Infertility I Flashcards
What is infertility
Failure to achieve clinical pregnancy after =>12 months of regular unprotected sexual intercourse
What is primary infertility
When you haven’t had a live birth previously
miscarriage / stillborn counted here
What is secondary infertility
When you’ve had a live birth > 12 months previously
What are the most common causes of infertility in a couple
1) male infertility 30%
2) female infertility 30%
3) combined male and female infertility 30%
4) unknown
10%
What are the impacts of infertility to the coupe
Psychological distress : No biological child Impact on mental wellbeing of couple and family Investigations are invasive treatments often fail
What are the impacts of infertility to society
Less births ( less tax income dude kinda harsh) Investigation + treatment costs
What are the 3 stages that can cause of male infertility
3 ways to think about male infertility
1) Pretesticular
2) testicular
3) Post testicular
What causes Pre testicular infertility
Congenital and acquired endocrinopathies :
Can be split into endo causes and physical causes
Physical causes
1) Klinefelter’s
47XXYY
3) Chromosome deletion
Endo causes:
4) HPG (hypothatmauls pituitary axis, Testosterone, prolactin
These can be due to 1ary , 2ary or 3ary hypogonadism
What are the causes of testicular infertility
1) congenital
2) Cryptorchidism
2) infection ie STD
3) Immunological ( antisperm ABs)
4) Vascular ( varcocoele)
5) Trauma/ surgery ( ie Vasectomy)
6) Toxin ( Chemo , DXT, Drugs, Smoking
What are the causes post testicular infertility
1) congenital ( absence of vas deference in CF)
2) Obstructive Azoospermia
3) Erectile dysfunction ( retrograde ejaculation , mechanical impairment , psychological)
4) Iatrogenic ( vasectomy)
What is cryptorchidism
Undescended testis (90% stuck in inguinal canal) normal path for testis descent through inguinal canal)
What are the 6 causes of female infertility and name some examples of each
6 ways to think about female infertility
Check pregnant or breastfeeding
1) Uterine causes ( 10% )
( unfavourable endometrium due to chronic endometritis (TB) , fibroid, adhesions ( synechiae, congenital malformation)
2) Tubal causes ( 30%)
( Tubopathy due to : infection , endometriosis , trauma)
3) Ovarian causes ( 40%)
( Anovulation ( endo problems) , Corpus luteum insufficiency)
4) Cervical causes 5%
( ineffective sperm penetration due to : chronic cervicitis , immunological ( antisperm Ab)
5) Pelvic causes 5%
( Endometriosis , adhesion issues)
6) unexplained 10%
What are the causes of uterine infertility
unfavourable endometrium due to chronic endometritis (TB) , fibroid, adhesions ( synechiae) , congenital malformation
What are the causes of tubular infertility
Tubopathy due to : infection , endometriosis , trauma
What are the causes of ovarian infertility
Anovulation ( endo problems) , Corpus luteum
What are the causes of Cervical infertility
ineffective sperm penetration due to : chronic cervicitis , immunological ( antisperm Ab
What are the causes of Pelvic infertility
Endometriosis , adhesion issues
What is endometriosis
Presence of function endometrial tissue outside the uterus most commonly in the :
- fallopian tube
- ovaries
- outer uterine surface
- cul de sac area
( 5% of women . This tissue will respond to oestrogen)
Symptoms of endometriosis
Increase menstrual pain + irregularities
Deep dyspareunia ( pain during intercourse)
Infertility
what are the Treatments for endometriosis
Hormonal ( continuous OCP , prog)
Laparoscopic ablation
Hysterectomy
Bilateral salpingo-oophorectomy
note OCP = oral contraceptive pill
What is fibroids
Benign tumour of the myometrium ( most commonly:
- submucosal
- pedunculated subseroal
- subserosal
- Intramural
occurs in 1-20% of pre menopausal woman ( increases with age)
Responds to oestrogen
Symptoms of fibroids
Usually asymptomatic
Increase menstrual pain + irregularities
Deep dyspareunia
infertility
Treatment for fibroids
Hormonal ( continuous OCP , prog , continuous GnRH agonists)
Hysterectomy
What is hypothalamic - pituitary gonadal axis
1) Kisspeptin released from neurons in hypothalamus
2) Stimulates the release of GnRH from GNRH neurons in hypothalamus
3) Acts on gonadotrophs ( in anterior pit)
4) Stimulates LH = FSH circulation into systemic circulation
5) Causes testosterone / oestrogen ( progesterone / activin / inhibin) release in gonads
6) Oestrogen ( aromatised from T in men ) and progesterone acts back on hypothalamus and gonadotrophs (
What is the rhythm of GnRH and LH
pulsatile
sex steroids have a diurnal rhythm
How does hyperthyroidism cause infertility in males
Increased SHBG –> drop in free testosterone
How does hypothyroidism cause infertility in males
Decreased testosterone secretion
What is Kallmann’s syndrome
Condition that causes hypogonadotropic hypogonadism and impaired sense of smell. This is due to a lack of GnRH.
This comes from the failure of migration of GnRH neurons with olfactory fibres from the olfactory placode to the hypothalamus
( Note can occur in females just more rare)
How does Kallmann’s syndrome effect different hormones
low GnRH ( unmeasurable) Low LH/FSH ( hypo gonadotrophic) low T ( hypogonadism)
What are the symptoms of kallmann’s syndrome
Anosmia ( loss / change of smell)
Reproductive features ie ( cryptorchidism, failure of puberty –> lack of testicle dvlpt, micropenis , primary amenorrhoea , infertility
What does prolactin do to kisspeptin neurons
Inhibits them
What is the mechanism of action of hyperprolactinaemia
1) Prolactin binds to kisspeptin neurons in hypo
2) inhibits kisspeptin release
3) Decreases downstream GnRH/LH/FSH/Oest
4) oligo or amenorrhea , low libido , infertility , osteoporosis
What is the treatment for hyperprolactinaemia
Dopamine agonists ( cabergoline) Surgery / DXT
What is Klinefelter’s syndrome
Sex chromosome disorder where males are born with XXY
Symptoms of Klinefelter’s
1) tall stature
2) Decreased facial hair
3) breast development
4) female type pubic hair pattern
5) small penis + testes
6) Infertility 3%
7) mildly impaired IQ
8) narrow shoulders
9) reduced chest hair
10) wide hips
12) Low bone density
symptoms are more sever if >3 X chromones are present ( ie 48 XXXY or 49XXXXY) due to trisomy
what hormones are effected in klinefelter’s
Increased FH/LSH ( hypergonadotropic) Decreased testosterone ( hypogonadism)
What 3 things would you look for to diagnose male infertility
1) history
2) Examination
3) investigation
What would finding the history of a man with infertility entail?
1) Duration
2) Prev children
3) pubertal milestones
4) associated symptoms ( T deficiency , PRL symptoms , CHH features) (CHH = HGP axis features)
5) medical and surgical history
6) family + social history
7) med / drugs
What would the examinations of a man with infertility entail?
BMI, sexual characteristics , testicular volume , epidydimal hardness, presence of vas , endocrine signs , syndromic features , anosmia
What would the investigations of a man with infertility entail?
1) semen analysis
( take a volume of 1.5 ml. Should have 15 mill / ml sperm
azoospermia = no sperm
oligospermia = reduced sperm
total motility = 40%
2) blood tests ( FHS /LH/PRL , morning fasting test , sex hormone binding globulin ( SHBG) , albumin , iron studies , pt / thyroid profile , karyotyping
3) microbiology ( urine test , chlamydia swab
4) imaging
( scrotal Ultrasound/Doppler for varicocoele / obstruction , testicular volume , MRI of pit glan if low LH/FSH or high PRL
Treatment for male infertility
1) lifestyle –> optimise BMI , stop smoking + drinking
2) Dopamine agonist for hyperPRL , gonadotropin treatment for fertility ( will increase test) , Test ( for symptoms if no fertility requires), Surgery ( micro testicular sperm extraction ( microTESE)
How long is a menstrual cycle
28 days ( 24 - 35 –> +/- 2 days each month)
What is primary amenorrhoea
Periods start later than 16yrs ( abnormal)
What is 2ary amenorrhoea
Irregular periods ( start then stop for at least 3-6 months)
( Remember common for periods to be irregular for first 18 months_)
What is amenorrhoea
absence or periods ( no periods for at least 3-6 months or up to 3 periods per year
What is oligomenorrhoea –> few periods
Irregular or infrequient periods >35 day cycles ( 4-9 cycles per year)
What is premature ovarian insufficiency ( POI)
what is it caused by and how is it diagnosed
Early menopause
same symptoms as menopause
diagnosed by high FSH > 25iU/L ( x2 at least 4 weeks apart)
causes:
autoimmune
genetic ( fragile X syndrom / turner’s syndrome , cancer therapy ( radio / chemo)
What is polycystic ovarian syndrome
most common cause of infertility and endocrine disorder in women
How do you diagnose PCOS
polycystic ovarian syndrome
Exclude all other reproductive disorders
must meet 2/3 Rotterdam PCOS diagnostic criteria
What are the 3 PCOS rotterdam diagnostic criteria
1) Oligio / Anovulation ( normally assed by menstural freq as oligomenorrhoea
<21d or >35d cycles
<8-9 cycles/y
>90d for any cycle
If necessary anovulation can be proven by:
Lack of progesterone rise or US
2) clinical +/- Biochemical hyperandrogenism
(CLINICAL
Acne, hirsutism (Ferriman-Gallwey score), alopecia (Ludwig score)
BIOCHEMICAL Raised androgens (eg Testosterone))
1 +2 are the worst metabolic risk combination
3) Polycystic ovaries (UltraSound)
≥20 follicles OR ≥10ml either ovary on TVUS (8 MHz)
Do not use US until 8y post-menarche (due to high incidence of multi-follicular ovaries at this stage)
Treatments for PCOS
1) oral contraceptive pill
to treat can cause irregular menses / amenorrhoea and infertility ( can be treated via clomiphene , letrozole , IVF)
2) Metformin ( can lead to irregular period / amenorrhoea and infertility and increased insulin resistance causing impaired glucose homeostasis ( T2DM, gestational DM)
3) Diet and lifestyle
4) Anti - androgens ( ie spironolactone , creams , waxing and laser ) used to treat hirsutism
5) Oral contraceptives and progesterone courses can increase endometrial cancer risk
What is turner’s syndrome and what are the effects on hormones
45 X0
high LH , FSH ( hypergonadotropic
Low test Hypogonadism
Symptoms of turner’s syndrome
Short stature low hairline shield chest wide spaces nipples short 4th metacarpal small fingernails brown nevi characteristic facies webbed neck coarctation of aorta poor breast development elbow deformity underdeveloped reproductive tract amenorrhoea
What is Anorexia nervosa induced amenorrhea:
hypothalamic dysfunction due to weight loss
leads to low FH, LSH , E2
What happens in history taking in women
: including duration, previous children, pubertal milestones, breastfeeding?,
Menstrual History: oligomenorrhoea or 1/20 amenorrhoea, associated symptoms (eg. E deficiency, PRL symptoms, CHH features), medical & surgical history, family history, social history, medications/drugs
What happens in examination of infertile women
including BMI, sexual characteristics, hyperandrogenism signs, pelvic examination, other endocrine signs, syndromic features, anosmia
What are the main investigations
1) Blood tests (LH, FSH, PRL , Oestradiol, Androgens Foll phase 17-OHP, Mid- Luteal Prog Sex Hormone Binding Globulin (SHBG) Albumin, Iron studies Also Pituitary/Thyroid profile Karyotyping
2) Pregnancy test ( urine or serum HCG)
3) Microbiology ( urine test and chlamydia swab)
4) imagining ( US (transvaginal)
Hysterosalpingogram
MRI Pituitary
(if low LH/FSH or high PRL)
What diseases in male infertility are associated with problems of the hypothalamus
and what does this due to hormones
1) Congenital Hypogonadotropic Hypogonadism
- -> Anomic ( kallmann syndrome) or Normosmic
2) Acquired hypogonadotropic hypogonadism
- -> low BMI, Xs exercise , stress
3) hyperprolactinaemia
(low GnRH unmeasurable , low LH, Low FSH , low testosterone)
What diseases in male infertility are associated with problems of the pituitary
and what does this due to hormones
1) Hypopituitarism
2) Tumour , infiltration , apoplexy , surgery , radiation
( Low LH, FSH + low T)
What diseases in male infertility are associated with problems of the gonads
and what does this due to hormones
1) Congenital primary hypogonadism ( Klinefelter’s 47XXY )
2) Acquired primary hypogonadism ( cryptorchidism , trauma , chemo , radiation )
High FH/LSH , Low T
What are other causes of male infertility
Androgen receptor deficiency ( rare)
Hyper/hypothyroidism ( reduced bioavailable testosterone)
What diseases in female infertility are associated with problems of the hypothalamus
and what does this due to hormones
1) Congenital Hypogonadotrophic Hypogonadism
- Anosmic (Kallmann Syndrome) or Normosmic
2) Acquired Hypogonadotrophic Hypogonadism
- Low BMI, XS exercise, Stress
2) Hyperprolactinaemia
low GnRH , low FH/LSH, low E2
What diseases in female infertility are associated with problems of the pituitary
and what does this due to hormones
Hypopituitarism
-Tumour, Infilatration, Apoplexy, Surgery, Radiation
↓LH ↓FSH Hypogonadotrophic
↓E2
What diseases in female infertility are associated with problems of the gonads
and what does this due to hormones
1) Polycystic Ovarian Syndrome (PCOS
2) Acquired Primary Hypogonadism
- Premature Ovarian Insufficiency (POI)
- Surgery, Trauma, Chemo, Radiation
3) Congenital Primary Hypogonadism
- Turners (45X0)
- Premature Ovarian Insufficiency (POI)
↑LH ↑FSH HYPERgonadotrophic
↓E2
what are other causes of female infertility
Hyper/Hypothyroidism (reduced bioavailable oestradiol)
