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Use of GnRH antagonists for IVF

Use of GnRH antagonists for IVF. Dr. Hakan Özörnek EUROFERTIL IVF Center. Structures of GnRH-antagonists in comparison to native GnRH. GnRH. Agonist - Initial Phase: Stimulation. Agonist. Increased secretion of LH/FSH. Chronic Administration agonist.

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Use of GnRH antagonists for IVF

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  1. Use of GnRHantagonistsfor IVF Dr. Hakan Özörnek EUROFERTIL IVF Center

  2. Structures of GnRH-antagonists in comparison to native GnRH

  3. GnRH Agonist - Initial Phase: Stimulation Agonist Increased secretion of LH/FSH

  4. Chronic Administration agonist Blockade post receptor mechanisms Some loss of receptors

  5. GnRH Antagonist: Immediate Suppression Antagonist Receptor blocked no microaggregation No effectimmediate decrease of LH (FSH)

  6. Hormon levels days

  7. Hormon levels days

  8. Advantages ofGnRH-antagonists • noflare-upeffect • nowithdrawlsymptoms • shorterstimulation • reducedgonadotrophinconsumption • fast reversibility

  9. LongAgonist vs Antagonist

  10. Antagonist protocols

  11. Timing of Antagonist Administration

  12. Suggestedprotocol

  13. Discontinuation of IVF therapy • Treatmentburden • Length of treatment • Side effects • Burden of risk • OHSS

  14. Advantages of Antagonists • No initialflareup • Shortertreatmentduration • Lessgonadotrophinconsumption • Lessclinicattendances • Lower risk of OHSS • No hypooestrogenemiceffects • Weightgain, headache, hot flushes, moodchanges, vomiting

  15. Agonist Antagonist

  16. Disadvantages of Antagonists • Lowerpregnancyrates ?

  17. Normoresponder-Antagonist Tubalinfertility - DIR Engel, et al., 2006

  18. Normoresponder-Antagonist Olivennes, et al., 2000

  19. Normoresponder-Antagonist TheEuropeanandMiddle East OrgalutranStudyGroup, 2001

  20. Duration of stimulation (PCOS) Grisinger G, RBM Online, 2006

  21. Gonadotrophinconsumption(poor) Grisinger G, RBM Online, 2006

  22. Gonadotropinconsumption (PCOS) Grisinger G, RBM Online, 2006

  23. Gonadotrophinconsumption Al-Inany HG, RBM Online, 2007

  24. Cancelledcycles (poor)

  25. Number of oocytes Al-Inany HG, RBM Online, 2007

  26. Number of oocytes (PCOS) Grisinger G, RBM Online, 2006

  27. Miscarriage rate Al-Inany HG, RBM Online, 2007

  28. OHSS Al-Inany HG, RBM Online, 2007

  29. OHSS • In a Cochranerewievtherelativeodds of hospitaladmissionfor OHSS wasreducedbye 54 % withantagonistscomparedwithagonists. Kolibianakis EM, HumanReprodUpdate, 2006

  30. Hiperresponder-Antagonist • Lower E2 levelsby antagonist cycles. • Ovulation can be triggeredbyagonistinstead of HCG.

  31. Clinicalpregnancy rate Al-Inany HG, RBM Online, 2007

  32. Clinicalpregnancy rate (PCOS) Grisinger G, RBM Online, 2006

  33. Clinicalpregnancy rate (Poor) Grisinger G, RBM Online, 2006

  34. LiveBirth Rate

  35. Livebirthrate(poor) Kolibianakis EM, HumanReprodUpdate, 2006

  36. Livebirthrate (PCOS) Kolibianakis EM, HumanReprodUpdate, 2006

  37. Livebirthrate (Gonadotropintype) Kolibianakis EM, HumanReprodUpdate, 2006

  38. Livebirthrate (protocoltype) Kolibianakis EM, HumanReprodUpdate, 2006

  39. Livebirthrate (agonisttype) Kolibianakis EM, HumanReprodUpdate, 2006

  40. Livebirthrate (antagonist protocol) Kolibianakis EM, HumanReprodUpdate, 2006

  41. Livebirthrate (antagonist type) Kolibianakis EM, HumanReprodUpdate, 2006

  42. Livebirth rate Al-Inany HG, RBM Online, 2007

  43. Livebirth rate Al-Inany HG, RBM Online, 2007

  44. Livebirth rate Kolibianakis EM, HumanReprodUpdate, 2006

  45. Livebirth rate Kolibianakis EM, HumanReprodUpdate, 2006

  46. Analoguse in EUROFERTIL

  47. Analoguse in EUROFERTIL 2006-08

  48. CPR in antagonist cycles

  49. Conclusions • ComparedwithGnRHagonists, GnRHantagonistsareassociatedwithreducedtreatmentdurationandreduced risk of ovarianhyperstimulationsyndrome • Use of GnRHantagonistsavoidspituitarydown-regulation, which is associatedwithhypo-estrogenicadverseevents.

  50. Conclusions • Meta-analysescomparingGnRHagonistsandantagonistshavecalculatedalmostidenticaloddsratios (0.82-0.86) fortheprobability of livebirth, althoughthedifferencewasstatisticallysignificant in oneanalysisand not in another. Thedifference is unlikelyto be of clinicalsignificance.

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