efficiency of heifers is needed. Oral administration of melengestrol acetate ( MGA; a synthetic progestogen) to heifers at a rate of .25 to .5 mg/d effectively suppressed estrus and ovulation and increased rate of gain by 10% (Lauderdale, 1983). Using MGA is not practical for heifers on pasture because MGA must be consumed daily. Although an injection of depot-formulated MGA prevented pregnancy in heifers on pasture, weight gain was not increased (Moseley et al., 1986; Hill et al., 1988; Floyd et al., 1989). Norgestomet is another synthetic progestogen that, like MGA, is 100 to 200 times more potent than progesterone. Because norgestomet has only minimal oral activity in ruminants, it has been used in ear implants to suppress estrus in cattle for short periods of time and has been used as a tool in estrus synchronization (Wishart and Young, 1974; Woody

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Table 1. Experiment locations and number of heifers per treatment Experiment/location Experiment 1 Illinois Mississippi Colorado Washington Nevada Total Experiment 2 Illinois Mississippi Florida Idaho Texas Total

0 mg

24 mg

36 mg

48 mg

26 21 22 24 25 118

26 23 21 25 24 119

26 21 22 25 25 119

25 23 22 25 25 120

24 21 16 23 20 104

24 20 16 24 22 108

24 22 19 24 19 108

24 20 14 23 19 100

and Abenes, 1975; Wishart et al., 1977). The objective of this study was to evaluate the estrous activity, occurrence of pregnancy, and pasture weight gain of postpubertal heifers that received implants containing different dosages of norgestomet.

Materials and Methods Postpubertal beef heifers ( n = 476, Exp. 1; n = 420, Exp. 2 ) were stratified by weight (318 ± 25 kg, Exp. 1; 317 ± 32 kg, Exp. 2 ) within each study location and randomly allocated to four treatments to receive either 0, 24, 36, or 48 mg norgestomet implants. Only heifers that had a progesterone concentration greater than 1.0 ng/mL on d −21 or d −11 were used in this study. Experiments 1 and 2 were conducted during the same year. Each experiment was replicated at five locations throughout the country, and some locations conducted both experiments (Table 1). Each study location had approximately equal numbers of heifers within each treatment. Norgestomet implants were administered s.c. by a single technician in the caudal surface of the right ear on d 0 of each experiment. Heifers at each location were exposed to fertile bulls for either 75 d ( d 0 to 74, Exp. 1 ) or 80 d ( d 75 to 154, Exp. 2 ) in a single pasture. Each bull passed a breeding soundness examination before its use in each experiment. Each bull was fitted with a chin-ball marker that was filled with a different color of paint weekly. Paint markings were recorded weekly for each heifer during bull exposure to serve as an indicator of estrous activity. The bull:heifer ratio used at each location was approximately 1:30. Heifer weights were recorded on d 0, 74, and 154 (Exp. 2 only). Implant sites were palpated and any remaining implants were excised from heifers on d 74 (Exp. 1 ) or d 154 (Exp. 2). The reproductive tract of each heifer was palpated rectally for pregnancy on d −11, 28, 74, and 109 (Exp. 1 ) or d −11, 98, 154, and 189 (Exp. 2). Uterine palpation on d −11 and 28 or 98 was conducted to

verify that heifers were not pregnant at the time of implanting. Palpations performed on d 74, 109, 154, and 189 were conducted to determine the number of pregnant heifers within each treatment and to estimate date of conception. All palpations were performed by technicians that were not aware of a heifer’s treatment. Norgestomet implants contained 98% norgestomet (17a-acetoxy-11b-methyl-19-norpreg-4-ene-3,20-dione): 2% cholesterol (wt/wt) erodible material (Hoffmann-La Roche, Nutley, NJ). Heifers received either one 11-mm × 1.6-mm norgestomet implant (24 mg), one 11-mm × 1.6-mm and one 5.5-mm × 1.6-mm norgestomet implant (36 mg), or two 11-mm × 1.6-mm norgestomet implants (48 mg). The 24, 36, and 48 mg dosages were formulated to deliver 160, 240, and 320 mg of norgestomet per day, respectively, for a period of 150 d. Within Exp. 1 and 2, differences in pregnancy rates between treatments were determined using chi-square analysis. Differences in estimated time of conception, within experiment, were analyzed using survival analysis methods that included Cox proportional hazards regression and the log-rank and Wilcoxin tests. Differences in the number of heifers in each treatment that exhibited estrus within the first 3 wk of bull exposure for Exp. 1 and 2 was analyzed using randomized complete block analysis of variance. Study location was used as the block with norgestomet dosage as the independent variable. Average daily gain of heifers was analyzed using randomized complete block analysis of variance. Study location was used as the block and norgestomet dosage as the independent variable (SAS, 1990).

Results In Exp. 1 and 2 (Figure 1), pregnancy rates of heifers that received norgestomet implants were lower ( P < .01) than pregnancy rates of control heifers. In Exp. 1, pregnancy rates were 96, 29, 6, and 4% for heifers that received 0, 24, 36, or 48 mg of norgestomet, respectively. Heifers that received 24 mg of norgestomet had a higher ( P < .01) pregnancy rate than heifers that received 36 or 48 mg of norgestomet. Pregnancy rates of heifers that received 36 or 48 mg of norgestomet were not different ( P > .10). In Exp. 1, the estimated time of conception for heifers that received norgestomet implants was later ( P < .01) than that of control heifers (Table 2). Within the first 20 d of the breeding season, 52% ( n = 61) of control heifers conceived, whereas only 8 ( n = 10), 3 ( n = 4), and 1% ( n = 1 ) of heifers receiving 24, 36, and 48 mg of norgestomet, respectively, conceived within that time period. In Exp. 2, the pregnancy rates of heifers exposed to bulls during an 80-d breeding season that began 75 d after implantation were 86, 36, 19, and 9% for heifers


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Table 2. Effect of norgestomet dosage (0, 24, 36, or 48 mg) on the percentage (mean ± SE) of heifers that conceived in 15-d intervals after exposure to fertile bulls from d 0 (day of implantation) to d 74 in Exp. 1 Norgestomet dosage, mg 0 24 36 48

(n (n (n (n

= = = =

18) 119) 119) 120)

Day 0−15 30 1 2 0

± ± ± ±

18 2 5 0

Day 16−30 39 9 2 1

± ± ± ±

18 7 4 2

Day 31−45 16 6 0 2

that received 0, 24, 36, and 48 mg of norgestomet, respectively (Figure 1; Exp. 2). Pregnancy rates were higher ( P < .01) for heifers that received 24 mg of norgestomet than for heifers that received 36 or 48 mg of norgestomet. Pregnancy rates of heifers that received 36 mg of norgestomet were also higher ( P < .05) than those of heifers implanted with 48 mg of norgestomet. In Exp. 2, the estimated date of conception was later ( P < .01) for heifers treated with 24, 36, and 48 mg of norgestomet than for control heifers (Table 3). The conception rates of heifers within the first 20 d of the breeding season were 55, 12, 3, and 1% for heifers implanted with 0, 24, 36, and 48 mg of norgestomet, respectively. In Exp. 1, the percentage that exhibited estrus within the first 3 wk of bull exposure was lower ( P < .05) for heifers that received norgestomet implants than for control heifers (Figure 2). Percentages of heifers in which estrus was suppressed did not differ

Figure 1. Pregnancy rates of postpubertal heifers that were implanted with either 0, 24, 36, or 48 mg of norgestomet and either exposed to mature bulls for 75 d after implantation (Exp. 1) or exposed for 80 d beginning 75 d after implantation (Exp. 2). Error bars indicate variation in pregnancy rates among five locations for each experiment. Bars without a common letter differ (P < .05).

± ± ± ±

18 8 0 4

Day 46−60 7 3 1 0

± ± ± ±

7 5 2 0

Day 61−74 4 5 0 0

± ± ± ±

3 4 0 0

Total d 0−74 96 24 6 4

± ± ± ±

6 14 9 9

( P > .05) among norgestomet treatment. Norgestomet implants did not completely abolish estrus at any dosage. Percentages of heifers in Exp. 1 that exhibited estrus during the first 3 wk of bull exposure were 73, 45, 40, and 35 for heifers treated with 0, 24, 36, and 48 mg of norgestomet, respectively. In Exp. 2, the percentage of heifers that exhibited estrus within the first 3 wk of bull exposure was lower ( P < .05) for heifers that received 48 mg of norgestomet than for control heifers. Percentages of heifers that exhibited estrus within the first 3 wk of bull exposure treated with 24 or 36 mg norgestomet implants were not different ( P > .05) from percentages of heifers that received either 0 or 48 mg of norgestomet. During the first 74 d of Exp. 1 and 2, heifers that received 36 or 48 mg of norgestomet gained weight at a faster rate ( P < .05) than control heifers (Figure 3). The response in ADG due to norgestomet implants was dose-dependent. Heifers that received 48 mg of norgestomet gained weight faster ( P < .05) than heifers treated with 0 or 24 mg of norgestomet but not faster ( P > .05) than heifers treated with 36 mg of norgestomet. Heifers that received 36 mg of norgesto-

Figure 2. Percentage of heifers exhibiting estrus within the first 3 wk of bull exposure for Exp. 1 (early bull exposure) and Exp. 2 (late bull exposure). Error bars indicate variation in estrous activity between study locations (n = 5) for each experiment. Bars without a common letter differ (P < .05).


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GEARY ET AL.

Table 3. Effect of norgestomet dosage (0, 24, 36, or 48 mg) on the percentage (mean ± SE) of heifers that conceived in 15-d intervals after exposure to fertile bulls from d 75 (d 0 = day of implantation) to d 154 in Exp. 2 Norgestomet dosage, mg 0 24 36 48

(n (n (n (n

= = = =

104) 108) 108) 100)

Day 75−90 36 9 3 0

± ± ± ±

9 8 6 0

Day 91−105 25 7 0 1

± ± ± ±

12 5 0 3

Day 106−120 14 3 3 1

met gained weight faster ( P < .05) than control heifers but at a rate that did not differ ( P > .05) from that of heifers that received 24 or 48 mg of norgestomet.

Discussion The results of these studies indicate that norgestomet implants were effective in reducing the incidence of pregnancy in heifers. Pregnancy rates of norgestomet-treated heifers were dose-dependent. Because norgestomet implants used in heifers on pasture should suppress pregnancy for at least 5 mo, retention of the implant may be a consideration. Hill et al. (1992) reported retention rates of 83 to 95% for heifers that received Silastic ear implants during a 122-d study. The implants used in the current study were synthesized of erodible material and could not be palpated for their presence or absence during these studies. Decreases in pregnancy rate similar to those described here, have been reported using MGA.

Figure 3. Mean ADG from d 0 (d of implantation) to 74 for postpubertal heifers implanted with either 0, 24, 36, or 48 mg of norgestomet in Exp. 1 and 2 (pooled data). Error bars (SE) without a common letter differ (P < .05).

± ± ± ±

5 2 4 2

Day 121−135 5 7 3 1

± ± ± ±

3 7 8 2

Day 136−150 5 11 10 6

± ± ± ±

5 6 16 4

Total d 75−150 84 36 18 9

± ± ± ±

14 24 289 5

Injection of 90 mg of depot-formulated MGA prevented pregnancy in greater than 90% of heifers for at least 141 d (Moseley et al., 1986; Hill et al., 1988; Floyd et al., 1989). The effect of norgestomet in reducing pregnancy rate is probably due to estrus suppression and a reduction in ovulation rate. The short-term effects of norgestomet on estrous activity and fertility have been evaluated previously. Short-term use of norgestomet implants ( 6 mg; Syncro-Mate B ) completely suppressed estrus (Mosely et al., 1979) and prevented normal luteal development in heifers (Miksch et al., 1978; Spitzer et al., 1978a,b). The calculated delivery rate of the 6 mg norgestomet implant is 240 mg/d. The calculated norgestomet delivery rates of the implants used in the present study were 160, 240, and 320 mg/d for implants containing 24, 36, and 48 mg norgestomet, respectively. Thus, we expected complete estrus suppression among heifers receiving the 36 and 48 mg norgestomet implants. The lack of complete estrus suppression may be due to less than 100% implant retention or to an inadequate dosage of norgestomet. Some heifers that displayed estrus may not have become pregnant due to low fertility. The decreased fertility of norgestomet-implanted heifers in this study may have been due to a lack of ovulation and(or) abnormal luteal development. Feedlot heifers receiving 24 mg norgestomet implants demonstrated estrus without ovulation and luteal development (Yavas, 1992). Short-term norgestomet implants prevented normal luteal development (Miksch et al., 1978; Spitzer et al., 1978a,b; Yavas, 1992). Normal luteal development was also prevented for 122 d in heifers receiving a Silastic implant containing 50 mg of norgestomet (Hill et al., 1992). Norgestomet may also decrease fertility by extending the life span of the oocyte within the dominant follicle beyond its optimal fertility. Previous researchers have demonstrated that the life span of the dominant follicle was extended with low dosages of progestogens and that it was the aged dominant follicle that was ovulated upon progestogen withdrawal (Sirois and Fortune, 1988; Savio et al., 1993a,b; Stock and Fortune, 1993). These persistent dominant follicles have been reported to produce high levels of estrogen under the influence of norgestomet (Sanchez et al., 1993). Elevated serum estrogen


NORGESTOMET IMPLANTS PREVENT PREGNANCY

production from persistent dominant follicles is the primary mechanism by which progestogen treatment increases weight gain in heifers (Bloss et al., 1966); this is probably the reason that heifers that received the 48 mg norgestomet implants had a 12% higher ADG than control heifers. In heifers that received norgestomet implants, fertilized embryos may develop abnormally and die. Estrogen and progesterone influence endometrial function in cattle (Bartol et al., 1981). Norgestomet has also been shown to bind to endometrial progesterone receptors with high affinity (Moffat et al., 1993). In the present study, elevated estrogen coupled with norgestomet may have altered the uterine environment required for early embryonic development.

Implications Norgestomet implants at the 48 mg dosage were effective in preventing pregnancies in > 90% of heifers on pasture for at least 154 d and resulted in a 12% increase in ADG. To prevent estrus in all the heifers implanted, a higher dosage of norgestomet may be needed.

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