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Sandro Esteves
             Diretor, ANDROFERT
             Campinas, São Paulo

Esteves, 1
US Census Bureau Estimates, 2004
40-50%
830.204                  48.420
          Total Ciclos
Fonte: Esteves & Agarwal. Sperm Retrieval Techniques; Published by Cambridge, UK, 2010.
From: Esteves & Agarwal. Sperm Retrieval Techniques; Published by Cambridge, UK, 2010.
ICSI


                 Outros




             ANDROFERT, 2006-2009
Esteves, 9
                         (n=2.870)
Bebê Nascido (%)
1985                                                              2004
                                        1997                                       2006
ICSI                                                           Hialuronan
                                      PGD/PGS                                      Salas Limpas
                 Fim anos 90            FISH                                       Brasil
                                                   2000
            Aspiração Fragmentos                                                   UE
                                                Spindle view                                   2010
           Transferência Citoplasma
                                                 Polscope                2005               Proteômica
             Transferência Núcleo
                                                                         IMSI




                                                                                          2009
                                      Blastocisto;
          1990                                          2004                           ANECOVA
                           1995         Cultura
       ROSI; ROSNI                                   HLAg solúvel           2005     Metabolômica
                        Hatching      Sequencial
                                                                             IVM          CGH
                                                                    Vitrificação    DNA fingerprinting
                                                                                      ICSI-robótico
Esteves, 13
AH on Assisted Conception
             Das S, Blake D, Farquhar C, Seif MMW
                    Cochrane Review 2009

Aumento relativo Gestação Clínica
               74%
                                                26%
                             45%


 25%
                                                15%


Frescos        Crio    Mau Prognóstico
AH on Assisted Conception
        Das S, Blake D, Farquhar C, Seif MMW
               Cochrane Review 2009




Aumenta chance de Gravidez Clínica, mas não
             de Nascido Vivo.
Espermatozóide:
 Ácido hialurônico; Huszar, 2003
 IMSI; Bartoov, 2003 & Cassuto, 2007
 Microsc. luz polarizada; Magli, 2007


Oócito:
          Microscopia luz polarizada; Montag,
          2007
   Bi-refringência fuso meiótico; Massaro,
   2007
   Biópsia corpúsculo polar; Magli, 2007
400X


     Gravidez Clínica                                      8450X
       66% vs 30% (n=50) Bartoov et al. 2003
       48% vs 20% (n=80) Bartoov et al. 2006
       39% vs 26% (P=.004; RCT; N=416); Antinori et al., 2008

     Parâmetros Laboratoriais
       Fertilização, Clivagem, TQE D2: NS (N=30); Mauri et al, 2010



Esteves, 17
Vacúolos tamanhos variados
   98,9% espermatozóides (ejaculado, epidídimo, testículo)
   Média: 1,5/célula
Taxas Fertilização , Blastulação, Fragmentação DNA:
   Independente presença e tamanho vacúolos
Sugere que vacúolos são fisiológicos !


                Watanabe S et al., J Mamm Ova Res 2008; 25:259-65
                                Tanaka A et al, ASRM 2009 (P-272)
PGD/PGS

              Blastocisto

              Metabolômica

              Proteômica

              CGH (comparative genomic hybridization)

              DNA fingerprinting blastocisto
Esteves, 19
In Vitro Fertilization with Preimplantation
             Genetic Screening
     Mastenbroek S, Twisk M, van Echten-Arends J et al
                  NEJM 2007; 357: 9-17

 N=408; RCT; Mulheres 35-41 anos

 Gravidez Clínica: 25% (PGS) X 35% (controle)

 Nascido Vivo: 24% (PGS) X 35% (controle)
         OR 0.68 [95% CI: 0.50-0.92]


Redução significativa nas taxas de gravidez e
                nascido vivo
Live birth rates after transfer of equal number of
 blastocysts or cleavage-stage embryos in IVF
   Papanikolaou E, Kolibianakis E, Tournaye H et al
            Hum Reprod 2008; 23: 91–99
N = 1654                Odds-         95% CI        P-value
                          ratio
  Nascido Vivo             1.39        1.10-1.76       0.005
  Cancelamento             2.21        1.47-3.32        0.02
  Criopreservação          0.28        0.14-0.55       <0.01
  Multiparidade            0.86        0.58-1.29         NS

              Papanikolaou E, Kolibianakis E, Tournaye H et al. Hum Reprod 2008; 23: 91–99




Esteves, 23
Esteves, 24
Esteves, 25
versus Congelamento Lento

Sobrevida:
   Oócitos: Laman et al., 2007: maior proteção fuso meiótico
   Embriões: Loutradi et al., Fertil Steril 2008; meta-análise: N=8.824
        Clivagem: OR 15,57; Blastocistos: OR 2,20

Gestação:
     OR: 1,82 [1,04-3,02]: Abdelhafez et al. RBM online 2010; meta-análise
     Resultados obstétricos/malformações iniciais: similares
1980              1995              2000               2002
        Gonadotrofina          hFSH              hLH                hFSH
           contendo        recombinante     recombinante        recombinante
1962 somente FSH                                                     fbm
                                                           2001
u-hMG e               1984              1999
                                                          r-hCG
u-hCG               Agonista         Antagonista
                                                      recombinante               2008
purificados           GnRH              GnRH
                                                                           hFSH+hLH
                                                                         recombinante
Esteves, 30
*Cálculo baseado na atividade específica                      4. Le Cotonnec et al. Hum Reprod 1993;8:1604–1611
1. Loumaye et al. Hum Reprod 1996;11:95–107                   5. Giudice et al. Hum Reprod 1994;9:2291–2299
2. van de Weijer et al. Reprod Biomed Online 2003;7:547–557   6. Bassett et al. Reprod Biomed Online 2005;10:169–177
3. Howles et al. Hum Reprod 1996;2:172–191                    7. Giudice et al. J Clin Res 2001;4:27–33
1. Bassett et al. Reprod Biomed Online 2005;10:169–177
   2. Driebergen et al. Curr Med Res Opin 2003;19:41–46
Variabilidade                            Variabilidade
           +20%, -25%                                  ± 2%
IU
          Risco de SHO
270

                                16.5 mcg
225
                                 (225 IU)

170
           Má-resposta

               Bioensaio                        Preenchido por Massa
      Urinários e Folitropina beta          Folitropina alfa (Gonal-F Fbm)


                              Driebergen & Baer. Curr M.Res Opin 2003; US Pharmacopoeia 1998
Saúde e
 Tecnologias                           bem-estar
                                      do paciente


Muito Esforço e Enorme Investimento   Negligenciado
Esteves, 39

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Avanços na reprodução assistida dr. sandro esteves

  • 1. Sandro Esteves Diretor, ANDROFERT Campinas, São Paulo Esteves, 1
  • 2. US Census Bureau Estimates, 2004
  • 4.
  • 5.
  • 6. 830.204 48.420 Total Ciclos
  • 7. Fonte: Esteves & Agarwal. Sperm Retrieval Techniques; Published by Cambridge, UK, 2010.
  • 8. From: Esteves & Agarwal. Sperm Retrieval Techniques; Published by Cambridge, UK, 2010.
  • 9. ICSI Outros ANDROFERT, 2006-2009 Esteves, 9 (n=2.870)
  • 10.
  • 12. 1985 2004 1997 2006 ICSI Hialuronan PGD/PGS Salas Limpas Fim anos 90 FISH Brasil 2000 Aspiração Fragmentos UE Spindle view 2010 Transferência Citoplasma Polscope 2005 Proteômica Transferência Núcleo IMSI 2009 Blastocisto; 1990 2004 ANECOVA 1995 Cultura ROSI; ROSNI HLAg solúvel 2005 Metabolômica Hatching Sequencial IVM CGH Vitrificação DNA fingerprinting ICSI-robótico
  • 14. AH on Assisted Conception Das S, Blake D, Farquhar C, Seif MMW Cochrane Review 2009 Aumento relativo Gestação Clínica 74% 26% 45% 25% 15% Frescos Crio Mau Prognóstico
  • 15. AH on Assisted Conception Das S, Blake D, Farquhar C, Seif MMW Cochrane Review 2009 Aumenta chance de Gravidez Clínica, mas não de Nascido Vivo.
  • 16. Espermatozóide: Ácido hialurônico; Huszar, 2003 IMSI; Bartoov, 2003 & Cassuto, 2007 Microsc. luz polarizada; Magli, 2007 Oócito: Microscopia luz polarizada; Montag, 2007 Bi-refringência fuso meiótico; Massaro, 2007 Biópsia corpúsculo polar; Magli, 2007
  • 17. 400X Gravidez Clínica 8450X 66% vs 30% (n=50) Bartoov et al. 2003 48% vs 20% (n=80) Bartoov et al. 2006 39% vs 26% (P=.004; RCT; N=416); Antinori et al., 2008 Parâmetros Laboratoriais Fertilização, Clivagem, TQE D2: NS (N=30); Mauri et al, 2010 Esteves, 17
  • 18. Vacúolos tamanhos variados 98,9% espermatozóides (ejaculado, epidídimo, testículo) Média: 1,5/célula Taxas Fertilização , Blastulação, Fragmentação DNA: Independente presença e tamanho vacúolos Sugere que vacúolos são fisiológicos ! Watanabe S et al., J Mamm Ova Res 2008; 25:259-65 Tanaka A et al, ASRM 2009 (P-272)
  • 19. PGD/PGS Blastocisto Metabolômica Proteômica CGH (comparative genomic hybridization) DNA fingerprinting blastocisto Esteves, 19
  • 20. In Vitro Fertilization with Preimplantation Genetic Screening Mastenbroek S, Twisk M, van Echten-Arends J et al NEJM 2007; 357: 9-17 N=408; RCT; Mulheres 35-41 anos Gravidez Clínica: 25% (PGS) X 35% (controle) Nascido Vivo: 24% (PGS) X 35% (controle) OR 0.68 [95% CI: 0.50-0.92] Redução significativa nas taxas de gravidez e nascido vivo
  • 21.
  • 22. Live birth rates after transfer of equal number of blastocysts or cleavage-stage embryos in IVF Papanikolaou E, Kolibianakis E, Tournaye H et al Hum Reprod 2008; 23: 91–99
  • 23. N = 1654 Odds- 95% CI P-value ratio Nascido Vivo 1.39 1.10-1.76 0.005 Cancelamento 2.21 1.47-3.32 0.02 Criopreservação 0.28 0.14-0.55 <0.01 Multiparidade 0.86 0.58-1.29 NS Papanikolaou E, Kolibianakis E, Tournaye H et al. Hum Reprod 2008; 23: 91–99 Esteves, 23
  • 26. versus Congelamento Lento Sobrevida: Oócitos: Laman et al., 2007: maior proteção fuso meiótico Embriões: Loutradi et al., Fertil Steril 2008; meta-análise: N=8.824 Clivagem: OR 15,57; Blastocistos: OR 2,20 Gestação: OR: 1,82 [1,04-3,02]: Abdelhafez et al. RBM online 2010; meta-análise Resultados obstétricos/malformações iniciais: similares
  • 27.
  • 28. 1980 1995 2000 2002 Gonadotrofina hFSH hLH hFSH contendo recombinante recombinante recombinante 1962 somente FSH fbm 2001 u-hMG e 1984 1999 r-hCG u-hCG Agonista Antagonista recombinante 2008 purificados GnRH GnRH hFSH+hLH recombinante
  • 29.
  • 31. *Cálculo baseado na atividade específica 4. Le Cotonnec et al. Hum Reprod 1993;8:1604–1611 1. Loumaye et al. Hum Reprod 1996;11:95–107 5. Giudice et al. Hum Reprod 1994;9:2291–2299 2. van de Weijer et al. Reprod Biomed Online 2003;7:547–557 6. Bassett et al. Reprod Biomed Online 2005;10:169–177 3. Howles et al. Hum Reprod 1996;2:172–191 7. Giudice et al. J Clin Res 2001;4:27–33
  • 32.
  • 33. 1. Bassett et al. Reprod Biomed Online 2005;10:169–177 2. Driebergen et al. Curr Med Res Opin 2003;19:41–46
  • 34. Variabilidade Variabilidade +20%, -25% ± 2% IU Risco de SHO 270 16.5 mcg 225 (225 IU) 170 Má-resposta Bioensaio Preenchido por Massa Urinários e Folitropina beta Folitropina alfa (Gonal-F Fbm) Driebergen & Baer. Curr M.Res Opin 2003; US Pharmacopoeia 1998
  • 35.
  • 36.
  • 37. Saúde e Tecnologias bem-estar do paciente Muito Esforço e Enorme Investimento Negligenciado
  • 38.