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History of
Azoospermia in Era of
        ART

     Khaled Mokhatr
           MD Urology
      Ain Shams University
History of infertility

 Ancient Egyptian papyri (2000 BC)
“Man is the source of life, through his seeds and
  woman is a reservoir of these seeds”.
History of infertility

          Leonardo Da Vinci (1500 AC):
          Anatomy of genital system




Netherland MRI 2002                      DaVinci 1500
History of infertility

   Anton Leeuwenhoek (1632-1723),
         discovered the sperms
               (Animalcules).
I am sending a letter to show my
  observation, you may consider it as
  scientific discovery or HOAX.
History of infertility


   Franzy Leydig, german Zoologist, (1850):




discovered Leydig cell
History of infertility


         Enrico Sertoli, Italin
         Anatomist, (1865):


         discovered Sertoli cell
Spermist vs Ovist
           1600 till 1700
 Spermist          Ovist
                    ovum is harboring
                     small fetous and it just
                     need to contact the
                     male fluid to be
                     released
Only in 1779
   Italian, Lazzaro Spallanzani,
   Scientific proof that the sperm fertilizes the
    ovum
   To produce pregnancy was first available
    (Spallanzani).
History of infertility

   Robert Dicknson
    (BJM, 1921) IUI




   Stepto& Edward
                           First Test-Tube Baby - Louise Brown
    (Lancet, 1977) IVF
History of infertility

   Palermo et al
    (Lancet, 1992)
    ICSI.



   Devroey et al
    (Hum. Reprod.,
    1995) TESE/ICSI
“Infertile men, wherever
they live, should have a
chance to become genetic
fathers”
   Westlander J (Human Reprod. 2000)
Azoospermia

   1% of all men
   10% of infertile men


                                 Azoo spermic
                                 Infertile
                                 fertile
Introduction

   Azoospermia is an absolute barrier against
    spontaneous pregnancy.
   Until recently, men with azoospermia have little
    or even no hope to be biologic father.
   Recent advances in microsurgery and
    reproductive technology have allowed many
    azoospermic men to father children.
   Pregnancy rate is a real reflection of all these
    advances
Obstructive
Azoospermia
Obstructive Azoospermia

   Obstructive azoospermia (OA) are
    potentially correctable with the aid of
    microsurgery (VE) or endoscopic (TURED).
   Irreparable OA e.g. CBAVD, requires sperm
    retrieval (PESA.MESA) combined with
    IVF/ICSI.
Obstructive Azoospermia:
             Sperm Retrieval Options

è   Epididymis
     MESA (microsurgical epididymal sperm
      aspiration)
     PESA (percutaneous epididymal sperm
      aspiration)
Obstructive Azoospermia:
        Sperm Retrieval Options
Testis
 TESA (testicular sperm aspiration)




   TESE (testicular sperm extraction - therapeutic
    testis biopsy)
Obstructive Azoospermia:
   Results with IVF/ICSI (Experienced
                 Centres)
                           Epididymal   Testicular
Sperm Retrieval                ~100%     ~100%
Fertilization rates            50-70%    40-70%
Clin. Pregnancy rates          30-50%    30-50%
Live birth rate                30-40%    20-40%

   Palermo et al, Hum Reprod 1999
   Devroey et al, Hum Reprod 1996
   De Croo et al, Hum Reprod 2008
Non Obstructive
Azoospermia..
Testicular failure


It is not an absolute failure
NOA

    Non Obstructive Azoospermia (NOA),
    recently, have been granted the hope to
    father their children after testicular extraction
    and ICSI (Devroey et al, Hum Rprod, 1995) .
New concept.
      +ve sperm identification in
             failed testes
   20% to 70% of non obstructed azoospermia still
    harbor foci of active spermatogenesis with
    mature spermatozoa that could be retrieved and
    the only way to use it is ICSI
Testicular histology in testicular
                  failure
          56

45
40
35
                20              SCO n=44
30
                          14    Mat. Arrest n=15
25
                     10         Hypo n=8
20
                                Mixed n=11
15
10
 5
 0
               NOA
Distribution of spermatogenesis in OA Vs
                         NOA

   There must be at least 4
    sperms per tubule as a
    minimum quantitative
    threshold of
    spermatogenesis to reach
    the ejaculate.
   Mapping of
    spermatogenesis in NOA
    testes shows that
    Spermatogenesis is
    diffuse rather than
    regional.
Silber et al, Hum Reprod 2000
Non-Obstructive Azoospermia: Sperm
           Retrieval Options
 TESE   (testicular sperm extraction)
  Singlevs multiple open biopsies
  Microdissection- microTESE



 TESA (testicular sperm aspiration)
 is not recommended
   Silber et al, Hum Reprod 1997
   Schlegel et al, Hum Reprod 2004
Non-Obstructive Azoospermia:
    Sperm Retrieval: Microdissection
   Small areas of spermatogenesis may be distinguished
    from areas of Sertoli cell-only by microscopic
    examination
   Microdissection enhances sperm yield and reduces
    volume of tissue excised
      Schlegel et al, Hum Reprod 1999
Micro. TESE
Doctor                             patient




           Minimally invasive procedure




 Minimally invasive for a Doctor is
 not Minimally invasive for patients
The only way to use retrieved sperms is via ICSI
Non-Obstructive Azoospermia (NOA):
   Results with IVF/ICSI (Experienced Centres)
                          NOA           OA
Testic. Sperm Retrieval   20-80%     ~100% *
Fertilization rates       40-60%     40-70%
Clin. Pregnancy rates       30-40%      30-50%
Live birth rate           20-30%      20-40%

   Nagy et al, Fertil Steril 1995
   Devroey et al, Hum Reprod 1996
   Kahraman et al, Hum Reprod 1996
   Palermo et al, Hum Reprod 2002
In Egypt..
We are different
In Egypt.. We are different, why?
   More prevalent of NOA > OA
   Low incidence of CF mutation gene
   Misdiagnosis of active spermatogenesis by many
    pathologists.
   However, we do not have good statistical
    reports of true incidence of any of theses
CONCLUSION

   OA can be effectively and successfully managed
    with microsurgery.
   non-constructible OA, (CBAVD) sperm retrieval
    combined with IVF/ICSI can be highly effective in
    achieving pregnancy.
   NOA has been recently revolutionized by successful
    TESE/ICSI with resultant successful pregnancy.
   The high cost compared to pregnancy outcome is a
    considerable    limiting  factor     against   the
    popularization of TESE/IVF-ICSI.
The future


   In vitro maturation of oocyte (IVM)
   In vitro spermatogenesis (Tesarik et al.,Lancet,
    1998) Tissue culture system fortified with
    RFSH, T. spermatogenesis could be
    completed in vitro with an unusual speed,
    but the resulting gametes are
    morphologically abnormal.
Design Final Touch:
Ahmad Al-Sabbagh
   March 2012*

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Azoospermia

  • 1. History of Azoospermia in Era of ART Khaled Mokhatr MD Urology Ain Shams University
  • 2. History of infertility  Ancient Egyptian papyri (2000 BC) “Man is the source of life, through his seeds and woman is a reservoir of these seeds”.
  • 3. History of infertility  Leonardo Da Vinci (1500 AC):  Anatomy of genital system Netherland MRI 2002 DaVinci 1500
  • 4. History of infertility  Anton Leeuwenhoek (1632-1723), discovered the sperms (Animalcules). I am sending a letter to show my observation, you may consider it as scientific discovery or HOAX.
  • 5. History of infertility  Franzy Leydig, german Zoologist, (1850): discovered Leydig cell
  • 6. History of infertility Enrico Sertoli, Italin Anatomist, (1865): discovered Sertoli cell
  • 7. Spermist vs Ovist 1600 till 1700  Spermist  Ovist  ovum is harboring small fetous and it just need to contact the male fluid to be released
  • 8. Only in 1779  Italian, Lazzaro Spallanzani,  Scientific proof that the sperm fertilizes the ovum  To produce pregnancy was first available (Spallanzani).
  • 9. History of infertility  Robert Dicknson (BJM, 1921) IUI  Stepto& Edward First Test-Tube Baby - Louise Brown (Lancet, 1977) IVF
  • 10. History of infertility  Palermo et al (Lancet, 1992) ICSI.  Devroey et al (Hum. Reprod., 1995) TESE/ICSI
  • 11. “Infertile men, wherever they live, should have a chance to become genetic fathers” Westlander J (Human Reprod. 2000)
  • 12.
  • 13. Azoospermia  1% of all men  10% of infertile men Azoo spermic Infertile fertile
  • 14. Introduction  Azoospermia is an absolute barrier against spontaneous pregnancy.  Until recently, men with azoospermia have little or even no hope to be biologic father.  Recent advances in microsurgery and reproductive technology have allowed many azoospermic men to father children.  Pregnancy rate is a real reflection of all these advances
  • 16. Obstructive Azoospermia  Obstructive azoospermia (OA) are potentially correctable with the aid of microsurgery (VE) or endoscopic (TURED).  Irreparable OA e.g. CBAVD, requires sperm retrieval (PESA.MESA) combined with IVF/ICSI.
  • 17. Obstructive Azoospermia: Sperm Retrieval Options è Epididymis  MESA (microsurgical epididymal sperm aspiration)  PESA (percutaneous epididymal sperm aspiration)
  • 18.
  • 19.
  • 20. Obstructive Azoospermia: Sperm Retrieval Options Testis  TESA (testicular sperm aspiration)  TESE (testicular sperm extraction - therapeutic testis biopsy)
  • 21.
  • 22. Obstructive Azoospermia: Results with IVF/ICSI (Experienced Centres) Epididymal Testicular Sperm Retrieval ~100% ~100% Fertilization rates 50-70% 40-70% Clin. Pregnancy rates 30-50% 30-50% Live birth rate 30-40% 20-40% Palermo et al, Hum Reprod 1999 Devroey et al, Hum Reprod 1996 De Croo et al, Hum Reprod 2008
  • 24. NOA  Non Obstructive Azoospermia (NOA), recently, have been granted the hope to father their children after testicular extraction and ICSI (Devroey et al, Hum Rprod, 1995) .
  • 25. New concept. +ve sperm identification in failed testes  20% to 70% of non obstructed azoospermia still harbor foci of active spermatogenesis with mature spermatozoa that could be retrieved and the only way to use it is ICSI
  • 26. Testicular histology in testicular failure 56 45 40 35 20 SCO n=44 30 14 Mat. Arrest n=15 25 10 Hypo n=8 20 Mixed n=11 15 10 5 0 NOA
  • 27. Distribution of spermatogenesis in OA Vs NOA  There must be at least 4 sperms per tubule as a minimum quantitative threshold of spermatogenesis to reach the ejaculate.  Mapping of spermatogenesis in NOA testes shows that Spermatogenesis is diffuse rather than regional. Silber et al, Hum Reprod 2000
  • 28. Non-Obstructive Azoospermia: Sperm Retrieval Options  TESE (testicular sperm extraction)  Singlevs multiple open biopsies  Microdissection- microTESE TESA (testicular sperm aspiration) is not recommended Silber et al, Hum Reprod 1997 Schlegel et al, Hum Reprod 2004
  • 29.
  • 30. Non-Obstructive Azoospermia: Sperm Retrieval: Microdissection  Small areas of spermatogenesis may be distinguished from areas of Sertoli cell-only by microscopic examination  Microdissection enhances sperm yield and reduces volume of tissue excised Schlegel et al, Hum Reprod 1999
  • 31.
  • 33. Doctor patient Minimally invasive procedure Minimally invasive for a Doctor is not Minimally invasive for patients
  • 34. The only way to use retrieved sperms is via ICSI
  • 35.
  • 36. Non-Obstructive Azoospermia (NOA): Results with IVF/ICSI (Experienced Centres) NOA OA Testic. Sperm Retrieval 20-80% ~100% * Fertilization rates 40-60% 40-70% Clin. Pregnancy rates 30-40% 30-50% Live birth rate 20-30% 20-40% Nagy et al, Fertil Steril 1995 Devroey et al, Hum Reprod 1996 Kahraman et al, Hum Reprod 1996 Palermo et al, Hum Reprod 2002
  • 37. In Egypt.. We are different
  • 38. In Egypt.. We are different, why?  More prevalent of NOA > OA  Low incidence of CF mutation gene  Misdiagnosis of active spermatogenesis by many pathologists.  However, we do not have good statistical reports of true incidence of any of theses
  • 39. CONCLUSION  OA can be effectively and successfully managed with microsurgery.  non-constructible OA, (CBAVD) sperm retrieval combined with IVF/ICSI can be highly effective in achieving pregnancy.  NOA has been recently revolutionized by successful TESE/ICSI with resultant successful pregnancy.  The high cost compared to pregnancy outcome is a considerable limiting factor against the popularization of TESE/IVF-ICSI.
  • 40. The future  In vitro maturation of oocyte (IVM)  In vitro spermatogenesis (Tesarik et al.,Lancet, 1998) Tissue culture system fortified with RFSH, T. spermatogenesis could be completed in vitro with an unusual speed, but the resulting gametes are morphologically abnormal.
  • 41. Design Final Touch: Ahmad Al-Sabbagh March 2012*