The List of the Common Drugs and Hormone Used in the Treatment of Animal Infertility

The List of the Common Drugs and Hormone Used in the Treatment of Animal Infertility

Dr Ankesh Kumar

Bihar Veterinary College

Bihar Animal Sciences University, Patna 

 

1. GnRH (Gonadotrophin Releasing hormones)
2. FSH and LH ( Follicle Stimulating Hormones; Luteinising Hormone)
3. hCG (Humane Chorionic Gonadotrophin)
4. eCG (Equine Chorionic Gonadotrophin Hormone)
5. Oxytocin
6. Estrogen
7. Progesterone as vaginal insert
8. Hydroxyprogesterone injection
9. Cabergoline
10. Agelepristone
11. Androgen
12. Antiandrogen
13. Prostaglandins and its analogue
14. Melatonin
15. GnRH (Gonadotrophin Releasing hormones): Naturally occurring hormone produced by the hypothalamus and transferred to the anterior pituitary gland in the hypophyseal portal circulation. It is a peptide and stimulates the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

Pharmacological action: Stimulates a short surge of FSH and LH following a single bolus injection

Indications

Cattle:

• Follicular cysts
• Delayed ovulation or anovulation
• Acyclicity (doubtful if a single bolus is very effective)
• For improving pregnancy rates, in cows with poor pregnancy rates, when used as ‘holding injection’ as a single bolus 12 days after insemination as part of estrus-synchronization regimens ( Ovsynch programme)

 Horse:

• For inducing ovulation (preovulatory gonadotrophin surge lasts several days in mare); single bolus may not be effective, requires frequent repeated doses, or the use of a slow-release implant.

Dose rates:

Cow, 10-20 µg; horse 40 µg preferably i.m. but can be given i.v. or s.c.

2. FSH (Follicle Stimulating Hormones) and LH:

Both FSH and LH can be obtained in a semi purified form but are expensive. Porcine FSH and recombinant-derived FSH are used to induce superovulation in donor cows for embryo transfer.

Commercially available Product: Stimufol (Reprobiol SPRL); Super-Ov (Glo bal Genetics UK)

3. 3. hCG (Humane Chorionic Gonadotrophin):

Human chorionic gonadotropin (hCG) has a potent luteinizing hormone (LH)-like   effect in cattle that extends the life span of the corpus luteum (CL) and increases progesterone synthesis, induces ovulation throughout the estrous cycle, promotes the formation of accessory corpora lutea when applied in the early luteal …

Commercial available Product: Chorulon

Dosage: Improvement of conception rate in cows & heifers- 1500 IU at AI or mating, by I/M or I/V route; or 4-6 days post AI

Induction of ovulation (Mares) – 1500-3000 IU, by I/M or I/V route, 24 hours     before AI / mating

4.  eCG (Equine Chorionic Gonadotrophin Hormone):

A protein hormone produced by the endometrial cups of the mare from about 40-120 days of pregnancy. It mainly has FSH like activity but with a much longer biological half life than FSI-1

Commercially available products:

eCG or serum gonado trophin, PMSG-Intervet (lntervet UK Ltd, Milton Keynes); Fostim 600 (Pfizer UK, Sandwich, Kent); Folligon® – MSD Animal Health India

Pharmacological action: Mainly FSH Like in its action but has some LH activity.

Indications

Cattle:

• Superovulation of donor cows for embryo transfer; rarely used because        overstimulation can be a problem
• Impaired spermatogenesis in bulls (doubtful value)
• At the time of withdrawal of intravaginal progesterone, preparations when used to treat acyclicity.

 

Sheep and goats:

• Intravaginal progestogen sponges to advance the onset of the breeding season.

Dog:

• For inducing oestrus during physiological anoestrus

Dosage Rate:

• Cattle: 1500- 3000IU s.c. or i.m.
• Sheep and goats: 500-5000 IU s.c. or i.m. (depending on the breed and time interval          to the onset of normal breeding season)
• Pig: 1000 IU s.c. or i.m.
• Dog: 50-200 IU

 

5. Oxytocin:

Oxytocin is a peptide hormone produced by the neurones of the supraoptic nucleus and is transported to, and stored in, the posterior pituitary gland. Synthetic oxytocin and an analogue with a longer half-life (carbetocin) are available.

Commercially available products: Oxytocin-S (Jntervet UK Ltd, Milton Keynes) Carbetocin (Reprocine, Vetoquinol UK Buckingham; Evatocin (Neon, India)

Pharmacological action:

Causes milk let-down, myometrial contractions to facilitate gamete transport,              myometrial contractions during parturition and postpartum

Indications

                       Cattle:

• Milk Let Down
• Hasten uterine involution following dystocia, caesarean operation, after        replacement of uterine prolapse, uterine trauma or haemorrhage

Horse:

• For inducing foaling
• Cause expulsion of retained fetal membranes
• Induce milk let-down.

Sheep: As for Cow

Pig:             

• Hasten second stage of parturition
• Induce milk let down
• Treatment of uterine inertia
• Cause expulsion of retained fetal membranes
• Hastening of uterine involution

Dog:

• Treatment uterine inertia
• Expulsion of retained fetal membrane
• Hastening of uterine involution after dystocia or caesarean operation (perhaps treat sub involution of placental sites)

Dosage

Many recommended dose rates are too high. The myometrium is very sensitive to the effects of oxytocin and high dose rates can cause spasm rather than synchronized contractions. The myometrium will also become refractory to its effect, hence increasing incremental dose rates should be used. Most effective when used in an intravenous d rip in saline.

• Cattle: 10 IU i.m. or i.v.
• Horse: 10 IU i.m. or i.v.
• Pig: 5 IU i.m. or i.v.
• Sheep and goat: 2-5 IU i.m. or i.v.
• Dog and cat: 0.5-5 IU i.m. or i.v

                         Dose rate (Carbetocin)

• Cattle: 0.21 – 0.35 mg per animal
• Pig: 0.105-0.21 mg per animal

 

6. Oestrogen:

Oestrogens, which are steroids, play a wide role in the reproductive process.   However, there are relatively few rational indications for estrogen therapy in the treatment of reproductive disorders in domestic species. Recently, all estrogens have been withdrawn from use in food-producing animals in European Union countries because of concern about residues in human food products; this ban is likely to be introduced in other countries throughout the world

Commercially available products

Estradiol benzoate (Mesalin, lntervet UK Ltd, Milton Keynes)-This contains 200µg/ml estradiol benzoate in oil;  Diethylstilbestrol (non-proprietary)-Tablets 1 mg and 5 mg. Ethinylestradiol (non-proprietary)-Tablets 10, 50 µg and 1 mg. Pregheat injection- This contain Oestradiol Benzoate 1mg/ml (Available in 2 ml)

 

Pharmacological action

Oestrogens are primarily responsible for oestrous behaviour in the female; they stimulate changes in the tubular genital tract that control gamete transport and, with progestogens, cause development of the mammary gland and increase the resistance of the genital tract to infection. They potentiate the ecbolic action of oxytocin and prostaglandins on the myometrium. They stimulate the pre-ovulatory surge of gonadotrophins. They also reverse the effects of androgens on androgen-dependent tissue changes.

Indication

Dog:

• Prevention of unplanned pregnancy
• Urinary incontinence in the spayed bitch
• Prostatic hyperplasia and anal adenoma in the

Male dog

• To depress hyper sexuality in the male dog.

Dose rate

Dog:

• Estradiol benzoate: following unplanned mating to prevent pregnancy 10  µg/kg, 3, 5 and possibly 7 days after mating s.c. or i.m.
• Diethylstilbestrol: for urinary incontinence I mg daily for 3 days followed by 1 mg every third day; for prostatic hyperplasia 1 mg/day
• Ethinylestradiol: 50-100 µg/day orally. Oestrogens are not without risk in the bitch, predisposing to cystic endometrial hyperplasia, and should not be used         without warning.
• Estrogens should not be used in cats.

7. Progesterone as vaginal insert

Progesterone targets uterine epithelium, mammary tissue, myometrium and hypothalmus causing endometrial secretion, inhibition of GnRH release and promotes maintenance of pregnancy. The level of progesterone in the serum and milk reflects the activity of the CL on the ovary.

Commercially available products

Progesterone-releasing intravaginal device (PRID, Ceva, Chesham, Bucks). Each device contains 1.55 g of progesterone. One device should be inserted into the vagina and left in situ for up to 12 days, PGF2 alpha should be administered 24 hours before removal if used for estrus synchronization. Estrus occurs 2- 5 days after withdrawal.

 

Controlled internal drug release (CIDR) devices (Eazi-Breed, CIDR, Animal Reproductive Technologies (ART UK) 4td, ‘Leominster). are used in livestock for the synchronization of estrus. They are T-shaped devices with a silicone-coated nylon core. The silicone coating is impregnated with progesterone. CIDRs are inserted intra-vaginally using a specialized applicator. Each device contains 1.38g of Progesterone and should be left in place for 7-12 days with PGF2″ treatment at the time of removal if used for estrus synchronization

Indications

• Synchronization of oestrus /ovulation in cows and heifers, in conjunction            with prostaglandin (PG) F2Alpha
• Treatment of acyclicity (true anoestrus) in cows and heifers
• Treatment of non-observed oestrus in cows
• Treatment of thin walled follicular cysts

8. Hydroxyprogesterone injection:

Veterinary Hydroxyprogesterone Injection helps solve the Reproductive Problems like, Habitual abortion, Repeat Breeders, Luteal deficiency, Prolapse of Uterus, induction of Oestrus and Infertility caused by Progesterone deficiency. Hydroxyprogesterone caproate has prolonged uterotrophic effect; it stimulates luteal actions, causes changes in uterus and vagina as seen in early pregnancy. The drug stimulates a proliferative endometrium into secretion as well as stimulates the growth of mammary alveolar tissues.

 

Indication:

• Habitual abortion
• Threatened abortion
• Vaginal / uterine prolapse
• Post-partum anoestrus

Dosages:

• Habitual abortion: 3ml of P Hydroxyprogestrone after 45 days of pregnancy repeat at every 10 days for 4-5 times.
• Repeat Breeding: 2-3 ml of Hydroxyprogestrone per week for 3 weeks
• Vaginal/Uterine prolapse: 3ml of Hydroxyprogestrone per day for 2 days
• Post-partum anoestrus: 3ml of Hydroxyprogestrone if no response repeat after 10 days

9. Cabergoline

Prolactin is a major luteotrophic hormone and appears to be an absolute requirement for canine and feline progesterone secretion by day 30 after ovulation. Dopamine agonists like cabergoline are ergot alkaloids, with strong dopamine D2-receptor agonist activity, and thus can reduce prolactin secretion thereby suppressing progesterone levels.

Indication

• For treatment of pseudopregnancy in bitch : 1-5µg/kg body weight once-daily orally

10. Agelepristone:

 

A progesterone-receptor blocker, aglepristone is used for the termination of pregnancy in mammals. This is synthetic steroids which have a high affinity for progesterone receptors, preventing progesterone from exerting its biological effects. They act as true receptor antagonists, preventing the uterine effects of progesterone without initially decreasing serum progesterone concentrations. The affinity of aglepristone for uterine receptors is three times greater than that of progesterone itself.

 

Indications

• Pregnancy termination in bitches and queens.
• Medical treatment of pyometra.
• Induction of parturition.
• Planning of an elective caesarean section.
• Treatment of feline mammary fibro adenomatosis.

Dosages

• For termination of pregnancy in bitch and queen from day 0- day 45 after matting – give subcutaneous injection of agelepristone at dosage rate of 10 mg/kg of body weight 24 hours apart. Ultrasonographic monitoring in bitch and queen must performed at least 30 days after matting. In case of treatment failure a repeated treatment is often successful.
• For treatment of pyometra in bitch- Aglepristone (10 mg/kg SC) injected 24 hours apart, followed by weekly injections at the same dose until complete recovery, absence of vaginal discharge, and absence of uterine lumen enlargement on ultrasound examination is confirmatory for recovery from pyometra. A protocol using aglepristone at Days 1, 3, 6, and 9 (Day 1: day of diagnosis) without subsequent injections showed a success rate of 100%
• For inducing parturition in bitch- Aglepristone (15 mg/kg SC) at Days 58 and 59 (Day 0: ovulation) + oxytocin (0.15 IU/kg SC) every 2 h from Day 59 until the end of delivering. Aglepristone (15 mg/kg SC) on Days 60 and 61 (Day 0: LH surge) + oxytocin (0.15 IU/kg SC) every hour from Day 61 until the end of delivering may also be effective
• Planning for an elective caesarean section- Aglepristone (15 mg/kg SC) injected on Day 59 or 60 after ovulation followed 20 to 24 hours later by a planned C-section. A C-section performed 1 to 2 days before the due date, after aglepristone treatment, is safe for dams and puppies, provided that the ovulation date had been accurately determined at the time of mating.
• In the goat, aglepristone has been used to induce parturition. Inject subcutaneously once at Day 145 of pregnancy. A dosage rate of 5 mg/kg is recommended.
• In cattle for pregnancy termination. Give aglepristone (5 mg/kg SC once at Day 47 of gestation or twice at Days 47 and 48 of gestation) induced foetal death.
• For inducing parturition in cattle, aglepristone is administered (5 mg/kg SC) at Days 270 and 271 of pregnancy for successful delivery of calves

11.                  Androgen:

Testosterone is the principal circulating androgen in the male, being produced by the interstitial cells of the testis. As well as being responsible for the secondary sex characteristics, it is also involved in spermatogenesis. Androgens, either naturally occurring or synthetic analogues, have limited application in animal reproduction or disease.

Commercially available products

Testosterone esters injection ( Durateston, I ntervet UK Ltd, Milton Keynes). Contains testosterone decanoate 20 mgfml, testosterone isocaproate 12 mg, testosterone propionate 6 mgfml and phenyl propionate 12 mg/ml.

 

Pharmacological action

Since testosterone is involved in controlling libido in the male it is used to improve any deficiency that might be present, although it must be stressed that libido and sexual behaviour are complex and not just a reflection of endogenous androgens; therefore, the results of such therapy will usually be disappointing. Androgens have anabolic effects and can be used to treat debilitated animals. They have been used to postpone oestrus in bitches and overcome some of the behavioural problems associated with pseudopregnancy in bitches, and reverse feminization associated with Sertoli cell tumours.

Dose rate: 0.05-0.1 ml/ kg s.c. or i.m. in the dog and cat

12. Antiandrogen

A substance that keeps androgens (male sex hormones) from binding to proteins called androgen receptors, which are found in normal prostate cells, some prostate cancer cells, and in cells of some other tissues. Preventing this binding blocks the effects of these hormones in the body. Treatment with antiandrogens may keep prostate cancer cells from growing. Examples of antiandrogens used to treat prostate cancer are apalutamide, bicalutamide, enzalutamide, flutamide, and nilutamide. Also called androgen receptor antagonist and androgen receptor blocker.

Commercially available products

Delmadinone acetate (Tardak Pfizer, Sandwich).

Indications

Dog:

• Hypersexuality in the male dog
• Prostatic hyperplasia and prostatitis.

Dose rate:

1.0-2.0 mgfkg body weight, s.c. or i.m.

13. Prostaglandins and its analogue

Prostaglandin is naturally produced by the uterus and terminates the normal cycle when a cow is not pregnant. This allows the cow to return to heat, ovulate and start a new cycle. Prostaglandins will synchronize heat only if cows are cycling; however, they are not effective on all days of the estrous cycle. Cloprostenol, Luprostiol and Tiaprost are synesthetic PGF2alpha analogue while Dinoprost is natural prostaglandin. The prostaglandin is also used for treatment of pyometra in bitch. Pyometra is a hormone-mediated diestrus disease and characterized by uterine pus accumulation. Prostaglandins are mostly used in pyometra for the uterine evacuation of pus. Pyometra is classified as open and closed cervix pyometra. Open cervix pyometra is less severe as compared to closed cervix pyometra concerning the systemic illness. The use of prostaglandins is contraindicated in closed cervix pyometra as there is a chance of uterine rupture.

Commercially available Product 

Cloprostenol (Estrumate and Planate, Schering Plough Animal Health, Harefield; Cyclix and Cyclix porcine, Intervet UK Ltd, Milton Keynes; Pragma, Intas Animal Health, India; Vetmate, Vetcare, India).For use in cattle, sheep, pigs, horses and goats.

Dinoprost (Lutalyse, Pfizer, Sandwich, Kent); Enzaprost, CEVA Chesham). For use in cattle, sheep, pigs, horses, goats and dogs.

Luprostiol (Prosolvin, Intervet UK Ltd, Milton Keynes). For use in cattle, sheep, pigs, horses and goats.

 Indications

Cattle:

• Synchronization of oestrus in cows and heifers
• Treatment of non-observed oestrus
• Induction of calving
• inducing abortion and expulsion of mummified

Calves

• Treatment of pyometra
• Treatment of endometritis
• Treatment of luteal (luteinized) cysts.

Horse:

• inducing abortion before 35 days
• Treatment of a persistent luteal phase
• Induction of foaling
• Hasten return to oestms if service is missed
• Hasten return to oestrus after the foal heat
• Planning the time of oestms for efficient use of

Stallion or AI.

Sheep and goat:

• Synchronization of oestms
• Inducing early abortion in sheep
• Treating pseudopregnancy in goats.

Pig:

• Induction of farrowing.

Dog:

• Treatment of open pyometra in the bitch ( dinoprost

and cloprostenol, use with care).

Dose rate

• Cloprostenol

Cattle: Single or repeat dose of 2 ml (500 µg).

Horse: Singe dose of 1 – 2 ml (250 – 500 µg)

Bitch for Open Pyometra: Cloprostenol is administered @5μg/kg, s/c on                         alternate days for 7 days

• Luprostiol: Cattle, 15 mg; horse, 7.5 mg; sheep and goats, 7.5 mg; pigs, 7.5 mg. All by i.m.
• Dino prost: Cattle, 25- 35 mg; horse, 5 mg; pig, 10 mg; sheep, 6-8 mg; dog, 0.25-0.5 mg/kg. All by i.m.

Reference

1. David E. Noakes, Timothy J. Parkinson and Gary C.W. England. 9^th Edition, Veterinary Reproduction and Obstetrics. Elsevier, Edinburgh London New York Oxford Philadelphia.
2. Robert, S. J. 1971. Veterinary obstetrics and genital diseases. 2^nd (Indian edition)