Male Infertility Flashcards
What determines sex of an individual?
the X and Y chromosomes - the Y chromosome will have the sex determining region
What effect does the Y chromosome have?
Y chromosome will cause development of the testis from the bipotential gland. The foetal testis will secrete testosterone and Mullerian Inhibiting Factor which will support the development of the Wollfian tract and the degradation of the Mullerian reproductive tract
Which tracts are developed in males and females?
Males - wollfian
Females - mullerian
What happens in the absence of the Y chromosome?
There is a lack of stimulus from testicular hormones (testosterone and mullerian inhibiting factor) so will develop internal female genital tract
Dihydrotestosterone will cause what?
presence and absence
The development of the genital tubercle and genital swelling (presence)
Regression of the genital tubercle to form the clitoris (absence)
When will external genitalia start to differentiate and when can it be seen on scan?
from 9 weeks
seen on scan at 16 weeks
What is the difference in function of testosterone and dihydrotestosterone?
Testosterone - produced by the testis and will cause increased expression of the Wolffian duct system (internal genitalia)
Dihydrotestosterone (converted from testosterone) will affect the external genitalia development
What is androgen insensitivity syndrome?
This is an X-linked disorder where the patient is phenotypically male (46XY) but there is insensitivity to androgens (testosterone).
What does androgen insensitivity syndrome cause?
As there is genetic insensitivity to androgen there will be no maturation of the Wolffian tract and the testis will not descend. Will also be phenotypically female as no dihydrotestosterone sensitivity to develop external genitalia.
There will be inhibition of the Mullerian ducts though so no ovaries or uterus.
How will androgen insensitivity syndrome tend to present?
Around puberty - will have primary amenorrhoea and lack of pubic hair
Vagina will be short, no ovaries or uterus
What forms the spermatic cord?
Vas deferens, pampiniform plexus, lymphatics and testicular artery
In which muscle bulk of the penis is the urethra located?
Corpus Spongiosum
What are the 3 muscle bulks in the penis?
Corpus spongiosum and 2 corpus cavernosum
Why is it important that the testis descend?
When does this happen?
there is a more ideal temperature in the scrotal sac for spermatogenesis (if delayed descent then can have impaired spermatogenesis and fertility problems) Before birth (androgen dependent)
What can be done in the scrotal sac to keep the testis at the optimum temperature?
contraction of the dartos muscle to raise and lower testis - this is a reflex
What is cryptorchidism?
This is when a person reaches adulthood but their testes have failed to descend.
What are the complications of cryptorchidism?
This is becoming increasingly common, it can cause infertility (although if unilateral then usually fertile), can increase risk of testicular germ cell cancer
What should be done to decrease risk of testicular germ cell cancer?
Orchidopexy - surgical movement of a testicle into the sac if <14 years old
If adult then consider and orchidectomy to remove undescended testicle.
What are the functions of the testis and where do these occur?
Spermatogenesis = seminiferous tubules (extension of the epididymis) around sertoli cells
Production of testosterone = leydig cells
What is the acrosome?
This is a covering on the head of the sperm that contains enzymes for penetrating the ovum surface
Discuss the roles of Sertoli cells
These are cells that are dedicated to supporting spermatogenesis and have many functions:
- Form a blood-testes barrier to protect cells from antibody attack
- provide nutrients to growing cells
- secrete seminiferous fluid to aid transport to the epididymis
- secretes androgen binding globulin to bind testosterone and ensure high concentration of testosterone (required for development)
- secretes inhibin and actin hormones to regulate spermatogenesis and FSH secretion
- phagocytoses cytoplasm excess and defective cells
What do FSH and LH stimulate in the male?
FSH = sertoli cells and spermatogenesis LH = leydig cells and production of testosterone
What will decrease secretion of LH and FSH?
LH is decreased by testosterone concentrations feeding back and suppressing GnRH release from hypothalamus and directly suppresses LH release from pituitary
FSH is decreased by inhibin hormone and increased by activin (released by sertoli cells)
What is GnRH?
Gonadotrophin releasing hormone is a decapeptide that is released from the hypothalamus in bursts every 2-3 hours starting from the age of about 8-12 years and continuing through adulthood
What is the function of GnRH?
To cause release of LH and FSH from anterior pituitary gland
What will cause decrease in GnRH?
high testosterone levels
How would you describe LH and FSH release in males and females?
Males = non-cyclical Females = cyclical
Describe testosterone
steroid hormone derived from cholesterol and produced by leydig cells in the testes
Will provide negative feedback to the hypothalamus and pituitary glands
What are the functions of testosterone at…
Foetus/Birth?
Puberty?
Adulthood?
Birth - encourages Wolffian duct expression and development of external genitalia and descent of testes
Puberty - spermatogenisis, secondary sexual characteristics (pubic hair, facial hair), growth and maturation of male repro tract
Adulthood - spermatogenesis, libido, erection, secondary characteristics, ?aggressive behaviour
Where does fertilisation occur?
Ampulla of the fallopian tube
What is the function of the vas deferens and epididymis
Provide an exit route for sperm from the testis and will store/concentrate sperm/allow for maturation
What are the functions of the seminal vesicles?
Secrete seminal fluid (semen) into the ejaculatory duct, supply fructose, prostaglandins (for motility) and fibrinogen (clotting precursor)
What is the function of the prostate gland?
To secrete alkaline fluid to counteract the vaginal acidic environment and to secrete clotting enzymes to cause semen to clot inside vagina
What is the function of the bulbourethral glands?
Secrete mucus to act as a lubricant
What is the function of the testes, scrotum, accessory glands (prostate, seminal glands and bulbourethral) and the penis?
Testes - produce sperm
Scrotum - sac of skin suspending the testes
Accessory glands - produce semen to suspend and sustain sperm
Penis - contains urethra through which semen is ejaculated
What is the route of sperm from production to ejaculation?
Testes > epididymis > vas deferens > ejaculatory duct > urethra
Which muscle becomes engorged in erection?
corpus cavernosa
What is the definition of male infertility?
The inability of the male sperm to normally fertilise the female egg
What are the 3 broad categories for male infertility?
Idiopathic (most common)
Obstructive (infection, vasectomy or cystic fibrosis)
Non-obstructive (lots of causes)
What are some causes of non-obstructive male infertility?
Congenital: cryptorchidism Infection: mumps orchitis Iatrogenic: radio/chemotherapy Genetic: chromosomal (Kleinfelter's, microdeletions of Y chromosome and robertsonian translocations) Malignancy: testicular cancer Specific sperm disorder (globozoospermia) Endocrine (e.g. androgen insensitivity) Systemic disorder
Expand on ‘endocrine causes of male infertility’
think pituitary, hypothalamus, thyroid, and others
Anything that will decrease testosterone levels and alter the LH/FSH axis:
- Hypothalamus: (decrease GnRH > LH and FSH) could be idiopathic, tumours, Kallman’s syndrome, anorexia
- Pituitary gland: tumour, acromegaly, cushings disease, hyperprolactinaemia
- thyroid: hyper and hypo (decrease sexual function and increase prolactin)
- Diabetes
- CAH
- Androgen insensitivity
- Steroid use
What is the effect of prolactin in LH and FSH?
Will suppress the GnRH secretion from the hypothalamus so will have an overall reduced LH and FSH too
What is normal testicular volume? (pre-pubertal and adult)
Pre-pubertal = 1-3ml Adult = 12-25ml
What is hypospadia?
This is where the urethral opening is in a diffierent from normal location on the penis
How can you investigate if suspect infertility?
Testicular volume - orchidometer
Semen analysis - volume, density, motility, morphology
Endocrine profile
Hormone analysis
Chromosomal testing
Testicular biopsy/scrotal scan/abdominal USS
What are the clinical indications for obstructive infertility?
Normal testicular volume, presence of secondary sexual characteristics, vas deferens may be absent
Normal LH,FSH and testosterone
What are some clinical indications for non-obstructive infertility?
Reduced testicular volume
Vas deferens present
Reduced or absent secondary characteristics
Dependent on cause may have a high LH/FSH (testes not responding) but will have a low testosterone.
What can you give to a patient if hyperprolactinaemia is the cause of their infertility?
Carbegoline
Can Vasectomy be reversed?
Yes
if within 3 years the 75% success rate
if within 3-8 years then 55%
if after 9-19 years then aprox 30-40%
What is intracytoplasmic sperm injection? (ICSI)
This is where sperm is taken from semen and injected directly into the ovum in the lab - has about 35% chance of success
When would you do a surgical sperm aspirate?
To assess if a patient has azoospermia (lack of sperm in semen)
Are sperm donors anonymous?
No - have to have details available and done altruistically, there is legal obligation to disclose any FHx of illness or illness of the donor themselves
What is Klinefelter’s disease?
This is the chromosomal make up of 47(XXY) - have an extra X chromosome
about 1 in 660 people have this
How will Klinefelter’s disease present?
Many will not experience symptoms or will have symptoms that are difficult to spot some may include:
shyness, low self-confidence, weaker, quieter
In puberty they may grow taller than expected in the family, have broader hips, a smaller penis and testes, may have enlarged breast tissue
Will be infertile and have low sex drive
How may Klinefelter’s be treated?
With testosterone replacement therapy (TRT) - this can help development of the deep voice, pubic hair, reduction in body fat, increase in muscle mass
Long term psychological therapy may be considered as there is risk of low mood, low self-esteem etc
What is a Robertsonian Translocation?
When there is a balanced translocation between the chromosomes - the short arm of 2 chromosomes becomes lost and these two long arms will join togeth (form one long chromosome)
May have extra chromosomal material e.g. XX+half a Y etc
What is globozoospermia?
This is where there is abnormal sperm making a male infertilie.
Normal = oval shaped with acrosome
Abnormal = round without acrosome
What is hypogonadotrophic hypogonadism?
This is a disorder where there is reduced GnRH produced from the testes. This results in decreased levels in sex hormones of both sexes
What are the clinical signs of hypogonadotrophic hypogonadism?
Males: micropenis with undescended testes, no secondary characteristics
Females: amenorrhea, no secondary characteristics (breast tissue, pubic hair)
Both will be infertile if untreated
How can you differentiate between hypogonadotrophic hypogonadism and Kallmann’s syndrome?
Kallman’s syndrome is a type of hypogonadotrophic hypogonadism but is defined by a lack of sense of smell
