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Antagonist or agonist
- 1. Antagonist ……..is the answer Dr Santosh Gupta MS,FRM Consultant Reproductive Medicine Manipal Ankur Reproductive Services
- 2. Evolving human wisdom Use of antagonist is also evolving in the hands of doctors worldwide
- 3. IVF : Miracle of millennium
- 4. From 1978 till today……………. • Natural cycle IVF • 1980s learned the ART of LH surge control by GnRH agonist • IVF became a global phenomenon “ BUT” a chapter of IVF related complications opened
- 5. Emergence of new Super HERO “ ANTAGONIST”
- 7. Commercially available • Cetrorelix • ganirelix
- 10. Advantages of GnRH antagonist • Shorter duration of treatment • Less injections • Less consumption of Gonadotropins • No flare up /no cyst formation • No pituatory desensitization “more physiological” • Lesser incidence of OHSS
- 13. Efficacy………
- 14. 1a
- 15. Endometrial receptivity Prapas et al 2009,rep biomed; prospective RCT Oocyte from each donor shared between 2 different recipients Recipients were randomly allocated to either receive antagonist concomitant to donor during endometrial priming (gp1) or solely continuing endometrial preparation (gp2) GnRH antagonist administration during the proliferative phase at a dose of 0.25mg does not appear to adversely effect endometrial receptivity GP1 GP2 Endometrium similar similar Implantation rate 26.1% 24.4% Clinical pregnancy rate 55.1% 59.1% 1b
- 17. Cochrane review 2002 Al Inany et al
- 18. Antagonist versus agonist Inexperience of the centre Use of antagonist in higher age group Use of antagonist in “unfavourable prognosis a priori”
- 19. Cochrane 2006
- 20. Cochrane review and meta-analysis 2011 45 RCTs 7511 randomized women Conclusion The GnRH antagonist protocol is short and simple protocol with a comparable live birth rate to long agonist protocol.It is associated with a highly significant reduction in the incidence of OHSS compared to the agonist protocol therefore justifies a move away from the standard GnRH agonist long protocol to a GnRH antagonist protocol 1A
- 21. Burden of treatment……OHSS 3 OHSS related death in 100000 ART cycles “In 2003-2005, 4 deaths (of the 12) were due to OHSS”.
- 22. 3 levels of safety • Less incidence of OHSS(1a) • Gives freedom to use GnRH agonist as a trigger to replace hCG • Use of antagonist in luteal phase
- 24. Preferred protocol in PCOS……….
- 25. Cochrane review 2011 8 Trials with 783 PCOS women OHSS rate 10% lower in Antagonist group 1A
- 26. 1 1
- 27. Poor Response…….
- 29. Friendly IVF
- 31. Reducing treatment stress De Clark et al 2006 ,human reproduction In a study involving 391 women who were undergoing IVF with the conventional long agonist protocol reported statiscally significantly more symptoms of depression during the week before stimulation than control patients who did not experience downregulation.
- 33. Fertility preservation in cancer patients Immediate treatment Allows shortest deferral of radio/chemotherapy Agonist protocol requires extra 2to 3 weeks Lower estradiol level, best for hormone responsive cancer Random start/luteul phase start stimulation Soft/mild ivf
- 34. Crystal ball where we are heading ……….???? IN Antagonist protocol OHSS free clinic OUT Long agonist protocol Severe OHSS OHSS related death
Editor's Notes
- Use of antagonist like humsn wisdom is evolving in the hands of learned doctors worldwide
- IVF is true miracle of millenium
- In 1978 it started with natural cycle ivf which had very high cancellation rate due to premature lh surge.soon the power of controling LH surged was gained by gnrh agonist.ivf became a global phenomenon and long agonist protocol became standard practice
- And in 1999 world saw emergence of new superhero called antagonist
- It is competitive inhibitor of Gnrh receptors at pituatory level acts immediately and block the lh release and action last for 24-30 hrs
- Antagonist can be used either as fixed or flexible protocol. In fixed protocol antagonist is started on d6 of the stimulation whereas in flexible protocol it is started after appearance of dominant follicle or serum E2 >400pg/ml
- In 2006 gnrh antagonist workshop was conducted and they came out with consessus
- Why antagonist is superior to agonist we discuss with specific evidence supportring the view
- Live birth rate and patients safety are the most important parameters to choose any protocol
- There were questions raised about possibility antagonist reducing endometrial receptivity. Such questions are best answered in donor recipient model.Praps etel conducted a rct
- Cochrane reviews have very important role in delayed establishment of antagonist
- In 2002 1st cochrane review got published which outrightly rejected antagonist
- This review has stopped clinicians worldwide to use antagonist , But many raised their eyebrows over this review and suggexsted that its not the molecule but the inexperience of the centre…. This was clearly shown by greissenger et la in german registry
- It has established the safety aspect of antagonist protocol
- newer challenges …Mild ivf can not be achieved without antagonist protocol
- As the medical field is advancing more more cancer pt are opting for fertility preservation
- See what he is annoucing … if you want safe ,simple friendly and efficacious………its antagonist only