Free Information Session 5th September 2012: Recent Breakthroughs in IVF


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Dr Louise Hull spoke about new technologies which are improving outcomes and making fertility treatment a more straightforward process. She covered how they fit into our current treatment plans, the reasons for developing them and the evidence regarding the benefits.

Dr Hull has worked in fertility services since she graduated as a doctor 15 years ago. She became Obstetrician and Gynaecologist (FRANZCOG) after gaining clinical experience in New Zealand and Cambridge and Somerset in the UK. Louise has a strong interest in reproductive medicine and has worked in IVF units in New Zealand, England and Australia, including Bourn Hall, the fertility centre where the first IVF baby was born. For more information about Dr Hull, please follow this link:

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  • Current treatments for COS are still complex. The long GnRH agonist protocol involves treatment for several weeks before the start of stimulation and requires many injections. There are usually 14 additional injections required in a long GnRH agonist protocol compared with GnRH antagonist protocols. † † Where only injectable formulations are used The GnRH antagonist protocol (developed in the early 2000s) has reduced the impact of COS on patient treatment burden by reducing the required number of injections, but still involves daily gonadotrophin administration for follicular development.
  • Formulation of non-pf and pf corifollitropin alfa drug product, respectively: Sucrose: 50 vs 70 mg/mL (Puregon 50 mg/mL) Sodium citrate: 14.7 vs 7.35 mg/mL (Puregon 14.7 mg/mL) L-methionine: none vs 0.5 mg/mL (Puregon 0.5 mg/mL) Polysorbate 20: 0.2 mg/mL vs 0.2 mg/mL (Puregon 0.2 mg/mL) The passive safety system means that you do not need to take or perform any additional action when using the device to activate it (at the end of a full stroke / injection).
  • Free Information Session 5th September 2012: Recent Breakthroughs in IVF

    1. 1. New Directions in IVFDr Louise HullSenior Lecturer andFertility Consultant
    2. 2. The IVF story
    3. 3. TheUntoldStory
    4. 4. Why don’t couples conceive with IVF?They have problems:We understand but can’t fix We don’t understand well Low ovarian reserve Implantation problems Poor sperm quality Miscarriage Genetic problems High levels of stress Improve selection Test new ideas
    5. 5. Low Ovarian Reserve patient centred options + supportive choices + outstanding results
    6. 6. 25 The march of 32 the eggs 38 42 45
    7. 7. Not many eggs toselect from
    8. 8. We can’t make more eggsCan we get more eggs onto the bridge for IVF ?
    9. 9. Higher levels of estrogen in thefollicle may entice eggs onto the bridge Growth hormone can increase estrogen levels in the follicle
    10. 10. Puregon and Gonal Fandrogens estrogen
    11. 11. Puregon and Gonal F Growth Hormoneandrogens estrogen
    12. 12. Does Growth hormone work?• We’re not sure:• Growth Hormone made no difference for all women undertaking IVF• In women with low ovarian reserve there was a trend to improved outcomes.
    13. 13. The Light Study (74 recruits)Women under 41 with low ovarian reserveRandomised trial to see if Growth hormone:1.increases the numbers of eggs2.Improves pregnancy outcomesAt FertilitySA50% pregnancy rate on the trialBut we don’t know who had growth hormone
    14. 14. Poor sperm quality
    15. 15. Fertilisation requires lots of sperm
    16. 16. Hyaluron receptors on sperm aidselection for natural fertilisation
    17. 17. How do we choose the best sperm for ICSI?The embryologist chooses on how they look
    18. 18. Selecting for the Hyaluron Receptor PICSI plates
    19. 19. At FertilitySAMore than 20 PICSI pregnancies last 7 months–first approx 30 weeks gestation nowClear benefit in fertilisation and embryo developmentfor some couples No benefit : very poor samples very good samples Surgical sperm
    20. 20. Genetic ProblemsA person will not know they have a translocation until investigated
    21. 21. Prenatal Genetic Diagnosis
    22. 22. Fluorescent In Situ Hybridisation Small number of Y 21 chromosomes tested 21 Subjectively assessed by 21 X embryologist looking down the microscope Down’s SyndromeBut:Studies showed increased chance of livebirth if didn’t use test
    23. 23. Array Prenatal Diagnosis 24 sure = Blue Gnome = CGH arrays Technological improvements: All chromosomes checked Several probes for each chromosome Results objectively read by machine
    24. 24. Are the outcomes better?Initial studies are very promising but large studiesover time not done.Melbourne IVF has the most experience in AustraliaFertilitySASmall numbers of cycles and good resultsPerforming the biopsy in our labSending the cells to Melbourne IVF for Array testingReplacing genetically competent embryos in Adelaide
    25. 25. Implantation ProblemsBeautiful Embryos but not implanting in the endometrium
    26. 26. Optimise lifestyle and Investigate
    27. 27. Endometrial biopsy before an IVF cycle
    28. 28. Why might a biopsy work?Human cycles with surgical instrumentation of theuterus have higher pregnancy rates (historical)Can induce endometrial receptivity in animals byinstrumenting the uterus
    29. 29. Does it work?Cochrane Database Syst Rev. 2012;7: (last week)Review of all randomised control trials (294 +297women) – Higher clinical pregnancy rate and live birth rate – Benefit when biopsy 1 week prior to an IVF cycleHow does it work?? Induces a repair process similar to implantation? Releases factors that help implantation? Promotes stem cell activity to facilitate implantation
    30. 30. At FertilitySAPerform outpatient biopsy or hysteroscopy andbiopsy in implantation windowSend the tissue to the labIVF cycle with following periodOutcomes:Several patients have become pregnant with goodoutcomesEffect lasts for at least 3 months
    31. 31. Recurrent Miscarriage
    32. 32. Optimise lifestyle and Investigate
    33. 33. Embryogen• IVF media with GMCSF growth factor• In Adelaide, laboratory and animal studies showed that culture media with this growth factor was associated with: – better embryos – better pregnancy outcomes
    34. 34. Human embryos have GM-CSF receptor 21 Day 8 embryo Day 5 embryo Sjolblom et al Biol Reprod 2002GM-CSF is in fallopian tubes, lining of womb and uterinefluidBut : IVF culture medias do not contain GM-CSF
    35. 35. In human embryoscontrol GM-CSF Total dead cells p<0.001 Robertson et al Biol Reprod 2001 5 6 4 3 2 1 APOPTOSIS Control GM-CSF % Total cell no. p<0.001 0 0 0 0 0 0 0 0
    36. 36. Improved Outcomes for women with a previous miscarriage in a large European trialOngoing Implantation EmbryoGen® Control Diff. P-valuerate mean (%)Previous miscarriage patients(327 subjects, 142/147 transfer cycles)Week 7 24.5 17.0 44.1 0.001Week 12 23.2 16.5 40.6 0.003* During the course of the study the concentration of human serum albumin (HSA) was increased in EmbryoGen ® as well as in EmbryoAssist™.This was done to improve the overall performance and robustness of EmbryoAssist™ 36
    37. 37. Safety study:GM-CSF has no effect on embryonic chromosomal constitutionEmbryos (%) Agerholm et al., 2010
    38. 38. At FertilitySA• Embryogen Trial• FertilitySA is the only unit registered to prescribe embryogen in South Australia (Only 2 units in Australia are registered to use Embryogen)• Inclusion criteria:• Women with a previous miscarriage under 41 years.• Couples can buy media outside trial• Day 3 transfer –growing frozen embryos out to Day 5
    39. 39. Results so far:6 patients have participated in the trial4 have completed the cycle -2 pregnancies -1 scannedOutcomesGood embryo qualityThe first embryogenpregnancy in Australiahad a normal first scan
    40. 40. Stress
    41. 41. Why couples withdraw from IVF
    42. 42. Can we make IVF easier?
    43. 43. Reducing the number of injections
    44. 44. Stimulation protocols have required multiple injections Long GnRH 1 2 3 4 5 6 7 8 9 10 agonist protocol GnRH Flare-up 1 2 3 4 5 6 7 8 9 10 antagonist protocol Pituitary downregulationLH Direct gonadotrophin suppression Time Figure adapted from de Greef R et al., 2010,1 The European Orgalutran Study Group, 20002 and Hodgen GD,1990.3
    45. 45. Long acting FSH -ELONVA rFSH hCG Corifollitropin alfa 1 2 3 4 5 6 7 8 9 10 Before use After use81% cumulative pregnancy rate in initial trials in good prognosis patientsReferences: 1. Elonva Product Information, July 2010.
    46. 46. The Create TrialInclusion Criteria:Women on an antagonist cycle<90kgAt low risk of hyperstimulation syndromeWomen in study use either Elonva or traditional injectionsParticipation:Answer 2 surveys regarding the ease and stress of IVF cycleMonitor outcomes during the cycle
    47. 47. Research and Education is importantBenefits to our patientsOur doctors stay up to date with the improvements in IVFCare can be individualised if its well understoodWe continually try to improve our treatment for everycouple under our careSome couples will become pregnant that wouldn’t haveotherwiseEverything we learn will help someone
    48. 48. Thank -YouStaff and patients at FertilitySAProf Sarah Robertson –University of AdelaideDr Michael Henman –OrigioDr Brett Johnson -MSD
    49. 49. patient centred options + supportive choices + outstanding results