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.’
WHO 2009
Regular intercourse = every 2-3 days
What is the difference between primary and secondary infertility?
Primary: Not had a live birth previously
Secondary: Not had a live birth >12 months previously
How common is infertility?
Affects 1 in 7 couples (= 14% of couples)
But ~ half of these will then conceive in the next 12 months (ie at 24months ~ 7% of couples)
What is the most common cause of infertility in a couple?
Male factor - 30%
Female factor - 30%
Male & female factor - 30%
Unknown - 10%
What are some psychological impacts of infertility on couples?
No biological child
Impact on couples wellbeing
Impact on larger family
Investigations
Treatments (often fail)
What are some impacts of infertility on society?
Less births
Less tax income
Investigation costs
Treatment costs
What are some pre-testicular causes of infertility in males?
Congenital & Acquired Endocrinopathies:
- Klinefelters 47XXY
- HPG, T, PRL issues
What are some testicular causes of infertility in males?
Congenital
Cryptorchidism
Infection: STDs
Immunological: antisperm Abs
Vascular: varicocoele
Trauma/surgery
Toxins: chemo/DXR/drugs/smoking
What are some post-testicular causes of infertility in males?
Congenital: absence of vas deferens in cystic fibrosis
Obstruction azoospermia
Erectile dysfunction: retrograde ejaculation, mechanical impairment and psychological
Iatrogenic: vasectomy
What happens in cryptorchidism?
Undescended testis - 90% in inguinal canal
What are the pelvic causes of female infertility?
Endometriosis
Adhesions
What are the tubal causes of female infertility?
Infection
Endometriosis
Trauma
What are the ovarian causes of female infertility?
Anovulation
Corpus luteum insufficiency
What are the uterine causes of female infertility?
Unfavourable endometrium due:
-Congenital malformations
-Infection/Inflammation/Scarring (adhesions)
- Fibroids
What are the cervical causes of female infertility?
Ineffective sperm penetration due:
- Infection/Inflammation
- Immunological (antisperm Ab)
What is endometriosis and how common is it?
Presence of functioning endometrial tissue outside the uterus
Occurs in 5% of women
Responds to oestrogen
What are the symptoms of endometriosis?
↑ Menstrual pain
Menstrual irregularities
Deep dyspareunia (painful intercourse)
Infertility
What are fibroids?
Benign tumours of the myometrium
Occur in 1-20% of pre-menopausal women (increases with age)
Respond to oestrogen
What are the symptoms of fibroids?
Usually asymptomatic
↑ Menstrual pain
Menstrual irregularities
Deep dyspareunia
Infertility
How would you describe GnRH and LH levels?
Pulsatile
How would you describe sex steroid levels?
Follow a diurnal rhythm
What would you expect to happen to LH, FSH and testosterone levels in hyperprolactinaemia?
Down, down, down
Hypogonadotrophic hypogonadism
What would you expect to happen to LH, FSH and testosterone levels in Primary Testicular Failure?
LH/FSH- Up
Testosterone- Down
Hypergonadotrophic hypogonadism
What are the causes of hypothalamic (low GnRH) hypogonadotrophic hypogonadism?
Congenital HH:
- Anosmic (Kallman Syndrome or Normosmic)
Acquired HH:
- Low BMI, excessive exercise, stress
Hyperprolactinaemia
What are the pituitary causes of hypogonadotrophic hypogonadism?
Hypopituitarism:
- tumour
- infiltration
- apoplexy
- surgery
- radiation
What are the causes of hypergonadotrophic hypogonadism in men?
Congenital primary hypogonadism:
- Klinefelters (47XXY)
Acquired primary hypogonadism:
- Cryptorchidism
- Trauma
- Chemo
- Radiation
What is the pathophysiology of Kallmann Syndrome?
Failure of migration of GnRH neurons with olfactory fibres causing anosmia and hypogonadotrophic hypogonadism
What are the reproductive features of Kallmann Syndrome?
Failure of puberty
Infertility
How does hyperprolactinaemia cause hypogonadatrophic hypogonadism?
Prolactin binds to prolactin receptors on kisspeptin neurons in hypothalamus - inhibits kisspeptin release
Decreases downstream GnRH/LH/FSH/T/Oest
Causes:
- Oligo (>35d menses) or amenorrhoea (3-6m no menses)
- Low libido (and other hypogonadal symptoms)
- Infertility
- Osteoporosis
What is the treatment of hyperprolactinaemia?
Dopamine agonist (Cabergoline)
Surgery/DXT
What is Klinefelters Syndrome and what are the features?
XXY causing hypergonadotrophic hypogonadism
Features:
Tall stature
Reduced facial hair
Breast development
Female-type pubic pattern
Small penis and testes
Infertility
Mildly impaired IQ
Narrow shoulders
Reduced chest hair
Wide hips
Low bone density
What must be considered when taking an initial history for male infertility?
Duration
Previous children
Pubertal milestones
Associated symptoms (testosterone deficiency, PRL symptoms, CHH features)
Medications/drugs
What are some key examinations for male infertility?
BMI
Sexual characteristics
Testicular volume
Anosmia
What are some key investigations for male infertility?
Semen analysis
Blood tests:
- LH, FSH, PRL
- Morning fasting testosterone
- Karyotyping
Imaging:
- Scrotal US/Doppler
- Pituitary MRI
What are typical findings in semen analysis and what are the terms used to describe no/reduced sperm?
1.5 mL
15 million sperm /mL
40% motility
Azospermia - no sperm
Oligospermia - reduced sperm
What are conservative treatments for male infertility?
Optimise BMI
Smoking cessation
Alcohol reduction/cessation
What are the medical treatments for male infertility?
Dopamine agonist - hyperprolactinaemia
Gonadotrophin treatment for fertility (also increases testosterone)
Testosterone (no fertility required)
Surgery (e.g. Micro Testicular Sperm Extraction - micro TESE)
What is Premature Ovarian Insufficiency?
Same symptoms as menopause (but at an earlier age)
Conception can happen in 20%
Diagnosis - high FSH >25 iU/L (x2 at least 4wks apart)
What are the causes of Premature Ovarian Insufficiency?
Autoimmune
Genetic eg Turner’s Syndrome
Radio-/chemo-therapy in the past
What are the causes of hypergonadotrophic hypogonadism in women?
Congenital Primary Hypogonadism
-Turners (45X0)
-Premature Ovarian Insufficiency (POI)
Acquired Primary Hypogonadism
-Premature Ovarian Insufficiency (POI)
-Surgery, Trauma, Chemo, Radiation
Polycystic Ovarian Syndrome
Describe 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 in women
What makes up the Rotterdam PCOS Diagnostic Criteria and when is it used?
Used after other reproductive disorders have been excluded
Criteria (2 out of 3):
- Oligo/anovulation
- Clinical (acne, hirsutism, alopecia) +/- biochemical hyperandrogenism (raised androgens)
- Polycystic ovaries (ultrasound)
What are the characteristics of PCOS?
Irregular menses/amenorrhea - infertility
Increased insulin resistance - T2DM/gestational DM
Hirsutism
Increased endometrial cancer risk (x2-6)
What drugs are used in the treatment of PCOS?
What is Turner’s Syndrome and what are the symptoms?
45 X0
Hypergonadotrophic hypogonadism
What are the key points covered in an initial history of female infertility?
Duration
Previous children
Pubertal milestones
Menstrual history
Medication/drugs
What key examinations are done for female infertility?
BMI
Sexual characteristics
Hyperandrogenism signs
Anosmia
What key investigations are done for female infertility?
Blood tests:
- LH, FSH, PRL
- Oestradiol, androgens
- Mid-luteal Prog
- Karyotyping
Pregnancy Test (urine or serum HCG)
Imaging:
- Transvaginal US
- Hysterosalpingogram
- Pituitary MRI
