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!!