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Male Infertility
 Review 2011


Paul J. Turek MD FACS, FRSM
 Director, The Turek Clinic, San Francisco, CA
 Former Professor and Endowed Chair, UCSF
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
4-6 wks


 6 wks

           Y chromosome (SRY gene)



7-15 wks




                                              Testis
                          Bipotential gonad

                                              Ovary
Embryology-Testis

Gonocytes                                     Testosterone
•  Inactive until puberty                     •  1st surge in utero
•  Meiosis inhibited by MIS                   •  2nd surge in neonatal period
•  Pubertal testosterone   meiosis            •  3rd rise at puberty; peaks in
                                                               2nd to 3rd
                                               decade
      Testosterone (ng/dL)




                             600
                             400
                             200
                             100
                              0
                                              Adult      Senescence
7-15 wks
Embryology-Bipotential Gonad

                          Upper gubernaculum
                          Mesonephros
                          Gonad



                         Urogenital cord
                         Dorsal mesentery
                         Mullerian duct
                         Metanephros
                         Mesonephric (Wolffian) duct
                         Lower gubernaculum
                         Intestine
Midline
Mullerian and
Wolffian Duct
Relationships
Embryology-Mesonephric Duct Abnormalities
Congenital Absence of the Vas Deferens (CAVD)
  • Unilateral: most azoospermic
  • Bilateral: all azoospermic
  • Any segment of Wolffian duct
  • If ipsilateral kidney also absent:
        No CFTR mutations
  • If ipsilateral kidney is present:
        80% have CFTR mutations

 CF results in: Pneumonia, pancreatic
 insufficiency, bowel obstruction, sinusitis,
 nasal polyps, and death by 35 years of age.
Embryology-Questions
When does meiosis begin in the human male?       Puberty

What hormone is responsible for regression of    MIS
      female internal genitalia?

What gene is responsible for male sexual         SRY, (SOX-9)
      differentiation?

What gene mutation should be examined           CFTR=cystic
      in men with idiopathic ejaculatory        fibrosis trans-
      duct obstruction?                         membrane
                                                regulatory gene
How many testosterone peaks have occurred by    3-First trimester,
     the time a man reaches age 30?
                                                neonatal and adult
(caput)

                 10 days
4 x 3 cm                      Rete testis
 (20mL)
                                  (corpus)

                                                      80
                64 days                              %ge
                                                      rm
                                                                     600
 10-15                                               cells
                               (cauda)                              million
lobules
                                                                    sperm


              Need 3 months to make and ejaculate sperm.
              Soft, small testes imply a sperm production problem
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Cremasteric artery!
SERTOLI CELL
Cycles-
         Production
         varies with
         time, same
         location




Waves-production
varies in different
locations
10%
                  Prostate



                  10%
                    Vas       80%
                  deferens   Seminal
                             vesicle

Premature ejaculation
Retrograde ejaculation
Anejaculation
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
The
H-P-G
 Axis
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
PRL
H-P-G Axis: Testosterone
• Testosterone comes in several forms.
• Only free and albumin (weakly bound) are “active.”
• SHBG-bound is inactive.
                Free/unbound
Albumin bound       1-2%
                                SHBG bound
    60%                            40%




                                      SHBG-T

                        Total           Free T
                     Testosterone                      Bioavailable
                                                       Testosterone
                                      Albumin-T
H-P-G Axis: Testis & Testosterone
Testosterone

           Testosterone

                                                Seminal
                                                Vesicle
                        5-a -Reductase
                                             Epididymis

         Dihydrotestosterone                Vas Deferens
                                         Ejaculatory ducts


     Prostate            Scrotum
                Penis


           External                        Internal
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Likely Kallmann Syndrome: Anosmia, delayed puberty, azoospermia,
small testes, micropenis.

DDx: Sickle cell disease, Hemochromatosis, Bardet-Biedl syndrome,
Cerebellar ataxia, Prader-Willi syndrome
Likely Klinefelter Syndrome: Delayed puberty, azoospermia, small
                 testes, micropenis.

                                        47, XXY
Likely Prolactinoma (MRI pituitary to r/o macroadenoma)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
History
  Physical Exam



Semen Analysis x 2




            Eliminate Gonadotoxins

                                  Improved

            Hormone
           Evaluation

                         Blood
                         Semen
                        Imaging
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
400%
Better!
Clinical Male Infertility: Chemotherapy


  Agent!


Cisplatin!
Cytoxan!
Adriamycin!
Vinblastine!




    Turek PJ. Fertility Preservat Males with Cancer, 2002
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Physical
                            Inguinal ring
Examination
Body habitus
20 sex characteristics   Varicocele
Breast exam
                                            Vas deferens



       Penis
                                       Epididymis


                                      Testis
       prostate
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
How to Approach
Varicocele Repair?



                         X




                         X

                     X
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
History
  Physical Exam



Semen Analysis x 2




            Hormone
           Evaluation

                          Blood
                          Semen
                        Imaging
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
% Normal Kruger Morphology!
Peroxidase stain
G
              R
              H
                      -

                  -
FSH

          +

      T
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Genetic Infertility is Subtle
                                               Low or
                                               no sperm
    Clean!!
                                Semen Analysis
                 History

                                  Hormones

                 Physical
                                 Other Tests
       Small
        testes                                 Normal
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
The CFTR Gene
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
1% all men; 5% infertile men



                               Rebuild
                               ICSI
                        Bx
                               ICSI
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Hemivasotomy
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Inner!



Outer!
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Nonobstructive Azoospermia: How to Best Find Sperm?
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)
Good Luck!!

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Male Infertility Review 2011 By Paul J. Turek MD FACS, FRSM, Director of The Turek Clinic and Former Professor and Endowed Chair, University of California San Francisco (UCSF)

  • 1. Male Infertility Review 2011 Paul J. Turek MD FACS, FRSM Director, The Turek Clinic, San Francisco, CA Former Professor and Endowed Chair, UCSF
  • 4. 4-6 wks 6 wks Y chromosome (SRY gene) 7-15 wks Testis Bipotential gonad Ovary
  • 5. Embryology-Testis Gonocytes Testosterone •  Inactive until puberty •  1st surge in utero •  Meiosis inhibited by MIS •  2nd surge in neonatal period •  Pubertal testosterone meiosis •  3rd rise at puberty; peaks in 2nd to 3rd decade Testosterone (ng/dL) 600 400 200 100 0 Adult Senescence
  • 7. Embryology-Bipotential Gonad Upper gubernaculum Mesonephros Gonad Urogenital cord Dorsal mesentery Mullerian duct Metanephros Mesonephric (Wolffian) duct Lower gubernaculum Intestine Midline
  • 9. Embryology-Mesonephric Duct Abnormalities Congenital Absence of the Vas Deferens (CAVD) • Unilateral: most azoospermic • Bilateral: all azoospermic • Any segment of Wolffian duct • If ipsilateral kidney also absent: No CFTR mutations • If ipsilateral kidney is present: 80% have CFTR mutations CF results in: Pneumonia, pancreatic insufficiency, bowel obstruction, sinusitis, nasal polyps, and death by 35 years of age.
  • 10. Embryology-Questions When does meiosis begin in the human male? Puberty What hormone is responsible for regression of MIS female internal genitalia? What gene is responsible for male sexual SRY, (SOX-9) differentiation? What gene mutation should be examined CFTR=cystic in men with idiopathic ejaculatory fibrosis trans- duct obstruction? membrane regulatory gene How many testosterone peaks have occurred by 3-First trimester, the time a man reaches age 30? neonatal and adult
  • 11. (caput) 10 days 4 x 3 cm Rete testis (20mL) (corpus) 80 64 days %ge rm 600 10-15 cells (cauda) million lobules sperm Need 3 months to make and ejaculate sperm. Soft, small testes imply a sperm production problem
  • 17. Cycles- Production varies with time, same location Waves-production varies in different locations
  • 18. 10% Prostate 10% Vas 80% deferens Seminal vesicle Premature ejaculation Retrograde ejaculation Anejaculation
  • 24. PRL
  • 25. H-P-G Axis: Testosterone • Testosterone comes in several forms. • Only free and albumin (weakly bound) are “active.” • SHBG-bound is inactive. Free/unbound Albumin bound 1-2% SHBG bound 60% 40% SHBG-T Total Free T Testosterone Bioavailable Testosterone Albumin-T
  • 26. H-P-G Axis: Testis & Testosterone Testosterone Testosterone Seminal Vesicle 5-a -Reductase Epididymis Dihydrotestosterone Vas Deferens Ejaculatory ducts Prostate Scrotum Penis External Internal
  • 30. Likely Kallmann Syndrome: Anosmia, delayed puberty, azoospermia, small testes, micropenis. DDx: Sickle cell disease, Hemochromatosis, Bardet-Biedl syndrome, Cerebellar ataxia, Prader-Willi syndrome
  • 31. Likely Klinefelter Syndrome: Delayed puberty, azoospermia, small testes, micropenis. 47, XXY
  • 32. Likely Prolactinoma (MRI pituitary to r/o macroadenoma)
  • 35. History Physical Exam Semen Analysis x 2 Eliminate Gonadotoxins Improved Hormone Evaluation Blood Semen Imaging
  • 38. Clinical Male Infertility: Chemotherapy Agent! Cisplatin! Cytoxan! Adriamycin! Vinblastine! Turek PJ. Fertility Preservat Males with Cancer, 2002
  • 41. Physical Inguinal ring Examination Body habitus 20 sex characteristics Varicocele Breast exam Vas deferens Penis Epididymis Testis prostate
  • 44. How to Approach Varicocele Repair? X X X
  • 46. History Physical Exam Semen Analysis x 2 Hormone Evaluation Blood Semen Imaging
  • 49. % Normal Kruger Morphology!
  • 51. G R H - - FSH + T
  • 57. Genetic Infertility is Subtle Low or no sperm Clean!! Semen Analysis History Hormones Physical Other Tests Small testes Normal
  • 73. 1% all men; 5% infertile men Rebuild ICSI Bx ICSI
  • 93. Nonobstructive Azoospermia: How to Best Find Sperm?