W12 L1 final Male infertility

Question 1

Incidence of male infertility

Answer 1

• 40-50% of infertile couples have some degree of male factor problems contributing to their reproductive issues
  *But.. Data mainly collected from western society
• Increasing

Question 2

Diagnosis of male infertility : history

Answer 2

• Family- – Your age!!, relatives (male or female)
• Medical – Childhood disease (mumps, cryptorchidism), acute infections, fevers, cancer, diabetes, neurological disorders, current medications
• Surgical (around the groin) – Bladder, prostate, groin, pelvis, hernia, genitalia, cancer
• Social – Occupation, toxicant & radiation exposure, drug use (tobacco, alcohol, caffeine, cocaine, marijuana, androgenic steroids, ibuprofen), hot baths or sauna usage, tight pants!
• Reproductive – Duration of infertility, earlier pregnancies
• Sexual – STIs, Timing and frequency, lubricants

Question 3

Diagnosis: Physical

Answer 3

• Phenotypic measures (e.g. BMI, blood pressure)
• Sexual development
• Hair distribution, gynaecomastia
• Penis, urethra
• Testis- size, consistency, masses
• Epididymis- fullness, discomfort
• Spermatic cord- vas deferens, varicoceles
• Rectal- midline cysts (if suspect obstruction)
• Peripheral syndromes, diseases and other abnormalities

Question 4

Diagnosis: Laboratory tests of semen analysis

Answer 4

• Semen analysis
  – 48-72 hours of sexual abstinence for best sperm quality
  – WHO criteria- volume & sperm characteristics
  – Repeat if abnormal in 30 days

Question 5

Normal criteria of male ejaculate

Answer 5

Volume 1.5-5.5 mL
Sperm concentration >15 mill/mL
Motility >50% forward progression
Morphology >15% or normal forms
Viscosity <2 on 1-3 scale
pH 7.2 to 7.8
Immune cells <1 million/ml
Agglutination None

Question 6

Cause for abnormal semen morphology

Answer 6

• Varicocele
• Stress
• Infection (mumps)

Question 7

Cause of abnormal sperm motility

Answer 7

• Immunologic factors
• Infections
• Defect in sperm structure
• Poor liquefaction
• Varicocele
• Exposure to environmental contaminants

Question 8

cause for no ejaculate

Answer 8

• Ductal obstruction
• Retrograde ejaculation
• Ejaculation failure
• Hypogonadism

Question 9

cause for low volume

Answer 9

• Obstruction of ducts
• Impaired seminal vesicles
• Partial retrograde ejaculation
• Infection

Question 10

additional semen test

Answer 10

• Semen immune (leukocyte) analysis
• Anti-sperm antibody test (both males and females can produce)
• Hypo-osmotic swelling test
• Sperm penetration assay
• Sperm chromatin structure
• Sperm DNA damage (TUNEL, COMET, HALO, sperm chromatin dispersal)

Question 11

lab test: seminal fluid

Answer 11

– Fructose: derived from the seminal vesicle (3mg/ml normal)

Question 12

Post-ejaculatory urine analysis

Answer 12

-see if semen is present or not

Question 13

lab test hormone assesment

Answer 13

Testosterone, Oestradiol, FSH
– Prolactin, LH
– Repeat if abnormal

Question 14

Chromosomal and genetic analysis

Answer 14

– 30-100X risk of genetic abnormalities in infertile men (Goldstein et al., 2006)
– Karotyping
– Y chromosome microdeletions (15% of men)
– Cystic fibrosis mutation

Question 15

Pre testicular cause of male infertility: hypothalamic disease

Answer 15

– Gonadotrophin deficiency (Kallmann syndrome)
– LH deficiency
– FSH deficiency
– Congenital hypogonadotrophic syndromes

Question 16

Pre testicular cause of male infertility: hypothalamic disease: Pituitary disease

Answer 16

– Pituitary insufficiency (Tumours, operations, radiation)
– Hyperprolactinaemia
– Growth Hormone deficiency
– Exogenous hormones
* Oestrogen, androgen, glucocorticoid, thyroid hormones
* Medications, supplements
* Environmental chemical

Question 17

What is Hypogonadotrophic Hypogonadism and the symptom

Answer 17

• Diminished functional activity and response of the HPG axis due to incomplete development at puberty.
  Symptoms
• Absent virilisation, hypotrophic testes, azoospermia
• Low FSH, LH and Testosterone
• Low libido

Question 18

Cause of Hypogonadotrophic Hypogonadism

Answer 18

– Congenital- Kallman, Klinefelter and Prader-Willi syndrome
– Acquired- Pituitary tumour, steroid abuse, testosterone replacement therapy
– Mumps
– DES exposure in utero

Question 19

Treatment for Hypogonadotrophic Hypogonadism

Answer 19

Daily hCG to ↑ spermatogenesis and androgens
* Clomiphene
* HRT with androgens

Question 20

Testicular cause: cyptochidism

Answer 20

absence of one/both testes to descend into scrotum (most common birth defect of male genitalia)
Ø Symptoms: visually apparent, ↓reproductive function, impaired fertility, permanent damage (not repaired)
Ø Causes: unknown, genetic evidence (dogs), endocrine chemicals, maternal diet/alcohol/obesity
Ø Treatment: mostly self-resolving, surgery to aid descent (can lead to impaired fertility in later life)

Question 21

Testicular cause, Varicocele

Answer 21

-enlargement of pampiniform venous plexus within scrotum (possible due to defective valve in testicle)
Ø Symptoms: usually left testicle (due to blood flow from heart), visual/palpable reduced size of testicle, aching
pain in scrotum, altered blood flow, low testosterone, ↑testis temperature, impaired sperm production
Ø Causes: unknown, possible issue – left testicular vein connects to renal vein
Ø Treatment: microsurgery (ligation), embolism (↓pressure from abdomen on testis)

Question 22

Other tetiscular cause

Answer 22

Chromosomal
– Klinefelter syndrome [XXY]
– Y chromosome microdeletions
* Sertoli-cell-only syndrome (germ cell aplasia)
* Gonadotoxins – Radiation and drugs
* Systemic disease
– Renal or liver failure
– Sickle cell anaemia
– Defective androgen activity
* Malnourishment
* Cancer (prostate, testes)
* Testis injury – Orchitis, torsion, trauma
-Idiopathic (40% of all infertility)

Question 23

Post-Testicular Causes : occlusion

Answer 23

blockage at any point in reprodcutive tract (epididymis, vas deferens, accessory glands)
Ø Symptoms: impaired fertility, semen composition/volume, diagnosis by Ultrasound/vasography, azoospermia
Ø Causes: vasectomies, congenital conditions, cysts/stones/stenosis, abdo surgery scar tissue, STDs, hernias
Ø Treatment: microsurgery to rejoin vas deferens after vasectomy (vasovasostomy), surgery to remove blockages/insert catheters (stenosis)

Question 24

Post testicular cause: epididymitis

Answer 24

discomfort/pain due to malfunction + inflammation of epididymis
Ø Symptoms: swollen/painful testicles, can be warm + red (whole body fever), dysuria/urethral discharge
Ø Causes: bacterial infection in tract, STIs (chlamydia, gonorrhoea)
Ø Treatment: antibiotics + anti-inflammatories

Question 25

Post testicular cause: sperm issue

Answer 25

↓conception – oligospermia (conc. ↓normal), astenozoospermia (poor motility), teratozoopermia (misshapen)
Ø Symptoms: abnormal semen analysis (>60% infertile men)
Ø Causes: genetic abnormalities, hormonal imbalance, physical damage to repro tract, dietary, metabolic syndromes/weight gain, STIs + systemic illness, medications, environment
Ø Treatment: depends on cause, often lifestyle changes (diet, exercise, ↓exposure to toxicants), treat primary cause (obesity, diabetes), ART

Question 26

Post testicular cause: Immunological infertility

Answer 26

reaction of immune system to sperm that renders them useless
Ø Symptoms: no obvious, infertility, abnormal semen analysis (antibody + genetic analysis)
Ø Causes: unproven (infection, cancer treatment physical damage, female tract antibodies)
Ø Treatment: depends on cause, steroids to ‘dampen’ immune system, antibiotics if infection, ART

Question 27

Post testicular cause: Retrograde ejaculation

Answer 27

partial/no ejaculation due to semen being ejaculated into bladder instead of urethra
Ø Symptoms: partial/no ejaculate, sperm in urine
Ø Causes: malfunction of urethra/bladder valves (failure to constrict during ejaculation), prostate + abdominal surgery, duct obstruction, diabetes, cancer, MS, neurologic disorders (nerve injury), cardiac/high BP medications (alphablockers), idiopathic
Ø Treatment: drugs (antihistamine to tighter bladder opening), oral sodium bicarbonate (neutralise urine acidity, collection of sperm in urine), collection of sperm using a catheter in bladder, ART

Question 28

Other testicular cause

Answer 28

§ Reproductive tract obstruction: congenital blockages (absence of vas deferens, young syndrome, prostate related problems, idiopathic epididymal obstruction, ejaculatory duct osbtruction), acquired blockages (vasectomy, groin surgery, infection), functional blockages (sympathetic nerve injury, pharmacologic)
§ Disorders of sperm characteristics: maturation defects, immunologic infertility, infection, temperature
§ Disorders of coitus: impotence, hypospadias, retrograde/premature/failed ejaculation, timing/frequency

Question 29

Preventable cause of male infertility

Answer 29

• Changes in lifestyle last few decades
• Alcohol, drugs, caffeine, smoking
• Environmental pollutants
  – Occupational and Social exposure
  – Endocrine Disruptors, heavy metals
• STIs and infections
• Obesity vs Exercise

Question 30

Treatments & New solutions: oral anti-oxidant therapy

Answer 30

e.g. Vitamin A,C,E, Zinc, Selenium
* ↑ sperm & hormone parameters → ↑ pregnancy rates (Showell et al. 2011 Cochrane
Review)
* Oxidative stress (ROS) → DNA damage impairs sperm function
* Requires
– Understanding optimal infertile cohorts
– Dosage and length of administration
– Combined effects of anti-oxidants

Question 31

Processing of sub-fertile samples

Answer 31

current methods sub-optimal, centrifugation ↑sperm DNA damage = ↓sperm quality
Ø New technologies: microfluidics (allows active sperm to swim away)