1. The Evolution and Implementation of Reproductive Synchronization ProtocolsRepro Protocology 101 Paul M. Fricke, Ph.D. Professor of Dairy Science University of Wisconsin-Madison

2. SynchTimeline 1980 2010 2005 2000 1995 1990 1985

3. Manipulating Luteal Function in Cattle

4. Mechanism of Luteolysis in Cattle 1956Hysterectomy was shown to extend luteal lifespan in cattle (Wiltbank and Casida, J AnimSci 15:134-140)

5. 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 ReprodFertil 14:225-229)

6. Conclusions: 1) The luteolytic substance originates from the uterus 2) Luteolysis is a local rather than a systemic process

7. A Brief History of Prostaglandin 1979– Lutalyse approved for use in cattle by the FDA DinoprostTromethamine Naturally occurring PGF2 in the form of the tromethamine salt Lutalyse® – Pfizer Cloprostenol Sodium Synthetic analog of PGF2 Estrumate® – Intervet

8. PGF2 PGF2 PGF2 TAI (80h) Targeted Breeding SystemUpjohn - 1980 46% CR 46% CR 4% CR Estrus Estrus 14 Days 14 Days

9. 1979 Lutalyse approved for use in cattle 1980 Targeted breeding system SynchTimeline 1980 2010 2005 2000 1995 1990 1985

10. Follicular Function during the Reproductive Cycle Ovarian Follicle Corpus Luteum

11. New Technology 1986 O.J. Ginther at Wisconsin J. E. Fortune at Cornell

12. Progesterone Ovulation Atresia Follicular Size Dominance Deviation Recruitment 10 Ovulation 21 Follicular Waves Day After Ovulation

13. 1979 Lutalyse approved for use in cattle 1986 Follicular waves discovered 1980 Targeted breeding system Synch Timeline 1980 2010 2005 2000 1995 1990 1985

14. GnRH PGF2 GnRH - PGF Twagiramungu et al., 1990 6 Days EDAI

15. 73% of cows detected in estrus on D 7 and 8 in the GnRH – PGF group GnRH or Saline PGF Twagiramungu et al., 1990

16. Ovsynch Pursley and Wiltbank, 1995 GnRH PGF2 GnRH TAI 7 Days 48 h 16 h

17. Ovsynch Schedule

18. Ovsynch Schedule

19. Jun, 2001 Mar, 2000 Distribution of DIM at 1st AI Service:Farm 1 DIM at 1st AI Fresh Date

20. Jun, 2004 Nov, 2003 Distribution of DIM at 1st AI Service:Farm 2 DIM at 1st AI Fresh Date

21. 1979 Lutalyse approved for use in cattle 1986 Follicular waves discovered 1995 Ovsynch protocol published 1980 Targeted breeding system Synch Timeline 1980 2010 2005 2000 1995 1990 1985

22. Pre-Synch Ovsynch Moriera et al., 2001 PGF2α TAI GnRH GnRH PGF2α PGF2α 7 days 16 h 12 days 56 h 14 days

23. Conception Rate to TAI Ovsynch vs. Presynch – 12 d interval n=262 n=272 n=264 n=278

24. Presynch/Ovsynch 14/12

25. Pre-Synch Ovsynch PGF2α TAI GnRH GnRH PGF2α PGF2α EDAI 10 to 12 days 16 h 7 days 56 h 14 days

26. Frequency of AI Relative to the Second PGF Injection of Presynch

28. 1979 Lutalyse approved for use in cattle 1986 Follicular waves discovered 1995 Ovsynch protocol published 2001 Presynch Ovsynch protocol published 1980 Targeted breeding system Synch Timeline 1980 2010 2005 2000 1995 1990 1985

29. PGF2 GnRH GnRH PGF2 PGF2 Compliance –Presynch/Ovsynch On 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%

30. To Resynch or Not to Resynch That is the question….

31. Presynch/Ovsynch & Resynch

32. G US+P G+TAI 23% (28/120) 19 26 28 T T R US+G G+TAI P 34% (41/121) 26 33 35 T T R US+G G+TAI P 38% (54/143) 33 40 42 T T R n=711 G+TAI 0 R Fricke et al., J. Dairy Sci. 86:3941-3950; 2003

33. G P G TAI T T R F 32 39 41 42 Synch and Resynch Presynch/ Ovsynch for first TAI G TAI P G P P R T T R R F 0 Resynch for nonpregnant cows

34. 1979 Lutalyse approved for use in cattle 1986 Follicular waves discovered 1995 Ovsynch protocol published 2001 Presynch Ovsynch protocol published 1980 Targeted breeding system 2003 Resynch protocol comparison published Synch Timeline 1980 2010 2005 2000 1995 1990 1985

35. GnRH PGF GnRH +TAI 48 h 7 Days GnRH PGF TAI GnRH GnRH PGF GnRH +TAI 7Days 56 h 16 h 7 Days 72 h 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

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

37. 1979 Lutalyse approved for use in cattle 1986 Follicular waves discovered 1995 Ovsynch protocol published 2001 Presynch Ovsynch protocol published 1980 Targeted breeding system 2003 Resynch protocol comparison published 2008 Ovsynch56 protocol published Synch Timeline 1980 2010 2005 2000 1995 1990 1985

38. Future Directions

45. Effect of Cyclicity Status on P/AI and Pregnancy Loss after first TAISterry et al., 2006; J Dairy Sci 89:4237 n=105 n=274

46. Double Your Pleasure Double Your Fun

47. Double Ovsynch ScheduleSouza et al., 2009

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

49. Effect of treatment onfertility 39 to 45 d after TAISouza et al., 2009 n=88 n=107 n=69 n=73

50. 1979 Lutalyse approved for use in cattle 1986 Follicular waves discovered 1990 GnRH + PGF protocol published 1995 Ovsynch protocol published 2001 Presynch Ovsynch protocol published 1980 Targeted breeding system 2003 Resynch protocol comparison published 2008 Ovsynch56 protocol published 2009 Double Ovsynch protocol published Synch Timeline 1980 2010 2005 2000 1995 1990 1985

52. 5-Day OvsynchProtocol

54. Comparison among Resynch protocolsGiordano et al., unpublished. GnRH PGF TAI GnRH 25% n=375 7Days 56 h 16 h GnRH PGF GnRH TAI GnRH 31% n=361 7Days 56 h 16 h GnRH PGF hCG TAI GnRH 33% n=346 7Days 56 h 16 h d 18 d 25 d 32 d 34 d 35