*

Not all GnRH are the sameReceptal® is the only veterinary GnRH with the highly potent Buserelin as its active constituent.

Registered to and distributed by: Intervet Ltd, 12 Shakespeare Ave, Upper Hutt. New Zealand, Phone: 0800 447 838 www.intervet.co.nzReceptal® is registered pursuant to the ACVM Act 1997, No. A4062. Prescription Animal Remedy (P.A.R.) Class 1 for use only under the authority or prescription of a veterinarian.

See www.nzfsa.govt.nz/acvm/ for registration conditions.

ACTIVE CONSTITUENTS:BUSERELIN 4 µg per ml

PRESENTATION:A ready-to-use colourless, aqueous injection solution for parenteral administration, containing synthetic releasing hormone analogue of both the luteinising and follicle stimulating hormones (GnRH equivalent to LH/FSH-RH).

Each ml contains 4 µg Buserelin and 10 mg benzyl alcohol, Ph.Eur., as antimicrobial preservative. Buserelin is equivalent to the natural LH/FSH releasing hormone produced in the hypothalamus. It causes simultaneous release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the anterior pituitary.

DIRECTIONS FOR USE:For the treatment of anovulatory anoestrous in dairy cows when used in conjunction with a progesterone device and a PGF 2α analogue with luteolytic activity

For the synchronisation of oestrous in cows and heifers when used in conjunction with a PGF 2α analogue with luteolytic activity and with or without a progesterone device as part of a 10 day fixed time insemination regime.

For the treatment of delayed ovulation in cows

For the treatment of cystic ovaries in cows

For the improvement of pregnancy rate in cows

To induce ovulation of a mature follicle and thereby to synchronise ovulation more closely with mating in mares

For the treatment of cystic ovaries and anoestrous in mares

PRECAUTIONSFollowing withdrawal of the first dose, use the product within 14 days. Discard unused material. Observe aseptic precautions.

DOSAGE AND ADMINISTRATIONReceptal® is preferably given by intramuscular injection. However, the intravenous or subcutaneous routes may also be used if desired. Syringes and needles should be from gamma irradiated packs or freshly sterilised by boiling for 20 minutes, but no alcohol or disinfectant should be used for this procedure.

DISPOSAL:Dispose of empty container by wrapping with paper and putting in garbage.

STORAGE:Store below 25°C (Air conditioning). Protect from light.

FIRST AID:If poisoning occurs, contact a doctor or the National Poisons Centre (0800 POISON).

Cattle:Dosage

Cows:

Anovulatory anoestrous 2 mL

Synchronisation of oestrous 2 mL

Follicular and Luteal cysts with or without prolonged signs of nymphomania

5 mL

Delayed ovulation 5 mL

Improvement in pregnancy rate of cows

2.5 mL

SPECIAL NOTESFollicular cystsIn the treatment of follicular cysts in cattle, it is unnecessary and contraindicated to manually express the cysts. A corpus luteum will usually be clearly detectable on either the affected or the normal ovary within about 8 days after administration of Receptal®. The ‘healthy corpus luteum’ can be left to spontaneously resolve or the time to the next oestrous can be shortened by giving a PGF 2α analogue with luteolytic activity 7 – 9 days after the Receptal® injection. Artificial insemination or service should take place during the first oestrous after treatment. Oestrous should occur within 21 days of Receptal® injection, if not re-examine and retreat if a further cyst has developed.

Delayed ovulationMay be treated at the time of artificial insemination or service, or up to 6 – 8 hours before. Ovulation is usually induced within 24 hours of treatment.

NoteThe induction of ovulation is not possible in the presence of a functional corpus luteum.

Horses: Dosage

Mares:

Cystic changes of the ovaries with or without prolonged or permanent oestrous

10 mL

To induce ovulation of a mature follicle and thereby to synchronise ovulation more closely with mating in mares

5 mL twice, with an interval of 24 hours

Anoestrous 5 mL twice, with an interval of 24 hours

In cystic changes of the ovaries, a single treatment is usually sufficient. If 10-14 days after treatment no response (i.e. regression of the cysts or remission of the prolonged or permanent oestrous) is seen, the treatment should be repeated.

In anoestrous mares if no oestrous occurs within 10 days, Receptal® should be administered again on the 11th and 12th day after the first treatment.

To induce ovulation of a mature follicle and thereby to synchronise ovulation more closely with mating.

Receptal® should be administered on the first day on which the follicle has reached its maximum size, this being determined by previous clinical history and rectal examinations.

Receptal® is best given approximately 6 hours prior to service. This may be achieved by administering Receptal® in the morning with service in the afternoon of the same day, or alternatively with the injection given in the early afternoon and service in the evening.

The mare should be served again the next morning if she is still in oestrous. If ovulation has not occurred within 24 hours after treatment, then the injection should be repeated.

Not all GnRH are the same:Buserelin – a unique active with unrivalled potencyReceptal® has the highly potent Buserelin as its active constituent. Buserelin acts the same as the natural LH/FSH releasing hormone produced in the hypothalamus. It causes simultaneous release of luteinising hormone (LH) and follicle stimulating hormone (FSH) from the pituitary.

Receptal® containing Buserelin:• is at least 50 – 60 times more effective than Gonadorelin, the alternative GnRH active* (as measured

in FSH and LH response)

• stimulates high production of LH for efficient induction of ovulation and better support of corpus luteum formation and early luteal function

• is the most potent GnRH analogue of standard formulation on the vet market

• is an international benchmark, enjoying world wide perception as the gold standard for GnRH based products

• was involved in the majority of the fundamental works on the application of GnRH in cattle – internationally and in New Zealand

*Nawito et al. (1977); Reeves et al. (1980); Loumaye et al. (1982); Chenault et al. (1990).

The New Zealand dairy industry has a major problem with anoestrous cows, treating around 500,000 cows annually to increase pregnancy rates.

Two fertility programmes for the treatment of anoestrous cows are recommended using Intervet’s Receptal – a synthetic gonadotrophin releasing hormone (GnRH), in conjunction with a progesterone device and prostaglandin analogue to stimulate the cow into oestrous prior to artificial insemination. The Fixed Time Insemination programme can also be used for synchronisation of oestrous cows and heifers.

OvulationOxytocin

Maturation

ProgesteroneOestrogens

Uterus

Ovary

Pituitary gland

Hypothalamus

LHFSH

PGF2α

Luteolysis

Growth

Follicle

GnRH

Luteini-zation

CorpusLuteum

Inhibinnegativefeedback

Oestradiolpositive

feedback

Progesteronenegativefeedback

FSH

Progesterone

Ovulation Ovulation

Oestrous Oestrous

Foll. phase Foll. phaseLuteal phase

LH LH

PGF2α

Hormone levels during the oestrous cycle of a cow

Inter-relationships in the control of female reproductive function

hormonelevel

Oestradiol

Receptal® – a question of potency

• The main uses of GnRH analogues in the management of reproduction in cattle rely on their ability to induce ovulation of the responsive ovarian follicle(s) present on the ovary at the time of injection.

• The final stimulus that triggers the ovulation comes in the form of the maximal concentrations of LH (so called preovulatory LH peak)

• As LH release is stimulated by GnRH, it is in fact the ability of a GnRH analogue to stimulate the release of LH from pituitary gland that decides about its efficacy

• It therefore makes sense to use the most potent analogues on the market to ensure the efficient ovulation induction

Why is Buserelin so potent?• Gonadorelin is identical in structure to

natural GnRH

• Buserelin has one amino-acid difference

• this gives it higher affinity for the GnRH receptors in the pituitary gland

• which results in higher levels of FSH/LH released

Synchronisation of oestrous cows and heifers Receptal®, when used as part of a 10 day fixed time oestrous synchronisation and insemination regime, will increase submission rates and significantly reduce the calving to conception interval. The regime requires Receptal® to be used in conjunction with a PGF 2α analogue with luteolytic activity and a progesterone implant device (see Fixed Time Insemination Programme).

When using fixed time insemination regimes, it is recommended that cows showing signs of oestrous after prostaglandin treatment should be inseminated when observed in oestrous rather than completing the synchronisation programme.

Prevention of early embryonic mortalityUse of Receptal® at 11-12 days post-inseminationEarly embryonic mortality is regarded as a major cause of reproductive failure in cattle; some estimates suggest that 25% of bovine embryos are lost during the first 3 weeks of life, with luteolysis suspected as a major cause. Studies show that the administration of GnRH at 11-13 days post-service suppresses oestradiol-17ß and PGF 2α, possibly representing a mechanism for a direct anti-luteolytic and embryo protective effect of GnRH. This effect has been demonstrated in a number of species including cattle, horses, sheep and rabbits.

The Chenault trial – Chenault et al. (1990): This involved investigating the LH and FSH response of Holstein heifers to fertirelin acetate, gonadorelin and buserelin, aimed at:

“Response to the treatment with GnRH analogues in terms of the induction of FSH and LH release was measured as average area under curve and determination of

differences in bioequivalence between three molecules tested.”

Results • 10µg of buserelin stimulated the largest release of LH in comparison to any

of the doses of gonadorelin used

• The largest dose (500μg) of gonadorelin recommended in cattle, released significantly less FSH and LH as compared to the lowest dose of buserelin used (10μg)

• Standard recommended dose of buserelin was proven to be the most efficient in terms of LH release and duration of action than any of the GnRH analogues tested

The benefits of high FSH/LHLH

• efficient induction of ovulation• better support for the formation of corpus luteum• better early luteal function

FSH• supports the selection and maturation of dominant follicle

Reference Potency of buserelin in relation to gonadorelin

In vivo (cattle)

Nawito et al. (1977) 50x

Chenault et al. (1990) 60x

In vitro — cell lines

Reeves et al. (1980) 50x

Loumaye et al. (1982) 60x

Interrelationships in the control of female reproductive function

OvulationOxytocin

Maturation

ProgesteroneOestrogens

Uterus

Ovary

Pituitary gland

Hypothalamus

LHFSH

PGF2α

Luteolysis

Growth

Follicle

GnRH

Luteini-zation

CorpusLuteum

Inhibinnegativefeedback

Oestradiolpositive

feedback

Progesteronenegativefeedback

FSH

Progesterone

Ovulation Ovulation

Oestrous Oestrous

Foll. phase Foll. phaseLuteal phase

LH LH

PGF2α

Hormone levels during the oestrous cycle of a cow

Inter-relationships in the control of female reproductive function

hormonelevel

Oestradiol

Hormone levels during the oestrous cycle of a cow

Using a GnRH? – Receptal® is your most potent option

• 1 dose (2.0ml) Receptal®

• Insert progesterone device (CIDR)

• Remove progesterone device (CIDR)• Inject Prostaglandin (PGF2α) analogue

at recommended luteolytic dose

• Inseminate on detection of oestrous

• 1 dose (2.0ml) Receptal® to non-detected cows• Fixed time artificial insemination immediately or within 24 hours

D E T E C T I O N O F O E S T R O U S P R O g R a m m E

• 1 dose (2.0ml) Receptal®

• Insert progesterone device

• Remove progesterone device (CIDR)• Inject Prostaglandin (PGF2α) analogue

at recommended luteolytic dose

• 1 dose (2.0ml) Receptal®

• Fixed time Artificial Insemination 16 – 20 hours after final Receptal® injection

F I X E D T I m E I N S E m I N a T I O N P R O g R a m m E

MacMillan et al, (1986), investigated this effect in lactating dairy cows of mixed breed in seasonally calving dairy herds in New Zealand. Treatment with Receptal® (10µg) increased pregnancy rate to first insemination by 11.5%. Sheldon and Dobson (1993), conducted a trial across 19 commercial dairy farms (1040 cows) in seasonal calving herds in the UK where the use of Receptal® (10ug) on day 11 post-service improved pregnancy rate by 9.4% compared to paired control cows. Other trials by Sheldon 1990/91 using Receptal® (10µg) showed a post service improved pregnancy rate of 13.2% when used on 2nd service repeat breeding cows, 28.3% and 30.0% when used on 3rd and 3rd plus service repeat breeding cows respectively.

A New Zealand cost benefit analysis indicates that returns on this programme are around 200%, based on milk production gains alone.

The table below shows results from selected trials summarising the effect on pregnancy rate of administering GnRH 11-13 days post-insemination

Author Sample size Service Time of GnRH administration

Post insemination

Improvement in preg rate cf controls

MacMillan et al 225 1 11-13 days 11.5%

Sheldon and Dobson 1993

1040 1 11days 9.4%

Drew and Peters 1994

643 1 12 days 12.0%

Adas 1989/90 660 1 12 days 12.0%

Sheldon 1990/91

272 2 11days 13.2%

Sheldon 1990/91

134 3 11days 28.3%

Sheldon 1990/91

80 3+ 11days 30.0%

-10

-3

-1

0

-9

-2

0

+1