Male Infertility Flashcards
what chromosomes are in a sperm
22 + x or Y
what chromosomes are in an oocyte
22 + x
how many chromosomes should you have
23 pairs = 46 in total
which chromosome has the sex determining region and what does it cause
Y
development of testis from the bipotential gonad
what do fetal testes secrete
testosterone and AMH (cause the development of the male internal genital tract)
what are the two primitive genital tracts
wolffian (male)
mullerian (female)
what happens the primitive genital ducts in males
wolffian ducts form epididymis, vas deferens, seminal vesicles
mullerian degenerates
what happens the primitive genital ducts in females
wolffian degenerates
mullerian forms uterus, fallopian tubes, cervix and upper 1/3rd of vagina
what happens to primordial germ cells during week 5-6
migrate to gonadal ridge
when do testis start to develop
week 7 onwards
what do leydig cells secrete
testosterone (converted to DHT)
what hormones do sertoli cells secrete
mullerian inhibiting factor
inhibin and activin (regulate FSH secretion)
what stimulates the formation of male external genitalia
dihydrotestosterone
when do external genitalia start to differentiate
week 9, able to recognise on scan at 16 weeks
what stimulates the formation of male external genitalia
absence of testosterone
what is androgen insensitivity syndrome
(a.k.a testicular feminisation) Congenital insensitivity to androgens X-linked recessive disorder Male karyotype (46XY) Testis develop (but do not descend) No androgen (T) Androgen induction of Wolffian duct does not occur, Mullerian inhibition does occur: born phenotypically external genitalia female, absence uterus and ovaries, with short vagina Commonly present at puberty with primary amenorrhoea, lack of pubic hair
where does spermatogenesis occur
seminiferous tubules
where do sperm mature
epididymis
what is the path of sperm
seminiferous tubules epididymis vas deferens ejaculatory duct (seminal vesicles and prostate) urethra meatus of penis
what cells are responsible for spermatogenesis
sertoli
what is the path of the testes
develop in abdominal canal - lower pole of kidney in retro peritoneum
internal ring
inguinal canal
scrotal sac
what is the descent of the testes dependent on
androgens
why do the testes need to descend
lower temp outside body to facilitate spermatogenesis
what does the dartos muscle do
lowers/ raises testes according to external termperature
what does the origin of testes mean for its anatomy
artery branch of aorta (gonadal)
veins: L testicular joins to L renal, R joins to IVC
lymphatic drainage to para aortic nodes
what does the cremaster muscle do
works in conjunction with the dartos muscle
what type of muscles are the dartos and cremaster
cremaster skeletal
dartos smooth
when do testes usually descend
6-9 months of age
what is cryptorchidism
undescended testes
what are the implications of cryptorchisism
reduces sperm count, if unilateral usually fertile
if undescended from 12 years onwards increased risk of ger cell cancer
what treatment for cryptorchidism
orchidopexy below to minimise risks
if adult consider orchidectomy
why does the corpus spongiosum not engorge with blood during erection
to maintain patency of urethra
what drives sertoli cell function
FSH
what is the steps of sperm production
germinal cell (diploid totipotent) primary spermatocyte (diploid) (meiosis 1) 2x secondary spermatocytes (haploid) (meiosis 2) 4x spermatids (haploid) spermatozoa
where is the genetic information in a sperm
nucleus in its head (has no cytoplasm)
what is in the neck of a sperm
mitochondria
what is acrosome
enzyme covering head of sperm, used in penetrating ovum
what are the roles of sertoli cells
form a blood testes barrier (protect the sperm from antibody attack, provides suitable fluid for sperm development)
provide nutrients
phagocytosis (removes surplus cytoplasm and destroys defective cells)
secrete seminiferous tubule fluid (carries cells to epididymis)
secretes androgen binding globulin (binds to testosterone)
secretes inhibin, AMH and activin hormones (regulates FSH secretion and controls spermatogenesis)
describe the hormonal control of spermatogenesis
GnRH-> FSH and LH
LH stimulates testosterone secretion
testosterone then decreases GnRH and LH
DHT causes: enlargement of male sex organs, secondary sexual characteristics and anabolism
FSH stimulates spermatogenesis together with testosterone
inhibin decreases FSH secretion
what type of hormone is GnRH and what releases it
decapeptide
released from hypothalamus in bursts every 2-3 hours from age 8-12 onwards
what does GnRH do
stimulates ant pituitary to produce LH and FSH
what is GnRH under negative feedback control from in males
testosterone
what type of hormones are LH and FSH
gonadotrophins- glycoproteins secreted by anterior pituitary
what is the role of LH
acts on leydig cells, regulates testosterone secretion
what is the role of FSH
acts on sertoli cells to enhance spermatogenesis
is production of gonadotrophins in males cyclical
no
what produces testosterone
leydig cells
what type of hormone is testosterone
steroid hormone- derived from cholesterol
what structures does testosterone have negative feedback on
hypothalamus and pituitary gland
what are the affects of testosterone from before birth to adult hood
before birth: masculinises repro tract, promotes descent of testes
puberty: promotes puberty and male characteristics
adult: controls spermatogenesis, secondary sexual characteristics (body shape, voice, thick skin), libido, penile erection
what type of hormone are inhibin and activin and what secretes them
petides secreted by sertoli cells
what liquifies sperm
enzymes from prostate gland
what is capacitation
series of changes that allow sperm to be able to fertilise egg
what are the steps of fertilisation
Penetration of cumulus complex bind to zona pellucida of oocyte Acrosome reaction Hyperactivated motility Zonal reaction Fusion with oocyte membrane and fertilisation
what do the seminal vesicles do
Produce semen into ejaculatory duct, supply fructose (energy supply), secrete prostaglandins (stimulates motility), secrete fibrinogen (clot precursor)
what is the role of the prostate
Produces alkaline fluid (neutralizes vaginal acidity), produces clotting enzymes to clot semen within female
what is the role of the bulbourethral glands
secretes lubricating mucous
what are the accessory glands
seminal vesicles, prostate gland, bulbourethral
what is responsible for erections
blood filling corpora cavernosa, under parasympathetic control
what is responsible for ejaculation
contraction of smooth muscles of urethra and erectile muscles, sympathetic control
how much of infertility is male factor
30%
same for female factor
what is happening to the prevalence of male infertility
increasing (possibly due to environmental oestrogens)
what is the most common cause of male infertility
idiopathic
what are the causes of obstructive male infertility
: cystic fibrosis (one faulty gene causes congenital bilateral malformation of vas deferens), vasectomy, infection
what are the non obstructive causes of male infertility
Congenital: Cryoptorchadism Infection: mumps orchitis Iatrogenic: chemotherapy/radiotherapy Pathological: testicular tumour Genetic: chromosomal (Klinefelter’s syndrome 47 xxy, microdeletions of Y chromosome, Robertsonian translocation) Specific semen abnormality e.g. globozoospermia Systemic disorder Endocrine
which form of male infertility has normal spermatogenesis
obstructive
what are the endocrine causes of male infertility
pituitary tumours: acromegaly, cushings, hyperprolactinaemia (all these decrease LH, FSH and testostrone)
hypothalamic: idiopathic, tumours, kallmanns (hypogonadotrophic hypogonadism, GnRH deficiency), anorexia (decrease LH, FSH and test)
thyroid: hyper or hypo (decreases libido increases prolactin)
diabetes (decreases sexual function and test)
CAH (increased testosterone)
androgen insufficiency (normal/ raised LH and test)
steroid abuse (decrease LH, FSH and test)
what does prolactin have negative feedback on
GnRH
what are you lacking if you dont get early morning erections
testosterone
what should you include in male infertility Hx
infertility- duration, primary or secondary, any Tx so far, libid, sexual function and activity
general health: diabetes, resp, recent illnesses
any GU infections (proven or suspected)
surgery to repro tract
exposure to meds (hormonal, steroids, antibiotics (sulphasalazine), alpha blockers, 5 alpha reductase inhibitors, chemo or radiotherapy, finasteride, narcotics
enviroment: heat and pesticides
recreational drugs: alcohol, marjuana
genetic abnormalities in patient or family
what are you looking for on exam
General examination:
- secondary sexual characteristics/ - presence of gynaecomastia
Genital Examination:
- testicular volume
- presence of vas deferens and epididymis
- penis (urethral orifice)
- presence of any varicocele/other scrotal - swelling- testicular cancer
what is normal testicular volume
pre pubertal 1-3mls
adult 12-25 mls
what are you looking for on semen analysis
volume density (number of sperm) motility (how many are moving) preogression (how well they move) morphology
what might cause low ejaculatory volume
problems with accessory glands
what factors can affect result of semen analysis
completeness of sample
period of abstinence (less than 3 days or longer than a week)
condition during sample (cold)
time between production and assessment (deteriorates after an hour)
natural variations between samples
health 2-3 months before
what further Ix are done into infertility
repeat semen analysis 6 weeks later if abnormal
endocrine profile (LH, FSH, testosterone, PRL, TSH)
chromosome analysis (including karyoptype, Y chromosome microdeletions), cystic fibrosis screening
Depending on results: testicular biopsy, scrotal scan
what are the clinical features of obstructive infertility
normal testicular volume
normal secondary sexual characteristics
vas deferens may be absent
what are the endocrine features of obstructive infertilitt
normal LF, FSH and testosterone
how much of male infertility is obstructive
20%
what are the clinical features of non obstructive infertility
low testicular volume
reduced secondary sexual characteristics
vas deferens present
what are the endocrine features of non obstructive infertility
high LH/ FSH +/- low testosterone
what are the treatments for male infertility
General advice
Treat any specific cause e.g. reversal of vasectomy if vasectomy, carbegoline if hyperprolactinamia, psychosexual Tx, medication review
Intracytoplasmic sperm injection (ICSI: may require surgical sperm aspiration)
Donor Insemination (DI)
what is the general advice for male infertility
Frequency sexual intercourse: 2-3 X per week and avoid lubricants that are toxic to sperm
Alcohol: < 5 units per day
Smoking: associated decrease semen quality and decreased health
Caffeine: nil evidence (<3/4 cups a day)
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)
who would benefit most from a vasectomy reversal
person with young female partner, takes a while so sperm retrieval quicker if female older
what is the process of ICSI
Sperm prepared from semen (or tissue from surgical sperm aspiration
Each egg is stripped
Sperm immobilised
Single sperm injected
what is the indication for surgical sperm aspiration
azoospermia
what are the indications for donor sperm insemination
azoospermia or very low count, failed ICSI treatment, genetic conditions, infective conditions
what are the steps in donor sperm insemination
Sperm donors (altruistic and not anonymous) 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
