infertility Flashcards
what is the who definition of infertility?
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
what is the epidemiology of infertility?
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
what are the impacts of infertility on a couple?
no biological child impact on wellbeing impact on larger family investigations treatment (often fail)
what are the impacts of infertility on society?
fewer births
less tax income
investigations cost
treatment cost
what are the male causes of infertility (overview)?
pre-testicular
testicular
post-testicular
what are pre-testicular causes of infertility?
pre-testicular:
congenital and acquired endocrinopathies
(kleinfeflters 47XXY, Y chromosome deletion, HPG/T/PRL)
what are testicular causes of infertility?
testicular: congenital chryptorchidism infection (stds) immunological (antisperm antibodies) vascular (varicocele) trauma/surgery toxins (chemo, drugs, smoking)
what are post-testicular causes of infertility?
post testicular:
congenital (absence of vas deferens in cystic fibrosis)
obstructive azoospermia
erectile dysfunction (mechanical, psychological)
iatrogenic (vasectomy)
what is cryptorchidism?
undescended testes
90% are in inguinal canal
what are the female causes of infertility (overview)?
{pelvic causes 5%}
ovarian causes 40%
tubal causes 10%
uterine causes 10%
cervical causes 5%
unexplained 10%
what are pelvic causes of infertility?
adhesions
endometriosis
what are ovarian causes of infertility?
anovulation (endo)
corpus luteum insufficiency (doesnt produce enough hormones)
what are tubal causes of infertility?
tubopathy due to:
infection
endometriosis
trauma
what are uterine causes of infertility?
unfavourable endometrium due to: chronic endometritis (TB) fibroid adhesions (synechiae) congenital malformation
what are cervical causes of infertility?
ineffective sperm penetration due to:
chronic cervicitis
immunological (anti sperm antibodies)
what is endometriosis? (symptoms and treatment)
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
what are fibroids (ovary)? (symptoms and treatment)
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
what is the HPG axis?
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
what are examples of hypothalamic male infertility (pre testicular)?
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)
what are examples of pituitary causes of male infertility?
low LH and FSH (hypogonadotrophic)
:. low Testosterone (hypogonadism)
hypopituitarism: tumour infiltration apoplexy (sudden loss pf blood supply) surgery radiation
what are examples of gonadal causes of male infertility?
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
how would hyper and hypothyroidism cause male infertility?
hyperthyroidism:
increase in SHBG (sex hormone binding globulin) so reduced bioavaliable T
hypothyroidism:
decreased testosterone secretion
what is Kallmann syndrome?
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
what is the effect of prolactin on kisspeptin?
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
what is kleinfelter syndrome?
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
how is male infertility assessed (history, examination, investigations)?
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)
how is male infertility treated?
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
what is primary ovarian insufficiency?
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
what are examples of hypothalamic causes of female infertility?
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
what are examples of pituitary causes of female infertility?
low FSH\LH
:. low E2
hypogonadotrophic hypogonadism
hypopituitarism:
tumour, infiltration, apoplexy, surgery, radiation
what are examples of gonadal causes of female infertility?
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
what is the epidemiology of PCOS?
affects 5-15% of women of reproductive age
frequent family history
most common endocrine disorder in women
most common cause of infertility on women
how is PCOS diagnosed?
exclude all other reproductive disorders then…
rotterdam PCOS diagnostic criteria
must have 2+ out of 3 of the following:
- oligo or anovulation
- clinical +- biochemical hyperandrogenism
(clinical - hirsuitism, acne, alopecia)
(bio - raised androgens eg. T) - polycystic ovaries
(ultrasound) (dont use US until 8 years post menarche)
how is PCOS treated?
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
what is turners syndrome?
45X0 (normal is 46XX)
1:2500 live female births
high LH and FSH
BUT low T
hypogonadism
what are the symptoms of turners syndrome?
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
how is female infertility assessed? (history, examination, investigations)
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)
