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How to Prevent Multiples in ART: Is it Possible?

How to Prevent Multiples in ART: Is it Possible?. Prof. Dr. Basil C . Tarlatzis Unit for Human Reproduction 1st Department of Obstetrics and Gynecology Aristotle University of Thessaloniki, Greece. ART Children. 1978: IVF, Louise Brown (R.Edwards, P.Steptoe)

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How to Prevent Multiples in ART: Is it Possible?

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  1. How to Prevent Multiples in ART: Is it Possible? Prof. Dr. BasilC. Tarlatzis Unit for Human Reproduction 1st Department of Obstetrics and Gynecology Aristotle University of Thessaloniki, Greece

  2. ART Children • 1978:IVF, Louise Brown(R.Edwards, P.Steptoe) • 1990 :ICSI(Palermo, Van Steirteghem, Devroey) • 2010 : World • Total: ~5 million children (200 000 per year ) • Approx. half from multiple pregnancies

  3. The Problem of Multiple Pregnancies

  4. Multiple Births in IVF: frequency per delivery ICMART 2002 • Natural reproduction : • Twin pregnancies0.8 to 1.2 %,triplets 1 p 10 000

  5. Fauser et al, Lancet 365, 1807, 2005

  6. Proportion of Multiple babies in ART, by Region, 1998 %

  7. Fauser et al, Lancet, 2005

  8. Fauser et al, Lancet 365, 1807, 2005

  9. Triplet or more Twin 39.5% 37.7% Singleton 0.7% 5.7% 32.8% 5.7% Live birth rate per transfer 32.6% 32.6% 32.1% 12.8% 2.0% 98.0% 66.7% 61.7% 62.3% 3 4 1 2 Number of embryos transferred SART 2002

  10. Stern, 9-2009

  11. Problems of multiple pregnancies • pregnancy related diseases • prematurity • increase of neonatal morbidity and mortality • costs

  12. Risk associated with a twin pregnancy Mother Hypertension, odds ratio: 1.8 to 3.4 Senat et al., 1998 Requirement for intensive care unit 15.5 times higher in twins compared to singletons Senat et al., 1998

  13. Risk associated with a twin pregnancy Offspring Prematurity 39.2% in twins versus 4.5% in singletons Blondel et al., 1996 Birth at<32 weeks of gestation 11% of the twins versus 3.1% of the singletons Kiely, 1998 Birth weight <2500 g 47.5% in twins versus 4.6% in singletons Blondel et al., 1996 very low birth weight (<1500 g) 10 times more frequent in twins than in singleton (1.1 versus 10.1) (Alexander et al., 1998)

  14. Risk associated with a twin pregnancy Offspring stillbirth rate 14.2 versus 4.4, early neonatal mortality rate 22.8 versus 2.9, the late neonatal mortality rate 3.9 versus 0.8, post-natal mortality rate 6.3 versus 2.4 infant mortality rate 33.0 versus 6.1 (Doyle, 1996). risk of cerebral palsy odd ratio: 10.2 compared with singletons Petridou et al., 1996 .

  15. The problem of multiple pregnancies: Solution To avoid multiple pregnancies without compromising pregnancy and life birth rate Solution: Transfer one selected embryo?

  16. Pregnancy rate after elective single embryo transfer (eSET) and elective double embryo transfer (eDET) eSET = 40.3% pregnancy rate 1% twins eDET = 44% pregnancy rate 32% twins Gerris, 2005

  17. Embryos transferred in Sweden EIM 2004, Andersen et al., 2008

  18. Sweden:Multiple pregnancies after ART EIM 2004, Andersen et al., 2008

  19. SET vs DET Risk difference for multiple pregnancy -21% (95%CI -21 to -14%) Kolibianakis et al, unpublished

  20. SET vs DET Risk difference for clinical pregnancy -17% (95%CI -22 to -12%) Kolibianakis et al, unpublished

  21. SET vs DET Risk difference for Live Birth -14% (95%CI -22 to -8%) Kolibianakis et al, unpublished

  22. SET is associated with a decreased probability of pregnancy both clinically and statistically important

  23. SET + FrSET vs. DET Risk difference for multiple pregnancy -28% (95%CI -34 to -21%) Kolibianakis et al, unpublished

  24. SET + FrSET vs. DET Risk Difference for Clinical Pregnancy -3% (95%CI -3 to +4%) Kolibianakis et al, unpublished

  25. SET + FrSET vs. DET Risk Difference for Live Birth -2% (95%CI -9 to +5%) Kolibianakis et al, unpublished

  26. SET + Fr SET appears to result in an equal probability of pregnancy as compared to DET, but more studies are necessary to support the above statement

  27. Number of embryos transferred after IVF and ICSI, 2004The Nordic countries

  28. Number of embryos transferred after IVF and ICSI, 2004Central Europe

  29. Number of embryos transferred after IVF and ICSI, 2004The largest countries

  30. Number of embryos transferred after IVF and ICSI, 2004Southern Europe

  31. Number of embryos transferred after IVF and ICSI, 2004Eastern Europe

  32. Percentage 3 or 4 embryo transfers in IVF and ICSI, 2004 EIM 2004, Andersen et al., 2008

  33. SET vs. DET SET vs. DET Selection of the best embryo for ET HOW? Better selection criteria for cleavage stage embryos Transfer at the blastocyst stage

  34. Embryo quality assessment Embryo quality evaluation systems are based on the assessment of several morphological characteristics of the embryo depending on the stage of development: • Zygote stage embryos • Cleavage stage embryos • Blastocyst stage embryos

  35. Embryo Selection > 30% < 5% Implantation

  36. The embryo interacts with it’s surroundingstake up – metabolise - secrete

  37. Embryo physiology as basis for selection “Metabolic profiling” • It is possible to measure embryo metabolism non-invasive • Metabolic profiling could then be used to select the most viable embryos? Pioneered by prof. Henry Leese , York

  38. HYPOTHETICAL BENEFITS OF BLASTOCYST TRANSFER • Better embryo selection? • More pregnancies with smaller number of transferred embryos?

  39. Live birth rates after transfer of equal number of blastocysts or cleavage-stage embryos in IVF. A systematic review and meta-analysis Papanikolaou E, et al, Hum Reprod, 2007 RD: 7% (95% CI: +2 to +12)

  40. Risk for embryo transfer cancellation OR: 2.2 95%CI 1.4 to 3.3 Papanikolaou E, et al, Hum Reprod, 2007

  41. Single vs. double blastocyst transfer What is the evidence?

  42. Implantation rates, clinical pregnancy rates, and twinning rates for donor cycles that met criteria for single blastocyst transfer Crinity et al 2005

  43. Implantation rates, clinical pregnancy rates, and twinning rates for non-donor cycles that met criteria for single blastocyst transfer. Crinity et al 2005

  44. SB DB Gardner et al 2004

  45. Effect of Belgian Legislation Leuven University Experience IR Stable at 21% Minimal  in CPR from 37.5% to 32.5%  Multiple rate from 25.9% to 8.0% – Debrock et al, Fertil Steril 2005; 83: 1572-4

  46. Effect of Belgian Legislation Multiple rate 8.5% compared with 24.4% nationwide multiple rate in the year prior – De Neuborg et al, Eur J Obstet Gynecol Reprod Biol 2006; 124: 212-5

  47. How to Prevent Multiples: Is it Possible? • Single embryo transfer is an effective method to abolish multiple pregnancies. • SET is associated with significantly lower pregnancy rates but, if combined with FRET, cumulative results are similar. • The main challenge is to identify the best embryo for transfer, although at this point blastocyst culture seems to be an effective way.

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