Date RECEPTAL® and ESTRUMATE® - short presentation of the products features MSD AH Animal Middle East Symposium Beirut 2012 Brought to you by Partners in Reproduction Health Platform Monika Ptaszynska, DVM, PhD Global Marketing and Technical Director Ruminant Reproduction and Uterine Health

2 RECEPTAL ® – meet the product Active: RECEPTAL ® contains buserelin a synthetic analogue of GnRH, in a concentration of 0.004mg/ml Formulation: Injectable solution for i.m., s.c and i.v. administration Presentations: 2.5ml, 5ml, 10ml, 50ml Indications for use in cattle: Therapeutic: -Treatment of COD Reproduction Management -Estrus induction and synchonization in various programs -Improvement of conception rates with administration at AI or at 10-12d post AI. Attention: RECEPTAL ® is also licensed for use in horses and rabbits

3 RECEPTAL® – the gentle power Buserelin, the active of RECEPTAL® was proven to offer very high potency, exceeding That of natural GnRH analogues (Chenault et al., 1990) and some synthetic ones (Driancourt et al.,2008). The potency of GnRH analogues is measured by evaluation of the magnitude of the LH release induced by administration of a standard clinical dose either in vivo or in vitro. Ability of an analogue to induce high quality LH release influences the efficacy of the product to induce ovulation and luteinization of the CL. Chenault et al. (1990): LH and FSH response of Holstein heifers to fertirelin acetate, gonadorelin and buserelin. Tested analogues (products): fertirelin acetate, buserelin (RECEPTAL®), gonadorelin (Cystorelin®, FERTAGYL®) Results: Standard recommended dose of buserelin (10mcg) was proven to be the most efficient in terms of LH release and duration of action among the GnRH analogues tested. Driancourt et a;. (2008):Potency of several GnRH agonists (Buserelin, Dalmarelin, Gonavet and Gonazon) versus natural GnRH (Cystorelin®) in an in vitro functional assay Results: Relative potency of buserelin measured in this set up exceeded that of lecirelin and gonadorein.

4 RECEPTAL® - treatment and improvement of fertility

5 ESTRUMATE ® – meet the product Active: ESTRUMATE ® contains cloprostenol a synthetic analogue of PGF2 . concentration 250mcg/ml cloprostenol Formulation: Injectable solution for i.m. administration Presentations: 10ml, 20ml, 50ml Indications for use in cattle: Therapeutic: -Treatment of CL persistent and luteal cysts -Auxillary treatment of endometritis -Suboestrus -Termination of abnormal pregnancy Reproduction Management -Estrus induction and synchonization in various programs -Induction of calving Attention: ESTRUMATE ® is also licensed for use in pigs and horses in some countries. Please check licensing conditions in your country

6 ESTRUMATE ® – the composition Cloprostenol, the active component of ESTRUMATE ® exists in two forms, so called isomers. Their molecules are structurally identical but look like mirror images of each other. They are called D and L isomers. Only the D isomer of cloprostenol is biologically active. ESTRUMATE ® is formulated as so called racemic mixture. It means that the product contains both D and L isomers of cloprostenol in equal quantities. This means that a clinical dose of ESTRUMATE ® in cattle contains 250mcg of the active isomer of cloprostenol. Amount of active isomer per ml Active isomer in 2ml dose ESTRUMATE ® 125mcg/ml250mcg

7 ESTRUMATE ® – high potency – reliable efficacy High concentration of the active isomer in a clinical dose Synthetic analogue = more potent and more resistant to metabolism than natural ones Fast and reliable luteolysis Fast and reliable decrease in progesterone levels Good quality of heat followed by fertility comparable to natural heat

8 ESTRUMATE® - a partner you can trust

9 Use of RECEPTAL ® and ESTRUMATE ® in the field – practical tips

10 Understand the physiological background – ensure high efficacy RECEPTAL® - almost all indications for the use in cattle reproduction base on induction of ovulation (estrus synchronization programs, fertility improvement at AI and post AI) clinical result can only be expected when a DF >10mm is present ESTRUMATE® - practically all uses in cattle base on luteolysis of the CL clinical result can only be expected when a CL sensitive to PG is present

11 Understand the physiological background – ensure high efficacy

12 Understand the physiological background – ensure high efficacy

13 Results of PGF administration vs. reproductive stage 5 d No result CL not sensitive to PGF2a 5-150d Luteolysis and abortion: CL sensitive to PGF2  and the only source of progesterone 150-approx. 270d Single dose of PGF2  will not cause abortion: both CL and placenta producing progesterone Last 1-2 weeks Induction of calving CL progesterone CL and placental progesterone This has practical consequences for the use of PGF:

14 Good understanding with the clients is essential… Direct result of PGF2  : luteolysis dramatic decrease of progesterone levels in blood How to detect: -Disappearance of corpus luteum: rectal palpation or ultrasound -Decrease in progesterone concentrations: progesterone test on milk or blood

15 Good understanding with the clients is essential… Indirect result of PGF2  : Disappearance of blocking heat and ovulation effect of progesterone Depends on: -Ability of the ovaries to respond: presence of a corpus luteum, presence of follicles able to grow and ovulate, adequate stimulation from the pituitary gland -Ability of the animal to demonstrate heat: body condition, general health, housing -Ability of the owner to correctly detect heat

16 RECEPTAL® & ESTRUMATE® - the perfect tandem Base of your reproduction management in cattle

17 Therapeutic possibilities based on RECEPTAL® and EsSTRUMATE® Routine estrus induction and synchonization Ovsynch and modifications Management of heat in summer months Ovsynch Treatment of COD with predictable service time Ovsynch, modified Ovsynch

18 Thank you very much for your kind attention Questions?