Current Management of Male Infertility

Diagnostic and Genetic Considerations

Andrew Kramer, MD, MBA

Assistant Professor, Department of Surgery, Division of Urology University of Maryland School of Medicine

Outline:

Male Reproductive Anatomy Male Reproductive History and Physical Exam Interpretation of the Semen Analysis Selected Cases Conclusion

3 Cases:

1. Obstructive Azoospermia
2. Nonobstructive azoospermia 3. Inability to ejaculate

A couple presents with inability to have children

HPI:

Male: 34
2 yrs of unprotected intercourse No children from previous relationships

Exam:

Testes scrotally located and of normal size and consistency

No vasa palpable Only caput of epididymis present

Semen Analysis:

Azoospermia

Semen Analysis:

Volume: 0.5cc
Count: 0 pH: 6.5

One Cause of Obstructive Azoospermia (congenital bilateral absence of the vas deferens)
* Caused by Mutations in CF genes

Transmission Pattern:
Male F508 F508 Female + F508/F508 F508/5T 5T

Clinical CF
F508/+ carrier

CBAVD 5T/+ carrier

 Clinical

manifestation depends on the amount of CFTR dysfunction

CBAVD: obstructive azoospermia

CF gene is located on chromosome 7 Encodes a membrane protein called CFTR (CF transmembrane conductance regulator) that regulates Cl- balance When abnormal, ion and water transport across epithelial cells is altered causing tenacious sections

Thickett, K., Stableforth, D. et al. Awareness of infertility in men with cystic fibrosis. Fertility and Sterility. Vol 76(2). August 2001, pp 407-408.

Cystic Fibrosis Transmembrane Conductance Regulator

Chromosome # 7

...

CFTR
CF Gene

Management:

Family counseling MESA: microsurgical epididymal sperm aspiration

Congenital Bilateral Absence of the Vas Deferens

Epididymal Remnant

Infertility: Part II

Infertility x 5 yrs

Husband: 45

Wife: 38

Wife has 2 children from a prior marriage

Physical Exam:

Testes measure 1.5cm x 1.5cm in size, slightly soft

Vasa and epididymides feel normal

No varicocele

Semen Analysis:

Volume: 3cc Count: 0 Color: clear pH: 8.1

Hormone Studies:

FSH: 15.2 (normal 2-20) LH: 5.1 Testosterone: 344 Prolactin: 8.5 Estradiol: <20 SHBG: 54.6 DHEA-S04: 198 Would you do a testis biopsy for diagnosis??

Genetic Testing:

Karyotype: abnormalities range from 1015% in azoospermic men; Klinefelter syndrome most common Y-chromosome microdeletions: 13% of men with azoo or severe oligospermia

Oates, RD. Genetic considerations in the treatment of male infertility. Infert Reprod Med Clin N America. Vol 13 (2002) 551-585.

Y Chromosome

Short arm: SRY--acts as an architectural transcription factor instigating male development Long arm: Contains genes critical to spermatogenesis

47, XXY

Klinefelters Karyotype

Infertility: Part III

Married for 9 years with no pregnancies

Husband: 38

Wife: 37

PMH: 1985 testicular CA on left, s/p orchiectomy, RPLND, and chemotherapy (cisplatinum/vinblastine/bleomycin)

Ejaculatory Dysfunction:

Two Types:

Retrograde Ejaculation (backwards flow of ejaculate) Anejaculation (failure of emission)

Retrograde Ejaculation Diagnosis:

1. Void to completion
2. Ejaculation (collection any antegrade) 3. Void to completion ASAP: look at sample for seminal fluid then spin to 1cc, analyze pellet

Anejaculation/Failure of Emission:

Failure of sympathetic nervous system due to:

-Spinal cord injury -RPLND (sympathetic nerve injury) -D.M.

Summary: Evaluation of the Infertile Male

Goal of Evaluation:

1. Identify correctable causes 2. Identify irreversible causes that may be amenable to ARTs 3. Irreversible conditions which are not amenable to ARTs but donor sperm may be an option 4. Reveal genetic abnormalities that may affect health of offspring if ARTs were to be used
Sharlip, Ira and Jarow, Jonathan et al. Best practice policies for male infertility. Fertility and Sterility, Volume77(5). May 2002. 873-882.

Azoospermia: Etiology

1. Pretesticular: endocrine 2. Testicular: disorders of spermatogenesis intrinsic to testes (non-obstructive) 3. Post-testicular: ejaculatory dysfunction or obstruction of sperm delivery to meatus (obstructive)

Pre and Post testicular are often treated, primary testicular causes can still achieve fertility

Remember:

Always evaluate patients as a couple Perform the womans workup simultaneously to the mans Just because one member of the couple is abnormal does NOT mean the other one is normal: both warrant a full workup

The End

Andrew Kramer, MD, MBA Division of Urology, Department of Surgery