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Lecture written and presented by Paul J. Turek MD FACS, FRSM. Dr. Turek is the Director of the The Turek Clinic in San Francisco and Former Professor and Endowed Chair at the University of California San Francisco (UCSF).
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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
Y chromosome (SRY gene)
4-6 wks
6 wks
7-15 wks
Bipotential gonad
Ovary
Testis
Embryology-Testis
Gonocytes • Inactive until puberty • Meiosis inhibited by MIS • Pubertal testosterone meiosis
Testosterone • 1st surge in utero • 2nd surge in neonatal period • 3rd rise at puberty; peaks in
2nd to 3rd decade
Adult Senescence
Test
oste
rone
(ng/
dL)
0
100 200
400 600
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?
What hormone is responsible for regression of female internal genitalia?
What gene is responsible for male sexual differentiation?
What gene mutation should be examined in men with idiopathic ejaculatory duct obstruction?
How many testosterone peaks have occurred by the time a man reaches age 30?
Puberty
MIS
SRY, (SOX-9)
CFTR=cystic fibrosis trans- membrane regulatory gene
3-First trimester, neonatal and adult
4 x 3 cm (20mL)
64 days
10 days
80%germ
cells 600 million sperm
10-15 lobules
Need 3 months to make and ejaculate sperm. Soft, small testes imply a sperm production problem
Rete testis
(cauda)
(corpus)
(caput)
Cremasteric artery!
SERTOLI CELL
Cycles- Production varies with time, same location
Waves-production varies in different locations
Premature ejaculation Retrograde ejaculation Anejaculation
10% Prostate
10% Vas
deferens 80%
Seminal vesicle
The H-P-G Axis
PRL
H-P-G Axis: Testosterone
Albumin bound 60%
SHBG bound 40%
Free/unbound 1-2%
• Testosterone comes in several forms. • Only free and albumin (weakly bound) are “active.” • SHBG-bound is inactive.
SHBG-T
Free T
Albumin-T
Total Testosterone Bioavailable
Testosterone
Testosterone
Testosterone
Dihydrotestosterone
5- a -Reductase Vesicle Seminal
Penis Prostate Scrotum
Vas Deferens
Epididymis
Ejaculatory ducts
H-P-G Axis: Testis & Testosterone
External Internal
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)
History Physical Exam
Semen Analysis x 2
Eliminate Gonadotoxins
Improved
Hormone Evaluation
Blood Semen
Imaging
400% Better!
Clinical Male Infertility: Chemotherapy
Turek PJ. Fertility Preservat Males with Cancer, 2002
Agent!
Cisplatin!Cytoxan!
Adriamycin!Vinblastine!
Vas deferens
Testis
Epididymis
Varicocele
Penis
Inguinal ring Physical
Examination
prostate
Body habitus
20 sex characteristics
Breast exam
X
X
X
How to Approach
Varicocele Repair?
History Physical Exam
Semen Analysis x 2
Hormone Evaluation
Blood Semen
Imaging
% Normal Kruger Morphology!
Peroxidase stain
+
-
-
FSH
T
G R H
History
Genetic Infertility is Subtle
Physical
Semen Analysis
Hormones
Other Tests
Clean!!
Small testes
Low or no sperm
Normal
The CFTR Gene
Rebuild ICSI
ICSI
1% all men; 5% infertile men
Bx
Hemivasotomy
Outer!
Inner!
Nonobstructive Azoospermia: How to Best Find Sperm?
Good Luck!!