NEW OPPORTUNITIES TO SYNCHRONIZE ESTRUS AND FACILITATE FIXED-TIME AI DJ Patterson, MF Smith, and DJ Schafer Division of Animal Sciences University of Missouri-Columbia July 6, 2005

reproductive technology in the U.S. beef cattle industry…… The current status of reproductive technology in the U.S. beef cattle industry……

Reproductive Technologies Available or on the Horizon Estrus synchronization and AI Ultrasonography Sexed semen Embryo transfer In vitro production of embryos Transgenics (pharming) Cloning Male fertility

The U.S. Beef Herd 69% of cow-calf enterprises are secondary income sources 50% of producers report an established breeding season of specific duration 34% of beef herds are routinely pregnancy checked 10% of beef cattle enterprises utilize AI

What’s happening in adoption of technology in the beef industry on a global basis?

Total Domestic Sales of Beef Semen In the U.S. …... Total Domestic Sales of Beef Semen 1980 1982 1984 1986 1988 1990 1994 1996 1998 2000 1992 Hough,, 2002

Comparison of AI Use In Beef Cattle (U.S. vs. Brazil)

Import and Domestic Beef Semen Sales (units sold) 1993 1,117,798 2003 1,025,116 1993 1,874,996 2003 4,896,204 -8% change +161% change From NAAB, 2003; ASBIA, 2003

Unless efforts are taken to implement change in the U. S Unless efforts are taken to implement change in the U.S. beef cattle industry, the products of our research and technology may be exported to more competitive international markets . . . . . . (Patterson et al., 2000).

Why are we here?

Artificial insemination and estrus synchronization are generally regarded as the most important and applicable of all available biotechnologies to the beef cattle industry (Seidel, 1995).

From NAHMS Survey, 1998

Improvements in methods to synchronize estrus create the opportunity to significantly expand the use of AI in the U.S. cowherd ………………….

A unique point in time for the U.S. beef industry……… Availability of tools and understanding of methods to control the estrous cycle in cattle A changing market structure that recognizes and rewards quality

A unique point in time……… If we don’t impact use of AI among beef producers in the U.S. in the near future, will we ever?

The challenge of transferring technology (estrus synchronization and AI) to the private sector exceeds the task of research and development of still newer technologies……….

Collectively Adopt common terminology regarding the various estrus synchronization protocols Identify and agree upon short lists of protocols heifers and cows heat detect and AI vs fixed-time AI Work to overcome the attitude of “What will this cost me?” ….to… “ I’m willing to make an investment in my herd”

Effective Estrus Synchronization Programs for Beef Cattle Facilitate AI & ET Reduce time required to detect estrus Cycling females conceive earlier in the breeding period Induce cyclicity in peripubertal heifers and anestrous postpartum cows

Objective: Development of highly effective & economical estrus synchronization programs Peripubertal heifers Postpartum cows Anestrus and estrous cycling Excellent pregnancy rates

Products Currently Available Prostglandin Lutalyse, Estrumate, ProstaMate, In Synch, EstroPlan GnRH Cystorelin, Factrel, Fertagyl, OvaCyst Progestins MGA CIDR

What We Know About MGA . . .

Progesterone MGA (melengestrol acetate) Pregn-4-ene-3, 20-dione CH3 MGA (melengestrol acetate) 6-methyl-17-alpha-acetoxy-16-methylene-pregn-4, 6-diene-3, 20-dione C O CH3 CH2

What We Know About MGA . . . Induces puberty in beef heifers (Imwalle et al., 1998) Prevents expression of behavioral estrus (Zimbelman and Smith, 1966; Imwalle et al., 2002) Blocks the preovulatory surge of LH (Imwalle et al., 2002) Blocks ovulation (Zimbelman and Smith, 1966; Imwalle et al., 2002)

HEIFERS

Reproductive Tract Scores (RTS) 4 5 Length 15 18 22 30 > 32 Height 10 12 15 16 20 Width 8 10 10 12 15 Ovarian Measurement (mm) Description Infantile Prepubertal Peripubertal Cycling Uterine horns Immature < 20 mm diameter No tone 20-25 mm diameter No tone 20-25 mm diameter Slight tone 30 mm diameter good tone > 30 mm diameter Ovarian Structures No palpable follicles 8 mm follicles 8-10 mm follicles > 10 mm follicles CL possible CL present Adapted from Anderson et al., 1991

Reproductive Tract Scores (RTS) Summary Pelvic Height (cm) 13.9a 14.1a 14.5b 14.7c Pelvic Width (cm) 10.9a 11.2a 11.4b 11.7c Pelvic Area (cm2) 152a 158a 166b 172c Estrous Response (%) 54a 66b 76c 83d 86d Weight (lb) 594a 620b 697c 733d 755d RTS 1 2 3 4 5 n 61 278 1103 494 728 a, b, c, d Numbers with different superscripts within a column differ (P < 0.05) Adapted from Patterson and Bullock, 1995

Comparison of reproductive performance in herds using natural service or synchronization and AI on replacement heifers by RTS Exposed 21-d PR2 42-d PR3 TPR4 RTS1 NS5 (n) SAI6 NS (%) SAI 1 8 55 38a 42a 63c 55c 63e 60e 2 108 661 31a 52b 54c 68d 75e 82e 3 336 3320 41a 58b 65c 74d 87f 4 322 3629 48a 62b 72c 77d 91e 5 242 2835 50a 64b 74c 80d 88e TOT 1016 10500 44a 61b 68c 73d 85e 87e a,b Means within rows for 21-d PR with different superscripts differ (P < .05) c,d Means within rows for 42-d PR with different superscripts differ (P < .05) e,f Means Within rows for TPR with different superscripts differ (P < .05) From Randle and Patterson, 2005

Synchronized Estrus estrus PG MGA (14 days) 1 14 16 20 31 33 36 1 14 16 20 31 33 36 Treatment days Brown et al., 1988

MGA-PG 14-19 d Improved estrous response Similar fertility More heifers in heat Similar fertility No change in conception or pregnancy rate Improved synchrony More heifers in heat in a shorter time (Deutscher et al., 2000; Lamb et al., 2000)

PG MGA (14 days) MGA (14 days) PG GnRH MGA-PG 1 14 33 MGA Select Treatment days MGA (14 days) 1 14 26 33 PG GnRH Wood et al., 2001

PG Follicle diameter (mm) Day of treatment ESTRUS Wood et al., 2001 5 5 10 15 20 25 30 35 16 17 18 19 21 22 23 24 26 27 28 29 31 32 33 34 36 37 38 39 40 Day of treatment Follicle diameter (mm) ESTRUS PG Wood et al., 2001

PG GnRH Follicle diameter (mm) Day of treatment Wood et al., 2001 5 10 5 10 15 20 25 30 35 16 17 18 19 21 22 23 24 26 27 28 29 31 32 33 34 36 37 38 39 40 Day of treatment Follicle diameter (mm) ESTRUS PG GnRH Wood et al., 2001

When to Add GnRH to an MGA-PG Protocol for Heifers Consideration of . . . . Age Weight Reproductive tract score (RTS) Pubertal status Wood et al., 2000; Kojima et al., 2001

How do MGA- and CIDR-based protocols compare in heifers?

Experimental Protocols MGA Select GnRH PG MGA (14 days) .. .. 12 days .. .. .. .. 7 days .. .. 1 14 26 33 14-d CIDR GnRH PG CIDR (14 days) .. .. 9 days .. .. .. .. 7 days .. .. 1 14 23 30 Treatment day Kojima et al., 2004

Experimental Procedures 352 yearling crossbred beef heifers at three locations Location 1 n = 154 (Southeast Missouri) Location 2 n = 113 (North Dakota) Location 3 n = 85 (North central Missouri) Heifers were assigned to one of two treatments (MGA or CIDR) by age and weight Kojima et al., 2004

Summary for Timing of AI % of Heifers Inseminated 80 CIDR (n = 177) MGA (n = 175) 69% 70 60 53% 50 % of Heifers Inseminated 40 30 21% PG 20 15% 16% 10% 10% 10 5% 0% 1% 1 2 3 4 5+ Days after PG No treatment x location effect (P > 0.10); therefore, data were pooled Distribution of AI dates were different between MGA- and CIDR-treated heifers (P < 0.02) Kojima et al., 2004

Estrous Response, AI Pregnancy, and Final Pregnancy Rates 154/177 (87 %) 112/177 (63 %)a 164/177 (93 %) CIDR 147/175 (84 %) 83/175 (47 %)b 159/175 (91 %) MGA 301/352 (86 %) 195/352 (55 %) 323/352 (92 %) Total a, b P = 0.01 Diff. + 3 % + 16 % + 2 % Kojima et al., 2004

Summary In yearling beef heifers: CIDR-GnRH-PG improved synchrony of estrus compared with MGA Select CIDR-GnRH-PG improved AI pregnancy rate over MGA Select Kojima et al., 2004

COWS

How do MGA-based protocols perform in synchronizing estrus in mixed populations of postpartum beef cows? (estrous cycling and anestrus)

Precise control of the bovine estrous cycle requires the synchronization of both luteal and follicular functions.

Protocols MGA Select GnRH PG PG 7-11 Synch GnRH PG Treatment day MGA (14 days) 1 14 26 33 PG 7-11 Synch GnRH PG MGA 1 7 11 18 Treatment day Kojima et al., 2000; Wood et al., 2001

These protocols were hypothesized to…… Improve estrous response and pregnancy rates during the synchronized period Effectively synchronize estrus in estrous cycling cows Induce cyclicity in anestrous cows Prevent short cycles among anestrous cows induced to ovulate

These protocols were hypothesized to…… Reduce the period of time required to detect estrus Facilitate fixed-time AI

How do MGA Select and 7-11 Synch compare on the basis of synchronized estrus and pregnancy rates in postpartum beef cows with AI performed on the basis of detected estrus?

MGA Select vs. 7-11 Synch AI performed after detected estrus No difference in estrous response Improvement in synchrony of estrus among 7-11 Synch treated cows (P < 0.01) No difference in synchronized conception or pregnancy rates No difference in final pregnancy rate Stegner et al., 2004

Stegner et al., 2004 45 MGA Select 40 7-11 Synch 35 30 25 Cows in estrus, no 20 15 10 5 12 24 36 48 60 72 84 96 108 120 132 144 NR Time after PG, h Stegner et al., 2004

Pregnancy Rates of Cows Inseminated after Detected Estrus No. (%) MGA Select Patterson et al., 2001 67/103 65 Patterson et al., 2002 67/101 66 Stegner et al., 2003 61/109 56 Combined total 195/313 62 7-11 Synch Kojima et al., 2001 30/44 68 Stegner et al., 2003 71/111 64 Combined total 101/155 65

How do MGA Select and 7-11 Synch compare on the basis of pregnancy rates in postpartum beef cows inseminated at predetermined fixed times?

MGA Select Time of AI after PG Pregnancy rate 48 hr 46% 72 hr 61% Stevenson et al., 2003 48 hr 46% Perry et al., 2002 72 hr 61% Stegner et al., 2003 72 hr 80 hr 64% 50%

7-11 Synch Time of AI after PG Pregnancy rate 48 hr 72% 48 hr 60 hr Hixon et al., 2001 48 hr 72% Kojima et al., 2003 48 hr 60 hr 52% 59% Unpublished data., 2002 60 hr 61% Kojima et al., 2002 60 hr 63% Kojima et al., 2003 60 hr 63%

Bader et al. (2004) compared pregnancy rates resulting from fixed-time AI among suckled beef cows assigned to the MGA Select or 7-11 Synch protocols.

Protocols AI MGA Select GnRH GnRH PG AI PG 7-11 Synch GnRH GnRH PG MGA (14 days) 1 14 26 33 … … … 72 hr AI PG 7-11 Synch GnRH GnRH PG MGA 1 7 11 18 … … 60 hr Treatment day Bader et al., 2004

Days postpartum, body condition score, and estrous-cycling status prior to initiation of synchronization treatments Location Days postpartum Body condition score Estrous cycling No. % 1 50 ± 1.0a 5.8 ± 0.1a 64/208 31a 2 39 ± 1.3b 31/122 25a,b 3 36 ± 1.5b 5.4 ± 0.1b 18/92 20b Combined 42 d 5.7 113/422 27 a,b(P < 0.05) Bader et al., 2004

Fixed-time AI and final pregnancy rates Location Treatment Fixed-time AI Final No. % 1 7-11 Synch 64/104 62 95/104 91 MGA Select 68/104 65 101/104 97 2 34/60 57 57/59 43/62 69 60/62 3 30/45 67 43/45 96 31/47 66 42/47 89 Combined 128/209 61 195/208 94 142/213 203/213 95 Bader et al., 2004

Fixed-time AI pregnancy rate based on pretreatment estrous cyclicity status MGA Select 7-11 Synch Cycling Anestrus Location No. Preg % No Preg 1 20/30 67 48/74 65 24/34 71 40/70 57 2 12/16 75 31/46 9/15 60 25/45 56 3 6/8 25/39 64 8/10 80 22/35 63 Combined 38/54 70 104/159 41/59 69 87/150 58 Bader et al., 2004

Pros and Cons Advantages Disadvantages MGA Select - effective in mixed - treatment length populations - MGA intake - synchrony of estrus - fertility after treatment 7-11 Synch - effective in mixed - multiple populations animal handlings - exceptional synchrony - drug costs of estrus - MGA intake - fertility after treatment - treatment duration

Pregnancy rates after AI based on detected estrus or at predetermined fixed times No. (%) 7-11 Synch Detected estrus 101/155 65 Fixed-time AI 446/728 61 MGA Select Detected estrus 195/313 62 Fixed-time AI 281/436 64

Implications This sequential approach to estrous cycle control (progestin-GnRH-PG) effectively synchronizes estrus with resulting high fertility among mixed populations of estrous cycling and anestrous postpartum beef cows.

How do MGA- and CIDR-based protocols compare on the basis of pregnancy rates in postpartum beef cows inseminated at predetermined fixed times?

MGA Select vs. CO-Synch + CIDR Schafer, 2005 GnRH PG GnRH MGA (14 d) AI 1 14 26 33……… GnRH PG GnRH CIDR (7 d) AI 0 7………. Treatment day

Timing of Insemination Time of AI Pregnancy Protocol after PG rate MGA Select Stevenson et al., 2003 48 h 46% Perry et al., 2002 72 h 61% Bader, 2004 72 h 67% Stegner et al., 2004 72 h 64% 80 h 50% CO-Synch + CIDR Lamb et al., 2000 48 h 56% 48 h 56% Bremer et al., 2004 54 h 67% 66 h 71% Larson et al., 2004 60 h 54%

MGA Select vs. CO-Synch + CIDR Schafer, 2005 AI GnRH PG GnRH MGA (14 d) 1 14 26 33 …… 72h AI GnRH PG GnRH CIDR (7 d) 0 7 …... 66h Treatment day

Experimental Procedures Schafer, 2005 Animals: Crossbred, suckled, beef cows (n = 650) at four locations were assigned to treatment within age groups by calving date and BCS

Experimental Procedures Schafer, 2005 Four different AI sires were used Location 1 = 3 Location 2 = 1 Location 3 = 1 Location 4 = 1 One of the sires that was used at location 1 was the same sire used at Locations 3 & 4

Experimental Procedures Schafer, 2005 Cows were exposed to fertile bulls 14 d after AI Pregnancy rate to fixed-time AI was determined with ultrasound 40 – 45 d after insemination

Number of cows at each location, DPP, BCS, and estrous-cycling status prior to initiation of synchronization treatments (Schafer, 2005) Location Days postpartum Body condition score Estrous cycling No. % 1 46 5.7 112/210 53 2 33 6.0 63/158 40 3 44 5.3 31/88 35 4 43 156/194 80 Combined 42 d 5.5 362/650 56

Fixed-time AI pregnancy rates between treatments and among locations (Schafer, 2005) No. % 1 MGA Select 70/106 66 CO-Synch+CIDR 67/104 64 2 53/80 56/78 72 3 26/45 58 29/43 67 4 52/96 54 62/98 61

Pregnancy rates to fixed-time AI Schafer, 2005 Treatment No. % MGA Select 201/327 61 CO-Synch+CIDR 214/323 66

Fixed-time AI pregnancy rate based on pretreatment estrous cyclicity status (Schafer, 2005) MGA® Select CO-Synch+CIDR Cycling Anestrus Location No. Preg % No Preg 1 38/62 61 32/44 73 30/50 60 37/54 69 2 20/29 33/51 65 25/34 74 31/44 70 3 11/16 15/29 52 8/15 53 21/28 75 4 41/78 11/18 50/78 64 12/20 Combined 110/185 59 91/142 113/177 101/146

Conclusions Schafer, 2005 The results from this experiment demonstrate that comparable pregnancy rates to fixed-time AI can be achieved using the MGA Select or CO-Synch+CIDR protocols to synchronize estrus in postpartum beef cows.

Do we know what to expect at calving from cows that conceive on the same day to the same sire?

Days relative to 285 d gestation due date; Bader et al., 2004 5 10 15 20 25 -13 -12 -11 -10 -9 -8 -7 -6 -5 -4 -3 -2 -1 1 2 3 4 6 7 8 5 10 15 20 25 -10 -9 -8 -7 -6 -5 -4 -3 -2 -1 1 2 3 4 A; Angus; +6.2 BW 272-292, 20 d B; Angus; +3.3 BW 275-292, 17 d 5 10 15 20 25 -11 -10 -9 -8 -7 -6 -5 -4 -3 -2 -1 1 2 3 4 5 10 15 20 25 -10 -9 -8 -7 -6 -5 -4 -3 -2 -1 1 2 3 4 6 7 8 9 C; Red Angus; –1.5 BW, 2 CED 274-289, 15 d D; Simmental; -0.6 BW, +14.8 CE 275-294, 19 d 25 B; Angus; +3.3 BW 274-291, 17 d 20 % of AI calves born 15 10 5 -11 -10 -9 -8 -7 -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 Days relative to 285 d gestation due date; Bader et al., 2004

Location 1; Sire A (Angus) BW EPD -0 Location 1; Sire A (Angus) BW EPD -0.3; CED = +11 Range 271-290 Mean = 281 Location 1; Sire B (Angus) BW EPD +3.5; CED = +6 Range 275-292 Mean = 281 Location 1; Sire C (Angus) BW EPD -1.1; CED = +11 Range 274-287 Mean = 281 Location 2; Sire D (Red Angus) BW EPD +2.3; CED = -2 Range 273-300 Mean = 283 Location 3; Sire B (Angus) BW EPD +3.5; CED = +6 Range 272-294 Mean = 283 Location 4; Sire B (Angus) BW EPD +3.5; CED = +6 Range 275-294 Mean = 284

Calving Distribution of AI sired calves (Schafer et al., 2005)

Consider the impact of estrus synchronization on calving distribution………

Hughes, 2005 Opportunities for increasing profits lie in managing females from the later calving intervals forward toward the first and second calving intervals. High production herds see 61% of the calves born by day 21, 85% by day 42 and 94% by day 63.

Stegner et al., 2004 100 MGA Select 90 7-11 Synch 80 70 Cows calving, % 60 50 40 30 20 10 First 15 d First 30 d Calving period Stegner et al., 2004

Calving distribution for locations 1, 2, & 3 (Schafer, 2005) Cumulative Calf % by: day 15 = 64% day 21 = 70% day 30 = 77% day 42 = 91%

MU Forage Systems Research Center cumulative calf crops

Cumulative calf crops (MU Thompson Farm) for the first 46 days over 10 calving seasons

Conclusions and Implications

Treatment Estrous response Pregnancy rate AI based on Estrous response and fertility in postpartum beef cows after treatment with various estrus synchronization protocols. Treatment Estrous response Pregnancy rate AI based on detected estrus No. % No. % 2 shot PG Select Synch* MGA-PG MGA Select 7-11 Synch 241/422 57 353/528 67 305/408 75 275/313 88 142/155 92 147/422 35 237/528 45 220/408 54 195/313 62 101/155 65 Fixed-time AI MGA Select 7-11 Synch CO-Synch + CIDR 482/763 63 446/728 61 214/323 66 * DeJarnette and Wallace

Treatment Estrous response Pregnancy rate Estrous response and fertility in postpartum beef cows after treatment with various estrus synchronization protocols. Treatment Estrous response Pregnancy rate AI based on detected estrus No. % No. % 2 shot PG Select Synch* MGA-PG MGA Select 7-11 Synch 241/422 57 353/528 67 305/408 75 275/313 88 142/155 92 147/422 35 237/528 45 220/408 54 195/313 62 101/155 65 Fixed-time AI MGA Select 7-11 Synch CO-Synch + CIDR 482/763 63 446/728 61 214/323 66 * DeJarnette and Wallace

Total 786 1217 CO-Synch + CIDR Results (FTAI @ 66 hr after PG) Herd (Year) No. Pregnant Total No. Percentage 1 (F03) 41 51 80 2 (S04) 67 104 64 3 (S04) 56 78 72 4 (S04) 29 43 5 (S04) 52 96 63 6 (S04) 60 90 7 (F04) 31 48 65 8 (F04) 87 143 61 9 (F04) 100 10 (F04) 44 69 11 (F04) 68 111 12 (F04) 47 13 (S05 224 Total 786 1217

Research is underway to develop new protocols for heifers that will facilitate fixed-time AI …. The technology now exists to successfully inseminate postpartum beef cows at predetermined fixed times with resulting high pregnancy rates . . . . . . . . .

Improvements in methods to synchronize estrus create the opportunity to significantly expand the use of AI in the U.S. cowherd . . . . . . .

Acknowledgements Faculty, Students, & Staff Jon Bader Dr. George Perry Roger Eakins Daniel Schafer Dr. Mark Ellersieck Jon Schreffler Freddie Kojima Dr. Mike Smith Dr. Matthew Lucy Jacob Stegner David McAtee Stacey Wood (Follis)

Acknowledgements Research Support Cooperators Select Sires, Inc. 4-M Ranch KABA/Select Sires, Inc. John Ranch ABS Global Jim Wallis Farms Merial Jim Clement, DVM Pfizer Animal Health SEMO University USDA-NRI MFA, Inc. MU Farms & Centers

Acknowledgements Beef Reproduction Leadership Team AI industry Pharmaceutical industry Veterinary practitioners North Central Region Bovine Reproduction Task Force