Infertility Flashcards
what is infertility?
a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12+ months of regular (every 2-3 days) unprotected sexual intercourse
what is primary infertility?
infertility with no previous live birth
Does male factor, female factor or a combination account for most cases of infertility?
what is secondary infertility?
infertility with a live birth 12+ months previously
what is the prevalence of infertility?
affects 1 in 7 couples
But ~ half of these will then conceive in the next 12 months (ie at 24months ~ 7% of couples)
55% seek help - positive association with socioeconomic status
what are the psychological impacts of infertility?
no biological child, impact on wellbeing of couple, larger family, investigations and treatments (often failing)
what are the societal costs of infertility?
less births, less tax income, investigation and treatment costs.
what are the male pre-testicular causes of infertility?
congenital and acquired endocrinopathies e.g Klinefelters, HPG, T, PRL issues
what are the testicular causes of male infertility?
congenital
cryptorchidism
infection - STDs
immunological - antisperm ABs
vascular - varicocoele
trauma/surgery
toxins - chemo, dxt, drugs, smoking
what are the post testicular causes of male infertility?
congenital - abscence of vas deferens in CF
obstructive azoospermia
erectile dysfunction - retrograde ejaculation, mechanical impairment, psychological
latrogenic - vasectomy
what is cryptorchidism?
undescended testes - 90% in inguinal canal, as normal pathway of descent is through inguinal canal
what are the types of causes of female infertility?
pelvic (5%)- endomteriosis, adhesions,
ovarian (40%)- anovulation, Corpus luteum insufficiency
tubal (30%)-Tubopathy due:
-Infection
-Endometriosis
-Trauma
uterine (10%)-Unfavourable endometrium due:
-Congenital malformations
-Infection/Inflammation/Scarring (adhesions)
-Fibroids
cervical (5%) Ineffective sperm penetration due:
-Infection/Inflammation
-Immunological (antisperm Ab)
and unexplained (10%)
what is endometriosis?
presence of functioning endometrial tissue outside the uterus
what is the prevalence of endometriosis in women?
5%
what are the symptoms of endometriosis?
menstrual pain and irregularity, deep dyspareunia, infertility
what are fibroids?
benign tumours of the myometrium
what is the prevalence of fibroids in women?
1-20% pre-menopausal women
are fibroids or endometriosis responsive to oestrogen?
both
what are the symptoms of fibroids?
usually asymptomatic
menstrual pain, irregularities
deep dyspareunia
infertility
what are the blood results for a hypothalamic cause of endocrine male infertility?
low LH/FSH
low testosterone
low GnRH (not measurable)
what are the blood results for pituitary causes of endocrine male infertility?
low LH/FSH
low testosterone
what are the blood results for gonad causes for endocrine male infertility?
high LH/FSH
low testosterone
Endocrine Male Infertility at different levels of HPG axis
what is Kallman’s syndrome?
failure of migration of GnRH neurons along with olfactory neurons to hypothalamus from olfactory placode (during first 10wks of development)
This leads to anosmia and reproductive features
what are the reproductive features of Kallmann’s?
Failure of puberty
Infertility
what are the blood test results for someone with Kallmann’s?
low LH/FSH
low testosterone
how is hyperprolactinemia treated?
cabergoline
or pit surgery/radiotherapy
what is the karyotype for Klinefelter syndrome?
47XXY
what is the karyotype for Turner syndrome?
45X0
what are the features of Klinefelters syndrome?
tall stature
decreased facial/chest hair
mildly impaired IQ
narrow shoulders
Slight breast deveolpment
female pattern pubic hair
wide hips
small penis/testes
low bone density
INFERTILITY
how would you approach a male history for infertility?
duration
previous children
pubertal milestones,
associated symptoms (eg. T deficiency, PRL symptoms, CHH features)
medications/drugs
how would you approach examining a male presenting with infertility?
BMI, sexual characteristics, testicular volume, anosmia
what are the 3 main investigations for males presenting with infertility?
semen analysis
blood tests
imaging
what is semen analysis?
measures volume (1.5ml normal), sperm concentration-15 million/ml (Azospermia = No sperm, Oligospermia = Reduced sperm)
and total mobility of a sperm sample (40%)
what are the main blood tests for a male presenting with infertility?
LH, FSH, PRL
Morning Fasting Testosterone
Karyotyping
what are the imaging methods used for males presenting with infertility?
Scrotal US/Doppler
(for varicocoele/obstruction, testicular volume)
MRI Pituitary
(if low LH/FSH or high PRL)
what are the typical lifestyle treatments for general male inferility?
optimise BMI
smoking cessation
alcohol cessation/ reduction
what are specific treatments for male hyperPRL?
dopamine agonist - cabergoline
What type of surgery can be used to treat male infertiliy?
Micro TESE (microtesticular sperm extraction)
how is testosterone prescribed to males not desiring fertility?
daily gel
3 weekly IM injections
3 monthly IM injections
implants/oral preparations less common
what to prescribe to males desiring fertility?
hCG injections (act on LH receptors) if no response after 6mnth, add FSH injections
what treatments are used for males wanting fertility?
gonadotrophin treatment
NO TESTOSTERONE - -ve feedback on LH/FSH
when is testosterone prescribed to males presenting with infertility?
if fertility is not desired, only for symptomatic relief
What blood results would you see in premature ovarian insufficiency?
How is POI diagnosed?
High FSH/ LH, low oestradiol
Diagnosis High FSH >25 iU/L (x2 at least 4wks apart)
Can conception occur in premature ovarian insufficieny?
Yes, in 20%
what is primary amenorrhoea?
menses not started after 16 years old
what is secondary amenorrhoea?
periods start at puberty but stop for at least 3-6mnths
what is amenorrhoea?
no periods for at least 3-6mnths
or up to 3 periods/yr
what is oligomenorrhoea?
irregular/infrequent periods, >35day cycles
or 4/9 cycles/yr
what is early menopause?
menopause occurring in a female under 45
how is early menopause diagnosed?
high FSH (>25iU/L) twice at least 4wk apart
what are the odds for conception in a female with early menopause?
20%
Causes of premture ovarian insufficiency?
Autoimmune
Genetic eg Turner’s Syndrome
Cancer therapy Radio- / Chemo-therapy in the past
What blood results would you see in Anorexia Nervosa-Induced Amenorrhoea?
Low FSH/LH/ oestradiol
how does hypothalamic causes of infertility in women show in a blood test?
low LH/FSH
low E2
hypogonadotrophic hypogonadism
what are the female congenital causes of hypogonadotropic hypogonadism?
anosmic (kallmann’s syndrome) or normosmic
what are the acquired female causes of hypogonadotrophic hypogonadism?
low BMI
stress
excessive exercise
hyperprolactinemia
what are the blood results for pituitary causes of female infertility?
low LH/FSH
low E2
what are the causes of female hypogonadotropic infertility? (pituitary causes)
hypopituitarism-
tumour
infiltration
apoplexy
surgery
radiation
what are the acquired gonadal causes of female primary hypogonadism?
early menopause/primary ovarian insufficiency surgery trauma chemo radiation polycystic ovarian syndrome (PCOS)
what are the congenital causes of female primary hypogonadism?
turners syndrome
early menopause/premature ovarian insufficiency
what are the blood results for PCOS?
high LH/FSH
low or normal E2
what are the blood results for female primary hypogonadism?
high LH/FSH
low E2
what is PCOS’ burden of disease?
affects 5-15% women of reproductive age
most common endocrine disorder in women, most common cause of infertility
how is PCOS diagnosed?
exclude other reproductive disorders
Rotterdam criteria - 2/3
what is the Rotterdam PCOS diagnostic criteria?
oligo or anovulation
clinical+/- biochemical hyperandrogenism
polycystic ovaries on utrasound
how is oligo/anovulation assessed for the rotterdam criteria of PCOS?
by menstrual frequency - oligomenorrhoea (<8-9 cycles a year)
how is clinical hyperandrogenism for the rotterdam PCOS criteria assessed?
clinical - acne, hirsutism, alopecia
how is biochemical hyperandrogenism for the rotterdam PCOS criteria assessed?
raised androgens on blood test (e.g testosterone)
why are polycystic ovaries on ultrasound not diagnostic for PCOS?
30% of women have polycystic ovaries so isn’t confirmational
how does Clomiphene act for female fertility?
oestradiol receptor antagonist
reduces negative feedback of oestrogen on hypothalamus/pituitary gland
therefore increases LH/FSH
FSH stimulates follicle growth
what treatments for PCOS aim to restore ovulation?
weight loss
letrozole (aromatase inhibitor)
clomiphene (oestradiol receptor modulator)
FSH stimulation
how does letrozole act for female infertility?
inhibits aromatase (test-oest)
therefore reduces negative feedback of oestrogen on LH/FSH
therefore increases serum LH/FSH leading to stimulation of follicle growth
what are the treatments for PCOS?
what are the physical features of Turner’s syndrome?
short stature
low hairline
shield chest
webbed neck
poor breast development, wide spaced nipples
elbow deformity
brown nevi
short 4th metacarpal
small fingernails
what are the internal features of Turner’s syndrome?
coarctation of aorta
underdeveloped reproductive tract
amenorrhoea
what are the main history points for a female presenting with infertility?
duration, previous children, pubertal milestones,
menstrual History, medications/drugs
what are the examinations to consider for females presenting with infertility?
BMI, sexual characteristics, hyperandrogenism signs, anosmia
what are the main types of investigations for females presenting with infertility?
blood tests
pregnancy test
imaging
what are the blood tests for a female presenting with infertility?
LH/FSH/PRL oestradiol, androgens follicular phase 17-OHP, mid-luteal progesterone sex hormone binding globulin albumin, iron studies pit/thyroid study karyotyping
what are the imaging methods used for a female presenting with infertility?
Ultrasound (transvaginal)
hysterosalpingogram
MRI pit
