MALE INFERTILITY

Omer Onur Cakir

MD, Assoc Prof, MSc, FEBU, FECSM, FRCS
Consultant Urological Surgeon and Andrologist
 Definition
• The disease of infertility affects approximately 15% of couples

• Male infertility is defined as the inability to impregnate partner

within one year with unprotected regular intercourses

• The chance of a normal couple conceiving is estimated to be

approximately:
• 25 % per month,

• 75 % by 6 months and

• 90 % by 1 year
 Definition
• Today, we mostly assess the couples earlier than 1 year with
unprotected regular intercourses.
• Late maternal age

• Expectation of the couple

• Fertility rates decline with age

• 20 % of infertility cases are due to a male factor, 30 % involve
both male and female factors
Primary vs secondary infertility

• Primary infertility is defined as the failure to conceive at any

time in the past with any prior partner,

• Secondary infertility indicates a prior conception with the

current or previous partner.
Evaluation
• All infertile men should undergo
• History

• Physical Examination

• At least two semen analysis

• 1-2 % of men evaluated for male infertility have significant medical

pathology.
• Such as Testis Tumor, Klinefelter Syndrome

• A normal semen analysis does not rule out male infertility.

Etiology

1. Pre-testicular causes
2. Testicular causes

3. Post testicular causes

 Etiology
• Pre-testicular causes – endocrine
• Pituitary diseases – surgery, infarction, tumors, radiation, infections

• Isolated hypogonadotropic hypogonadism – Kallmann’s syndrome, idiopathic

• Isolated FSH and LH deficiencies CORTEX

• Other congenital syndromes

• Obesity HYPOTHALAMUS
• Gym Steroids

PITUITARY

LH FSH

SPERM
ANDROGENS GONAD
INHIBIN
Etiology

• Testicular causes
• Genetic abnormalities – Klinefelter’s Syndrome, XYY Syndrome,
XX Male, Androgen abnormalities, Noonan’s Syndrome etc...
• Bilateral anorchia
• Cryptorchidism

• Varicocele
• Sertoli Cell – Only Syndrome
Etiology

• Testicular causes
• Gonadotoxins – alcohol, cigarettes, narcotics, drugs, chemicals
• Chemotherapy
• Radiation
• Orchitis – postpubertal mumps
• Trauma

• Testes tumor
Etiology

•Post testicular causes

• Ductal obstruction
• Ejaculatory problems
• Sexual dysfunction
• Psychogenic problems
History
• Sexual history
• Past history
• Developmental – age of puberty
• Surgical
• Medical
• Drugs
• Occupation and habits
• Past marital history of both partners
• Previous infertility treatments

• Female reproductive history

Timing and frequency of intercourse

• Viability of spermatozoa within the female reproductive tract is

between 2 and 5 days in favorable cervical mucus

• Intercourse frequency every 1-2 days near the time of ovulation

maximizes pregnancy

• Intercourse that is too frequent does not allow replenishment of

adequate numbers of spermatozoa within the epididymis
• Infrequent intercourse may miss the potential window for
fertilization
 Physical examination
• Systemic examination
• Habitus
• Pattern of virilization

• Genital examination
• Penis – anomalies
• Testes – volume, consistency, absence
• Epididymis
• Vas deferens
• Varicocele
• Prostate
Prof. T. Tarcan, 2021
Semen analysis

• Cornerstone of the laboratory evaluation

• Except in cases of azoospermia,

• does not allow for the separation of patients into sterile
and fertile groups
• decrease in quality : the statistical chance of conception
decreases but does not reach zero
Semen analysis

• Sexual abstinence of 2 –3 days

• Must be collected and examined on site

• Must be collected in a glass, clean, dry container

• Must be repeated at least 2 times with an interval

of 3 months
Ejaculate analysis according to the WHO Laboratory Manual for
the Examination and Processing of Human Semen (5th edn.)

Prof. T. Tarcan, 2021

Interpretation of semen analysis

• Azoospermia – no sperm cells in the specimen

• Oligozoospermia – counts less than normal

• < 15 million spermatozoa/mL

• Asthenozoospermia – defects in sperm movement

• < 32% progressive motile spermatozoa;

• Teratozoospermia – defects in morphology

• < 4% normal forms.
 Semen Analysis

• Always make sure you have two semen analyses

• (if >20% discrepancy, get third)

• If ejaculatory volume is very low, suspect

• retrograde ejaculation or

• ejaculatory duct obstruction or

• CABVD (congenital bilateral absence of the vas deferens)

• If you suspect retrograde ejaculation get a Post-ejaculatory (or post-

coital) urine test
Evaluation for Retrograde Ejaculation in azoospermia
with hypovolemia
Post-ejaculatory(or coital) urine test

—Drink lots of water

—Void

—Masturbate (or coit)

—Void again for sample:

Retrograde ejaculation
Second level testing

• Purpose is to find out specific etiologies

• Not all patients need all tests

• Genetic tests
• Hormonal tests
Hormonal evaluation

• < 3 % patients are involved

• Rare in patients with sperm counts > 5 millions/ml

• FSH, LH, testosterone, prolactin are the principle

hormones to evaluate

• FSH is directly related with spermatogenesis

FSH levels do not accurately predict the
spermatogenesis status!
Men with maturation arrest could have
normal FSH and normal testis volume and
still be azoospermic!
 Genetic testing
• 7% of infertile men will have structural or numeric chromosomal
abnormalities.
• Karyotype and y-linked microdeletion assessment
• used for evaluation of both non-obstructive azoospermia (NOA) and severe oligospermia,
• Microdeletions of the Y chromosome in 10% to 15% of patients with severe oligospermia or
azoospermia.
• Cystic fibrosis transmembrane conductance regulator (CFTR) gene,
• in 88% of men with obstructive azoospermia due to CBAVD.
Internal and external genitalia development
 Clinical implications of Y microdeletions
• AZFc deletions are most common (65-70%),
• followed by Y-deletions of the AZFb and AZFb+c or AZFa+b+c regions (25-30%).
• AZFa region deletions are rare (5%).

• Complete removal of the

• AZFa region is associated with severe testicular phenotype (Sertoli cell only
syndrome),
• AZFb region is associated with spermatogenic rest.
• AZFc region causes a variable phenotype ranging from azoospermia to
oligozoospermia.

• Classical (complete) AZF deletions do not confer a risk for cryptorchidism or testicular
cancer
Classification of obstructive azoospermia (OA)
• Intratesticular obstruction
• occurs in 15% of men with OA

• Epididymal obstruction
• most common cause of OA, affecting 30-67% of azoospermic men

• CBAVD

• Vas deferens obstruction

• most common cause of acquired obstruction following vasectomy

• Ejaculatory duct obstruction

• 1-5% of cases of OA

• classified as cystic or post-inflammatory or calculi of one or both ejaculatory ducts

• Functional obstruction of the distal seminal ducts

• local neurogenic dysfunction leading to Impaired sperm transport
Algorithm for evaluation of azoospermia.
CFTR, Cystic fibrosis transmembrane conductance regulator; FSH, follicle-stimulating
hormone; TLA, testis longitudinal axis measured by caliper orchidometer.
 Treatment
Medical Surgical

• Empiric therapy: Not recommended • Spermatic vein ligation to treat

testicular varicocele
• Hormonal treatment:
• TUR – ED: Obstruction of the
• Hypogonadotropic hypogonadism:
Ejaculatory Ducts
combined hCG and recombinant FSH

• Hyperprolactinaemia: dopamine agonist

• Do not use testosterone therapy for the

treatment of male infertility!!!

Treatment: Assisted reproductive techniques
• Intrauterine insemination
• the placement of the prepared sperm into the uterine cavity timed around ovulation

• IVF - In vitro fertilization

• involves using controlled ovarian hyperstimulation to recruit multiple oocytes during
each cycle from the female partner. Follicular development is monitored ultrasonically,
and ova are harvested before ovulation with the use of US-guided needle aspiration.
The recovered oocytes are mixed with processed semen to perform IVF. The
developing embryos are incubated for 2-3 days in culture and then placed trans-
cervically into the uterus.

• ICSI - Intracytoplasmic sperm injection

• Intracytoplasmic sperm injection is a procedure through which a single sperm is
injected directly into an egg using a glass micropipette.
 ICSI

• most commonly used assisted reproductive technology,

• ICSI is highly efficient at producing fertilization as long as the

spermatozoa are conceivable and can be retrieved from male
reproductive tract.
Sperm retrieval techniques in azoospermic
patients for the use in ICSI

• Testicular sperm extraction (TESE)

• Only option for sperm retrieval in patients with non-obstructive azoospermia
(NOA)

• Micro-TESE is the gold standard

• Epididymal obstruction
• Microsurgical epididymal sperm aspiration (MESA)

• Testicular sperm aspiration (TESA)

• Percutaneous epididymal sperm aspiration (PESA)

Can we predict positive sperm retrieval at
TESE in patients with NOA?

• No pre-operative biochemical and clinical variables may be

considered sufficient and reliable predictors of positive sperm
retrieval at surgery in patients with NOA.

• In patients with complete AZFa and AZFb microdeletions, surgery is

contraindicated since the chance of sperm retrieval is zero.
Interactive Session begin here…

@omeronurcakir

omeronurcakir

Omer Onur Cakir