Male Infertility

A.M. Gouda
 Introduction: Anatomy of the Male Reproductive System

Seminal
Testes
Epididymis: Vas Deferens: Vesicles & Urethra: Penis:
(Testicles):
Prostate Gland:
• The primary • A coiled tube • A long duct • Produce • A tube that • The external
male on top of that fluids that carries both organ that
reproductive each testis. transports nourish semen and delivers
organs. • Stores and mature sperm and urine out of sperm during
• Produce matures sperm from form semen. the body intercourse.
sperm and sperm. the through the
testosterone epididymis to penis.
the urethra.
 Functional Compartments of the Testes

Compartment Main Structures Function

- Site of spermatogenesis
- Sertoli cells (sperm production)
- Developing germ cells - Sertoli cells provide
Seminiferous Tubules
(spermatogonia to support, nutrition, and
spermatozoa) regulation of sperm
development
- Produce testosterone,
- Leydig cells (located which regulates
Interstitial (Leydig) Cells between seminiferous spermatogenesis and male
tubules) secondary sexual
characteristics
 Hormonal Control of Spermatogenesis

Spermatogenesis Hypothalamus: Anterior Pituitary: Testes: Negative Feedback

is tightly regulated Regulation:
by the Releases Secretes luteinizing LH acts on Leydig Testosterone
hypothalamic- gonadotropin- hormone (LH) and cells → stimulates inhibits GnRH and
pituitary-gonadal releasing hormone follicle-stimulating testosterone LH secretion to
(HPG) axis through a (GnRH), which hormone (FSH) in production. maintain hormonal
series of hormonal stimulates the response to GnRH.
signals: FSH acts on Sertoli balance.
anterior pituitary.
cells → supports Inhibin B selectively
spermatogenesis inhibits FSH
and stimulates the secretion.
production of
inhibin B.
 Hormonal
Control of
Spermatogenesis
Male Infertility: Definition and Types

Male infertility is the inability to

achieve pregnancy with a fertile
female partner after 12 months
Definition of regular, unprotected
intercourse due to issues
related to sperm production,
function, or delivery.
Types of Male Infertility

Type Definition

A man has never achieved a pregnancy

Primary Infertility
despite at least 12 months of trying.

A man who was previously able to achieve

Secondary Infertility pregnancy is now unable to do so after at
least 12 months of trying.
Etiology of
Male
Infertility
Pre-Testicular Causes (Hormonal & Systemic
Disorders)

Cause Explanation
Hypogonadotropic Hypogonadism Low LH & FSH lead to impaired testosterone
(Kallmann Syndrome, Pituitary Tumors) production and spermatogenesis
Hyperprolactinemia (Prolactinoma, High prolactin suppresses GnRH, reducing
Medications) testosterone & sperm production
Thyroid Disorders Affects metabolism, hormone levels, and
(Hypothyroidism/Hyperthyroidism) sperm quality
Chronic Illnesses (Diabetes, Liver Affect hormonal balance and semen
Disease, Kidney Failure) parameters
Increases estrogen, reduces testosterone
Obesity
and sperm count
Drugs & Toxins (Anabolic Steroids,
Suppress hormone production &
Alcohol, Opioids, Chemotherapy,
spermatogenesis
Radiation)
Testicular Causes (Primary Testicular Failure)

Cause Explanation

Genetic Disorders (Klinefelter Syndrome) Cause testicular dysfunction & azoospermia

Higher intra-abdominal temperature impairs

Cryptorchidism (Undescended Testes)
spermatogenesis
Increases testicular temperature, damaging
Varicocele
sperm
Cuts off blood supply, leading to testicular
Testicular Torsion
atrophy
Causes inflammation and permanent testicular
Orchitis (e.g., Mumps Orchitis)
damage
Testicular Trauma/Radiation/Chemotherapy Directly damages sperm-producing cells
Idiopathic Oligospermia No identifiable cause of low sperm count
 Post-Testicular Causes (Obstruction & Ejaculatory
Disorders)

Cause Explanation

Congenital Bilateral Absence of the Vas

Deferens (CBAVD) (Associated with Cystic Sperm is produced but cannot be transported
Fibrosis)

Obstructive Azoospermia (Epididymal or Vas

Sperm is blocked from reaching the urethra
Deferens Blockage)

Retrograde Ejaculation (Diabetes, Spinal Cord Sperm enters the bladder instead of exiting
Injury, Alpha-Blockers) through the urethra

Ejaculatory Duct Obstruction (Infection,

Prevents semen from being released normally
Congenital Defects)
 Klinefelter Syndrome

Feature Details

A genetic disorder where a male has an extra X chromosome (47,XXY

Definition
karyotype), leading to testicular dysfunction and infertility.

Hormonal - Low testosterone

Profile - High FSH & LH (due to testicular failure)

Testicular - Small, firm testes (testicular atrophy)

Features - Impaired spermatogenesis (azoospermia or oligospermia)

- Tall stature with long limbs

Physical - Gynecomastia (breast enlargement)
Features - Reduced muscle mass
- Decreased facial and body hair
 Retrograde Ejaculation

Feature Details

A condition where semen enters the bladder instead of being expelled through the
Definition
urethra during ejaculation.

- Nerve damage (e.g., diabetes, spinal cord injury)

- Surgery (e.g., prostate or bladder neck surgery)
Causes
- Medications (e.g., alpha-blockers, antidepressants)
- Congenital abnormalities

- Dry orgasm (little to no semen during ejaculation)

Symptoms - Cloudy urine after ejaculation (due to sperm in the bladder)
- Infertility

- Medications (e.g., pseudoephedrine to improve bladder neck closure)

Treatment
- Assisted reproductive techniques (e.g., sperm retrieval for IVF)
Diagnosis of Male Infertility

MEDICAL HISTORY & LABORATORY TESTS. IMAGING STUDIES TO

PHYSICAL EXAMINATION. IDENTIFY UNDERLYING
CAUSES AND GUIDE
APPROPRIATE TREATMENT.
Medical History & Physical Examination

Medical History

Reproductive history: Duration of infertility, previous pregnancies, miscarriages

Sexual history: Frequency of intercourse, erectile or ejaculatory dysfunction, libido issues

Medical conditions: Mumps, orchitis, STIs, diabetes, hormonal disorders, varicocele

Surgical history: Testicular surgery, hernia repair, prostate surgery, vasectomy

Medications: Anabolic steroids, chemotherapy, finasteride, antidepressants

Lifestyle factors: Smoking, alcohol, drug use, excessive heat exposure, stress, diet
Physical Examination

General examination:

• Body habitus, secondary sexual characteristics, gynecomastia

Genital examination:

• Testicular size & consistency (Normal: ~15-25 mL; Small testes suggest
primary testicular failure)
• Varicocele detection (palpable or Doppler-confirmed)
• Epididymis and vas deferens (absence suggests congenital conditions)
• Penis abnormalities (hypospadias)
• Signs of infection (epididymitis, prostatitis)
Semen Analysis

First-line test, performed after 2-7 days of

abstinence
At least two tests (collected 2-3 weeks apart
for accuracy)
Semen Analysis: Patient Counseling for Accurate Testing
Factor Instructions & Rationale
2-7 days before sample collection to ensure optimal sperm
Abstinence Period
concentration.
At least two tests, collected 2-3 weeks apart, to confirm results and
Number of Tests
account for natural variations in sperm production.
Masturbation preferred (clean, sterile container); avoid condoms (may
Collection Method
contain sperm-killing agents). If at home, deliver within 1 hour.
Keep sample at body temperature (avoid heat/cold exposure) during
Environmental Factors
transport.
Avoid alcohol, smoking, excessive caffeine, and drugs that affect sperm
Medication & Lifestyle
quality (e.g., anabolic steroids, finasteride).
Recent fever or illness may temporarily reduce sperm quality; repeat
Infection & Illness
testing after recovery if needed.
Lubricants Avoid lubricants, as they can affect sperm motility.
Stay hydrated and maintain a balanced diet rich in vitamins (e.g., zinc,
Hydration & Diet
vitamin C, folate) for better sperm health.
Stress and anxiety can impact sperm parameters; relaxation techniques
Emotional Stress
may help.
 Parameter Normal Range Abnormal Findings
Semen Analysis: Color White or grayish-white Yellow, red, brown
Physical & Volume ≥ 1.4 mL (WHO 2021)
Low (<1.4 mL) or High (>6
Microscopic mL)
Characteristics Liquefaction
Time
Within 60 minutes
Delayed or absent
liquefaction
<7.2 (acidic) or >8.0
pH 7.2 – 8.0
(alkaline)
Increased thickness
Viscosity Normal: pours in droplets
(hyperviscosity)
Low (<16 million/mL =
≥ 16 million/mL (WHO 2021),
Sperm Count oligospermia)
≥39 million/ejaculate
None = azoospermia
Low motility (<30%) =
Motility Progressive ≥ 30%
asthenospermia

Vitality ≥ 58% live sperm <58% live = necrozoospermia

Morphology ≥ 4% normal forms <4% = teratospermia

WBCs <1 million/mL >1 million/mL
Agglutination Absent Present
 WHO Normal Semen Analysis Criteria
Parameter Normal Reference Range
Volume ≥ 1.4 mL
pH ≥ 7.2
Sperm Concentration ≥ 16 million/mL
Total Sperm Count ≥ 39 million per ejaculate
Motility (Progressive + Non-progressive) ≥ 42%
Progressive Motility ≥ 32%
Morphology (Normal Forms) ≥ 4%
Vitality (Live Sperm Percentage) ≥ 54%
White Blood Cells (WBCs) < 1 million/mL (higher suggests infection)
Absent (suggests antisperm antibodies if
Agglutination
present)
Viscosity Normal (not highly viscous)
Abnormal Semen Parameters and Their Indications
1. Physical Abnormalities
Parameter Abnormal Finding Possible Indication
Partial or complete ejaculatory duct
Volume < 1.4 mL (Hypospermia) obstruction, retrograde
ejaculation, androgen deficiency.
Prolonged abstinence, seminal
Volume > 5 mL (Hyperspermia)
vesicle hypersecretion.
Obstruction of seminal vesicles,
pH < 7.2 (Acidic semen)
congenital abnormalities.
Infection of the prostate or seminal
pH > 8.0 (Alkaline semen)
vesicles.
Urine contamination, infection,
Color Yellowish
jaundice, drugs (e.g., vitamins).
Blood contamination, infection,
Color Reddish (Hematospermia) prostate/seminal vesicle disease,
trauma.
Infection, prostatic dysfunction,
Viscosity Increased (Hyperviscosity)
reduced sperm motility.
 Microscopic Abnormalities

Parameter Abnormal Finding

Sperm Concentration < 16 million/mL (Oligozoospermia)
Sperm Concentration Absent sperm (Azoospermia)
Motility < 42% total motility (Asthenozoospermia)
Progressive Motility < 30%
Morphology < 4% normal forms (Teratozoospermia)
Vitality (Live Sperm) < 54% (Necrozoospermia)
White Blood Cells (WBCs) > 1 million/mL (Leukocytospermia)
Sperm Agglutination Present (Antisperm antibodies)
 Hormonal Evaluation
Hormone Normal Range Abnormal Findings & Causes

High: Testicular failure

FSH 1.5-12 IU/L
Low: Hypogonadotropic hypogonadism

High: Primary testicular failure

LH 1.8-8.6 IU/L
Low: Pituitary dysfunction

Testosterone 300-1000 ng/dL Low: Hypogonadism, testicular dysfunction

High: Hyperprolactinemia (pituitary tumor,

Prolactin 2-18 ng/mL
medication-induced)
Genetic Testing
Indicated for severe oligospermia or azoospermia.

Test Indications

Karyotyping (Chromosome Suspected Klinefelter

Analysis) syndrome (47,XXY)

Congenital bilateral absence

CFTR Gene Mutation Analysis
of the vas deferens (CBAVD)
Advanced Sperm Function Tests
For unexplained infertility, recurrent pregnancy loss, or ART failures.

Test Purpose
Assesses sperm DNA integrity (High
Sperm DNA Fragmentation Test (SDFT) damage → poor embryo quality,
miscarriage risk)
Evaluates oxidative stress (linked to
Reactive Oxygen Species (ROS) Test
smoking, varicocele, infections)
Detects immune-mediated infertility
Antisperm Antibody Test
(e.g., after vasectomy, trauma)
Hypo-osmotic Swelling Test (HOS) Checks sperm membrane integrity
 Testicular Biopsy: Why?

Aspect Details

To determine the cause of non-obstructive azoospermia

Why is it
(NOA) or confirm obstructive azoospermia (OA). It helps
done?
assess sperm production and guides fertility treatments.
Imaging Studies
Test Indications

Used to detect varicocele, testicular masses, and

Scrotal Doppler Ultrasound
epididymal abnormalities.

Helps evaluate ejaculatory duct obstruction and

Transrectal Ultrasound (TRUS)
abnormalities in the seminal vesicles.

Indicated if hypogonadotropic hypogonadism or

MRI of the Pituitary Gland hyperprolactinemia is suspected, to assess pituitary
function.

Abdominal Ultrasound Used to evaluate undescended testes.

What to Do Why

Avoid hot baths, saunas, tight pants Heat harms sperm production

Don’t smoke Smoking lowers sperm count

Avoid alcohol and drugs They harm hormones and sperm

Eat healthy Good diet helps sperm quality

Exercise regularly Boosts hormones naturally

Maintain healthy weight Obesity affects fertility

Reduce stress Stress affects sperm production

Infections can block sperm flow, Antibiotics in case of genital tract
Treat infections early
infections (e.g., chlamydia, gonorrhea)
Avoid toxins (like pesticides) Harm sperm and hormone balance

Practice safe sex Prevents STIs that can cause infertility

Avoid unnecessary meds (like TRT) Some meds stop sperm production

Fix testicular problems early E.g., varicocele, undescended testes

 Hormonal Therapy (For Hypogonadotropic Hypogonadism & Low
Testosterone Cases)
Drug Class Examples Mechanism Indications
hCG (Human Chorionic
Hypogonadotropic
Gonadotropin), hMG (Human Stimulate spermatogenesis by
Gonadotropins hypogonadism, low
Menopausal Gonadotropin), mimicking LH & FSH
sperm count
Recombinant FSH
Gonadotropin-
Stimulates pituitary release of LH & Central hypogonadism
Releasing Hormone Pulsatile GnRH
FSH (GnRH deficiency)
(GnRH) Therapy

Selective Estrogen Block estrogen receptors in the Oligospermia (low sperm

Receptor Modulators Clomiphene Citrate, Tamoxifen hypothalamus, increasing LH & FSH count), idiopathic male
(SERMs) secretion infertility

Reduce estrogen production,

High estrogen levels in
Aromatase Inhibitors Anastrozole, Letrozole increasing testosterone & sperm
obese or aging men
production

Testosterone Replacement Therapy (TRT (NOT for fertility)

 GnRH Agonist (e.g.,
Feature Pulsatile GnRH
goserelin)
Mode of
Pulsatile Continuous
administration
Suppresses (after
Effect on FSH/LH Stimulates
initial flare)
Fertility Hormone-sensitive
Main use
treatment conditions
TRT is not used in male infertility

• TRT provides external testosterone, which tells the hypothalamus and

pituitary: “We have enough testosterone.”
• As a result, GnRH → ↓, LH & FSH → ↓
• Without LH and FSH, the testes stop producing sperm
(spermatogenesis stops).
• Can lead to azoospermia (zero sperm count) and temporary or even
permanent infertility.
Main indication of TRT
Male hypogonadism (either primary or secondary)

Confirmed by:

• Low total testosterone (usually < 300 ng/dL on two separate mornings)
• AND presence of symptoms, such as:
• Low libido
• Erectile dysfunction
• Fatigue
• Depression
• Decreased muscle mass or bone density
• Reduced body/facial hair
• Poor concentration
 Medications for Specific Causes of Infertility
Condition Drugs Mechanism
No direct pharmacological
Varicocele treatment (surgical correction -
preferred)
Strengthen bladder neck closure
Retrograde Ejaculation Pseudoephedrine, Imipramine to direct semen out through the
urethra
Enhances dopamine levels to
Retarded Ejaculation Bupropion
improve ejaculation reflex
Reduce prolactin levels, restoring
Hyperprolactinemia-Induced Cabergoline, Bromocriptine
normal testosterone &
Infertility (Dopamine Agonists)
spermatogenesis
Antioxidants (Vitamin C, Vitamin
Oxidative Stress-Induced Improve sperm quality & motility
E, Coenzyme Q10, L-Carnitine,
Infertility by reducing oxidative damage
Zinc, Selenium)
 Surgical Options & Sperm Retrieval Techniques
Procedure Indication Description Outcome

Clinically significant
Ligation of dilated scrotal veins Improves semen quality
Varicocelectomy varicocele(abnormal semen
(microsurgery/laparoscopy) and testosterone
parameters and infertility)

Obstructive azoospermia
Vasovasostomy Reconnection of vas deferens Return of sperm in semen
(e.g., post-vasectomy)

Connection of vas deferens to

Epididymovasostomy Epididymal blockage Restores sperm flow
epididymis

Needle aspiration from

PESA Obstructive azoospermia Used for ICSI
epididymis

Non-/Obstructive
TESA Needle aspiration from testis Used for ICSI
azoospermia

Non-Obstructive Surgical retrieval of sperm from

TESE / Micro-TESE May find limited sperm
azoospermia testis
 Assisted Reproductive Techniques (ART)

Technique Indication Process

Washed sperm Educate on
IUI (Intrauterine Mild male
injected into uterus ovulation meds
Insemination) infertility
during ovulation (e.g., clomiphene)
Moderate/severe Guide on IVF
IVF (In Vitro Fertilization in lab,
male infertility or meds, hormone
Fertilization) embryo transfer
failed IUI support
ICSI Severe
Injection of a single
(Intracytoplasmic oligospermia,
sperm into oocyte
Sperm Injection) azoospermia
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