Male Infertility Flashcards
What is gender defined as?
The socially constructed roles and behaviours that society typically associates with males and females
What are genotype and phenotype determined by?
Sex
Where does the key to sexual differentiation lie?
In the SRY region of the Y chromosome
Where do primordial germ cells migrate to?
Move to gonadal ridge in weeks 5-6 = leads to bipotential gonad
What is the SRY region?
Sex determining region of the Y chromosome = causes development of testes from week 7 onwards
How is the SRY region responsible for sexual differentiation?
Leydig cells secrete testosterone (converted to dihydrotestosterone)
Sertoli cells secrete mullerian inhibiting factor
What are the two primitive genital tracts?
Wolffian and Mullerian tracts
What causes the development of the male internal genital tract?
Testosterone and mullerian inhibiting factor
What does an absence of male testicular hormones cause?
Development of the female internal genital tract
How does the male internal genital tract develop?
Testosterone cause Wolffian ducts to form the epididymis, vas deferens and seminal vesicles
Mullerian ducts degenerate due to mullerian inhibiting factor
How does the female internal genital tract develop?
Wolffian ducts degenerate
Mullerian ducts form uterus, fallopian tubes, cervix and upper 1/3 of vagina
What does dihydrotestosterone cause?
Stimulates formation of male external genitalia = prostate, penis, scrotum
What occurs in the absence of dihydrotestosterone?
Female external genitalia develop = clitoris, labia, vagina
When do external genitalia begin to differentiate?
Starts from 9 weeks = recognisable on US from 16 weeks
What is androgen insensitivity syndrome also known as?
Testicular feminisation
What is androgen insensitivity syndrome?
Congenital insensitivity to testosterone = x-linked recessive, male karotype (46XY), testis develop but don’t descend
What are some features of androgen insensitivity syndrome?
No testosterone so induction of Wolffian duct doesn’t occur
Absent uterus and ovaries, but have female external genitalia with short vagina (upper 1/3 absent)
How does androgen insensitivity syndrome present?
Present at puberty with primary amenorrhoea and lack of pubic hair
What is the function of the seminiferous tubules?
Spermatogenesis
What do the Leydig cells produce?
Testosterone
What happens to the testes when in utero?
Testes develop in abdominal cavity of foetus
Descend into scrotal sac before birth (androgen dependent)
Why do the testes need to descend to outside of the body?
Temperature is lower outside body = allows for production of sperm
What are the muscles involved in lowering/raising the testes in response to temperature?
Dartos muscle and cremaster muscle
What are some features of the dartos muscle?
Smooth muscle = contraction lowers the testes
What are some features of the cremaster muscle?
Skeletal muscle = continuation of internal oblique, contraction raises testes
Do the testes hang at an equal level?
No = left testis typically hangs lower than right
What are the testes covered by?
Double layer of tunica vaginalis then tunica albuginea and protrudes into testis to create lobules
What is cryptorchidism?
Undescended testes = individual has reached adolescence/adulthood and testes haven’t descended
What can cryptorchidism affect?
Spermatogenesis = usually fertile if unilateral
When should an orchidopexy be performed on a patient with cryptorchidism?
Perform by 12 months due to strong association with infertility or by age 12 to minimise risk of testicular germ cell cancer
What should be done if an adult has undescended testes?
Consider orchidectomy
What are the parts of the penis?
Base, shaft, glans, foreskin
What are the tissues that make up the penis?
Dorsal nerve, blood vessels, connective tissue, erectile tissue
What are the erectile tissues found in the penis?
Corpus cavernosum and corpus spongiosum
What are the corpus cavernosum?
Two columns of erectile tissue running along sides of the penis = blood fills tissue to cause erection
What is the corpus spongiosum?
Column of sponge-like tissue running along the front of the penis and ending at glans = fills with blood during erection to keep urethra open
What are some of the functions of sertoli cells?
Form blood-testes barrier
Provide nutrients for developing cells
Phagocytosis
Secrete seminiferous tubule fluid, androgen binding globulin, inhibin and activin
What are the functions of the blood-testes barrier?
Protects sperm from antibody attack
Provides suitable fluid composition which allows later stages of sperm development
Why do sertoli cells carry out phagocytosis?
Removes surplus cytoplasm from packaging process and destroys defective cells
What is the purpose of seminiferous tubule fluid?
Carries cells to the epididymis
What is the function of androgen binding globulin?
Binds testosterone so concentration stays high in lumen = essential for sperm production
What is the function of inhibin and activin?
Regulate FSH secretion and control spermatogenesis = inhibin inhibits FSH production and activin promotes FSH secretion
What is GnRH?
Decapeptide = released from hypothalamus in bursts every 2-3hrs, begins at age 8-12
What is the function of GnRH?
Stimulates anterior pituitary to produce LH and FSH
Under negative feedback control from testosterone
What are gonadotrophins?
Glycoproteins secreted by the anterior pituitary = production in males is non-cyclical
What are the functions of the gonadotrophins?
LH = acts on Leydig cells, regulates testosterone secretion FSH = acts on sertoli cells to enhance spermatogenesis , regulated by negative feedback from inhibin
What is testosterone?
Steroid hormone derived from cholesterol = produced in Leydig cells
Where is testosterone secreted?
Secreted into blood and seminiferous tubules for sperm production
Exerts negative feedback on 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 = growth and maturation of male reproductive system
What are the effects of testosterone in adults?
Controls spermatogenesis, secondary sexual characteristics, libido, penile erection and aggressive behaviour
What liquifies spermatozoa?
Enzymes from prostate gland
What is capacitation?
Series of biochemical cellular events before fertilisation
What happens to the spermatozoa after ejaculation?
Liquification and capacitation Chemoattraction to oocyte 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 are the functions of the seminal vesicles?
Produce semen into ejaculatory duct
Supply fructose
Secrete prostaglandins to stimulate motility
Secrete fibrinogen
What are the functions of the prostate gland?
Produces alkaline fluid to neutralise vaginal acidity
Produces clotting enzymes to clot semen in female
What is the function of the bulbourethral gland?
Secrete mucous to act as lubricant
What is the route that sperm takes?
Testes - epididymis - vas deferens - ejaculatory duct - urethra
What occurs in an erection?
Blood fills corpus cavernosa = under parasympathetic control
What occurs in emission of sperm?
Contraction of accessory sex glands and vas deferens so semen is expelled to urethra
What occurs in ejaculation?
Contraction of smooth muscles of urethra and erectile muscles
What is the definition of male infertility?
Infertility resulting from failure of sperm to normally fertilise egg
What are some features of male infertility?
Usually associated with abnormalities in semen analysis
Common = 30% of infertility cases due male factor
What is the most common cause of male infertility?
Idiopathic = >50% of cases
What are the obstructive causes of male infertility?
Vasectomy, cystic fibrosis, infection
What are the non-obstructive causes of male infertility?
Cryptorchidism, mumps orchitis, chemo/radiotherapy, testicular tumour, Klinefelter’s syndrome, microdeletions of Y chromosome, Robertsonian translocation, specific semen abnormality, systemic disease, endocrine cause
What are some endocrine causes of non-obstructive male infertility?
Idiopathic, tumours, Kallman’s syndrome, anorexia, acromegaly, Cushing’s disease, hyperprolactinaemia, hyper/hypothyroidism, diabetes, congenital adrenal hyperplasia, androgen insensitivity, steroid abuse
What do you want to cover in an infertility history?
Duration, any treatments tried, libido, sexual function and activity
What are important features of a history in a male with infertility?
History of STIs, epididymo-orchitis or mumps orchitis
Surgery of reproductive tract = vasectomy
History of testis cancer or undescended testes
Exposure to pesticides or extreme heat
What drugs are linked with male infertility?
Steroids, sulphasalazine, alpha blockers, 5-alpha-reductase inhibitors, marijuana, excessive alcohol
What are you looking for on general examination?
Secondary sexual characteristics and presence of gynaecomastia
What should be covered in a genital examination?
Testicular volume, presence of vas deferens and epididymis, penis and urethral orifice, presence of any scrotal swelling
What is the normal testicular volume?
Pre-pubertal = 1-3ml Adults = 12-25ml
How is testicular volume measured?
Using orchidometer
What testicular volume would indicate infertility?
Unlikely to be fertile if below 5ml
What parameters are assessed in semen analysis?
Volume, density, motility, progressive motility, morphology
What are some confounding variables that may affect semen analysis?
Completeness of sample
Period of abstinence (e.g <3 days)
Condition during transport (e.g cold)
Time between production and assessment = deterioration if >1hour
Natural variation between samples
Current health and health in prior 2-3 months
What are some further assessments that can be done for infertile males?
Repeat semen analysis in 2-3 months if abnormal
Endocrine profile = LH, FSH, testosterone, prolactin
Chromosome analysis and cystic fibrosis screening
Testicular biopsy or scrotal scan
What are the features of obstructive azoospermia?
Normal testicular volume and secondary sexual characteristics
Vas deferens may be absent
Normal LH, FSH and testosterone
What are the features of non-obstructive azoospermia?
Low testicular volume
Reduced secondary sexual characteristics
Vas deferens present
High LH and FSH +/- low testosterone
What general advice would be given to an infertile male?
Sexual activity 2-3x per week
Avoid lubricants toxic to sperm
<5 units of alcohol per week and stop smoking
BMI <30 and avoid tight fitting underwear
Prolonged hot baths and saunas may help
How successful are reversals of vasectomies?
75% success rate if reversed within 3 years
Up to 55% success rate after 3-8 years
How is hyperprolactinaemia treated?
Cabergoline
What may be needed to treat anejaculation?
Psychosexual treatment
What occurs in intracytoplasmic sperm injection?
Sperm prepared from semen or surgical sperm aspirate
Each egg is stripped and sperm is immobilised
Single sperm is injected = 35% success rate
What are some surgical methods of sperm retrieval?
PESA, TESA, testicular biopsy
What is micro-TESA?
Specialised microsurgery = high power magnification (12-16x)
What occurs in micro-TESA?
Microscopic dissection and direct examination of seminiferous tubules to identify regions with spermatogenesis
What happens to sperm donors for insemination?
Sperm donor is altruistic and not anonymous
Matched for recipient characteristics
Screened for STIs and genetic conditions
What are some features of donor insemination?
Sperm quarantined by cryopreservation and rescreened
Prepared thawed semen sample inserted intrauterine at time of ovulation
How successful is donor insemination?
Pregnancy rate = 15% per treatment cycle
