The Evolution and Implementation of Reproductive

Synchronization ProtocolsRepro Protocology 101

Paul M. Fricke, Ph.D. Professor of Dairy Science University of Wisconsin-Madison

Paul M. Fricke , Ph.D.

SynchTimeline 1980 201020052000199519901985

Paul M. Fricke , Ph.D.

ManipulatingLuteal

Functionin Cattle

Paul M. Fricke , Ph.D.

1956 Hysterectomy was shown to extend luteal lifespan in cattle (Wiltbank and Casida, J Anim Sci 15:134-140)

Mechanism of

Luteolysisin Cattle

Paul M. Fricke , Ph.D.

1967 – Removal of the uterine horn ipsilateral to the CL prevented luteal regression, whereas regression occurred normally when the uterine horn contralateral to the CL was removed (Ginther et al., J Reprod Fertil 14:225-229)

Paul M. Fricke , Ph.D.

Conclusions:1) The luteolytic

substance originates from the uterus

2) Luteolysis is a local rather than a systemic process

Paul M. Fricke , Ph.D.

1979 – Lutalyse approved for use in cattle by the FDA

Dinoprost TromethamineNaturally occurring PGF2 in the form of the

tromethamine saltLutalyse® – Pfizer

Cloprostenol SodiumSynthetic analog of PGF2

Estrumate® – Intervet

A Brief History of Prostaglandin

Paul M. Fricke , Ph.D.

Targeted Breeding SystemUpjohn - 1980

14 Days

PGF2 PGF2

Estrus Estrus

PGF2

14 Days

TAI (80h)

46% CR 46% CR 4% CR

Paul M. Fricke , Ph.D.

1980Targetedbreedingsystem

SynchTimeline 1980 201020052000199519901985

1979Lutalyseapprovedfor use in

cattle

Paul M. Fricke, Ph.D.

Follicular Function during the Reproductive Cycle

OvarianFollicle

CorpusLuteum

Paul M. Fricke , Ph.D.

New Technology

1986O.J. Ginther at WisconsinJ. E. Fortune at Cornell

Paul M. Fricke , Ph.D.

Progesterone

10Ovulation 21

Follic

ula

r S

ize

Day After Ovulation

Recruitment

Deviation

Dominance

Atresia Ovulation

Follicular Waves

Paul M. Fricke , Ph.D.

1980Targetedbreedingsystem

Synch Timeline 1980 201020052000199519901985

1979Lutalyseapprovedfor use in

cattle

1986Follicular

wavesdiscovered

Paul M. Fricke, Ph.D.

6 Days

GnRH PGF2

GnRH - PGFTwagiramungu et al., 1990

EDAI

Paul M. Fricke, Ph.D.

Twagiramungu et al., 1990

0 1 2 3 4 5 6 7 8 9 100

10

20

30

40

50Saline - PGF

GnRH - PGF

Day of Experiment

% o

f cow

s in

est

rus

GnRHorSaline PGF

73% of cows detected in estrus onD 7 and 8 in the GnRH – PGF group

Paul M. Fricke, Ph.D.

7 Days 48 h

GnRH PGF2 GnRH

16 h

TAI

Pursley and Wiltbank, 1995

Paul M. Fricke, Ph.D.

Ovsynch Schedule

Sun Mon Tue Wed Thu Fri Sat

GnRH

PGF GnRH TAI

Paul M. Fricke, Ph.D.

Ovsynch Schedule

Sun Mon Tue Wed Thu Fri Sat

GnRH

PGF GnRH TAI

Distribution of DIM at 1st AI Service: Farm 1

Fresh Date

DIM

at

1st A

I

Jun, 2001Mar, 2000

Distribution of DIM at 1st AI Service: Farm 2

Fresh Date

DIM

at

1st A

I

Jun, 2004Nov, 2003

Paul M. Fricke , Ph.D.

1980Targetedbreedingsystem

Synch Timeline 1980 201020052000199519901985

1979Lutalyseapprovedfor use in

cattle

1986Follicular

wavesdiscovered

1995Ovsynchprotocol

published

Paul M. Fricke, Ph.D.

56 h

GnRH

PGF2α

GnRH

7 days

14 days

12 days

PGF2α PGF2α

TAI

16 h

Moriera et al., 2001

Paul M. Fricke, Ph.D.

Conception Rate to TAI Ovsynch vs. Presynch – 12 d interval

Ovsynch Presynch0

10

20

30

40

50

60

29

4336

48

Florida Kansas

%

n=262 n=272 n=264 n=278

Paul M. Fricke, Ph.D.

Presynch/Ovsynch 14/12

Sun Mon Tue Wed Thu Fri Sat

PGF

PGF

GnRH

PGF GnRH TAI

Paul M. Fricke, Ph.D.

56 h

GnRH

PGF2α

GnRH

7 days

14 days

10 to 12 days

PGF2α PGF2α

TAI

16 h

EDAI

Paul M. Fricke , Ph.D.

Frequency of AI Relative to the Second PGF Injection of Presynch

Paul M. Fricke , Ph.D.

1980Targetedbreedingsystem

Synch Timeline 1980 201020052000199519901985

1979Lutalyseapprovedfor use in

cattle

1986Follicular

wavesdiscovered

1995Ovsynchprotocol

published

2001PresynchOvsynchprotocol

published

PM Fricke, PhD

GnRH

PGF2

GnRHPGF2 PGF2

Compliance – Presynch/OvsynchOn any given day, 95% of your cows get the correct injection

0.95 x 0.95 x 0.95 x 0.95 x 0.95 = 77%

0.9 x 0.9 x 0.9 x 0.9 x 0.9 = 59%

To Resynch or Not to Resynch

That is the question….

Presynch/Ovsynch & Resynch

Paul M. Fricke, Ph.D.

0

R

G+TAI

G

19

T

26

T

US+P

28

R

G+TAI

US+G

26

T

33 35

T R

P G+TAI

US+G

33

T

40 42

T R

P G+TAI

23%(28/120

)

34%(41/121

)

38%(54/143

)Fricke et al., J. Dairy Sci. 86:3941-3950; 2003

n=711

Paul M. Fricke , Ph.D.

Synch and Resynch

0

G

T T R

P G TAI

R

P

R

PPresynch / Ovsynch for

first TAI

Resynch for nonpregnant cows

F

G

32

T

39 41

T R

P G TAI

42

F

Paul M. Fricke , Ph.D.

1980Targetedbreedingsystem

Synch Timeline 1980 201020052000199519901985

1979Lutalyseapprovedfor use in

cattle

1986Follicular

wavesdiscovered

1995Ovsynchprotocol

published

2001PresynchOvsynchprotocol

published

2003Resynchprotocol

comparisonpublished

Comparison among Cosynch and Ovsynch 56 protocolsBrusveen et al., 2008. J. Dairy Sci. 91:1044-1052.

Cows were submitted for TAI after Presynch or as Resynch treatment

1507 TAI in 927 lactating Holstein cows

GnRH PGF GnRH +TAI

7 Days 48 h

7 Days 72 h

GnRH PGF GnRH +TAI

7 Days 56 h

GnRH PGF GnRH TAI

16 h

Cosynch48

Ovsynch56

Cosynch72

CR d 31-33 (%) 27 (494) 36 (494) 27 (494)

Least squares est. 29a 39b 25a

CR d 52-54 (%) 25 (493) 33 (494) 25 (494)

Least squares est. 27a 36b 23a

Preg. Loss (%) 5 (131) 5 (158) 7 (137)

a,b Within a row, treatments differ (P<0.05)

Effect of Treatment on conception rate and pregnancy loss Brusveen et al., 2008. J. Dairy Sci. 91:1044-1052.

Paul M. Fricke , Ph.D.

1980Targetedbreedingsystem

Synch Timeline 1980 201020052000199519901985

1979Lutalyseapprovedfor use in

cattle

1986Follicular

wavesdiscovered

1995Ovsynchprotocol

published

2001PresynchOvsynchprotocol

published

2003Resynchprotocol

comparisonpublished

2008Ovsynch56

protocolpublished

Future Directions

Paul M. Fricke, Ph.D.

Paul M. Fricke, Ph.D.

Paul M. Fricke, Ph.D.

D 7 D 10 D 13 D 15 D 20 D 26 D 28 D 30 D 34 D 37 D 40 D 42 D 45 D 48 D 50 D 53

0

5

10

15

20

25

30

5193 Short Luteal PhaseS

ize

(m

m)

Paul M. Fricke, Ph.D.

D 5 D 7 D 9 D 12

D 14

D 16

D 19

D 21

D 23

D 26

D 28

D 30

D 33

D 35

D 37

D 40

D 42

D 44

D 47

D 49

D 51

D 54

D 56

D 58

D 61

D 63

D 65

D 68

D 70

D 72

2

4

6

8

10

12

14

4615 Anovular

PM Fricke, Ph.D.

D 7 D 9 D 11 D 14 D 16 D 18 D 21 D 23 D 25 D 28 D 30 D 32 D 35 D 37 D 39 D 42 D 44 D 46 D 49 D 51 D 53 D 56 D 58 D 60 D 63 D 65 D 67 D 70

0

5

10

15

20

25

4689 Anovular

PM Fricke, Ph.D.

D 7 D 9 D 12 D 14 D 16 D 19 D 21 D 23 D 26 D 28 D 30 D 33 D 35 D 37 D 40 D 42 D 44 D 47 D 49 D 51 D 54 D 56 D 58 D 61 D 65 D 68 D 70 D 72

0

5

10

15

20

25

30

35

40

4642 Short luteal phase + cystic S

ize

(m

m)

Paul M. Fricke, PhD

18%

31%

6%

52%

0

10

20

30

40

50

60

70

P/AI (61 d) Loss (33-61 d)

CR

/AI (

%)

Anovular Cycling

n=105 n=274

Effect of Cyclicity Status on P/AI and Pregnancy Loss after first TAISterry et al., 2006; J Dairy Sci 89:4237

Paul M. Fricke, Ph.D.

Double Your Pleasure Double Your Fun

Paul M. Fricke, Ph.D.

Double Ovsynch ScheduleSouza et al., 2009

Sun Mon Tue Wed Thu Fri Sat

GnRH

PGF

GnRH

GnRH

PGF GnRH TAI

Paul M. Fricke, Ph.D.

Effect of synchronization protocol on pregnancies per AI, DIM, lactation number, BCS and locomotion score in lactating dairy cowsSouza et al., Theriogenology 2009

Double Ovsynch

Presynch Ovsynch P-value

P/AI (%) 50 (78/157)

42(75/180)

0.03

DIM (range) 77.0 ± 0.16(74 – 81)

77.2 ± 0.15(74 – 81)

0.57

Lactation Number (range)

2.2 ± 0.12(1 –11)

2.4 ± 0.13(1 – 10)

0.64

BCS (range) 2.91 ± 0.03(2.25 – 4.00)

2.89 ± 0.02(2.25 – 4.25)

0.54

Locomotion Score (range)

1.45 ± 0.08(1 – 5)

1.48 ± 0.07(1 – 4)

0.34

Presynch Ovsynch Double Ovsynch0

10

20

30

40

50

60

70

80

45

65

39 38

PrimiparousMultiparous

Effect of treatment onfertility 39 to 45 d after TAISouza et al., 2009

Effect P-value

Treatment 0.03

Parity 0.02

n=73 n=88n=107 n=69

Paul M. Fricke , Ph.D.

1980Targetedbreedingsystem

Synch Timeline 1980 201020052000199519901985

1979Lutalyseapprovedfor use in

cattle

1986Follicular

wavesdiscovered

1990GnRH

+PGF

protocolpublished

1995Ovsynchprotocol

published

2001PresynchOvsynchprotocol

published

2003Resynchprotocol

comparisonpublished

2008Ovsynch56

protocolpublished

2009Double

Ovsynchprotocol

published

Paul M. Fricke , Ph.D.

Paul M. Fricke, Ph.D.

5-Day Ovsynch Protocol

Sun Mon Tue Wed Thu Fri Sat

GnRH

PGF PGF GnRH TAI

Maximize Fertility

Minimizeinterbreeding

interval

IdealResynch

Comparison among Resynch protocolsGiordano et al., unpublished.

7 Days 56 h

GnRH PGF GnRH TAI

16 h

7 Days 56 h

GnRH PGF GnRH TAI

16 h

7 Days 56 h

GnRH PGF GnRH TAI

16 h

GnRH

hCG

d 18 d 25 d 32 d 34 d 35

33%n=346

31%n=361

25%n=375