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 unprotected sexual intercourse.’
What is primary infertility
What is secondary infertility
Not had a live birth previously
Have had a live birth > 12 months previously
What are psychological distress impacts of infertility on a couple
- No biological child
- Impact on couples wellbeing
- Impact on larger family
- Investigations
- Treatments (often fail)
What is the cost to society of infertility
- Less births
- Less tax income
- Investigation costs
- Treatment costs
What are pre testicular causes of infertility in men
Congenital & Acquired Endocrinopathies
Klinefelters 47XXY
HPG, T, PRL issues
What are the testicular causes of infertility in men?
(Congenital)
Cryptorchidism
Infection STDs
Immunological Antisperm Abs
Vascular Varicocoele
Trauma/Surgery
Toxins
Chemo/DXT/Drugs/Smoking
What are the post-testicular causes of infertility in men?
Congenital Absence of vas deferens in CF
Obstructive Azoospermia
Erectile Dysfunction -
Retrograde Ejaculation
Mechanical Impairment
Psychological
Iatrogenic Vasectomy
What is cryptorchidism?
Normal path for testis descent is from abdomen through inguinal canal to testicular sac
Undescended testis (90% of this is in the inguinal canal)
What are causes of infertility in women
Ovarian Causes (40%)
-Anovulation (Endo)
-Corpus luteum insufficiency - insufficient progesterone so failure to implant
Pelvic Causes (5%)
-Endometriosis
-Adhesions
Tubal Causes (30%)
Tubopathy due:
-Infection
-Endometriosis
-Trauma
Uterine Causes (10%)
Unfavourable endometrium due:
-Congenital malformations
-Infection/Inflammation/Scarring (adhesions)
-Fibroids
Cervical Causes (5%)
Ineffective sperm penetration due:
-Infection/Inflammation
-Immunological (antisperm Ab)
What is endometriosis?
Presence of functioning endometrial tissue outside the uterus
-5% of women
-Responds to oestrogen
What are the symptoms of endometriosis?
↑ Menstrual pain
Menstrual irregularities
Deep dyspareunia
Infertility
What are fibroids?
Benign tumours of the myometrium
-1-20% of pre-menopausal women (increases w age)
-Responds to oestrogen
What are the symptoms of fibroids?
Usually asymptomatic
↑ Menstrual pain
Menstrual irregularities
Deep dyspareunia
Infertility
Explain the HPG axis
Kisspeptin neurones secrete kisspeptins that binds to GnRH neurones and then that causes secretion into the hypophyseal portal circulation
That causes LH and FSH to be released from the gonadotrophs
That then causes testosterone or oestrogen to be produced in the gonads
What are causes of hyperprolactinaemia
Tumour - micro/macro
Macro can press optic chiasm just above pituitary
Pregnancy
Medications - dopamine antagonists
What happens in hyperprolactinaemia
LH AND FSH AND TESTOSTERONE all down
What patterns would you see in primary testicular failure? e.g. Klinefelter’s Syndrome
LH and FSH up
Testosterone down
What happens in hypogonadotropic and hypogonadism?
Where
Lower GnRH
Lower LH and FSH
Lower T
Hypothalamus and anterior pituitary
What happens in hypergonadotropic and hypogonadism?
LH and FSH up
T down
In Gonads
What causes problems in hypothalamus for infertility
Congenital Hypogonadotrophic Hypogonadism
-Anosmic (Kallmann Syndrome) or Normosmic
Acquired Hypogonadotrophic Hypogonadism
-Low BMI, XS exercise, Stress
Hyperprolactinaemia
In women: hypothalamic ameneorrhoea
What causes problems in the anterior pituitary infertility
Hypopituitarism
-Tumour, Infiltration, Apoplexy, Surgery, Radiation
What causes problems in men in the gonads infertility
Congenital Primary Hypogonadism
-Klinefelters (47XXY)
Acquired Primary Hypogonadism
-Cryptorchidism, Trauma, Chemo, Radiation
Explain Kallmann Syndrome
Failure of migration of GnRH neurons with olfactory fibres from olfactory placode (primitive nose) to hypothalamus
Low GnRh
Low LH and FSH - hypogonadotrophic
Low T - hypogonadism
Anosmia
Failure of puberty
Infertility
How does hyperprolactinaemia inhibit kisspeptin neurones
Prolactin binds to prolactin receptors on kisspeptin neurons in hypothalamus
Inhibits kisspeptin release.
Decreases downstream GnRH/LH/FSH/T/Oest
Oligo (>35d menses) or amenorrhoea (3-6m no menses)/Low libido (and other hypogonadal symptoms)/ Infertility/Osteoporosis
What is the treatment for hyperprolactinaemia
Dopamine agonist - cabergoline
Surgery/ DXT
What are the signs of Klinefelter’s syndrome
Tall stature
↓ Facial hair
Breast development
Female-type pubic hair pattern
Small penis & testes
Infertility
(accounts for up to 3% of cases)
Mildly impaired IQ
Narrow shoulders
Reduced chest hair
Wide hips
Low bone density
High LH and FSH, low T
What do you do to diagnose male infertility
Key History: duration, previous children, pubertal milestones,
associated symptoms (eg. T deficiency, PRL symptoms, CHH features), medications/drugs
Key Examination: BMI, sexual characteristics, testicular volume, anosmia
Key Investigations:
Semen Analysis:
Blood Tests:
LH, FSH, PRL
Morning Fasting Testosterone - carbohydrates can supress it
Karyotyping
Imaging:
Scrotal US/Doppler
(for varicocoele/obstruction, testicular volume)
MRI Pituitary
(if low LH/FSH or high PRL)
What are treatment options in terms of male infertility
General Lifestyle
Optimise BMI
Smoking cessation
Alcohol reduction/cessation
Specific Treatment:
Dopamine agonist for hyperPRL
Gonadotrophin treatment for fertility (will also increase testosterone)
Testosterone
(for symptoms if no fertility required – as this requires gonadotrophins)
Surgery
(eg. Micro Testicular Sperm Extraction (micro TESE))
What pattern would you see in premature ovarian insufficiency?
LH and FSH up
Oestradiol down
What are symptoms for premature ovarian insuffiency?
What are the causes
Same Symptoms as per Menopause
Previously called ‘Premature Ovarian Failure’ POF
Conception can happen in 20%
Diagnosis High FSH >25 iU/L (x2 at least 4wks apart)
Causes
Autoimmune
Genetic eg Turner’s Syndrome
Cancer therapy Radio- / Chemo-therapy in the past
What pattern would you see in Anorexia Nervosa-Induced Amenorrhoea
All down
In female infertility, what causes problems in the Gonads
Polycystic ovarian syndrome (normal or low E2)
Acquired Primary Hypogonadism
-Premature Ovarian Insufficiency (POI)
-Surgery, Trauma, Chemo, Radiation
Congenital Primary Hypogonadism
-Turners (45X0)
-Premature Ovarian Insufficiency (POI)
How do you diagnose Polycystic ovarian syndrome
Rotterdam PCOS Diagnostic Criteria (2 out of 3)
Oligo or Anovulation
-Normally assessed by menstrual frequency as oligomenorrhoea:
e.g. <8-9 cycles/y
Clinical +/- Biochemical Hyperandrogenism
CLINICAL
Acne, hirsutism, alopecia
BIOCHEMICAL
Raised androgens (eg Testosterone)
Polycystic Ovaries (US)
What are consequences of POS
Irregular menses / amenorrhoea
–> Infertility
Metabolic:
↑ Insulin resistance
–>Impaired glucose homeostasis
(T2DM, gestational DM)
Hirsutism
↑ Endometrial cancer risk (2-6)
What is the treatment for POS?
Oral contraceptive pill to help with irregular menses
Ovulation induction - IVF to help with infertility
Metformin to help with menses and with insulin resistance - diet and lifestyle will also help
Anti androgens (e.g. spironolactone) and creams, waxing, laser for hirsutism
Progesterone courses for endometrial cancer risk
What are the symptoms in Turner’s syndrome (45 X0)
Short stature
Low hairline
Shield chest
Wide-spaced nipples
Short 4th metacarpal
Small fingernails
Brown nevi
Amenorrhoea
Characteristic facies
Webbed neck
Coarctation of aorta
Poor breast development
Elbow deformity
Undeveloped reproductive tract
Amenorrhoea
Increase in LH and FSH
Decrease in T
What do you do to diagnose female infertility
Key History: duration, previous children, pubertal milestones,
menstrual History, medications/drugs
Key Examination: BMI, sexual characteristics, hyperandrogenism signs, anosmia
Key investigations:
Blood Tests:
LH, FSH, PRL
Oestradiol, Androgens
Mid- Luteal Prog
Karyotyping
Imaging:
US (transvaginal)
Hysterosalpingogram
MRI Pituitary
(if low LH/FSH or high PRL)
Pregnancy Test
(urine or serum HCG)
