Male Infertility

Question 1

which chromosome has the sex determining region?

Answer 1

y chromosome

*causes development of testis from bipotential gland

Question 2

what do the foetal testes secrete?

Answer 2

testosterone and mullerian inhibiting factors

*these cause development of male internal genital tract

Question 3

what are the two primitive genital tracts?

Answer 3

wolffian and mullerian ducts

Question 4

how is the male reproductive tract formed from the two primitive genital tracts?

Answer 4

wolffian ducts become repro tract

mullerian ducts degenerate by mullerian inhibiting factor

Question 5

how is the female reproductive tract formed from the two primitive genital tracts?

Answer 5

wolffian ducts degenerate through lack of testosterone

mullerian ducts become repro tract

Question 6

what hormone causes the differentiation of external genitalia at week 9?

Answer 6

dihydrotestosterone

• present = male
• absent = female

Question 7

although external genitalia start to differentiate from 9 weeks, when are you able to recognise it on scan?

Answer 7

16 weeks

Question 8

what is androgen insensitivity syndrome (with karyotype 46XY)?

Answer 8

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

Question 9

what conditions have the possibility to cause reduced penile size?

Answer 9

obesity
smoking
environmental
endocrine (testicular failure eg kleinfelters syndrome, crypto-orchidism)

Question 10

describe the descent of testis and why it is important that this occurs?

Answer 10

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

Question 11

what is cryptorchidism?

Answer 11

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)

Question 12

what are the functions of the testis?

Answer 12

spermatogenesis (seminiferous tubules)

production of testosterone (leydig cells)

Question 13

where in the spermatozoon contains enzymes for penetrating the ovum?

Answer 13

acrosome

Question 14

what are the roles of sertoli cells within the testes?

Answer 14

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)

Question 15

describe the different hormonal controls of spermatogenesis

Answer 15

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

Question 16

what is the role of gonadotrophin releasing hormone?

Answer 16

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

Question 17

what are the roles of LH and FSH?

Answer 17

LH = acts on leydig cells to regulate testosterone secretion

FSH = acts on sertoli cells to enhance spermatogenesis, regulates by negative feedback from inhibin

Question 18

is production of LH and FSH in males cyclical or non-cyclical?

Answer 18

non-cyclical (unlike in females)

Question 19

what is the role of testosterone?

Answer 19

steroid hormone derived from cholesterol produced in leydig cells which is secreted into blood and seminiferous tubules for sperm production

Question 20

what are the effects of testosterone in the following circumstances:

a) before birth?
b) puberty?
c) adult?

Answer 20

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

Question 21

what is the role of inhibin and activin?

Answer 21

peptides secreted by sertoli cells which act as feedback on FSH (inhibin inhibits and activin stimulates)

Question 22

what liquifies spermatozoa?

Answer 22

enzymes from prostate gland

Question 23

what is capacitation of spermatozoa?

Answer 23

a series of biochemical and electrical events before fertilisation (hyperactive mobility, ability to bind ZP and AR)

Question 24

what is the 6 steps of capacitation of spermatozoa?

Answer 24

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

Question 25

where does fertilisation occur?

Answer 25

ampullary region of fallopian tube

Question 26

what are the functions of the epididymis and vas deferens?

Answer 26

exit route from testes to urethra concentrate and store sperm site for sperm maturation

Question 27

what are the functions of seminal vesicles?

Answer 27

``` produce semen into ejaculatory duct supply fructose secrete prostaglanding (stimulates motility) secrete fibrinogen (clot precursor) ```

Question 28

what are the functions of the prostate gland?

Answer 28

produces alkaline fluid (neutralises vaginal acidity) | produces clotting enzymes to clot semen within female

Question 29

what is the function of the bulbourethral glands?

Answer 29

secrete mucus to act as lubricant

Question 30

what is the route sperm normally takes?

Answer 30

testes -> epididymis -> vas deferens -> ejaculatory duct -> urethra

Question 31

what happens during an erection?

Answer 31

blood fills corpora cavernosa (under PS control)

Question 32

what happens during emission?

Answer 32

contraction accessory sex glands and vas deferens so semen expelled into urethra

Question 33

what happens during ejaculation?

Answer 33

contraction of smooth muscles of urethra and erectile muscles (shoot = sympathetic control)

Question 34

what conditions could cause retrograde ejaculation?

Answer 34

neuropathy prostate surgery anticholinergic drugs

Question 35

what is the definition of male infertility?

Answer 35

infertility resulting from failure of the sperm to normally fertilise the egg *usually associated with abnormalities in semen analysis

Question 36

male factor infertility is the most common cause of infertility - true or false?

Answer 36

true - approx 1/3 of all infertility

Question 37

what is the most common cause of male infertility?

Answer 37

idiopathic

Question 38

what are obstructive causes of male infertility?

Answer 38

cystic fibrosis vasectomy infection

Question 39

what are the non-obstructive causes of male infertility?

Answer 39

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

Question 40

what are the different endocrine causes of male infertility?

Answer 40

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)

Question 41

what should you look for in genital examination of male infertility?

Answer 41

testicular volume presence of vas deferens and epididymis penis (urethra orifice) presence of any variocele / other scrotal swelling

Question 42

what are the normal testicular volumes?

Answer 42

``` pre-pubertal = 1-3mls adults = 12-25mls ``` * if below 5ml unlikely to be fertile * measured using orchidometer

Question 43

what is assessed during semen analysis and what are the lower reference limits for these?

Answer 43

``` volume (mL) = 1.5 density (number) = 39x10^6 motility (what proportion moving) = 40 progression (how well they move) = 32 morphology = 4 ```

Question 44

what factors can affect the result of semen analysis?

Answer 44

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

Question 45

what other further assessments, after semen analysis, can be undertook for male infertility?

Answer 45

repeat analysis 6 weeks later endocrine profile chromosome analysis cystic fibrosis screening depending on results - testicular biopsy, scrotal scan

Question 46

what are the diagnostic features of obstructive infertility?

Answer 46

clinical = normal volume, normal secondary sexual characteristics, vas deferens may be absent endocrine = normal LH, FSH and testosterone

Question 47

what are the diagnostic features of non obstructive infertility?

Answer 47

clinical = low testicular volume, reduced secondary sexual characteristics, vas deferens present endocrine = high LH, FSH +/- low testosterone

Question 48

what assisted conception methods can be used for male infertility?

Answer 48

``` ICSI donor insemination (DI) ```

Question 49

what general advice can be given to men in regards to treatment infertility?

Answer 49

``` 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) ```

Question 50

what is the success rate of a vasectomy reversal?

Answer 50

75% if within 3 years 55% after 3 to 8 years approx 30-40% after 9 to 19 years

Question 51

what medication can be used for hyperprolactinaemia?

Answer 51

carbegoline

Question 52

when could psychosexual treatment be useful?

Answer 52

in anejaculation conditions

Question 53

what is the indication for surgical sperm aspiration?

Answer 53

azoospermia

Question 54

how is surgical sperm aspiration performed and what is the success rate?

Answer 54

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

Question 55

what is the indications for donor sperm insemination?

Answer 55

azoospermia or very low count failed ICSI treatment genetic conditions infective conditions

Question 56

how is donor sperm insemination carried out and what is success rate?

Answer 56

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