Male infertility Flashcards
What determines gender?
Socially constructed roles and behaviours that a society typically associated with males and females
Genotype and phenotype are determined by
Sex
What is the phenotype of androgen insensitivity syndrome
- female external genitalia
- lack of pubic hair
What is the common presentation of androgen insensitivity syndrome
Present with amenorrhoea
Androgen sensitivity is an _-______ ______ disorder
Androgen sensitivity is an x-linked recessive disorder
What is the karyotype of androgen insensitivity disorder?
46 XY
Describe the pathogenesis of androgen insensitivity disorder?
Testis develop but don’t descend, no androgen and so induction of wolffian duct does not occur. Absent uterus and ovaries with short vagina and female external genitalia
What is the function of the testis?
- Spermatogenesis (seminiferous tubules)
- Production of testosterone (leydig cells)
Testicular artery is a branch of what artery?
The aorta
The left testicular vein joins the _____ _____ ____ and right testicular vein drains into _________ ____ ____
The left testicular vein joins the left renal vein and right testicular vein drains into inferior vena cava
Where is the lymphatic drainage of the testis?
Into the abdomen
Why is it important that the testes descend?
Lower temperature outside the body for spermatogenesis
______/______ muscle contraction in scrotal sac _____/______ testes according to external ______
dartos/cremaster muscle contraction in scrotal sac lowers/raises testes according to external temperature
The dartos muscle is ______ ______
The dartos muscle is smooth muscle
The cremaster muscle is _____ _______ and a continuation of the _______ _______
The cremaster muscle is skeletal muscle and a continuation of the internal oblique
What is contained in the spermatic cord?
Arteries, veins, nerves, lymphatics, vas deferens
What covers the testis
Tunica vaginalis- peritoneal remnant and then tunica albuingea (firm fibrous covering)
What is cryptorchidism?
Individual has reached adolescence/adulthood and testes have not descended
When do testes normally descend?
Between 6-9 months of age
When should orchidopexy be performed?
By 12 months because of strong association with infertility (azoospermia) and by 12 years to minimise risk of testicular germ cell cancer
What should be done if undescended testis are discovered as an adult?
Consider orchidectomy as risk of cancer is 6x baseline
What is corpus cavernosum?
Two columns of tissue running along the sides of the penis- blood fills to cause an erection
What is corpus spongiosum?
A column of sponge like tissue running along the front of the penis ending at the glans penis; it fills with blood during an erection keeping the urethra open
Spermatozoa contain ______ genetic material
Spermatozoa contain haploid genetic material
What are the roles of Sertoli cells?
- form blood-testes barrier
- provide nutrients
- phagocytosis
- secrete seminiferous tubule fluid
- secrete androgen binding globulin
- secrete inhibin and activin hormones
What is the function of the blood-testes barrier?
- Protects the sperm from antibody attack
- Provides a suitable fluid composition which allows later stages of development of sperm- v different from blood.
What is the role of phagocytosis by Sertoli cells?
Remove surplus cytoplasm from packaging process & destroys defective cells
What is the role of seminiferous tubule fluid?
Carries cells to epididymis
What is the role of androgen binding globulin?
Binds testosterone so concentration remains high in lumen
Essential for sperm production
What is the role of inhibin and activin hormones?
regulates FSH secretion and controls spermatogenesis
GnRH is a ____peptide released from the ________ in ______ every ___ hours (beginning at age ____ years)
GnRH is a decapeptide released from the hypothalamus in bursts every 2-3 hours (beginning at age 8-12 years)
GnRH stimulates the anterior pituitary to produce __ and ____ and is under _______ ______ ____ from testosterone
GnRH stimulates the anterior pituitary to produce LH and FSH and is under negative feedback control from testosterone
Gonadotrophins are _______ secreted by the anterior pituitary
Gonadotrophins are glycoproteins secreted by the anterior pituitary
What is the role of LH in men?
Acts on leydig cells- regulates testosterone secretion
What is the role of FSH in men?
Acts on Sertoli cells to enhance spermatogenesis
Regulates by negative feedback from inhibin
Production of gonadotrophins is ______ in females and __________ in males.
Production of gonadotrophins is cyclical in females and non-cyclical in males.
Testosterone is a _____ hormone derived from cholesterol
Testosterone is a steroid hormone derived from cholesterol
Testosterone has negative feedback on which glands?
Hypothalamus and pituitary
What are the effects of testosterone before birth?
Masculinises reproductive tract and promotes descent of testes
What are the effects of testosterone during puberty?
Promotes puberty and male characteristics and maturation of male reproductive system
What are the effects of testosterone in adulthood ?
Controls spermatogenesis, secondary sexual characteristics (male body shape, deep voice, thickens skin), libido, penile erection, aggressive behaviour
Inhibin and activin are what type of hormones
Peptides
What secretes inhibin and activin?
Sertoli cells
What do inhibin and activin do?
Feedback on FSH
What liquefies the ejaculate?
Enzymes from the prostate gland
What is capacitation?
Series of biochemical cellular events before fertilisation (hyper activated motility, ability to bind to ZP and AR)
How does the spermatozoa find the oocyte?
By chemoattraction
Describe the process of fertilisation?
- Penetration of cumulus complex
- acrosome reaction/zona binding
- Fusion with oocyte membrane and fertilisation
What are the functions of the epididymis and vas deferens?
Exit route from testes to urethra, concentrate and store sperm, site for sperm maturation
What is the function of the seminal vesicles?
Produce semen into ejaculatory duct, supply fructose, secrete prostaglandins (stimulates motility), secrete fibrinogen (clot precursor)
What is the function of the prostate gland?
Produces alkaline fluid (neutralises vaginal acidity), produces clotting enzymes to clot semen within female
What is the function of the bulbourethral glands
Secrete mucus to act as lubricant
Describe the route of sperm
testes –> epididymis –> vas deferens –> ejaculatory duct –>urethra
What controls erection?
Parasympathetic control
What is emission
Contraction of accessory sex glands and vas deferens so semen is expelled to urethra
What is ejaculation
Contraction of smooth muscles of urethra and erectile muscles
What are the three aetiologies of MF infertility?
Idiopathic
Obstructive
Non-obstructive
What causes obstructive MF infertility
Vasectomy
Cystic fibrosis- absence of vas
Infection
What causes congenital non-obstructive MF infertility
cryptoorchidism
What causes infectious non-obstructive MF infertility
Mumps orchitis
What causes iatrogenic non-obstructive MF infertility
Chemotherapy/radiotherapy
What causes pathological non-obstructive MF infertility
testicular tumour
What causes genetic non-obstructive MF infertility
chromosomal (kleinfelter’s syndrome, micro deletions of Y chromosome, robertsonian translocation)
What specific semen abnormality causes non-obstructive MF infertility
Globozoospermia
What are the hypothalamic endocrine causes of male factor infertility?
Idiopathic, tumours, Kallman’s syndrome, anorexia
What are the pituitary endocrine causes of male factor infertility?
Acromegaly, cushings disease, hyperprolactinaemia
What are the thyroid endocrine causes of male factor infertility?
Hyper or hypothyroidism (decreases sexual function and increases prolactin)
How does diabetes cause MF infertility?
Decrease sexual function and testosterone
How does CAH cause MF infertility?
Increased testosterone
How does steroid abuse cause MF infertility?
Decrease testosterone, LH and FSH
How should an assessment of infertility be carried out?
See as couple
History (Andrology)
Examination (general and genital)
Investigations (semen analysis, others depending on results)
Describe the examination of MF infertility
General
- 2ry sexual characteristics
- gynaecomastia?
Genital -testicular volume -presence of vas deferens and epididymis -penis (urethral orifice) presence of any varicocoele/other scrotal swelling
What is normal testicular volume?
Pre-pubertal 1-3mls
Adults 12-25 mls
If <5mls unlikely to be fertile
What is looked at when analysing semen?
- Volume
- Density (number of sperm)
- Motility
- Progressive motility
- Morphology
What needs to be taken into account for a valid semen analysis
- Completeness of sample
- Period of abstinence
- Condition during transport
- Time between production and assessment (deteriorates after 1 hr
- Natural variation
- Current health and health of man in 2-3 months before production
What further tests should be done after initial semen analysis and examination
Repeat semen analysis if abnormal in 2-3months
Endocrine profile (LH, FSH, PRL, TSH, testosterone)
Chromosome analysis (including karyotpie, Y chromosome micro deletions) CF screening
Testicular biopsy or scrotal scan
What are the clinical features of obstructive azoospermia?
Normal testicular volume
Normal 2ry characteristics
Absent vas deferens
What are the endocrine features of obstructive azoospermia?
Normal LH, FSH and testosterone
What are the clinical features of non-obstructive azoospermia?
Low testicular volume
Reduced 2ry characteristics
Vas deferens present
What are the endocrine features of obstructive azoospermia?
High LH, FSH +/- low testosterone
What is given for high PRL in MF infertility
Cabergoline
What general advice should men be given if infertile?
-Frequency sexual intercourse: 2-3 X per week
-Avoid lubricants that are toxic to sperm
-Alcohol: < 5 units per week
-Smoking: associated decrease semen quality and decreased health
-BMI: < 30 likely to improve fertility and health
-Avoid tight fitting underwear and prolonged hot baths/sauna may improve
=Certain occupations: overheating/exposure to chemicals
-Complementary therapies and non-prescription drugs
-Possible benefits of anti-oxidants (vitamin C or zinc)
What is the success rate of vasectomy reversal?
75% if vasectomy within 3 years
55% after 3-8 years
30-40% after 9-19 years
What is the treatment for anejactulation?
Psychosexual treatment
How can sperm be retrieved?
- PESA (Percutaneous Epididymal Sperm Aspiration)
- TESA (Testicular Sperm Aspiration)
- testicular biopsy
What is micro TESE?
Specialise urological surgery under high power magnification to dissect and direct examination of seminiferous tubules to identify regions with spermatogenesis
What is the pregnancy rate of donor insemination?
15% per treatment cycle