Male Infertility Flashcards
which chromosome has the sex determining region?
y chromosome
*causes development of testis from bipotential gland
what do the foetal testes secrete?
testosterone and mullerian inhibiting factors
*these cause development of male internal genital tract
what are the two primitive genital tracts?
wolffian and mullerian ducts
how is the male reproductive tract formed from the two primitive genital tracts?
wolffian ducts become repro tract
mullerian ducts degenerate by mullerian inhibiting factor
how is the female reproductive tract formed from the two primitive genital tracts?
wolffian ducts degenerate through lack of testosterone
mullerian ducts become repro tract
what hormone causes the differentiation of external genitalia at week 9?
dihydrotestosterone
- present = male
- absent = female
although external genitalia start to differentiate from 9 weeks, when are you able to recognise it on scan?
16 weeks
what is androgen insensitivity syndrome (with karyotype 46XY)?
x linked recessive disorder where testes develop but do not descend
androgen induction of wolffian duct does not occur, mullerian inhibition does occur
born phenotypically external genitalia female with absence of uterus and ovaries and short vagina
commonly present at puberty with primary amenorrhoea and lack of pubic hair
what conditions have the possibility to cause reduced penile size?
obesity
smoking
environmental
endocrine (testicular failure eg kleinfelters syndrome, crypto-orchidism)
describe the descent of testis and why it is important that this occurs?
in utero, testes develop in abdominal cavity and drop into scrotal sac before birth (androgen-dependent)
important due to the lower temperature outside body to facilitate spermatogenesis
*nervous reflexes trigger dartos muscle contraction in scrotal sac to lower/raise testes according to external temperature
what is cryptorchidism?
individual has reached adulthood and tests have not descended
reduces sperm count, but if unilateral then usually fertile
- ochidopexy should be performed below age 14 to minimise risk of testicular germ cell cancer
- if undescended as adult, consider orchidectomy (risk cancer increase 6x)
what are the functions of the testis?
spermatogenesis (seminiferous tubules)
production of testosterone (leydig cells)
where in the spermatozoon contains enzymes for penetrating the ovum?
acrosome
what are the roles of sertoli cells within the testes?
form a blood-testes barrier (protects sperm from antibody attack and provides suitable fluid composition which allows later stages of development of sperm)
provide nutrients for developing cells
phagocytosis (remove surplus cytoplasm from packaging process and destroy defective cells)
secrete seminiferous tubule fluid (used to carry cells to epididymis)
secrete androgen binding globulin (binds testosterone, essential for sperm production)
secrete inhibin and activin hormones (regulates FSH secretion and control spermtogenesis)
describe the different hormonal controls of spermatogenesis
FSH stimulates spermatogenesis together with testosterone
*inhibin decreases secretion of FSH
sertoli cells in seminiferous tubule secretes androgen binding globulin (ABG) and inhibin
LH stimulates testosterone secretion
*testosterone decreases release of GnRH and LH
dihydrotestosterone causes enlargement of male sex organs, secondary sexual characteristics and anabolism
what is the role of gonadotrophin releasing hormone?
decapeptide which is released from hypothalamus in bursts every 2-3 hours (begins age 8-12)
stimulates anterior pituitary to produce LH and FSH
under negative feedback control from testosterone
what are the roles of LH and FSH?
LH = acts on leydig cells to regulate testosterone secretion
FSH = acts on sertoli cells to enhance spermatogenesis, regulates by negative feedback from inhibin
is production of LH and FSH in males cyclical or non-cyclical?
non-cyclical (unlike in females)
what is the role of testosterone?
steroid hormone derived from cholesterol produced in leydig cells which is secreted into blood and seminiferous tubules for sperm production
what are the effects of testosterone in the following circumstances:
a) before birth?
b) puberty?
c) adult?
a) masculinises reproductive tract and promotes descent of testes
b) promotes puberty and male characteristics (growth and maturation of male repro system)
c) controls spermatogenesis, secondary sexual characteristics, libido, penile erection and aggressive behaviour
what is the role of inhibin and activin?
peptides secreted by sertoli cells which act as feedback on FSH (inhibin inhibits and activin stimulates)
what liquifies spermatozoa?
enzymes from prostate gland
what is capacitation of spermatozoa?
a series of biochemical and electrical events before fertilisation (hyperactive mobility, ability to bind ZP and AR)
what is the 6 steps of capacitation of spermatozoa?
1) chemoattraction to oocyte and bind to zona pellucida of oocyte
2) docking (specific recognition)
3) acrosomal exocytosis
4) hyperactivated motility
5) penetration and fusion with oocyte membrane
6) zonal reaction
where does fertilisation occur?
ampullary region of fallopian tube
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 seminal vesicles?
produce semen into ejaculatory duct supply fructose secrete prostaglanding (stimulates motility) secrete fibrinogen (clot precursor)
what are the functions 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
what is the route sperm normally takes?
testes -> epididymis -> vas deferens -> ejaculatory duct -> urethra
what happens during an erection?
blood fills corpora cavernosa (under PS control)
what happens during emission?
contraction accessory sex glands and vas deferens so semen expelled into urethra
what happens during ejaculation?
contraction of smooth muscles of urethra and erectile muscles (shoot = sympathetic control)
what conditions could cause retrograde ejaculation?
neuropathy
prostate surgery
anticholinergic drugs
what is the definition of male infertility?
infertility resulting from failure of the sperm to normally fertilise the egg
*usually associated with abnormalities in semen analysis
male factor infertility is the most common cause of infertility - true or false?
true - approx 1/3 of all infertility
what is the most common cause of male infertility?
idiopathic
what are obstructive causes of male infertility?
cystic fibrosis
vasectomy
infection
what are the non-obstructive causes of male infertility?
congenital - cryoptorchadism
infection - mumps orchitis
iatrogenic - chemotherapy / radiotherapy
pathological - testicular tumour
genetic - klinefelters syndrome, microdeletions of Y chromosome, robertsonian translocation
specific semen abnormality - globozoospermia
systemic disorder
endocrine
what are the different endocrine causes of male infertility?
pituitary tumours - acromegaly, cushings, hyperprolactinaemia
hypothalamic causes - idiopathic, tumours, kallmans syndrome, anorexia
thyroid disorders - hyper or hypothyroidism (decrease sexual function and increase prolactin)
diabetes (decrease sexual function and testosterone)
CAH (increased test)
androgen insensitivity (normal or increased LH and test)
steroid abuse (decrease LH/FSH and test)
what should you look for in genital examination of male infertility?
testicular volume
presence of vas deferens and epididymis
penis (urethra orifice)
presence of any variocele / other scrotal swelling
what are the normal testicular volumes?
pre-pubertal = 1-3mls adults = 12-25mls
- if below 5ml unlikely to be fertile
- measured using orchidometer
what is assessed during semen analysis and what are the lower reference limits for these?
volume (mL) = 1.5 density (number) = 39x10^6 motility (what proportion moving) = 40 progression (how well they move) = 32 morphology = 4
what factors can affect the result of semen analysis?
completeness of sample
period of abstinence eg less than 3 days
condition during transport eg cold
time between production and assessment eg deteriorates if after 1 hour
natural variations between samples
health of man 3 months before production
what other further assessments, after semen analysis, can be undertook for male infertility?
repeat analysis 6 weeks later
endocrine profile
chromosome analysis
cystic fibrosis screening
depending on results - testicular biopsy, scrotal scan
what are the diagnostic features of obstructive infertility?
clinical = normal volume, normal secondary sexual characteristics, vas deferens may be absent
endocrine = normal LH, FSH and testosterone
what are the diagnostic features of non obstructive infertility?
clinical = low testicular volume, reduced secondary sexual characteristics, vas deferens present
endocrine = high LH, FSH +/- low testosterone
what assisted conception methods can be used for male infertility?
ICSI donor insemination (DI)
what general advice can be given to men in regards to treatment infertility?
frequent sexual intercourse and avoid lubricants that are toxic to sperm alcohol <4 units per day stop smoking BMI <30 avoid tight underwear certain occupations (overheating and chemicals) complementary therapies anti oxidants (vitamin C or zinc)
what is the success rate of a vasectomy reversal?
75% if within 3 years
55% after 3 to 8 years
approx 30-40% after 9 to 19 years
what medication can be used for hyperprolactinaemia?
carbegoline
when could psychosexual treatment be useful?
in anejaculation conditions
what is the indication for surgical sperm aspiration?
azoospermia
how is surgical sperm aspiration performed and what is the success rate?
sperm aspirated surgically (can be done as diagnostic procedure or at time of oocyte recovery)
sperm then injected into oocyte (ICSI)
95% success in obstructed azoospermia and 50% non-obstructive azoospermia
what is the indications for donor sperm insemination?
azoospermia or very low count
failed ICSI treatment
genetic conditions
infective conditions
how is donor sperm insemination carried out and what is success rate?
sperm donors matched for recipient characteristics and screened for genetic conditions and STIs
sperm quarantined by cryopreservation and rescreened
prepared thawed semen sample inserted intrauterine at time of ovulation
*15% per treatment cycle
