infertility

Question 1

what is the who definition of infertility?

Answer 1

a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months of regular unprotected sexual intercourse

primary - not had a live birth previously (still born/miscarriage still primary)
secondary - have had a live birth > 12 months previously

Question 2

what is the epidemiology of infertility?

Answer 2

affects 1/7 couples (14%)
but half of these will conceive in the following 12 months (24 months total)

55% seek help

causes:
male factor
female factor
combined male/female
unknown factor

the top three are all equally common

Question 3

what are the impacts of infertility on a couple?

Answer 3

no biological child
impact on wellbeing 
impact on larger family
investigations
treatment (often fail)

Question 4

what are the impacts of infertility on society?

Answer 4

fewer births
less tax income
investigations cost
treatment cost

Question 5

what are the male causes of infertility (overview)?

Answer 5

pre-testicular

testicular

post-testicular

Question 6

what are pre-testicular causes of infertility?

Answer 6

pre-testicular:
congenital and acquired endocrinopathies
(kleinfeflters 47XXY, Y chromosome deletion, HPG/T/PRL)

Question 7

what are testicular causes of infertility?

Answer 7

testicular:
congenital 
chryptorchidism
infection (stds)
immunological (antisperm antibodies)
vascular (varicocele)
trauma/surgery 
toxins (chemo, drugs, smoking)

Question 8

what are post-testicular causes of infertility?

Answer 8

post testicular:
congenital (absence of vas deferens in cystic fibrosis)
obstructive azoospermia
erectile dysfunction (mechanical, psychological)
iatrogenic (vasectomy)

Question 9

what is cryptorchidism?

Answer 9

undescended testes

90% are in inguinal canal

Question 10

what are the female causes of infertility (overview)?

Answer 10

{pelvic causes 5%}

ovarian causes 40%

tubal causes 10%

uterine causes 10%

cervical causes 5%

unexplained 10%

Question 11

what are pelvic causes of infertility?

Answer 11

adhesions

endometriosis

Question 12

what are ovarian causes of infertility?

Answer 12

anovulation (endo)

corpus luteum insufficiency (doesnt produce enough hormones)

Question 13

what are tubal causes of infertility?

Answer 13

tubopathy due to:
infection
endometriosis
trauma

Question 14

what are uterine causes of infertility?

Answer 14

unfavourable endometrium due to:
chronic endometritis (TB)
fibroid
adhesions (synechiae)
congenital malformation

Question 15

what are cervical causes of infertility?

Answer 15

ineffective sperm penetration due to:
chronic cervicitis
immunological (anti sperm antibodies)

Question 16

what is endometriosis? (symptoms and treatment)

Answer 16

presence of functioning endometrial tissue outside the uterus (eg. on ovaries, on outer uterine areas, in cervix (cul de sac area))
occurs in 5% of women
responds to oestrogen

symptoms:
increased menstrual pain
menstrual irregularities
deep dyspareunia 
infertility 

treatment:
hormonal (OCP, prog)
laparoscopic ablation
hysterectomy
bilateral salpingo-oophorectomy

Question 17

what are fibroids (ovary)? (symptoms and treatment)

Answer 17

benign tumours of the myometrium
1-20% of pre menopausal women
responds to oestrogen

symptoms:
usually asymptomatic
increased menstrual pain 
menstrual irregularities
deep dyspareunia
infertility

treatment:
hormonal (OCP, prog, continuous GnRH agonists)
hysterectomy

Question 18

what is the HPG axis?

Answer 18

kisspeptin neurones secrete kisspeptin ->

stimulates GnRH neurones to secrete GnRH (pulsatile) ->

stimulates gonadotrophs to release LH and FSH (pulsatile) ->

stimulates gonads to release testosterone/oestrogen (diurnal)

oestrogen and progesterone and T have negative feedback effect on kisspeptin neurones and gonadotrophs

Question 19

what are examples of hypothalamic male infertility (pre testicular)?

Answer 19

low GnRH
:. low LH and FSH (hypogonadotrophic)
:. low Testosterone (hypogonadism)

congenital hypogonadotrophic hypogonadism:
anosmic (Kallmann syndrome) or normosmic

acquired hypogonadotrophic hypogonadism:
low BMI, stress, excess exercise

hyperprolactinaemia (prolactin inhibits kisspeptin)

Question 20

what are examples of pituitary causes of male infertility?

Answer 20

low LH and FSH (hypogonadotrophic)
:. low Testosterone (hypogonadism)

hypopituitarism:
tumour
infiltration
apoplexy (sudden loss pf blood supply)
surgery 
radiation

Question 21

what are examples of gonadal causes of male infertility?

Answer 21

high LH and FSH
BUT low testosterone (hypogonadism)

congenital primary hypogonadism:
Klienfelters 47XXY

acquired primary hypogonadism:
cryptorchidism 
trauma
chemo 
radiation

rare, but you can also get androgen receptor deficiency

Question 22

how would hyper and hypothyroidism cause male infertility?

Answer 22

hyperthyroidism:
increase in SHBG (sex hormone binding globulin) so reduced bioavaliable T

hypothyroidism:
decreased testosterone secretion

Question 23

what is Kallmann syndrome?

Answer 23

LOW GnRH
:. low FH and LSH
:. low T

hypogonadotrophic hypogonadism

anosmia (lack of sense of smell) is a big sign

caused by failure of migration of GnRH neurones with olfactory fibres into pituitary

reproductive symptoms:
cryptorchidism
failure of puberty (lack of testicle development, micropenis, primary amenorrhoea)
INFERTILITY

Question 24

what is the effect of prolactin on kisspeptin?

Answer 24

prolactin inhibits kisspeptin neurones by binding to prolactin receptors on kisspeptin neurones

(kisspeptin neurones stimulate GnRH and :. LH and FSH and :. T and E2 secretion)

so increased prolactin –> decreased testosterone

causes:
oligo/a menorrhoea
low libido
infertility
osteoporosis

this can be treated with a dopamine agonist (inhibits PRL) eg. cabergoline

Question 25

what is kleinfelter syndrome?

Answer 25

most common sex chromosome disorder (but only a quarter get diagnosed)

normal is 46XY, Kleinfelter is 47XXY (can have more extra Xs)

symptoms:
tall stature
decreased facial hair
breast development
female type pubic patters
small penis and testes
infertility
mildly impaired IQ
narrow shoulders
wide hips
low bone density

Question 26

how is male infertility assessed (history, examination, investigations)?

Answer 26

history:
duration, previous children, pubertal milestones, associated symptoms, medical history, Family, social, drug

examination:
BMI, sexual characteristics, testicular volume, epididymal hardness, presence of vas deferens, other endocrine signs, anosmia

investigations:
semen analysis (volume (1.5ml), sperm concentration (15 million/ml) , total motility (40%))
blood tests (LH, FSH, PRL, morning testoterone, SHBG, albumin, iron, pituitary/thyroid profiling, karyotyping)
microbiology (urine test, chlamydia swab)
imaging (scrotal US/doppler, pituitary MRI if low LH/FSH or high PRL)

Question 27

how is male infertility treated?

Answer 27

lifestyle:
optimise BMI
smoking cessation
alcohol reduction

treatment:
dopamine agonist for high PRL
gonadotrophin treatment for infertility (LH and FSH stimulate sperm production) (will also increase T)
testosterone (if no fertility required)
surgery

Question 28

what is primary ovarian insufficiency?

Answer 28

early menopause

same symptoms as menopause
conception can happen in 20%
diagnosis with high FSH (at least two readings 4 weeks apart)

causes:
autoimmune
genetic (eg. fragile X syndrome/turners syndrome)
cancer therapy

Question 29

what are examples of hypothalamic causes of female infertility?

Answer 29

low GnRH
:. low FSH/LH
:. low E2

in women: hypothalamic amenorrhoea
hypogonadotrophic hypogonadism

congenital hypogonadotrophic hypogonadism:
anosmic (kallman syndrome)

acquired hypogonadotrophic hypogonadism:
low BMI, excess exercise, stress

hyperprolactinaemia

Question 30

what are examples of pituitary causes of female infertility?

Answer 30

low FSH\LH
:. low E2

hypogonadotrophic hypogonadism

hypopituitarism:
tumour, infiltration, apoplexy, surgery, radiation

Question 31

what are examples of gonadal causes of female infertility?

Answer 31

high LH/FSH
BUT low E2

PCOS

acquired primary hypogonadism:
premature ovarian insufficiency
surgery, trauma, chemo, radiation

congenital primary hypogonadism:
turners (45X0)
premature ovarian insufficiency

Question 32

what is the epidemiology of PCOS?

Answer 32

affects 5-15% of women of reproductive age
frequent family history

most common endocrine disorder in women

most common cause of infertility on women

Question 33

how is PCOS diagnosed?

Answer 33

exclude all other reproductive disorders then…

rotterdam PCOS diagnostic criteria
must have 2+ out of 3 of the following:

1. oligo or anovulation
2. clinical +- biochemical hyperandrogenism
   (clinical - hirsuitism, acne, alopecia)
   (bio - raised androgens eg. T)
3. polycystic ovaries
   (ultrasound) (dont use US until 8 years post menarche)

Question 34

how is PCOS treated?

Answer 34

treat the symptoms:

irregular menses + infertility:
oral contraceptive pill

increased insulin resistance:
diet and lifestyle
metformin

hirsuitism:
anti androgens (eg. spironolactone)
creams, waxing, laser

increased endometrial cancer risk:
progesterone courses

Question 35

what is turners syndrome?

Answer 35

45X0 (normal is 46XX)

1:2500 live female births

high LH and FSH
BUT low T

hypogonadism

Question 36

what are the symptoms of turners syndrome?

Answer 36

short stature
low hairline
shield chest
wide spaced nipples
short 4th metacarpal
small fingernails
brown nevi (dots)
webbed neck
coarctation of aorta
poor breast development
elbow deformity
underdeveloped reproductive tract
amenorrhoea
infertility

Question 37

how is female infertility assessed? (history, examination, investigations)

Answer 37

history:
duration, previous children, pubertal milestones, breastfeeding, menstrual history, medical history, family, social, drugs

examination:
BMI, sexual characteristics, hyperandrogenism signs, pelvic examination, other endo signs, syndromic features, anosmia

main investigations:
blood tests (LH,FSH, PRL, E2, androgens, mid luteal progesterone (rise means an egg has been released|), SHBG, albumin, iron, pituitary, thyroid, karyotype
pregnancy test
microbiology (urine, chlamydia)
imaging (ultrasound, hysterosalpingogram, pituitary MRI (if low LH/FSH or high PRL)