MALE INFERTILITY

Dr. Haider Ahmed Abu Almaaly

Consultant urologist
Fellow Iraqi Board- Baghdad / European Board- Netherland

Infertility:

Is the inability of sexually active , non-contraceptive couple to achieve

spontaneous pregnancy after one year .

It affect about 15% of couples.

Roughly; 40% of infertility is due to male factor , 40% is due to female

factor , and 20% is due to both factors.

PHYSIOLOGY
I-Hormone classes:
the major hormones contribute in spermatogenesis are :
1- Peptide: like luteinizing hormone (LH) and follicle-stimulating
hormone (FSH).
2- Steroids: Testosterone and Estradiol.

II-The hypothalamo-pituitary-gonadal axis (Picture 1) :

The hypothalamo-pituitary-gonadal axis provides pulsatile secretion of

GnRH and subsequently LH and FSH release from the anterior
pituitary to stimulate spermatogenesis and testosterone production.

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 The testis is a specialized structure that functions optimally in 2°C to
4°C below body temperature.
LH stimulates testosterone production by Leydig cells
FSH, through stimulation of Sertoli cells, supports
spermatogenesis in the seminiferous epithelium.

Picture 1 : hypothalamo-pituitary-gonadal axis

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III-Spermatogenesis: (300 sperm/gm/sec.)
# Spermatogenesis is an androgen-dependent process that occurs with
very high intratesticular levels of testosterone.
# This process takes approximately 64 days in humans and results in a
haploid germ cell that acquires natural ability to fertilize oocytes during
epididymal transport (Picture 2).
# Spermatogenesis pass through several steps starting from
Spermatogonia , Primary spermatocyte , Secondary spermatocyte ,
Spermatid and Mature sperm (Picture 3).

Picture 2 : haploid germ cell

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Picture 3 : Spermatogenesis

IV-Fertilization:
It normally occurs within the ampullary portion of the fallopian tubes.
During the middle of the female menstrual cycle when the cervical
mucus changes, becoming more abundant and watery.
These changes facilitate the entry of sperm into the uterus and protect
the sperm from the highly acidic vaginal secretions.

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CAUSES OF MALE INFERTILITY
Pretesticular , Testicular and post-testicular

1- Pretesticular:

1.1-Hypothalamic diseases :
1.1.1- Kallmann syndrome ,
1.1.2- Isolated L.H. deficiency ,
1.1.3- Isolated F.S.H. deficiency ,
1.1.4- Congenital hypogonadotropic syndrome.

1.2- Pituitary disease:

1.2.1- Pituitary insufficiency(tumors ,radiation) , Hyperprolactinemia

1.2.2- Exogenous hormones(excess of estrogen , androgen ,

glucocorticoid )

1.2.3- Hyper and hypothyroidism ,

1.2.4- Growth hormone deficiency.

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Hyperprolactinemia
Elevated prolactin usually results in decrease FSH , LH & testosterone
by negative feedback mechanism .

Causes:
-- prolactin secreting pituitary adenoma which is either macro adenoma
(more than 10 mm) or micro adenoma( less than 10 mm)
-- stress,
-- medications.

Clinical features:
impotence , loss of libido ,
gynecomastia , galactorrhea.

Diagnosis: by hormonal assay which is reveal increase level of prolactin

and decrease in FSH , LH , Testosterone levels
Brain CT-scan or MRI to diagnose pituitary adenoma.

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2- Testicular:

2.1- Varicocele,
2.2- Maldescended testis or Ectopic testis ,
2.3- Orchitis
2.4- Torsion
2.5- Trauma ,
2.6- Systemic diseases ,
2.7- Gonadotoxins ( radiation ,drugs ) ,
2.8- Klinefelter syndrome ,
2.9- Noonan syndrome ( male turner syndrome ).

Varicocele:
A varicocele is an abnormal tortuosity and dilatation of the testicular
veins within the spermatic cord.
Varicocele is found in approximately 15% of the male general
population, in 35% of men with primary infertility, and in 80% of men
with secondary infertility.
The varicocele is the most common correctable cause of male
infertility.
90% of varicoceles are left sided. 10% is bilateral .

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Clinical features:
Varicoceles are associated with smaller ipsilateral testis or upper scrotal
heaviness or pain or infertility.

Diagnosis:
By seminal fluid analysis which shows all or some of the below signs :
1. decreased motility (asthenospermia) ,or
2. low sperm count (oligospermia) or ,
3. abnormal sperm morphology .

Doppler U/S ;

Shows dilated veins (more than 2.8 mm) and reverse flow Grades of

varicocele :

Grade I varicocele, an impulse can be palpated in the scrotum during a

Valsalva maneuver.

Grade II varicocele is large enough for tortuous and dilated veins to be

palpated without a Valsalva maneuver.

Grade III varicocele is visible through the scrotal skin.

Subclinical varicocele diagnosed only by Doppler U/S on valsalva.

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3-- Postesticular:

3.1- Disorders of coitus :

3.1.1- Impotence ,

3.1.2- Hypospadias ,

3.1.3- Timing and Frequency.

3.2- Disorders of sperm function :

3.2.1- Immotile cilia syndrome ,

3.2.2- Immunologic infertility ,

3.2.3- Infection .

3.3- Reproductive tract obstruction

3.3.1- Vasectomy ,

3.3.2- Groin surgery ,

3.3.3- Infection ,

3.3.4- Congenital absence of the vas,

3.3.5- Ejaculatory duct obstruction.

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Immunologic infertility: (Antisperm Antibody-ASA-):

It contribute to 10% of male infertility.

Causes :

like Trauma , Torsion , Vasectomy , Testicular biopsy .

these will cause a broken to the Blood-Testes Barrier and the sperm pass

to the blood stream which is highly antigenic leading to the formation of

Antibody against the sperm.

Sperm Ab. cause sperm clumping and agglutination that inhibit

passage and be destroyed within the uterus , also block the sperm

binding to the oocyte.

An assay to ASA should be obtained when:

1-SFA (Seminal Fluid Analysis) shows sperm clumping and

agglutination

2-SFA shows low sperm motility

3- SFA shows increase in round cells(wbc)

4-Unexplained infertility.

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Examination:

1. Hair distribution ,

2. Gynecomastia ,

3. Testes,

4. Epididymus (posterolateral to the testes) ,

5. Absence of the vas deference ,

6. Varicocele ,

7. Penile abnormalities.

Investigations :
1. Seminal fluid analysis (picture 4)

2. Hormonal assay

3. Adjunctive Tests

4. Radiological imaging

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picture 4 : Seminal fluid analysis

Hormones:
The most important hormones concerning work up of infertility are ;

FSH ,testosterone ,prolactin and some times LH .

Indications of hormonal analysis are :

1. Sperm concentration <10 milions /ml

2. Impaired sexual function ( Impotence , Low libido)

3. Findings of endocrinopathy ( thyroid or cushing’s).

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Adjunctive Tests for male infertility:

1. Antisperm Antibody test ; in semen or serum or in cervical mucus

2. Hypoosmotic swelling test ; measure the sperm viability (viable

sperm with functional membrane should swell when placed in a

hypoosmotic fluid).

3. Chromosomal studies; XXY , 45XO, XYY.

Radiological Tests:

1. Scrotal ultrasound and Doppler ; for Varicocele , and other scrotal

pathology ,

2. Venography; for Varicocele

3. Trans rectal U/S(TRUS) ; for Seminal vesicle and Ejaculatory ducts

4. CT-Scan and MRI of the pelvis; for undescended testes ,

Retroperitoneal pathology

5. Vasography; to exclude obstructive causes.

Testes Biopsy

Indications:

1- Azospermia( Sperm concentration = zero)

2- Elevated FSH

3- Atrophic testes.

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TREATMENT OF MALE INFERTILITY

1- MEDICAL Rx.

1.1- Pyospermia: appropriate antibiotics

1.2- Immunologic infertility: low dose of steroid for several weeks.

1.3- Hyperprolactinemia: Bromocryptine tab. 2.5-5 mg/day (with

monitoring of blood level)

1.4- Testosterone deficiency: by giving Testosterone (Intramuscular)

200-400 mg every 2-4 weeks

1.5- Hypogooadotropic hypogoadism : start HCG 1500 IU

3 times/week then HMG 75 IU 3 times/week.

1.6- Emperical Therapy - for 3-6 months

about 25% of infertility are with no identified causes so here we can use

emperical treatment.

1.6.1- Clomiphene citrate: Anti estrogen , given for idiopathic low sperm

count , 50 mg/day

1.6.2- Tamoxifen: Anti estrogen , given for idiopathic oligospermia ,20 mg

daily

1.6.3- Antioxidant Therapy: Vitamin E 400-1200 U/day

1.6.4- Glutathion : For asthenospermia 600 mg /day.

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2- SURGICAL Rx.

2.1- Varicocelectomy: for dilated varix over 2.8 mm

2.2- Vaso-vasostomy: For vassal obstruction (trauma , infection ,

vasectomy)

2.3- Trans Urethral Resection of Ejaculatory duct (TURED) for

ejaculatory duct obstruction

2.4- Pituitary ablation: for Macroadenoma.

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3- ASSISTED REPRODUCTIVE TECHNOLOGIES

3.1- Intra Uterine Insemination (IUI)

3.2- Invetro fertilization (IVF)

3.3-Intracytoplasmic Sperm Injection (ICSI).

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Kalmann syndrome:
is a rare disorder ( 1 /50 000) ,characterized in deficiency of olfactory

neurons and neurons that secret GnRH which explain the two most

common clinical deficits , anosmia and absence of GnLH .

clinical features; are anosmia, facial asymmetry ,color blindness , renal

abnormalities ,microphallus ,cryptorchidism ,

the hallmark of the syndrome is a delay of pubertal development.

Hormonal assay ; low LH, FSH and testosterone.

Treatment :

virulization and fertility can be achieved by FSH and LH to stimulate

testes.

Sertoli only cell syndrome

Also called germ cell aplasia ,the hallmarks are azooppapermia and

testiculer biopsy shows presence of all testicular cells except germinal

epithelium.

Testosterone and LH are normal and FSH is elevated .

There is no known treatment for this syndrome.

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Klinefelter syndrome:
It is the most common genetic cause of azoospermia.

It occurs 1/500 male

It has classic triad ; small firm testes , gynecomastea , and

azoospermia,with increase in height ,delay sexual maturation ,decrease

intelligence, and increase likelihood of gonadal tumor and breast cancer,

90% of men are with extra X chromosome ( 47 ,XXY) AND 10% are

mosaic with combination of XXY /XY chromosome.

Paternity of this man is very rare.

Serum FSH ,LH are frankly elevated due to low testosterone.

XYY syndrome:

Similar in incidence of klinefelter syndrome

typically the man with 47 /XYY chromosome are tall and aggressive

with antisocial behavior .

SFA shows oligospermia or azoospermia.

Testosterone and LH are normal and FSH is high.

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Young syndrome :
Triad of chronic sinusitis ,bronchiactasis ,obstructive azoospermia , the

pathophysiology is unclear but may be due to abnoraml ciliary

movement or abnormal mucus quality.

Adult polycystic kidney disease:

The causes of infertility is due to obstructing cyst in the epididymis or

seminal vesicles.

Noonan syndrome:

Also called male turner syndrome( 45/X )

The karyotype is either normal or mosaic
(45 /XY – 45 / X )
Clinical features: dysmorphic features like webbed neck ,short stature
,low set ears , wide set eyes .

References :
1- Smith textbook of urology / 16th edition- 2004 (p. 678 – 712)
2- European urology guideline / Edition 2016 (p. 226 – 241)

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