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plusetpluset®® Superovulation raised to maximum potency
PLUSET : MAIN FEATURES
Ramon CalongeLaboratorios Calier S.A.
Barcelona - Spain Presentation prepared by Calier and given at AETS Conference August 2004.
plusetpluset®® Superovulation raised to maximum potency
2 vials of freeze-dried powder:2 vials of freeze-dried powder:
• 500 IU FSH + 500 IU LH each500 IU FSH + 500 IU LH each
1 vial of diluent:1 vial of diluent:
• Normal saline to 20 mlNormal saline to 20 ml
plusetpluset®® Superovulation raised to maximum potency
BackgroundBackground
• Developed by Serono (Italy)Developed by Serono (Italy)
• First approval: 1991, in Italy. Later on in USA, Mexico, First approval: 1991, in Italy. Later on in USA, Mexico,
Argentina, Brazil, New Zealand.Argentina, Brazil, New Zealand.
• 1998: acquired 1998: acquired by Laboratorios Calier, S.A. Production plant by Laboratorios Calier, S.A. Production plant
moved to Barcelona (Spain). Settlement of the industrial extraction moved to Barcelona (Spain). Settlement of the industrial extraction
and production process.and production process.
• Approval in Colombia, Venezuela, Ecuador.Approval in Colombia, Venezuela, Ecuador.
• 2003: Approved in 5 EU member states (UK, DE, NL, ES, PT) 2003: Approved in 5 EU member states (UK, DE, NL, ES, PT)
• 2004: Approved in Australia2004: Approved in Australia
plusetpluset®® Superovulation raised to maximum potency
Frozen Pituitary GlandsFrozen Pituitary GlandsFrozen Pituitary GlandsFrozen Pituitary Glands
Acetonic Acetonic powderpowderAcetonic Acetonic powderpowder
Alcoholic Alcoholic powderpowderAlcoholic Alcoholic powderpowder
Crude FSH / LHCrude FSH / LHCrude FSH / LHCrude FSH / LH
SeparationSeparation phasephase (4 days)(4 days)
FSHFSH
LLHH
LLHH
FSFSHH
Acetonic phaseAcetonic phase (2 days)(2 days)
ExtractionExtraction phasephase (4 days)(4 days)
AlcoholicAlcoholic phase phase (3 (3 days)days)
Extraction MethodExtraction Method
plusetpluset®® Superovulation raised to maximum potency
FSHFSH
LLHH
LLHH
FSFSHH
Final productFinal product
Biological analysisBiological analysis
IU IU FSHFSH
IU LIU LHH
IU LIU LHH
IU IU FSHFSH
Vial fillingVial fillingLyophilisationLyophilisation
Biological analysisBiological analysis(to confirm activity)(to confirm activity)
Vial fillingVial fillingLyophilisationLyophilisation
Biological analysisBiological analysis(to confirm activity)(to confirm activity)
plusetpluset®® Superovulation raised to maximum potency
Biological analysisBiological analysis
FSH: Steelman & Pohley method FSH: Steelman & Pohley method (ovarian weight)(ovarian weight)
LH: Parlow method LH: Parlow method (Ascorbic Acid depletion)(Ascorbic Acid depletion)
• Described by the WHODescribed by the WHO
• The only ones accepted by pharmacopoeial The only ones accepted by pharmacopoeial
monographsmonographs to determine FSH and LH potency of to determine FSH and LH potency of
therapeutic preparationstherapeutic preparations
• Measures biologically active hormones Measures biologically active hormones
• No equivalence with other methods (RIA)No equivalence with other methods (RIA)
plusetpluset®® Superovulation raised to maximum potency
LH contentLH content
• The same proportion of the hMG The same proportion of the hMG
(human Menopausal Gonadotrophin)(human Menopausal Gonadotrophin)
• LH content is known and constantLH content is known and constant
• Proportion in weight is Proportion in weight is 25:1 25:1
• FSH t ½: 2:30 hFSH t ½: 2:30 h
• LH t ½: 40 minLH t ½: 40 min
plusetpluset®® Superovulation raised to maximum potency
Recommended Administration Schedule in Holstein-Friesian Dairy Cows - 800 I.U.
Day 1 AM
PM
Day 3 AM
PMDay 4 AM
PM
Day 2 AMPM
2.5 ml i.m.
2.5 ml i.m.
3 ml i.m.
3 ml i.m.
1 ml i.m.
1 ml i.m.
1.5 ml i.m.
1.5 ml i.m.
* 1 ml Pluset: 50 I.U. FSH + 50 I.U. LH
Start treatment between 9th and 12th dayof the cycle, preferably on 11th day
Onset of oestrus
PGF2
•2 AI: Inseminate at 12h and 24h of onset of oestrus
•3 AI: Inseminate at 12h, 24h and 36h of onset of oestrus
•Optional: add a dose of GnRH or hCG at 1st AI to induce a contemporaneous ovulation
•Flushing at 6-8 days (7 days) of the 1st AI
PGF2
plusetpluset®® Superovulation raised to maximum potency
Day 1 AM
PM
Day 3 AM
PMDay 4 AM
PM
Day 2 AMPM
2 ml i.m.
2 ml i.m.
2.5 ml i.m.
2.5 ml i.m.
1 ml i.m.
1 ml i.m.
1.5 ml i.m.
1.5 ml i.m.
Onset of oestrus
PGF2
• Beef cows: 600-700 I.U. • Beef heifers: 500 I.U. • Dairy heifers: 500 I.U. • Bos Indicus (zebu): 200-300 I.U. • Buffalo: 250 I.U. • Sheep: 250-350 I.U.
PGF2
AI
* 1 ml Pluset: 50 I.U. FSH + 50 I.U. LH
Recommended Administration Schedule in Spain in Beef cows - 700 I.U.
plusetpluset®® Superovulation raised to maximum potency
Use of different commercial FSH preparations in the superovulation of high producing Holstein cows
Fuentes, S. and De la Fuente, J.
Proceedings, XXI World Buiatrics Congress.Punta del Este, Uruguay, 2000
Total dose: 850 IU
Day 1: PRID insertionDay 9: 175 IU + 175 IUDay 10: 125 IU + 125 IUDay 11: 75 IU + 75 IU
PRID removalPG (AM and PM)
Day 12: 50 IU + 50 IU
Holstein Cows, 5-6 years old3-4 calvingsInterval calving-SOV treatment: 5.8-6.5 monthsMean milk prod: 27-30 kg/day
n Totalembryos
Unfertilisedembryos
Transferableembryos
Pluset 66 9.4 ± 4.7 2.3 ± 2.6 6.2 ± 4.0a
Ovagen 35 7.3 ± 4.8 2.1 ± 2.8 3.9 ± 3.4b
FSH-p 33 7.8 ± 5.2 3.7 ± 4.3 3.2 ± 2.9c
a vs b: P< 0.05. a vs c: P< 0.001
plusetpluset®® Superovulation raised to maximum potency
Study of different doses of Pluset for the lactating cow superovulation
Fuentes, S. and De la Fuente, J.Unpublished data
Holstein Cows, 5 years old2.5 calvingsInterval calving-SOV : 6 months
800 IU 850 IU 1000 IUAM PM AM PM AM PM
Day 9 150 IU 150 IU 175 IU 175 IU 175 IU 175 IUDay 10 125 IU 125 IU 125 IU 125 IU 150 IU 150 IUDay 11 75 IU 75 IU 75 IU 75 IU 100 IU 100 IUDay 12 50 IU 50 IU 50 IU 50 IU 75 IU 75 IU
Day 1: PRID insertionDay 11: PRID removal
PG (AM and PM)
Dose N Total embryos Transferableembryos
Unfertilised ova
800 30 10,9 5,3a 6,9 4,1a 2,8 2,5850 75 9,5 5,1ab 5,9 3,9ab 3,1 3,1
1000 30 7,2 4,2b 4,2 3,0b 2,7 3,2a vs b: P< 0.01
plusetpluset®® Superovulation raised to maximum potency
Study of the effect of a similar dose of PLUSET over dairy cows with different parity number
Fuentes, S. and De la Fuente, J.
Unpublished dataHolstein CowsInterval calving-SOV : 4.5-6 months
Group A, First calving. n= 12.Group B, Second calving. n= 14.Group C, Third calving. n= 17.Group D, Fourth calving. n= 14.
Total dose: 850 IU
Day 1: PRID insertionDay 9: 175 IU + 175 IUDay 10: 125 IU + 125 IUDay 11: 75 IU + 75 IU
PRID removalPG (AM and PM)
Day 12: 50 IU + 50 IU
Calving N E.TOT E.VIA NF1 12 9,2 ± 5,9 7,1 ± 3,9 a 1,2 ± 1,3 a
2 14 9,8 ± 4,1 7,8 ± 3,1 a 0,9 ± 0,9 a
3 17 10,7 ± 4,7 7,1 ± 4,5 a 2,9 ± 2,6 a
4 14 9,0 ± 2,3 5,7 ± 2,5 a 2,7 ± 2,2 a
ETOT: Total embryos mean. EVIA: Viable embryos mean.NF: Non-fecundated ova.
a vs. b: P<0.05
plusetpluset®® Superovulation raised to maximum potency
Superovulation with different doses of PLUSET in relation to parturition number in high production dairy cows
Fuentes, S. and De la Fuente, J.
IX Jornadas sobre Producción Animal, ITEA, Zaragoza, abril’01
800 IU 850 IU 1000 IUAM PM AM PM AM PM
Day 9 150 IU 150 IU 175 IU 175 IU 175 IU 175 IUDay 10 125 IU 125 IU 125 IU 125 IU 150 IU 150 IUDay 11 75 IU 75 IU 75 IU 75 IU 100 IU 100 IUDay 12 50 IU 50 IU 50 IU 50 IU 75 IU 75 IU
Day 1: PRID insertionDay 11: PRID removal
PG (AM and PM)
Group A, 800 IU, one calving. n= 15
Group B, 850 IU, two calving. n= 15
Group C, 1000 IU, three calving. n= 14
Interval calving-SOV : 6 months (3-7 m)
Calving Dose N ETOT EVIA NF1 800 15 11,1 4,1 8,5 4,0 1,7 1,02 850 15 9,5 4,6 7,7 3,0 1,1 1,43 1000 14 9,6 4,0 8,3 2,8 1,0 2,4
ETOT: Total embryos EVIA: Viable embryos NF: Non-fecundated ova
plusetpluset®® Superovulation raised to maximum potency
Superovulation of Holstein-Friesian cows with reduced dose of FSH-pBényei B, Barros CWC
Arq. Fac. Vet. UFRGS, Porto Alegre, V. 27, n. 1, 1999 (supl.): p. 203
Control: 1000 IU FSH/4 days (n=99)
Experiment: 600 IU FSH/4 days (n=83)
PG at the 3rd day; AI at 45 and 60h
600 IU 1000 IUNo. Ovulations 13.6 6.0 12.3 6.9Good quality embryos 5.3 3.9 4.8 3.7Discarted ova 4.8 3.9 4.1 3.6Cystic ovaries 3.6% 20.2%
plusetpluset®® Superovulation raised to maximum potency
Effect of superovulation on performance of bovine embryo donors imported from temperate zone to tropical climate during the first two
years of adaptationBényei B, Barros CCW
Arq Bras Med vet Zootec Vol 52, n 4, Belo Horizonte Aug 2000
Holstein-Friesian heifers imported pregnant from Hungary to Brazil
In the 2nd year were superovulated with Folltropin or Pluset (600 IU / 4 days)
FSH in decreasing doses for 4 days, PG at 3rd day, AI at 60-72h
Folligon Pluset Folltropin
Cows flushed 6 40 15Total structures 7.4 0.9a 11.7 6.9b 7.7 5.4a
Degen. / unfertil. 3.4 0.6a 5.6 4.8a 4.8 4.9a
Viable embryos 4.0 0.8a 6.0 4.4b 2.9 3.3c
plusetpluset®® Superovulation raised to maximum potency
Superovulation in cattle: effect of FSH type and methods of administration on follicular growth, ovulatory response and endocrine
patternsKelly P., Duffy P., Roche J.F. and Boland M.P. Animal Reproduction Science 46 (1997): 1-14
Group SF: (n=23) Single Folltropin. 270 mg NIH-FSH-P1 in a single s.c injection.
Group MF: (n=23) Multiple Folltropin, 270 mg in 4 days
Group SP: (n=22) Single Pluset, 1.000 IU in a single s.c injection
Group MP: (n=22) Multiple Pluset, 1.000 IU in 5 daysDay 1
(AM/PM)Day 2
(AM/PM)Day 3
(AM/PM)Day 4
(AM/PM)Day 5
(AM/PM)MF (mg NIH) 50/50 40/40 28/28 17/17 --MP (UI) 150/150 125/125 100/100 75/75 50/50
Treatment SF SP MF MP No. CL 10.5 2.6a
22.6 3.5 b 17.7 2.1c
23.3 2.3 b
No. Embryos Rec. 5.7 1.1 a 13.6 2.2 b
12.2 1.7 b 16.4 1.4 c
No. Gr. 1+2 2.2 0.5 a 2.6 0.8 a
5.5 1.2 c 3.8 1.0 b
No. Gr. 3 1.0 0.3 a 1.3 0.4 a
2.7 0.9 b 2.7 0.9 b
No. Gr. 4+5 0.7 0.2 a 2.5 0.8 b
1.6 0.4 c 1.5 0.4 c
No. Unfert/Deg. 1.9 0.6 a 7.2 1.9 b
2.4 0.9 a 8.4 1.8 b
a-c Means with the same superscript within rows do not differ (p>0.05)
plusetpluset®® Superovulation raised to maximum potency
Effect of timing of oestradiol benzoate injection relative to gonadotropin treatment on superovulatory response, and on embryo yield and quality
in beef heifersYaakub H, Duffy P, O’Callaghan D, Boland MP
Animal Reproduction Science (1998) 52: 191-204
Group I: only CIDR for 9 daysGroup II: 5 mg ODB at CIDR insertionGroup III: 5 mg ODB 1.5 days after CIDR insertionGroup IV: 5 mg ODB 3 days after CIDR insertion
Sov started 6.5d after CIDR insertion3 doses: 400, 600, 800 IU Plusetin 8 equal i.m injections each 12h
RESULTS:•No interaction between treatment and dose of Pluset •Combination of ODB and CIDR do not improve embryo yield• best results achieved with CIDR only
Dose of FSH (IU) 400 IU 600 IU 800 IUNo. heifers 31 29 31No. CL 11.7 1.0 a 15.8 1.4 a,b 18.0 1.9 b
No. ova/Emb. recovered 5.8 0.9 a 7.0 0.8 a,b 9.1 1.0 b
No. transferable emb. 2.8 0.7 a 4.2 0.6 b 4.1 0.7 a,b
No. degen. ova/emb. 1.0 0.5 a 2.8 0.5 a 5.0 0.9 b
plusetpluset®® Superovulation raised to maximum potency
Dose effect of porcine gonadotropin extract containing FSH and LH on superovulatory response and fertility of Friesian heifers
Mantovani R et al - 12nd Meeting AETE - Lyon, 1996: 168
60 cycling heifers, 13-16 months
Dose in 9 i.m doses, each 12h (4 1/2 days), giving 35%, 25%, 20%, 15% and 5% of the total dose
Results: Optimal response with 500 IU FSH, with no effects on subsequent reprod. Performance
higher dose affects embryo yield and quality, but not fertilityDose of Pluset
100 IU 300 IU 500 IU 700 IUNo. Heifers 15 16 14 15Recovered Embryos 1.3 4.2 8.0 3.4Unfertilised ova 0.2 2.5 0.8 2.6Transferable embryos 1.2 3.0 6.5 2.5Grade 1+2 embryos 1.2 2.6 5.9 2.2Service period (days) 42 41 60 49No. Services 2.2 2.7 2.5 2.4Pregnancy rate (%):
At 1st AI 46.1 38.8 47.1 27.8After 3 months 86.1 76.8 75.7 84.9
plusetpluset®® Superovulation raised to maximum potency
Effects of prepartum lipid supplementation on FSH superstimulation and embryo quality in multiparous beef cows
Bader JF et al
Theriogenology, v 57, n 1, 2002: 760
40 mature cows, prepartum lipid supplement 40 days prior to calving
WSB: whole soybean supplement
GnRH-7 days- GnRH- 7 days- PG: 28 cows responded
Superovulation started days 8-10 cycle (60d postpartum)
600 IU at decreasing doses for 4 days, PG: 96h and 108h after start treatment
27 cows showed oestrus: AI 0, 12 and 24h after onset oestrus
Total Embryos
Transferable Embryos
Degenerate Embryos
Unfertilised Ova
WSB 14.73 3.54 10.33 2.49 3.33 1.13 1.07 0.47 Control 17.5 2.95 13.58 2.61 1.58 1.68 2.33 1.23
plusetpluset®® Superovulation raised to maximum potency
Evaluation of an estrus synchronization protocol prior to superovulation in beef cowsKojima FN et al
24 crossbred non-lactating beef cows
Protocol 7-11 synch (n=11) or control (n=13)
7-11 Synch: MGA for 7 days + PG 7th day + GnRH 11th day
Control synchronised with 2 PG 14 days apart
2 days after GnRH: 600 IU FSH, decreasing doses twice daily, for 4 days
PG: 2 adm. on the last day FSH - 5th Day: PG, AI at 48h and 60h
Theriogenology, v 57, n 1, 2002: 766
Treatment Total
structures Total
embryos Transferable
embryos Freezable embryos
Degenerated embryos
Unfertilized ova
7-11 Synch 20.9 3.2 21.0 1.8 9.9 1.6 8.3 1.4 2.1 0.7 8.9 2.7 Control 20.8 3.1 17.7 2.9 15.3 2.6 13.1 2.3 2.3 0.8 3.1 1.1
plusetpluset®® Superovulation raised to maximum potency
Breed Age Minimum Maximum
Nelore Heifer 220 UI 260 UICow 250 UI 350 UI
Simmental Heifer 280 UI 350 UICow 320 UI 400 UI
Holstein Heifer 350 UI 420 UICow 400 UI 500 UI
Crossbred
Zebu/European
Heifer 230 UI 280 UICow 260 UI 350 UI
Total Doses Recommended in BrazilTotal Doses Recommended in Brazil
plusetpluset®® Superovulation raised to maximum potency
Efficiency of two different hormonal products for superovulation of Nelore cowsDiniz EG et al
Rev. Bras. Reprod. Anim., v.23, n.3, 1999: 319-321
Comparison of 250 IU Pluset vs. 20 mg NIH Folltropin in Nelore Cows (Bos indicus)
FSH in decreasing doses, in 4 days. PG: 2 doses (AM-PM) of the 3rd day
AI: 12 + 24h post-oestrus
NViable
embryosDegenerated
Non-fecundated
Totalstructures
Folltropin 200 5.9 5.1 5.8 8.8 1.1 3.7 10.7 8.6Pluset 33 6.8 7.3 5.1 5.9 0.7 1.8 12.6 8.4
plusetpluset®® Superovulation raised to maximum potency
Infuence of age on the superovulatory response of Nelore donors: preliminary results
Oliveira MAL et al
Rev. Bras. Reprod. Anim., v.26, n.3, 2002: 246 - 248
Comparison of superovulatory response of 100 Nelore donors allocated by age:
GI: 2-5 years; GII: 6-8 years; GIII: 9-12 years; GIV: >12 years
400 IU FSH in decreasing doses, in 4 days. PG: on the 3rd day.
AI: 12 + 24h post-oestrus
Group N cows Totalstructures
Viableembryos
Degenerateembryos
Ova
2-5 y 25 15.8 ± 10.9 9.8 ± 8.4 2.3 ± 2.2 2.9 ± 3.7
6-8 y 25 18.5 ± 12.3 11.5 ± 10.0 3.3 ± 3.7 4.0 ± 4.8
9-12 y 25 13.6 ± 13.6 6.5 ± 5.1 3.1 ± 2.9 4.3 ± 5.5
> 12y 25 9.2 ± 5.0 4.0 ± 2.6 1.6 ± 2.0 3.6 ± 4.3
plusetpluset®® Superovulation raised to maximum potency
Now available in Australia!
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