Principles of contraception, incomplete Ovariectomy

• What are the actions of GnRH Agonists (male and female)

  Endogenous release causes increase in LH and FSH, and therefore a pivotal event in the hypothalamic-gonadal cascade.

  Preparations are either:

  • Short-term in action (e.g. buserelin injection) or deslorelin implant.
  • Causes stimulation of LH and FSH release.
  • Long term in action (e.g. descoring implant)
  • Causes initial stimulation and the receptor down-regulation.
• Long-term GnRH Agonists

  Causes initial stimulation and then the receptor down-regulation

  Licensed use:

  • Control of behaviour and fertility in male dogs
  • Temporary suppression of oestrus in bitches
  • Delaying puberty in bitches

  This can be use to inhibit reproduction in males and females of all species (dose-dependant)

  Implant has 2 sizes i.e. you choose 1 of 2 fixed doses. The mg/kg dose to animal thus varies according to animal bodyweight, as such duration is variable
• Actions of Progestogens

  Exert powerful negative feedback effect upon the hypothalamus/pituitary.

  Central sedative effects (Alfaxalone)

  Closes cervix

  Stimulate endometrial activity

  Mammary enlargement
• What are the adverse effects of progestogens?

  Increased appetite/ weight gain.

  Mammary enlargement

  • Benign nodules/ neoplasia (except proligestone)

  Risk of cystic endometrial hyperplasia - related to amount/duration of treatment.

  Diabetogenic (insulin antagonism)

  Acromegaly

  Coat changes especially local reactions following subcut injection.

  Masculinised female pups and cryptorchid male pups if given in pregnancy.

  Suppression of spermatogenesis.
• Treatment of pseudopregnancy - progestogens

  Progestogens inhibit the release of prolactin from the pituitary gland.

  Depot therapy e.g. proligestone
• Progestogens in males

  Reduction of FSH and LH secretion.

  • LH -> Leydig cells -> Androgens
  • Treatmetn of:
  • Antisocial behaviour
  • Prostate disease
  • Anal adenoma

  FSH -> Spermatogenesis

  • So the consequence is a reduction of spermatogenesis.
  • For short term suppression this may be minor but for long term treatment this impacts fertility.
• What are the actions of oestrogens?

  Causes oedema of the reproductive tract.

  Pheromone production.

  Changes in function of the uterine tube and uterus (support transport and the environment for fertilisation).
• What are the adverse effects of oestrogens?

  Potentiate the effects of progesterone on the uterus -> pyometra.

  Dose-related bone marrow suppression:

  • Anaemia, thrombocytopenia -> death

  Stimulate signs of oestrus

  Non-pruritic bilaterally symmetrical alopecia and hyperpigmentation.

  If administered during pregnancy may produce abortion.
• Oestrogens in unwanted mating

  Prevention of implantation and/or interference with transport of zygotes.

  Licensed preparation in oestradiol benzoate (Mesalin)

  Animals may continue to show signs of oestrus

  • May be re-mated - unlikely to become pregnant.
• Oestrogens - direct effect on reproductive tract

  Urinary incontinence

  • Increase urethral mucosal thickness.
  • Estriol (Incurin)
  • Many regimes suggested
  • Daily for up to 7 days then repeated as necessary
  • Daily for up to three weeks

  Alternative is Phenylpropanolamine (Propalin)

  Topical oestrogens may also be used for vaginitis

  • Pre-pubertal
  • Atrophic
• Gonadotrophins - use of hCG

  Testing of Gonadal function

  • e.g. are there any ovaries/testes - stimulate the release of oestrogen in female or testosterone in male which we then measure.

  Hastening of ovulation:

  • Female has to be in oestrus with large follicles that are capable of responding i.e. they have to have LH receptors.

  Forcing ovulation:

  • e.g. in cases of follicular cysts, but again follicles will only respond if they have LH receptors.
• What are the actions of prostaglandins?

  Lysis of the corpus leteum

  EarlyCLs are usually not responsive.

  Ecblic
• What are the adverse effects of Prostoglandins?

  Restlesness

  Hypersalivation

  Vomiting

  Abdominal pain

  Diarrhoea

  Pyrexia.
• Prostaglandins - treatment of luteal phase conditions

  Open-cervix pyometra

  • Low doses twice daily for 5-10 days.
  • Fluid therapy
  • Suitable antimicrobials

  Termination of pregnancy

  • Low doses twice daily for 5-10 days
  • Commence after day 20
  • Termination by resorption or abortion.

  Actually this use is largely superseded by combinations of prolactin inhibitors with prostaglandins.
• Prostaglandins - treatment on non-luteal phase conditions

  Post-partum metritis

  • Low doses twice daily for 3-5 days.
  • Fluid therapy
  • Suitable antimicrobials.
• What are the clinical uses of oxytocin?

  Stimulation of uterine contraction to facilitate parturition in the presence of a fully dilated cervix.

  Promote involution of the post-parturient uterus and thus aid the passage of retained placenta.

  Aid in the control of post-partum heamorrhage.

  ProMotion of milk ‘let-down’ in cases of agalactia.
• What are the use of prolactin inhibitors?

  Removal of prolactin causes demise of the CLs

  Progesterone rapidly declines.

  Termination of the luteal phase is an action similar to using prosta gland is but:

  • Fewer (different) adverse effects
  • No effect on the uterus

  Available product is Cabergoline
• What are the adverse effects of prolactin inhibitors?

  Nausea and vomiting

  Lethargy

  Abortion

  Return to oestrus
• Prolactin inhibitors - termination of pregnancy


  Treatment with prolactin inhibit or from 25 days after ovulation onwards as earlier treatment ineffective.

  Treatment at 28-35 days causes pregnancy loss by resorption.

  Treatment commencing after day 35 causes pregnancy loss by abortion.

  Treatment efficacy increased by concomitant use of PG

  Treatment >95% effective when treatment commences at day 28.

  Always confirm termination with an ultrasound.
• Prolactin inhibitors - treatment of pyometra

  Aim is to remove progesterone and stimulate uterine contractions.

  Prolactin inhibitors cause a decline in progesterone.

  Prostaglandins cause a decline in progesterone and uterine contractions.

  Cabergoline daily at 5mcg/kg combined with cloprostenol every third day at 2.5mcg/kg:

  • Can be use for closed cervix pyometra if prostaglandin delayed until day 3 i.e. when it is open-cervix pyometra.

  Treatment over at lest 10 days.

  Ensure cure using ultrasound of the uterus, or continue to treat until there is not further discharge.
• Progesterone receptor antagonists - overview

  Aglepristone (Alizin)

  Synthetic steroid which binds to progesterone receptor.

  Affinity for receptor 3 times higher than progesterone.

  Outcome is receptor binding but without any message

  Progesterone cannot bind to its receptor - essentially progesterone becomes invisible and not effective.
• Progesterone receptor antagonists - adverse effects

  Local tolerance

  • 9% if bitches have injection site reaction in one of the 2 injection sites.
  • Resolve within 2-8 weeks
  • Always use at least 2 injection sites (more in large bitches)
  • Clinical signs typical of normal parturition.
• Progesterone receptor antagonists - potential uses

  Prevention of implantation

  Termination of pregnancy at any stage

  Treatment of pyometra?
• Progesterone receptor antagonists - treatment of pyometra

  Multiple repeated doses

  Cervix relaxes and uterine fluid expelled

  Few studies performed

  • Some show subsequent fertility
  • Advantages over PG-Prolactin antagonist regimes.
• Melatonin (female)

  Endogenous production in response to decreasing daylight

  • Up-regulation of short day breeders
  • Down-regulation of long-day breeders.

  EWE:

  • Melatonin implant administered at base of ear in May-June to hasten onset of cyclicity (+introduction of the ram).

  Queen:

  • Off-label administration of Melatonin will suppress oestrus temporarily.
• Behaviour after surgery

  Hormone concentrations decline quickly after castration however some behaviour s learned and in some cases libido may be retained for years if castrated after puberty.

  No change in hormone concentration after vasectomy.
• Infertility after castration

  Onset of infertile ejaculate will depend upon the degree of sperm storage in the ampulla.

  • Dogs have very small ampulla therefore azoospermic within a few days.
  • Stallions have significant ampulla therefore sperm may be detected for several weeks or until he ejaculates
• Bitch presented during a period of alleged oestrus - observation of behaviour and clinical examination

  Test is diagnostic at this stage. Bitches habe IO and are in proestrus/oestrus/ have jsut ovulated, have behavioural changes that differentiate them from bitches with no ovaries and these include features of standing oestrus behaviour and tail deviation.
• IO in the queen

  Generally cycle very 2-3 weeks.

  Simplest approach is to examine when they are in alleged oestrus.