Practical guide to bovine reproduction management

Full text

Practical guide to
bovine reproduction management

Reproductive efficacy is a major limiting factor in the economic success of
cattle operations world wide.
The first problem faced is oestrus detection: oestrus of continuously decreasing duration,
accompanied by less and less expressive behaviour is currently becoming characteristic
in dairy cows. Abnormal cycles, in particular those with a persistent corpus luteum, are
becoming more frequent in herds (up to 40% of cycles), making it difficult for the farmer to
meet breeding time targets.
Secondly, the success rate of artificial insemination in dairy cows is decreasing by 1
percentage point every year, this indicates an urgent need for easy to follow treatment
protocols that address problems such as ovulation failure, early embryonic mortality and
chronic endometritis. This practical guide presents the main solutions for treatment and
prevention of the majority of reproductive disorders frequently diagnosed by the veterinary
practitioner in the cattle herds.
Sylvie Chastant-Maillard
Docteur Vétérinaire, Maître de conférences, Responsable de l’Unité de Reproduction
Ecole Vétérinaire d’Alfort.

Proper reproduction management is widely acknowledged as a key to successful cattle breeding, high quality veterinary
advice is of prime importance to achieve this. At Intervet Schering Plough AH, we strive to provide veterinarians with
therapeutic and management solutions to contribute to the economic success of their clients, the farmers, as well as
their own professional success.
Intervet Schering Plough AH supports veterinarians with:
• A wide range of products that demonstrate our leadership in
the field of reproduction management in domestic animals.
• Training activities by invited opinion leaders and Intervet experts,
bringing you the latest technical information and its applications
in the field, including luteal support during early pregnancy
• A website, www.Partners-in-Reproduction.com, containing easily
accessible technical reference information and printable treatment
schedules.
This practical guide, focused on reproduction management of dairy cattle, has been created to assist veterinarians in
their daily work.
The following sections are covered:
• Prophylactic and treatment schemes adapted to various situations encountered in the field
• Zootechnical protocols – oestrus management made as clear and simple as possible
• Latest knowledge on physiology of reproduction and its practical applications
• Practical information on the use of Intervet products in reproduction management in cattle
Intervet Schering Plough AH – your partner in reproduction

Reproductive disorders in the cow: preventive and therapeutic approaches
1. Diagnostic guide
2. Metritis/Pyometra
3. True anoestrus
4. Pseudo anoestrus/sub-oestrus
5. Cystic Ovarian Disease
6. Repeat breeding/Embryonic mortality/Fertility improvement
7. Selected infectious causes of infertility in cattle
Protocols for management of reproduction in cattle herds
8. Oestrus synchronization
9. Treatment of unwanted pregnancy/induction of calving

Reproductive disorders in the bull
10. Cryptorchidism/Poor libido/Oligospermia
Physiological background of reproductive function in the cow
11. Follicular dynamics and its practical implications
11a. Hormonal regulation
Intervet Products
12. Function of selected reproductive hormones and related products
13. Detailed product information

Diagnostic guide
When are certain disorders of the female reproduction tract suspected?
Signs of decreased
reproduction performance
of the cow
Possible underlying reproductive
disorders
Remarks
Abnormal vaginal discharge within
first two weeks post calving
Acute metritis In general characterised by abundant foul smelling vaginal
discharge. Often accompanied by general clinical signs of
illness.
Abnormal vaginal discharge from
14 days post calving
Clinical endometritis/Chronic endometritis In general the vaginal discharge is limited and is observed
mainly during oestrus. Vaginoscopic/speculum examina-
tion is sometimes required for diagnosis
Often associated with AI failure.
Absence of behavioural signs of
oestrus
True anoestrus Acyclia
Inactive (smooth) ovaries.
Developmental abnormalities should be ruled out in heif-
ers.
Sub-oestrus/silent heat Ovarian cyclic activity present but oestrus not accompanied
by adequate behavioural signs of heat. Failure to detect
heat signs should be ruled out.
Ovarian cysts Common cause of oestrus irregularities
Corpus luteum persistent Often seen in highly producing dairy cows.
May be associated with pyometra.
Always rule out possible pregnancy

1
Diagnostic guide
Irregular oestrus Pseudo-anoestrus/silent heat Poor oestrus demonstration and/or inadequate oestrus
detection can lead to a diagnosis of oestrus irregularities.
Ovarian cysts Common cause of oestrus irregularities.
Nymphomaniac behaviour can also be present.
Late embryonic mortality Cows losing their embryos after the initial recognition of
pregnancy repeat oestrus more than 21 days post service.
Corpus luteum persistent Not uncommon in highly producing dairy cows.
May be associated with pyometra.
Always remember that inadequate oestrus detection is most often responsible for the diagnosis of oestrus irregularities
Regular oestrus but failure to
conceive after insemination in more
than two consecutive cycles
Repeat breeding The underlying cause is often difficult to diagnose
Cause 1
Endometritis
Always rule out endometritis in repeat breeders
Cause 2
Hormonal disorders
• Failure of fertilisation (delayed ovulation)
• Early embryonic mortality
• (precocious luteolysis, luteal insufficiency)
Adequate corrections in the nutritional status of the cows
and AI timing should precede any pharmaceutical treat-
ment
Simple hormonal programs exist to address some of the
underlying hormonal problems
Other causes:
• Nutritional deficiencies and metabolic
• diseases (elevated urea levels in circulation
• etc.)
• Certain infectious diseases (BVD, IBR etc.)
• Poor heat detection and insemination of •
• cows not in oestrus
Adequate corrections in the nutritional status of the cows
and AI timing should precede any pharmaceutical treat-
ment
All cows should be monitored and subjected to
BVD and IBR prophylaxis.

(Endo)metritis
Definition of the problem:
• Uterine infections
Actions:
Clinical metritis: adequate intrauterine therapy. In cows with elevated body temperature (>39° C)
parenteral therapy with antibiotics and NSAIDs should be considered.
Clinical/subclinical endometritis:
- intrauterine antibiotics according to the bacterial sensitivity
- in the presence of corpus luteum - PGF2α
Diagnosis
Heat
Intrauterine antibiotics
In cows with elevated body temperature parental therapy with antibiotics and NSAID’s
Remarks on clinical/subclinical endometritis:
- Can be difficult to diagnose by external examination alone.
- Should be treated as soon as possible after diagnosis to avoid continuous
reproduction failure and irreversible morphological changes in the endometrium
Acute metritis:
- occurs within the first 2 weeks post partum
- predominantly caused by E.coli
- can be associated with systemic clinical signs

2
Metritis/Pyometra
Pyometra
- uterine infection with closed cervix
- accumulation of pathological discharge (pus)
in the uterine lumen
- persistent corpus luteum
As the effect of Metricure on the sperm survival and function is not known it is not advisable to use
the product simultaneously with insemination
When diagnosing repeat breeding syndrome always consider uterine infections as possible cause.
Diagnosis
Heat
Estrumate
Metricure
2-4 days
Diagnosis
Heat
Estrumate
Metricure
2-4 days
Diagnosis
Heat
Metricure
Clinical/subclinical endometritis:
- within 21 days or more post partum not
accompanied by systemic signs
- predominantly caused by Arcano-
bacterium pyogenes and Gram negative
anaerobes
Non cyclic cows/cows with no
luteal tissue on their ovaries
detected
In cows with luteal tissue
detected on their ovaries

True anoestrus
Definition of the problem:
In general two clinical pictures are possible:
- inactive ovaries, with no functional structures detected
during rectal examination (smooth ovaries)
- ovaries with larger follicular structures (persistent anovulatory
follicles or follicular cysts)
Action:
Induction of oestrus and ovulation. In both cases growth, maturation
and ovulation of a dominant follicle originating from a new follicular
wave needs to be induced.
Progestagens: Crestar®
Insemination timing in heifers – 48h after implant removal
Insemination timing in cows – 56h after implant removal
(independent of production type)
Crestar injection
Crestar implant removal
Folligon
9-10 days 48/56h
Al
Crestar implant insertion
48h

3
True anoestrus
Dose of PMSG (Folligon®) used with the Crestar® method
- Adjust the dose of PMSG according to the age of the cow or heifer, production type and breed
- You can skip the PMSG injection in dairy heifers that are in good body condition
Dairy cows and heifers
Holstein, Jersey, crosses of HF with other Bos Taurus breeds 400-500IU
Bos Indicus breeds (zebu) 300IU
Beef heifers
Bos Taurus breeds (Charolais, Hereford, Angus, Limousine, Salers etc) 400-500IU
Bos Indicus breeds (Nelore, Brahman) 300IU
Beef cows
Bos Taurus breeds non lactating 400-500IU
Bos Taurus breeds nursing calves 500-600IU
Bos Indicus breeds 300-350IU

Recommended timing for initiation of Crestar® treatment in cattle
in relation to age of the animals and time post partum
Dairy heifers From 15-18 months of age onwards
Attention! Heifers should have obtained at least 75% of their adult body weight
Dairy cows From 45 days post partum
Cows should have a BCS of at least 2.5 or greater
Beef heifers Heifers should have obtained at least 75% of their adult body weight.
Beef cows From 60 days post partum
Cows should have a BCS of at least 2.5 or greater

3a
True anoestrus
- cont.
GnRH – Receptal® (providing that follicles larger
than 10mm are present on the ovary)
More than 50 days post calving →
Stage 1
In the absence of heat within 10 days after the treatment with Receptal →
Stage 2
Rectal examination/ultrasonography
- CL present on the ovary
- No CL detected
Calving Receptal 5ml
>50 days 2-3 days
Al
Heat
Receptal 5ml Estrumate
10 days 2-4 days
Al
Heat
Detection
of CL
Receptal 5ml Receptal 5ml
10 days
Al
Heat
No CL
detected

Pseudo-anoestrus/Sub-oestrus
Definition:
Cow with normal cyclic ovarian activity, heat is however not detected due to:
• the absence of behavioural signs of oestrus (pseudo-anoestrus), or
• poorly expressed oestrus signs (sub-oestrus/silent heat)
Action:
During the luteal phase, an injection of PGF2α (Estrumate) induces luteolysis and initiates the next oestrus cycle. The cow will come
into heat within an average of 3-5 days.
The cows should be inseminated at detected heat.
Protocol 1
PGF2α
This system is especially recommended for heifers
Estrumate
Cow not seen in heat
3-5 days
Al
Heat observation

4
Pseudo-anoestrus/
sub-oestrus
Protocol 2
Ovsynch
This system has an important advantage of possible fixed time insemination without the necessity for oestrus detection
This system allows for insemination without heat detection. The Crestar
system is especially recommended in beef cows as it causes an effective
artificial luteal phase that is beneficial for corpus luteum function.
This system is not recommended for heifers and nursing beef cows.
Protocol 3
Crestar
Estrumate
Day 0
Fixed time Al
Receptal 2.5 ml Receptal 2.5 ml
7 days 48 h 17-24 h
Day 7 Day 9
Folligon
Al
Crestar injection
9 - 10 days 48/56 h 17-24 h
Crestar implant removal
Crestar implant insertion

Receptal 5ml
Chorulon 3.000 iu
Al at detected heat
Heat
Diagnosis of a
follicular cyst
Cystic Ovarian Disease
Definition:
Ovarian cysts are defined as:
- Fluid filled ovarian structures of a diameter larger than 2.5cm that persist on the ovary for more than 8-10 days in
the absence of a normal corpus luteum.
- They frequently appear during the early post partum period, intervention is not considered necessary before 40 days post calving
- They are associated with various oestrus cycle abnormalities such as anoestrus, irregular oestrus signs or
nymphomania
- Thought to be caused by inadequate LH release from the pituitary gland and consequent ovulation failure or a lack of
reactivity of the follicular cells to physiological LH stimulation. Negative energy balance and lack of previous
exposure to adequate progesterone concentrations (in the previous oestrus cycle) are listed as the most important
predisposing factors.
- Two types of ovarian cysts can be distinguished:
- follicular (can be estrogenically active or not)
- luteal (produce progesterone)
Diagnosis is by rectal palpation, ultrasound examination or measurement of progesterone in milk or serum.
Follicular cysts
Action: restore follicular
turnover and induce ovulation
of the dominant follicle from
a new follicular wave
→ GnRH or hCG
Important tip: the physical disappearance of the cyst is not necessary for successful treatment. Induction of oestrus and
ovulation is the outcome that we are looking for!
The time from treatment to oestrus depends on the stage of follicular development at the moment of injection.
The cows can be inseminated during the first detected heat.

5
COD
Estrumate
Al at detected heat
Heat
Diagnosis of a
luteal cyst
Receptal 5ml
Chorulon 3.000 iu
Al at detected
heat
Heat
Diagnosis
of a cyst
Estrumate
10-14 days 3-5 days
Luteal cyst
Action: Induce luteolysis and restore cyclicity
Important tip: The time from treatment to oestrus depends on
the stage of follicular development at the moment of injection.
The cows can be inseminated during the first detected heat.
Shortening the time to oestrus & treatment of cysts of uncertain nature
With this system both types of cysts can be addressed while a
combination of GnRH/hCG and PGF2α ensures induction of ovulation
of the dominant follicle from a new follicular wave in a predictable and
controlled time. Treated cows can thus be inseminated at a relatively
short time after diagnosis.

Repeat breeding/Early Embryonic Mortality
Definition:
Cows with normal cyclic ovarian activity and no apparent disorders of reproductive tract that do not fall pregnant after
insemination during more than two consecutive oestrus cycles.
Thought to be caused by early embryonic losses.
Pattern of returns
Possible actions:
- Induction of ovulation to avoid delay of failure of ovulation → GnRH/hCG at AI
- Prevention of precocious luteolysis and creation of additional CL → GnRH at 11-12 d post AI
AlHeat
17-21 days
>25 days
‘Early repeats’
Heat
Embryo mortality before
pregnancy recognition
‘Late repeats’
Embryo mortality
after initial pregnancy
recognition
Heat

6
Repeat breeding
Induction of Ovulation for AI
This system is especially recommended in highly producing
dairy cows exposed to high ambient temperatures.
GnRH at 11-12 day post AI
This system is especially recommended in cases of so called “late repeats”.
Heat
detection
Morning/Evening
Al
Receptal 2.5 ml
Evening/Morning
Al
Receptal 2.5 ml
11-12 days
Heat
detection
Morning/Evening
Al
Chorulon 1500 iu
Evening/Morning

Selected infectious causes of fertility problems and abortions in cattle
Affected function Infectious disease
Negative influence on ovarian activity and the function of
higher endocrine regulatory centres
BVD, IBR, mastitis, endometritis
Negative effect on semen and oocyte quality ♂BVD, IBR, acute phase of almost all infectious diseases accompanied by fever
♀BVD, IBR, Hemophilus (?)
Direct negative influence on the embryo development
(<42d of pregnancy) and placental function
BVD, IBR, Neospora caninum, Trichomonas foetus, Leptospira, Campylobacter foetus
Direct negative influence on foetal development (>42d of
pregnancy) and placental function causing abortion
Leptospira
Brucella abort.
Listeria
Campylobacter
Hemophilus
Ureaplasma
Epizootic
bovine abortion
Mycoplasma
Anaplasma
Salmonella
IBR
BVD
Bluetongue
Vesiviruses
Cache Valley
virus
Tritrichomonas
Neospora can.
Sarcocystis
neuroni
Aspergillus fum.
Mucor spp.
Mortierella
wolfii
Remember: Careful monitoring of BVD and IBR status of the herd and vaccination against BVD with vaccines providing foetal protection and
preventing cell free viraemia as well as against IBR should form an integral part of a modern reproduction management program in cattle herds.

7
Oestrus
management
Oestrus Management
The critical requirements for any effective oestrus cycle control system are predictable and high oestrus and ovulation
responses during a specified 12-24h period followed by a high pregnancy rate to a single pre-programmed AI after
treatment.
Pharmacological systems used in oestrus management in cattle should be perceived as useful tools that facilitate:
1. Successful insemination of cows
2. Improved management of females
3. Organisation of service
4. Corrections of problems such as inadequate oestrus detection, irregular oestrus cycles, silent heat or
ovulation induction
Benefits of pharmacological oestrus management in cattle – why we want to induce and synchronize oestrus in cows
• To improve the organisation of breeding
- improve reproduction results
- maintain the same results but with less labour
• To correct only certain elements of reproductive management
- improve heat detection
- eliminate heat detection
• To correct certain reproductive disorders in the herd
- silent heat
- anoestrus
- repeat breeding

Oestrus Management
Pharmacological systems used for oestrus induction and synchronization in cattle can be divided as follows:
• Systems that control only luteal function
- prostaglandins used alone
• Systems that control only follicular function
- progestagens used alone
• Systems that control both luteal function and follicular dynamics
- combinations of prostaglandins and GnRH
- combinations of progestagens with gonadotrophins and prostaglandins

8
Oestrus
management
Oestrus synchronization with prostaglandins
Injection of prostaglandin causes luteolysis and allows for the final growth and maturation of the dominant follicle
followed by ovulation at a predictable time post injection.
Requirements:
- oestrus induction and synchronization systems are only effective in cycling animals (animals must have a
functional corpus luteum that is sensitive to prostaglandins at the time of PG injection)
- for satisfactory results animals must have an adequate body condition score of ≥ 3.0.
Target group:
Oestrus synchronization systems based on prostaglandins alone are recommended for:
- Cycling dairy and beef heifers
- Cycling dairy cows in good body condition
- Herds where labour resources for heat detection are limited (animals for heat observation are grouped and
identified)

Single prostaglandin injection
Attention:
The presence of luteal tissue must be confirmed before
synchronization systems based on a single prostaglandin
injection are used. This can be done by rectal palpation,
ultrasound examination, measurement of progesterone
concentrations in milk (>2ng/ml) or blood (>5ng/ml) or
based on the date of the last heat observed.
Double prostaglandin injection
Attention:
This system can be used without detection of a CL but still
only applies to cycling animals.
Multiple prostaglandin injection
Detection of CL or
Measurement of P4
PGF2α,
Estrumate 2 ml
Al at detected
heat
Oestrus observation
3-5 days
Oestrus observation and Al of
cows detected in heat
PGF2α,
Estrumate 2 ml
Al at
detected
heat
Oestrus
observation
11-14 days 3-5 days
PGF2α,
Estrumate 2 ml
Oestrus observation and Al
of cows detected in heat
PGF2α,
Estrumate 2 ml
Fixed
Time Al
11-14 days 70-80hrs
PGF2α,
Estrumate 2 ml
PGF2α,
Estrumate 2 ml
28-35 days 11-14 days
Calving
Oestrus observation and Al
of cows detected in heat

8
Oestrus
Management
Efficacy of oestrus synchronization based on prostaglandin administration
Injection of prostaglandin modifies the lifespan of the corpus luteum and induces the final growth of a new follicular
wave. It has however no influence on the time from injection to oestrus and ovulation. The time interval from treatment
to ovulation depends on the degree of follicular development at the moment of PGF administration.
Because of the variability of oestrus and ovulation post PGF injection, insemination at detected heat is recommended
and gives the best results.
Days after PGF injection
% of animals
Day 1 Day 2 Day 3 Day 4 Day 5 Day 6
2-3 days
Day of cycle
Day of cycle
Serum progesterone
4-5 days
Serum progesterone
Distribution of oestrus in cows treated with PGF
Interval from PGF injection to ovulation in cattle

Combination of prostaglandins and GnRH – Ovsynch type systems
Systems combining luteolysis, induced with PGF, and induction of follicular growth and ovulation with GnRH, control the
lifespan of the corpus luteum and the follicular growth dynamics. Some of these systems thus allow for fixed time AI.
Classical Ovsynch protocol
Target group
- Dairy cows
- Dairy cows exposed to heat stress
Attention:
- Ovsynch system allows for insemination at fixed time without observation of behavioural signs of heat
- The classical Ovsynch is not recommended for heifers and animals in anoestrus
Receptal 2.5 ml
Fixed
Time Al
7 days 17-24 hrs
Estrumate Receptal 2.5 ml
48 hrs
Day 0 Day 7 Day 9

8
Oestrus
Management
Modifications of the classical Ovsynch
Receptal 2.5 ml
Fixed
Time Al
7 days
17-24 hrs
Estrumate Receptal 2.5 ml
48 hrs
Day 0 Day 7 Day 9
Receptal 2.5 ml
Fixed
Time Al
7 days
Estrumate Receptal 2.5 ml
48 hrs
Day 0 Day 7 Day 9Day-12
Estrumate
Pre Synch
Co Synch
hCG Synch
Receptal 2.5 ml
Fixed
Time Al
7 days
Estrumate Chorulon 1.500iu
48 hrs
Day 0 Day 7 Day 9
17-24 hrs

Progestagens
Progestagens combined with prostaglandins and GnRH/PMSG modify both the CL function and follicular dynamics.
Thanks to the creation of an artificial luteal phase oestrus synchronization with progestagens can also be used in
anoestrus animals.
System Crestar allows for fixed time insemination. Heat detection is not necessary.
Crestar
AI:
Heifers of dairy and beef type – 48h post implant removal
Cows of dairy and beef type: 56h post implant removal
PMSG dosage: see page 10
Target group:
- Dairy and beef cows regardless of their cycling status
- Synchronisation of donors and recipients in ET programs
Crestar injection
Al
Folligon
48/56 hrs9 - 10 days
Crestar implant
insertion
Crestar implant
removal
Estrumate

9
Abortion/calving
induction
Unwanted pregnancy
Pharmacological pregnancy termination is undesirable in general but may be necessary in certain cases such as the
accidental mating of heifers in feedlot units.
Abortion with prostaglandins can be achieved up to 150 days of pregnancy.
Attention:
- Between 100 and 150 days of pregnancy the efficacy of prostaglandins can be reduced. It might be necessary to
administer more than one dose in order to terminate pregnancy.
- After day 150, prostaglandins alone are not effective abortifacients in cattle as the placenta produces enough
progesterone to maintain pregnancy.
Undesired mating
10-16 days or
If not obeserved in heat 21 days later
Estrumate

Induction of calving
Induction of calving
Reasons for calving induction in cattle:
- To shorten calving intervals or to tighten the calving pattern.
- To reduce the incidence of dystocia by preventing foetal oversize.
- To terminate abnormal pregnancies.
- To advance the date of calving in late-conceiving cows, where breeding and production is seasonal
Attention:
- Induction of calving with prostaglandins is associated with an increased incidence of placental retention
- Induction of parturition should not be attempted more than 7 days before the expected calving date to avoid
the birth of premature and weak calves
Gestation
Estrumate
Dexadresson 15 ml (optional)
24-72h Calving
Day 273-280

10
Cryptorchidism/
Poor libido
Reproductive problems in the bull
Cryptorchidism
Definition: one or both testes fail to descend normally into the scrotal sac. The testis/testes can be located in
the abdominal cavity or inguineal canal.
Attention:
- Pharmacological treatment is usually unsuccessful
- If a hereditary cause is suspected treatment and use of the male for breeding is not recommended.
Poor libido:
Definition: weak or absent sexual drive in a sexually mature bull
Treatment: Injection of hCG (Chorulon, 2 injections/week for 4-6 weeks at a dose of 500-1000iu)
Attention: Before any pharmacological treatment is initiated, morphological (painful conditions of muscles and
bones, systemic diseases) and managerial causes (stress, inappropriate handling) of poor libido should
be ruled out or corrected

Oligospermia
Definition: insufficient number of sperm cells in the ejaculate
Treatment: improvement of semen quality can be attempted with prolonged treatment with PMSG.
Results are however variable and dependant on the underlying physiological causes.
Attention: Before any pharmacological treatment is initiated, functional disorders such as systemic diseases
accompanied by elevated body temperature, nutritional deficiencies and genital tract infections as well
as the influence of a high ambient temperature should be ruled out.

11
Follicular
dynamics
Physiology
Follicular dynamics and its practical implications
In cattle, ovarian follicles grow and develop in so called waves (two or three
waves per cycle). Only the dominant follicle of the last wave ovulates.
Did you know that?
Duration of the oestrus cycle
The duration of the oestrus cycle can vary between 18 and 25 days
depending on the number follicular waves that develop during a cycle.
An inter-oestrus interval of 25 days is still considered physiological!
Resumption of cyclicity post partum
Dairy cows Beef cows
Appearance of the first dominant follicle Between 4 and 40 days post partum Between 5 and 40 days post partum
Fate of the first dominant follicle 75% - ovulation
20% - cyst formation
5% - atresia
10-20% ovulation
10% - cyst formation
70-80% - atresia
Follicular dynamics in cattle
± 21 days Corpus luteum
regression
Corpus luteum
Follicle
Atresia
Recruitment
phase
Selection
phase
Dominance
phase
Heat Follicular wave
Follicular phase Luteal phase
Heat
Abnormal heats – the explanation:
- Between two consecutive ovulations typical oestrus behaviour may be observed due to the influence of oestrogens
secreted by the growing dominant follicle
During gestation the growth of follicular waves continues. In rare cases behavioural signs of oestrus can be observed in
pregnant cows

Physiology
Hormonal regulation of reproductive function
Mechanism of hormonal regulation of reproductive function in cattle
Hormone levels during the Oestrus cycle of a cow.
Hypothalamus
Progesterone
negative
feedback
Oestradiol
positive
feedback
Inhibin negative
feedback on
FSH release
GnRH
Anterior
Pituitary
LH
FSH
Follicle
Growth
Ovary
Luteolysis
PGF2a
Maturation
Luteini-
sation
Ovulation
Oestrogens Progesterone
Uterus
Oestrus
behaviour
Progestational
changes
Oestrus
changes
Oxytocin
Hormone
Level
Foll. phase Luteal phase Foll. phase
Progesterone
Oestradiol
FSH
Ovulation
Oestrus
LH
OV OV
OV

0
3
6
9
12
0D28 D56 D84
D
112
D140
0
3
6
9
12
0D28 D56 D84 D112 D140
0
3
6
9
12
0D28 D56 D84 D112 D140
0
3
6
9
12
0D28 D56 D84 D112 D140
11a
Hormonal
regulation
The role of LH and Progesterone
Luteinising hormone and progesterone are crucial to reproduction function in cattle.
LH support is necessary for:
• the final stage of follicular growth and maturation
• timely ovulation
• the formation and early function of corpus luteum.
The quantity of LH released and the release pattern determine successful ovulation and luteal function.
Normal profile Abnormal profile
NB: This type of progesterone profile can be frequently found in the early post partum period and should be corrected.
Progesterone is essential for high fertility of cows
There are four main types of progesterone profiles in the early post partum period (source: Mann 2002)
Impaired LH secretion
(quantitative and qualitative)
Early embryonic mortalityAnoestrus
Absence of follicular growth
Formation of follicular cystPoor oocyte quality
Impaired corpus luteum
function
Delayed ovulation
Lack of rapid and adequate rise in progesterone concentrations is an important
risk factor in early embryonic mortality
Progesterone
(ng/ml)
Progesterone
(ng/ml)
Progesterone
(ng/ml)
Progesterone
(ng/ml)
CalvingCalving Calving Calving
Anoestrus Corpus luteum
persistent Cysts

IA
1 2 3 4
IA1 IA2 IA3 N°IA
Relationship between the hormonal profile and infertility in cattle
Type of hormonal
disorder
Risk AI at risk Therapeutic option Treatment
Asynchronous follicu-
lar development
Fertilisation failure Especially 3rd AI and
subsequent AI’s.
Induction and
synchronization of
follicular development
and LH peak
Ovsynch protocol or
Receptal - 7-9 days
post PGF2α
Delayed ovulation or
ovulation failure
Fertilisation failure
or poor development
of the embryo (early
embryonic mortality)
Especially 3rd AI and
subsequent AI’s
Induction of LH peak
and ovulation within
24h before insemina-
tion
Receptal/Chorulon at
AI, Complete Ovsynch
protocol
Precocious luteolysis
due to inadequate
progesterone levels
and stimulation of
luteolytic cascade by
luteal phase follicles
Early Embryonic
Mortality
At any AI Elimination of grow-
ing follicles, increase
of progesterone levels
through formation
of additional corpora
lutea
Receptal - 11-12 days
post AI
Improvement of fertility: therapeutic options
Hormonal disorders leading to suboptimal fertility
Schematic evolution in the risk of hormonal disor-
ders in subsequent inseminations
D-9 D0 D5 D12 D15
Luteal origin –
progesterone defficiency
% of risk Follicular origin –
date of preovulatory LH peak
4 periods
of risk
Risk period
Risk Ovulation
failure
Insufficient
luteal function
Increased risk
of precocious
luteolysis

12
Function of
horm. and prod.
Information about Intervet reproduction range
Product Active ingredient Indications for use in
cattle
Posology Presentations
Hormonal products
Chorulon® hCG • Induction of ovulation at AI
• Improvement of fertility and induction of
• ovulation at Al
• Treatment of Follicular cysts (preferably in
• combination with PGF at 7-9d later)
• Induction of ovulation and im
provement of fertility – 1.500 IU
• Treatment of cysts – 3.000 IU
i.m. or slow i.v.
Vials of 500, 1.500, 2.500, 5.000 and
10.000 IU with solvent
Crestar® Norgestomet
Oestradiol valerate
Oestrus induction and synchronization for fixed
time AI in cows and heifers (beef and dairy)
Implant insertion + injection,
implant removal after 9-10 days
accompanied with PMSG injection.
In dairy cows PGF injection at 48h
before implant removal
Boxes with 25 treatments (implants
+injections)
Estrumate® Cloprostenol racemate (synthetic
PGF2α)
Zootechnic:
• Oestrus induction and synchronization
• Induction and synchronization of calving
Therapeutic:
• Corpus luteum persistent and luteal cysts
• Pyometra and as additional treatment in other
• uterine infections
• Pseudo anoestrus/silent heat
2ml/cow i.m. Vials with 2, 20 and 50ml
Folligon® PMSG/eCG • Oestrus induction
• Improvement of fertility rate in progestagen-
based oestrus synchronization systems
• Superovulation
• Induction of oestrus
500-1.000 IU i.m.
• In combination with progestagens
– 300-750IU i.m. at removal of
progestagen source
• Superovulation – 3.000 IU i.m.
on 8-13d of oestrus cycle
Vials of 400, 500, 600, 700, 1.000,
5.000 and 6.000 IU with solvent

Product Active ingredient Indications for use in
cattle
Posology Presentations
Intertocine S® Synthetic oxytocin • Stimulation of uterine contractions during labour
• Improvement of post partum uterine involution
• Stimulation of milk secretion
10-50IU s.c. or i.m. Vials of 10, 25 and 50ml containing
10IU/ml
Receptal® Buserelin (GnRH analogue) • Induction of ovulation at AI
• Improvement of fertility post AI (10-12d post AI)
• Treatment of ovarian cysts
• Induction of ovulation and
improvement of fertility – 2.5ml
• Treatment of cysts – 5ml
i.m., s.c., i.v.
Vials of 2.5ml, 5ml, 10ml and 50ml
Antibiotics
Metricure® Cephapirin Treatment of subacute and chronic endometritis • Treatment of endometritis –
1 intrauterine injector
Box with 10 or 12 injectors

We provide solution to all problems that take place during the reproduction
season of the cows
Acute
metritis
Endometritis
Subacute/
chronic
Improvement
of fertility
Repeat
breeding
Parturition
induction
Metricure
Estrumate
Receptal/
Chorulon at Al
Receptal Estrumate
Dexadreson
Day 0 Day 90Day 14
Calving Insemination Calving
True anoestrus Ovarian cysts
Receptal
Crestar follicular
Receptal
Chorulon
Estrumate luteal

Product information
The information below provides the basic facts about Intervet products used for management of reproduction in cattle
throughout the world. Please bear in mind that not all of these products will be present in all countries.
With respect to withdrawal times, consult the product leaflet valid in your country.
Chorulon®
Composition: Chorulon contains human Chorionic Gonadotrophin (hCG) as a white freeze-dried crystalline powder. Indications: Chorulon can be used for the control of fertility problems in domestic
animals: - improvement of conception rate in female animals (cattle); induction of ovulation in female animals (horses, dogs, cattle); cystic ovaries with irregular oestrous cycle, nymphomania or ab-
sence of oestrus in female animals (cattle); anoestrus in female animals (horses, dogs); delayed ovulation, prolonged oestrus in female animals (dogs); deficiency of libido and cryptorchidism in male
animals (dogs) Dosage and administration: cattle, horses: 1.500-3.000IU, dogs: 100-800IU. Contraindications: As with all protein-containing preparations, in rare cases anaphylactoid-type reactions
may occur shortly after administration. In such circumstances, prompt medication with adrenaline (1:1000) or glucocorticosteroids may be indicated Withholding period: Milk, meat – nil. Storage
conditions: Store at 8-15° C. Protect from light Presentations: Vials of 500, 1500, 2500, 5000 and 10000 IU hCG, together with solvent for reconstitution.
Crestar®
Description: Crestar is a part of a system suitable to control oestrus in heifers and cows in order to apply a planned insemination program. Crestar consists of: Crestar implant containing 3 mg of
the progestagen Norgestomet (17α-acetoxy-11β-methyl-19-norpregna-4-en-2.20-dione) and Crestar injection of 2 ml, containing 3 mg Norgestomet and 5 mg oestradiol valerate. Mode of action:
Crestar injection: The oestrogen plus the Norgestomet compound shortens the luteal phase if treatment is given in an early stage of the cycle and induces so called follicular turnover (ovulation or
luteinisation of any LH-sensitive follicle present on the ovary at the time of injection) preventing this way the formation of persistent dominant follicles. At the same time the Norgestomet compound
suppresses oestrus and ovulation by pituitary inhibition. Crestar implant: The continuous release of Norgestomet maintains the suppression of oestrus and ovulation. After removal of the implant the
blocking effect on the pituitary ceases and a new follicular phase starts. In non-cyclic animals the priming effect of Norgestomet is enhanced by combining the removal of the implant with an intramus-
cular PMSG injection that stimulates synchronized follicular development.
Indications: Oestrus control in both cyclic and non-cyclic cattle (heifers and cows). Posology: Place the implant under the skin of the outer surface of the ear and inject the Crestar injection. In dairy
cows administer a dose of prostaglandin 48h before implant removal. After 9-10 days remove implant and administer PMSG. The dosage of Folligon (PMSG) depends on age, breed, season, post-par-
tum interval, management, etc. Note: Cows and heifers can be inseminated without oestrus detection. If two AI’s are performed the timing of AI is 48 and 72 hours after implant removal. Contraindi-
cations: Crestar is not a therapeutic and therefore is to be applied in healthy animals only. Heifers to be treated should have reached at least 65-70% of the adult weight and the age should be 15-20
months, depending on breed. Cows should not be treated within 45 days after the last calving. Withholding period: Milk: nil, Meat: 2 days after removal of implant. Storage conditions: Store in a dry
place at room temperature (15-25° C). Protect from light. Presentations: Box with 5x5 Crestar implants and 5x5 vials of 2 ml Crestar injection.
Estrumate®
Description: Estrumate is a clear colourless aqueous solution containing: 0.263mg/ml of racemic cloprostenol sodium, equivalent of 0.250mg/ml of racemic cloprostenol. Cloprostenol is a synthetic
prostaglandin F2a analogue. Indications for use: Cattle: Treatment of reproductive pathologies (subestrus, pyometra, luteal cysts and corpus luteum persistent), improved management of reproduc-
tion (i.e. synchronization of oestrus and ovulation combined in some cases with fixed time artificial insemination, induction of calving). Dosage and Administration: The dose of 2ml/animal is applied
intramuscularly in cows and heifers. Withdrawal times: Milk, meat – nil. Contra-indications: Animals with spastic disorders of the gastro-intestinal tract and/or the respiratory system.
Not to be used in pregnant animals, unless abortion or induction of calving is required. Undesirable effects: Use for Induction of parturition or abortion in cattle is accompanied by an increased
incidence of retained foetal membranes. Storage conditions: Store at temperatures below 20ºC, protected from light. Special precautions to be taken by the person administering the veterinary
medicinal product to animals: Women of child bearing age, asthmathics and persons with bronchial or other respiratory problems should handle the product with care, as cloprostenol is readily
absorbed through the skin and may cause abortion or bronchial spasm. In case of accidental self-injection, seek medical advice immediately and show the package insert or the label to the physician.
Accidental spillage on the skin should be washed immediately with soap and water. Presentation: 2ml, 20ml and 50ml colourless, glass vials, closed with a rubber stopper.

Dexadreson®
Description: Dexadreson contains dexamethasone as the disodium phosphate ester in a clear solution of 2 mg dexamethasone per ml. Dexamethasone is a very potent corticosteroid (activity at least
30 times greater than cortisone). Sodium retention and potassium loss are almost negligible at the recommended dosage. Indications: Dexadreson can be used therapeutically for its anti-inflamma-
tory, anti-allergic, anti-shock and gluconeogenic action and for induction of parturition in ruminants. Administration by intravenous, intramuscular or intra-articular injection. Repeated treatment is
possible after 24-48 hours. When treatment is prolonged, withdrawal should be gradual and ACTH stimulation of the adrenal is advisable. All injections into joints should be preceded by the removal
of a volume of synovial fluid equal to that of the intended injection. Dosage: cattle, horses and pigs: 0.06mg/kg, dogs and cats: 0.1mg/kg. In cases of shock Dexadreson can be administered intrave-
nously, thus ensuring a very rapid action. In such cases the intravenous dose should be at least 10 times the clinically advised systemic (i.m.) dose. Contraindications: The normal conditions for which
potent glucocorticosteroids are contraindicated apply to Dexadreson. Diabetes mellitus, osteoporosis, renal diseases and cardiac congestion are all indications for avoiding corticosteroid therapy.
Infectious diseases should not be treated unless suitable anti-infective therapy is given at the same time (antisera, antibiotics, etc.). Due to their immunosuppressive activity, corticosteroids can lead
to a reduced response to vaccination. Therefore it is recommended that Dexadreson is not used in combination with vaccines. Unless abortion or early parturition is required, the use of Dexadreson
during late pregnancy is contraindicated. A reduced viability of the offspring, or increased incidence of retained placenta and foetal abnormalities have been associated with the induction of parturition
with corticosteroids. Subsequent fertility is usually not adversely affected. In cases of laminitis in horses Dexadreson should only be used very early in the disease process. In order to obtain a rapid
response in very acute hypersensitivity reactions and anaphylactic conditions, it may be necessary to administer antihistamines and/or adrenaline together with the corticosteroid. In cases of shock
treatment, intravenous fluids should be given to maintain circulating blood volume, and the acid base balance should be controlled. Withholding period: Milk: nil. Meat: 2 days. Storage conditions:
Store at room temperature (15-25° C). Protect from light. Presentation: Vials of 50 ml
Folligon® (Chrono®-gest PMSG)
Description: Folligon contains the hormone Pregnant Mare Serum Gonadotrophin (PMSG; Equine Chorionic Gonadotrphin - ECG) as a white freeze-dried crystalline powder together with solvent
for reconstitution. Mode of action: The active compound of Folligon is PMSG/ECG, a complex glycoprotein. PMSG/ECG is a gonadotrophin with Follicle Stimulating Hormone (FSH) and Luteinizing
Hormone (LH) activities. In females, PMSG stimulates the growth and maturation of the follicles. In the male, PMSG stimulates development of the interstitial tissue of the testis and spermatogenesis.
Indications: Folligon can be used for the management of reproduction and treatments of reproductive disorders in domestic animals: Anoestrus (oestrus induction and increase of ovarian activity
leading to an increased fertility) in the cow, the rabbit, the bitch and in mink. Induction of multiple ovulation (Superovulation) in embryo/oocyte donors in the cow, the rabbit and in deer. Increase of
fertility rate after progestagen treatment (oestrus induction and synchronisation, increase of ovarian activity) in the cow, the ewe, the goat and in deer. Dosage: Cattle – anoestrus: 500-1000IU, oestrus
management with progestegens: 300-750IU, superovulation: 3000IU; Dogs – 500IU, Sheep – 400-750IU, Goats – 400-750IU, Rabbit – 40IU, Mink – 100IU, Deer – 200IU. Contraindications: In rare
cases, as with all protein-containing preparations, anaphylactoid-type reactions may occur shortly after administration. In such circumstances, prompt medication with adrenaline (1:1000) or gluco-
corticosteroids may be indicated. Withholding period: milk, meat – nil. Storage conditions: Store at 8-15°C. Protect from light. Reconstituted product should be used within 12 hours. Presentations:
Folligon: vials of 1000 and 5000 IU together with solvent for reconstitution. Chrono-gest PMSG: vials of 400, 500, 600, 700, 5000 and 6000 IU together with solvent for reconstitution.
Intertocine®-S (Oxytocin-S)
Description: Intertocine-S is a synthetic oxytocin at a concentration of 10 IU per ml. There are no vasopressor or anti-diuretic fraction impurities. Mode of action: Intertocine-S causes contractions of
the smooth muscle of the oestrogen-sensitized uterus and mammary gland. It also stimulates uterine involution. Indications: Stimulation of uterine contractions, to facilitate parturition. Improvement
of involution of the post-parturient uterus and thus aid the passage of retained placentae and removal of detritus. Control post-partum haemorrhage. Stimulation of milk let-down in cases of agalactia.
Dosage and administration: Mare – 5-50IU, cow – 10-50IU, Sheep, sow goat – 5-30IU, bitch – 2-10IU, queen – 1-5IU. The product is administered by intramuscular or subcutaneous injection: repeat if
necessary after 40 minutes. If a very quick effect is required, intravenous injection is possible. Therefore a quarter of the above mentioned dosage, diluted 1 in 10 with water for injection, is to be pre-
pared. Inject slowly. By any route and especially when used during parturition, low initial dosage is recommended as repeat administration is permissible. In post-parturient animals larger doses may
be employed. Contraindications: The use of Intertocine-S is contraindicated in any form of obstructive dystocia. When Intertocine is used as an aid to parturition, cervical dilatation must be confirmed
prior to administration. Excessive doses of Intertocine-S may delay parturition by producing uncoordinated uterine contractions which interfere with the progress of the foetus, especially in multiple
pregnancies. Adrenaline reduces the effect of oxytocin on the uterus or mammary gland. For this reason the animal should not be frightened when complete oxytocin effect is desired. Withholding
period: milk, meat – nil.
Storage conditions: Store at 2-8°C. Protect from light. Presentations: Vials of 10, 25 and 50 ml, containing 10 IU Oxytocin/ml.
Metricure®
Description: Each syringe of Metricure intra-uterine suspension contains 500 mg of cephapirin (as benzathine). Mode of action:
Cephapirin - a first generation cephalosporin - is a broad spectrum antibiotic with bactericidal action against Gram-positive and Gram-negative bacteria. Cephapirin is resistant to the action of penicil-
linase produced by staphylococci, and is active in the anaerobic environment of the uterus. After a single treatment with Metricure, concentrations of cephapirin in the endometrium tissue above the
MIC of sensitive bacteria are maintained for at least 24 hours. The suspension is well tolerated, enables good diffusion of cephapirin into the endometrium and can be infused easily. Indications:
Subacute and chronic endometritis in cattle (> 14 days after parturition). Treatment of repeat breeder cows at the day after AI. Dosage and administration: The contents of the Metricure syringe are
introduced into the lumen of the uterus using the disposable catheter provided with each syringe. 1. Fix the syringe to the catheter. 2. Take the cervix of the uterus into one gloved hand introduced

into the rectum. 3. Introduce the catheter through the cervix into the lumen of the uterus by gentle oscillating movements of the cervix. 4. Inject the contents of the syringe into the lumen of the
uterus. One treatment with Metricure is generally sufficient for complete cure. If necessary, treatment can be repeated after 14 days. In animals that are inseminated, Metricure can be used at one day
after insemination. In cases of pyometra it is advised to start treatment with an injection of prostaglandin in order to induce regression of the corpus luteum and to remove the debris from the uterine
cavity before treatment with Metricure. Contraindications: Animals with known allergy to cephalosporins. Withholding period: Meat: 48 hours, Milk: nil. Storage conditions: Store at room tempera-
ture (15-25° C). Presentation: Box with 10 syringes plus 10 catheters and 10 gloves.
Receptal®
Description: Gonadotrophin-Releasing Hormone Analogue. Composition: Solution for injection: 1 ml contains 0.0042 mg buserelin acetate equivalent to 0.004 mg buserelin. Indications: Reduced
fertility by ovarian disfunction, induction of ovulation and improvement of conception rate. Cows: Cystic ovaries with and without symptoms of nymphomania. Anoestrus. Delayed ovulation. Anovula-
tion. Improvement of conception rate after artificial insemination and oestrus synchronisation. Prophylaxis of fertility disorders by early induction of cycle post partum. Mares: Anoestrus. Induction of
ovulation. Fixing time of ovulation and service. Improvement of conception rate. Prolonged or continuous oestrus. Rabbits: Induction of ovulation at post partum insemination. Improvement of concep-
tion rate. Dosage and Administration: Dosage and administration: Cattle: ovulation induction, improvement of fertility-2.5ml, treatment of cysts and anoestrus -5ml, Horses: 10ml; Rabbits: 0.2ml.
The preferred route of administration for Receptal is intramuscular injection, but it may also be injected intravenously or subcutaneously. Withholding period: Milk, meat: nil. Storage: Store at room
temperature. Contra-indications: None. Side effects: Unknown. Interactions: None. Presentation: Vials of 2.5ml, 10 ml and 50ml.

Intervet International bv
PO box 31, 5830 A A Boxmeer
The Netherlands
Phone: +31 485 587600
E-mail: info@intervet.com
www.intervet.com
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