May 15, 2012

Induction of Estrus for medical purposes


  • For an excellent review see: Estrus induction and synchronization in canids and felids, M.A. Kutzler, Theriogenology Volume 68, Issue 3, August 2007, Pages 354-374 Proceedings of the Annual Conference of the Society for Theriogenology, Proceedings of the Annual Conference of the Society for Theriogenology  
  • Before inducing estrus, it is important that the bitch has undergone the mandatory endometrial repair period. Attempting to induce estrus in a bitch that is in diestrus, or that has not completed endometrial repair following the luteal phase will surely result in infertility.



Normal Induction of Estrus

  • FSH concentrations are high and  LH concentrations are low during most of anestrus. 
  • Both FSH and LH increase progressively at the end of the anestrus period. The rise in the LH concentration  causes  folliculogenesis at the end of anestrus.


Gonadotrophins

  • Gonadotrophins are compounds which have stimulating effect on the ovary.
Follicle stimulating hormone (FSH), Equine chorionic gonadotrophin (eCG) (formerly named Pregnant mare serum gonadotrophin - PMSG)
  • There are many reports using these compounds are results have been extremely variable.
  • The very successful report by Moses and Shille using LH and FSH has never been reproduced clinically (even by Shille).
  • Availability of the gonadotrophins is also variable, with some products available at some times, and not others.
  • Recent abstract from Argentina
    • SFT 2009
    • 50 IU/Kg (one dose) and 7 days later 500 IU hCG IM (much lower doses that previous)
    • 14/14 showed estrus
    • 4.1 + 3.5 days to estrus
    • 16.6  + 0.6 days from treatment to diestrus
    • 13/14 bred
      • 10/13 pregnant
      • 3.6 + 0.4 pups

PG 600
  • PG 600 is marketed for inducing estrus in prepubertal gilts.
  • It has been shown to be clinically effective in the bitch.
  • One 'dose' followed by second dose in 7 days was clinically effective at inducing estrus in 17/19 bitches.
  • It was noted however, that if it was given during proestrus, superovulation may result.


Gonadotrophin releasing hormone (GnRH)

  • You must use a surgically implanted pulsatile infusion pump.
  • Gonadotrophin releasing hormone causes release of FSH and LH from the anterior pituitary. It is not a gonadotrophin. The natural FSH causes the follicular growth.
  • These pumps are hard to get, cumbersome to install, expensive, and not that reliable.

Gonadotrophin releasing hormone (GnRH)


analogue Deslorelin (Ovuplant)

  • Ovuplant is the equine implant containing 2.1 mg deslorelin
  • Placed in vestibular mucosa 
    • Progesterone followed
    • Implant removed day of LH surge (as determined by P4)
      • 0-13 days (50% on day 9 post implantation)
  • Day 1 diestrus 14-18 days
  • 5/7 conceived 
  • Deslorelin 2.1 mg implant in  vestibular submucosa once (proestrus within 5–6 d) 100% ovulated good pregnancy rate (several studies) 
  • Cannot get the implant from the company in 2004, but some compounding pharmacies have it (BET).
  • In a study done at LSU were induced a progesterone rise (estrus?) in 14/16 bitches.
     



 Estrogen


Diethylstilbestrol - DES (Bouchard et al.)
  • This seems as though it is the most reliable yet.
  • You may not be able to obtain DES anymore.
  • Make sure the bitch has completed endometrial repair i.e. the interestrus interval is 150 days.
  • Administer 5 mg Diethylstilbestrol (DES) PO for 7 days or until bleeding starts.
  • Give DES 2 more days after bleeding is observed. Count the first day of bleeding as the first day of the induced estrous cycle.
  • Experimentally 5/5 conceived and averaged 6.3 pups/litter. We have had success using this technique.
  • Currently not commercially available, but as of 4/1/99 (not an April Fools Joke) is available at Portland Professional (207-774-5440), a formulating pharmacy and in Lafayette, LA "Professional Arts Pharmacy" 318-237-4767 or 888-237-4737.
  • In a study done at LSU we were 0/5 at inducing estrus.



Dopamine agonists


Action of dopamine agonists in inducing estrus
  • The precise mechanism by which dopamine agonists shortens anestrus is not yet known. Link to a review article in Communications in Theriogenology (Vol 1 Issue 1) on estrus induction with dopamine agonists.
  • Direct dopaminergic action on either the gonadotrophic axis or on ovarian gonadotrophin receptors.
  • Bromocriptine does increase FSH concentration that results in enhancement of follicle development, but there is no correlation between PRL and LH, and there is basal PRL concentration found during anestrus.
  • There is a direct stimulating effect of dopamine in the synthesis of gonadotrophin releasing hormone (GnRH) by hypothalamus-hypophysis neurons, but the role of the dopaminergic paths in the control of gonadotrophin secretion is still unknown in the bitch. Dopamine agonists may have a have a direct effect on the ovaries. Cabergoline might mature gonadotropin ovarian receptors by its dopaminergic agonist action. Dopaminergic agonists may act by either releasing gonadotrophins or by an action on ovarian tissue.

 






Bromocriptine (Parlodel)

  • Administered at a dose of 50 ug/kg, BID until estrus starts.
  • It may take 18-28 days of treatment before estrus starts.
  • Experimentally 4/5 bitches came into proestrus, but fertility was not monitored.
  • Another study used bromocriptine in 4 bitches orally at 20mg/kg twice daily. A pregnancy rate greater than 60% was obtained using the same bromocriptine protocol in a study that compared administration from the onset of the luteal period or from about 21 days after the onset of the luteal period
Cabergoline (Dostinex)
  • 5ug/kg/day 5-18 days
  • Bitches treated late in anestrus came into estrus and have become pregnant
  • Expensive in the US if you can get it.




Prostaglandin


Lutalyse
  • Lutalyse does not really induce estrus, but if it is given during diestrus the next cycle will be about one month sooner than it normally would be.
  • This could be useful in breeding colonies. If a bitch is not pregnant, prostaglandin could be given to shorten the time to the next heat. This would result in more potential puppies in a given time.




by: Bruce E Eilts

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