Male Reproduction

What are the key components of a focused male fertility history?

Infertility history, sexual history, developmental history, medications/toxins/lifestyle, family history, past medical/surgical history

What is primary infertility?

A pregnancy has never been achieved by a person

What is secondary infertility?

At least one prior pregnancy has been achieved

What should be asked in the sexual history?

Erectile/ejaculatory dysfunction and libido

What developmental history is important in male infertility?

• Puberty onset

• Cryptorchidism

What lifestyle/medication factors affect male fertility?

• Alcohol

• Smoking

• Drugs

• Heat exposure

• Diet

• Medications

• Toxins

What family history is relevant?

• Infertility

• Genetic disorders

Which past medical/surgical histories are relevant to male infertility?

• Mumps orchitis

• Chemotherapy

• Inguinal hernia

• Testicular torsion

• Orchiectomy

• Hydrocelectomy

• Spermatocelectomy

• Varicocelectomy

• Vasectomy

Is Erectile Disfunction (ED) age dependent?

Yes, it is highly age-dependent

What percentage of men <40 years old have ED?

5-10%

What percentage of men at age 40 have ED?

22%

What percentage of men by age 70 have ED?

49%

What are the major risk factors for ED?

• Diabetes mellitus (DM)

• Cardiovascular disease (CVD)

• Hypertension

• Decreased HDL levels

What increases the risk of ED?

• Medications (for DM, hypertension, CVD, depression)

• Prostate cancer radiation/surgery

• Lower spinal cord injury

• Neurological diseases (Parkinson’s, MS)

• Lifestyle factors (smoking, alcohol, sedentary behavior)

What triggers penile erection?

Parasympathetic reflex initiated by sensory stimuli

What happens to penile arterioles during erection?

They dilate due to smooth muscle relaxation via nitric oxide

How is venous outflow affected during erection?

Expansion compresses the veins, slowing blood leaving the penis

What initiates ejaculation?

Spinal reflex and sympathetic discharge to genital organs

What happens in reproductive ducts/accessory glands during ejaculation?

They contract peristaltically, discharging contents into the urethra

What is the role of the bulbocavernosus muscle?

Rapid contractions propel semen from the urethra

What is the physiological pathway of penile erection?

Acetylcholine → Nitric oxide → cGMP → smooth muscle relaxation → arteriolar dilation → increased penile blood flow

How is cGMP normally regulated?

Degraded by phosphodiesterase 5 (PDE5), which terminates its action

How does Viagra work?

Inhibits PDE5, preventing cGMP breakdown, prolonging arteriolar dilation and erection

How does alcohol affect GnRH secretion?

Alcohol metabolites decrease membrane excitability of GnRH-secreting cells, reducing GnRH and LH/FSH secretion

How does alcohol affect Leydig cells?

Causes mitochondrial dysfunction, reducing steroidogenesis

How does alcohol affect Sertoli cells hormonally?

Increases aromatase activity → hyperestrogenism → decreased testosterone production

What are direct testicular effects of alcohol on Sertoli cells?

Disrupts tight junctions of the blood–testis barrier → impaired germ cell development

What are direct effects of alcohol on germ cells?

Oxidative stress, DNA fragmentation, apoptosis of spermatogonia, reduced mitochondrial membrane potential → poor sperm motility

What epigenetic/genetic effects can alcohol cause?

DNA methylation changes in sperm, increased aneuploidy risk from meiotic errors

How does mumps orchitis cause infertility?

• Inflammatory oedema → ↑ cytokines (IL-1/6, TNF-α)

• ↑ Intratesticular pressure → impaired blood flow & ischemia

• Sertoli cells: blood–testis barrier disruption → autoimmune orchitis (anti-sperm antibodies)

• Leydig cells: ↓ testosterone → ↓ spermatogenesis

• Germ cells: ↑ apoptosis, loss of spermatogonia

What are long-term testicular consequences of mumps orchitis?

Fibrosis of seminiferous tubules/interstitium → testicular atrophy, oxidative stress in spermatogonia, mitochondrial dysfunction, DNA fragmentation, poor sperm motility, abnormal morphology.

Clinical correlation of mumps orchitis?

• 20–40% of postpubertal males with mumps develop orchitis

• ~30–50% bilateral → high risk of permanent infertility

What are key features of a focused male fertility physical exam?

• Virilization state, body habitus, gynecomastia

• Scrotal exam: varicocele, hydrocoele, spermatocele, vas deferens, testicle, epididymis

• Abdominal exam: inguinal scars, hernia repairs, radiation tattoos

• Special cases: Kallmann syndrome

What is a hydrocele?

• Collection of fluid in scrotum

• Painless soft swelling

• Transilluminates

• Treated by hydrocelectomy

What is a varicocele?

• Dilated veins of spermatic cord

• Feels like "bag of worms”

• More common on left

• Treated by varicocelectomy

What is a spermatocele?

• Cystic swelling from epididymal duct containing sperm

• Usually painless and smooth

• Treated by spermatocelectomy.

What is Kallmann syndrome?

Rare genetic disorder causing hypogonadotropic hypogonadism due to defective migration of GnRH neurons

What genetic mutations cause Kallmann syndrome?

ANOS1 (KAL1) → X-linked

What is the hormonal profile of Kallmann syndrome?

• Low GnRH

• Low LH/FSH

• Low sex steroids

What sensory deficit is associated with Kallmann syndrome?

Anosmia/hyposmia (absent or reduced smell)

Why is anosmia associated with Kallmann syndrome?

• GnRH neurons and olfactory structures develop together

• KS mutations disrupt migration → olfactory bulb aplasia/hypoplasia

What is aspermia?

No semen ejaculated

What is hematospermia?

Blood in semen

What is leucocytospermia?

White blood cells in semen

What is azoospermia?

No spermatozoa in semen

What is normospermia?

Normal semen parameters

What is oligospermia?

Low sperm concentration

What is asthenospermia?

Poor sperm motility/forward progression

What is teratospermia?

Low % of morphologically normal sperm

What is necrospermia?

No live sperm in semen

What is semen made of?

Seminal plasma + cells

What are the sources of seminal plasma?

• Prostate (30%)

• Epididymis (5%)

• Seminal vesicle (remainder)

What cells are found in semen?

• Spermatozoa

• Leukocytes

• Bacteria

• Epithelial cells

Reference ranges for semen (volume, pH, count, motility, viability, WBCs, morphology, RBCs)

• Volume: 2.0–6.0 ml (WHO cutoff 1.5 ml)

• pH: 7.2–8.0

• Count: >100 million/ml (WHO cutoff 15 million/ml)

• Motility: >40% (WHO cutoff 30%)

• Viability: >75% (WHO cutoff 56%)

• WBCs: <1 million/ml

• Morphology: >30% normal (WHO cutoff 4%)

• RBCs: none

What is the role of seminal vesicle fructose?

Energy source, marker of seminal vesicle function

What is the role of seminal vesicle prostaglandins?

• Sperm motility

• Egg activation

• Immunity

What is the role of alkaline fluid from seminal vesicle?

Neutralises acidic prostate secretion and vaginal tract

What is the role of ascorbic acid?

Antioxidant, protects against ROS

What is the role of semenogelin?

• Coagulates sperm after ejaculation

• Protects sperm

• Inhibits motility

• Cleaved by PSA

What does neutral α-glucosidase indicate?

• Marker of epididymal function

• Low levels in oligospermia, obstruction, or infection

What is CD52?

• Seminal glycoprotein incorporated into sperm membrane

• Key maturation antigen

What is the role of free L-carnitine?

Supports functional maturation and motility

What is the role of glycerophosphocholine?

Positively associated with sperm number; inhibits capacitation until fertilisation

What is the role of prostate calcium?

Essential for motility and fertilisation capability

What is the role of prostate zinc?

• Inhibits citrate oxidation enzyme

• Low zinc is linked to prostate cancer

What is the role of prostate citrate?

• Calcium buffer regulating ionised calcium in seminal plasma

• Reduced in prostate cancer

What is prostatic specific acid phosphatase (PSAP)?

• Marker for prostatic function

• Increased in prostate cancer

What is PSA (prostatic specific antigen)?

• Protease cleaving semenogelin

• Biomarker for prostate cancer (>4 ng/ml)

Why is pH important in semen?

• Sperm die at pH <6.9

• Normal pH range is 7.2–8.4

What can alter semen pH?

Inflammatory disorders of accessory glands

What are the categories of sperm motility?

• Rapid progressive: >25 µm/s

• Slow progressive: 5–25 µm/s

• Non-progressive: <5 µm/s

• Immotile: no movement

What DNA/sperm function tests exist?

• DNA fragmentation assays (TUNEL)

• ROS testing

• Chromatin integrity

• High-magnification morphology

What hormonal/genetic tests are done?

• Endocrine panel (FSH, LH, testosterone, prolactin)

• Sertoli markers (Inhibin B, AMH)

• Genetic testing (karyotype, Y-chromosome microdeletions, CFTR)

What functional tests are used?

• Acrosome reaction

• Zona binding

• Hypo-osmotic swelling test (HOS)

• CASA (computer-assisted motility analysis)

What imaging/tissue evaluations are used?

• Scrotal and transrectal ultrasound

• Testicular biopsy

What immunological testing can be done?

Anti-sperm antibody assays