W12 L1 final 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

• 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

• 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

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

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

• Varicocele • Stress • Infection (mumps)

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

• Ductal obstruction • Retrograde ejaculation • Ejaculation failure • Hypogonadism

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

• 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)

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

-see if semen is present or not

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

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

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

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

• 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

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

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

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)

-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)

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)

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)

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