Chronogest CR and Folligon
Feb 2012
M.A. Driancourt, MSD AH, R&D Pharmaceuticals
Chronogest CR
Chronogest CR: What is it?
• A vaginal sponge containing 20mg of FGA (cronolone) developed to
synchronize estrus and ovulation in sheep and goats.
• Produced according to GMP (several millions each year) on a high tech
machine at our Igoville (France) production site
• Cronolone is a potent synthetic progestagen (about 25 five times more
potent than progesterone)
• Duration of residence is set at 14 days in sheep (duration of the luteal
phase) and at 11 days in goats (this duration implies that a prostaglandin
injection has to be administered as the duration of treatment is shorter than
the luteal phase
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Chronogest CR: Why does it contain 20mg
cronolone?
20mg is the minimum cronolone load delivering good fertility data
Chronogest CR registration file
And a minimal drug load minimizes
drug residues in milk
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(zero withdrawal time) and meat
Chronogest CR: What is its FGA release profile ?
Two key phases during sponge residence:
1. Peak concentrations during the first two days
2. Plateau concentrations until sponge removal
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Chronogest CR: What are the physiological effects
of FGA?
During treatment
1. FGA acts by negative feed back on the pituitary to block LH secretion
2. High FGA concentrations (following insertion) induce atresia of the large
follicles present (if any) (hence preventing estrus & ovulation). Steady FGA
concentrations (later during treatment) slow down follicular growth and
maturation (no estrogen produced, hence no estrus and ovulation). An
homogeneous population of medium size follicle (4-6mm) is formed.
After sponge removal
1. In sheep and goats during the breeding season, sponge removal and the
immediate collapse of FGA concentrations allows resumption of pulsatile
LH secretion. In the non breeding season (when LH pulsatility is reduced),
PMSG is injected to further support follicular growth and maturation
2. The homogeneous population of medium size follicles grows and matures
in a synchronous way in all treated ewes, hence synchronizing estrus and
ovulation
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Take home message regarding Chronogest CR
•Chronogest CR can be used at all times of the year (anoestrus and
breeding season) as opposed many other breeding tools (Ovsynch,
prostaglandins, ram effect…)
•Chronogest CR generates a tight synchronization of the time of ovulation,
therefore allowing to use fixed time AI (vs prostaglandins, melatonin and
ram effect)
•Chronogest’s use, when combined with Folligon is associated with good
fertility and increased prolificacy
•In sheep, Chronogest CR has a zero withdrawal time for milk and a short
withdrawal time for meat.
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Folligon
Folligon: What is it?
• A glycosylated equine gonadotropin (PMSG/eCG) produced during
equine pregnancy
• Displaying a dual FSH and LH activity
• Displaying a long half life (64h in sheep)
• Administered at the end of synchronization treatments
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Doses of Folligon that may be used in sheep and goats
GOATS
Milk production
PMSG/eCG (Folligon)
dose
< 3.5 L/day
400iu
> 3.5 L/day
500iu
< 3.5 L/day
500iu
SHEEP
Reproductive status
Dose of Folligon
(PMSG/eCG)
Ewes
In season
300-500 iu
Out of season
400-600 iu
In season
250-400iu
Out of season
300-500iu
In season
Transitional period
> 3.5 L/day
600iu
< 3.5 L/day
600iu
Ewe lambs
Out of season
> 3.5 L/day
700iu
Lower doses of PMSG should be used in breeds which have a natural high prolificacy
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Folligon: What are its effects on follicles?
• Its FSH activity supports growth of follicles between 2 and 6 mm in
diameter. Its also induces expression of aromatase, the enzyme
needed for conversion of androgens to estrogens
• Its LH activity has several effects
1. It supports growth of follicles between 6 and 8mm in diameter
2. It maximizes production of androgens by the large follicles
PMSG
Theca cells
Granulosa
cells
+
+ androgens
estrogens
oocyte
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Chronogest CR + Folligon: Why is PMSG needed in
cycling ewes and why is it injected at sponge removal?
(Zeleke et al 2005)
Zeleke et al (2005)
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Chronogest CR + Folligon works in all sheep types (dairy
vs meat) and equally well in cycling vs anoestrous ewes
Fertility
Prolificacy
Dairy ewes, breeding
season, (n= 950), FR
71%
1.69
Meat ewes, end anoestrus,
(n= 333), FR
63%
1.62
Meat ewes, anoestrus,
(n=960), FR
67%
1.92
Meat ewes, breeding
season (n= 198), IRE
83%
1.99
Chronogest CR registration file
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Chronogest CR + Folligon efficiently synchronize
estrus and the LH surge in goats
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Leboeuf et al (2003)
Chronogest CR+ Folligon also works in goats
Fertility
Chronogest
CR
Fertility
control
sponge
Prolificacy
Prolificacy
Chronogest control
CR
sponge
Dairy,
anoestrus
(n= 986)
62.6%
70%
1.97
2.01
Dairy,
breeding
season
(n= 549)
60.2%
62.1%
1.90
2.07
Intervet’s registration file
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In goats, Folligon should be used not too often, as
antibodies develop in some goats following repeated
injections
Some goats treated
several times with PMSG
display anti PMSG
antibodies
There is a large individual
variation in the immune
response to PMSG
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Roy et al 1999
Fertility at fixed time AI of
goats displaying antibody
concentrations exceeding
2.5µg/ml is decreased
Take home message for the
Chronogest CR/Folligon combination
1. The Chronogest CR/Folligon combination is an effective, robust and
flexible approach to optimize lamb and kid production allowing to move
towards semi-intensive production systems (with 3 lambings in 2 years)
2. As it works well irrespective of the time of the year, the Chronogest
CR/Folligon combination allows to time production of the lamb/kid crop
as well as the time of peak milk production.
3. Its precise synchronization of estrus also allows fixed time AI (and
increase in genetic merit)
4. Residues associated with the use of Chronogest CR are low (in sheep,
zero withdrawal time for milk and short withdrawal time for meat).
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Questions?
With all these
MSD products,
my life is either
hectic or boring!
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