fertility & health Flashcards
lifestyle factors affecting male fertility (7)
- obesity: ROS damage sperm
- opioids → dynorphin signalling (co-expressed by Kiss neurones) → switches off HPG axis → hypogonadotrophic hypogonadism
- anabolic steroids → negative feedback on LH, FSH + ∴ intratesticular testosterone
also smoking, cannabis, caffeine, alcohol
diagnostic criteria of PCOS (3)
- oligo/anovulation
- androgen excess (biochemical/clinical)
- polycystic ovaries on USS#
- > need 2/3
mechanisms causing symptoms in PCOS
increased LH and/or insulin resistance -> increased androstendione production
cause of anovulation not well understood: increased follicles and stroma -> oestrogen and progesterone -> negative feedback and decreased FSH -> antral follicle arrest
5alpha-reductase converts testosterone to DHT -> hirsutism, acne, etc.
causes of anovulation (3)
primary ovarian insufficiency
deficiency/disordered regulation of gonadotrophins
PCOS
causes of hypogonadism (2)
primary ovarian insufficiency
disorders of gonadotrophin regulation
causes of secondary ovarian dysfunction (3 categories, 11)
organic: hyperprolactinaemia, Kallman syndrome, destructive lesions of hypothalamus functional (most common): weight loss, stress, exercise gonadotrophin deficiency (rare): pituitary tumours/surgery/irradiation, granulomatous/inflammatory infiltration, iron overload
FSH and oestrogen levels in:
- primary ovarian insufficiency
- hypothalamic/pituitary disorders
- PCOS
- high FSH, low oestrogen
- normal/low FSH, low oestrogen (should measure prolactin)
- normal FSH, normal oestrogen, high LH
treatment of hypothalamic amenorrhoea (3)
Hyperprolactinaemia: dopamine agonists
Functional: diet, psychotherapy
Familial: give pulsatile GnRH
main cause of hyperprolactinaemia
pituitary adenoma (50%)
treatment of hyperprolactinaemia (1)
dopamine agonists, even in pts w pituitary tumours
normalizes prolactin, restores ovulation and can cause shrinking of prolactinoma
how does arrested antral follicle development occur in PCOS
more follicles and stroma in PCOS → increased oestrogen + progesterone → negative feedback on FSH → arrest of follicle maturation
PCOS investigations (5)
Oligo/amenorrhoea: FSH, (LH), prolactin, oestradiol
Hirsutism: testosterone
Obesity (BMI >30): glucose tolerance test
definition of infertility
inability to conceive after 1 year of regular unprotected intercourse
features of Klinefelter syndrome
47XXY
loss of sperm production in late teens/early 20s
low IQ, tall stature
genetic causes of male infertility
- Klinefelters
- CFTR mutations
- Y microdeletions (spontaneous or inherited)
- chromosomal rearrangements: SRY translocation -> XX male (cannot produce sperm w/o Y chromosome; infertile)
CFTR
- what is it
- mutations lead to?
- cystic fibrosis transmembrane regulator (cAMP-activated chloride channel)
- mild: poor sperm quality
moderate: congenital bilateral absence of vas deferens (CBAVD)
severe: CBAVD, clinical cystic fibrosis, pancreatic and liver disease
define premature ovarian insufficiency
Accelerated loss of ovarian follicles + ∴ ovarian reserve before age of 40 years
Due to rapid depletion of oocytes or complete lack of oocytes
Aetiology unclear; Turner’s, fragile X syndrome
long term health consequences of premature ovarian insufficiency (4)
- increased cardiovascular mortaility
- increased risk of Parkinsons disease
- increased risk of dementia
- increased risk of osteoporosis
treatment of premature ovarian insufficiency + principles (4)
HRT:
- Pre pubertal POI: To induce development of secondary sexual characteristics
- To relieve immediate sequelae of menopause i.e. symptom relief and quality of life
- To prevent long term sequelae of menopause
- To create an environment conducive to successful replacement of donated embryos
triad of POI (clinical features)
- elevated gonadotrophins
- oestrogen deficiency
- amenorrhoea
osteoporosis treatments and MOA (4)
- bisphosphonates: cause apoptosis of osteoclasts (bone resorption)
- statins:
a. inhibit RANKL receptor activation → ↓differentiation of osteoclasts → ↓resorption
b. ↓apoptosis of osteoblasts - pulsatile teriparatide (recombinant human parathyroid hormone): ↓resorption and ↑synthesis → ↓fragility fractures
- Denosumab: monoclonal antibody against RANKL (osteoclast receptor) -> inhibition of osteoclast activation
Led to fatal cases of severe hypocalcaemia
investigations for fertility
tests for ovarian reserve
1. antral follicle count (USS)
2. FSH (responds to number of oocytes available for recruitment)
3. AMH: produced by granulosa cells around pre-antral follicles (best test)
assessment of tubal patency
4. hysterosalpingogram: X-ray test w injection of dye
5. Sono-hysterosonography: slow infusion of sterile saline solution into uterus during USS
6. Laparoscopy and dye-test-in presence of co-morbidities (e.g. endometriosis)
other
7. semen analysis
menstrual cycle
- Menstruation
- Recruitment of antral follicles → ↑FSH
a. Dominant follicle produces inhibin
b. Granulosa cells produce oestradiol → proliferation of endometrium and ↓FSH - high levels of oestrogen → +ve feedback → LH surge → ovulation
- Corpus luteum → ↑progesterone → remodelling of endometrium in prep for pregnancy:
a. ↑blood flow and uterine secretions
b. ↓contractility of smooth muscle in uterus
c. ↑basal body temperature - Absence of implantation + hCG → ↓progesterone → menstruation
basic structure of endometrium (2)
- Stratum functionalis shed each month in menstruation
2. Basal layer contains stem cells for regeneration
common causes of female infertility (7)
- Polycystic ovarian syndrome
- Smoking
- Tubal blockage
- Obesity
- Pelvic inflammatory disease
- Advanced maternal age
- Endometriosis
MOA of clomiphene citrate
SERM: inhibits -ve feedback to hypothalamus → ↑FSH
