W12 L1 final Male infertility Flashcards
Incidence of male infertility
- 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
Diagnosis of male infertility : history
- 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
Diagnosis: Physical
- 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
Diagnosis: Laboratory tests of semen analysis
- Semen analysis
– 48-72 hours of sexual abstinence for best sperm quality
– WHO criteria- volume & sperm characteristics
– Repeat if abnormal in 30 days
Normal criteria of male ejaculate
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
Cause for abnormal semen morphology
- Varicocele
- Stress
- Infection (mumps)
Cause of abnormal sperm motility
- Immunologic factors
- Infections
- Defect in sperm structure
- Poor liquefaction
- Varicocele
- Exposure to environmental contaminants
cause for no ejaculate
- Ductal obstruction
- Retrograde ejaculation
- Ejaculation failure
- Hypogonadism
cause for low volume
- Obstruction of ducts
- Impaired seminal vesicles
- Partial retrograde ejaculation
- Infection
additional semen test
- 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)
lab test: seminal fluid
– Fructose: derived from the seminal vesicle (3mg/ml normal)
Post-ejaculatory urine analysis
-see if semen is present or not
lab test hormone assesment
Testosterone, Oestradiol, FSH
– Prolactin, LH
– Repeat if abnormal
Chromosomal and genetic analysis
– 30-100X risk of genetic abnormalities in infertile men (Goldstein et al., 2006)
– Karotyping
– Y chromosome microdeletions (15% of men)
– Cystic fibrosis mutation
Pre testicular cause of male infertility: hypothalamic disease
– Gonadotrophin deficiency (Kallmann syndrome)
– LH deficiency
– FSH deficiency
– Congenital hypogonadotrophic syndromes
Pre testicular cause of male infertility: hypothalamic disease: Pituitary disease
– Pituitary insufficiency (Tumours, operations, radiation)
– Hyperprolactinaemia
– Growth Hormone deficiency
– Exogenous hormones
* Oestrogen, androgen, glucocorticoid, thyroid hormones
* Medications, supplements
* Environmental chemical
What is Hypogonadotrophic Hypogonadism and the symptom
- 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
Cause of Hypogonadotrophic Hypogonadism
– Congenital- Kallman, Klinefelter and Prader-Willi syndrome
– Acquired- Pituitary tumour, steroid abuse, testosterone replacement therapy
– Mumps
– DES exposure in utero
Treatment for Hypogonadotrophic Hypogonadism
Daily hCG to ↑ spermatogenesis and androgens
* Clomiphene
* HRT with androgens
Testicular cause: cyptochidism
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)
Testicular cause, Varicocele
-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)
Other tetiscular cause
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)
Post-Testicular Causes : occlusion
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)
Post testicular cause: epididymitis
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
Post testicular cause: sperm issue
↓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
Post testicular cause: Immunological infertility
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
Post testicular cause: Retrograde ejaculation
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
Other testicular cause
§ 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
Preventable cause of male infertility
- 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
Treatments & New solutions: oral anti-oxidant therapy
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
Processing of sub-fertile samples
current methods sub-optimal, centrifugation ↑sperm DNA damage = ↓sperm quality
Ø New technologies: microfluidics (allows active sperm to swim away)
