Fertility and subfertility Flashcards
What is the definition of subfertility?
When a couple has been having regular unprotected intercourse for a year with no conception.
What are the 4 basic conditions required for pregnancy?
- Ovulation of an egg (30% of cases have anovulatory cycles)
- Viable sperm (25% cases have a problem)
- Sperm reaching the egg (damage to fallopian tube in 25% of cases)
- Fertilised egg implanting in the uterus endometrium
What are the most common contributors to subfertility?
Ovulatory problems (30%) Male problems (25%) Tubal problems (25%) Coital problems (5%) Cervical problems (<5%) Unexplained (30% - most likely to do with implantation)
More than one cause might be present which is why the total is more than 100%.
What is the physiological process of ovulation?
Anti-mullerian hormone (AMH) is produced from small (not large) ovarian follicles and reduces the release of oestrogen.
At the beginning of each cycle, low oestrogen levels exert a positive feedback to cause hypothalamic GnRH pulses to stimulate the pituitary gland to produce FSH and LH.
As the follicle grows, production of AMH reduces and oestrogen increases.
Intermediate oestrogen levels cause negative feedback on FSH and LH so less is produced.
The maturing follicles are competing for the LH and FSH and only one is large enough (dominant follicle) to survive and continue to grow.
When high oestradiol is attained, the negative feedback is reverse and positive feedback causes FSH and LH to rise dramatically - it is the LH peak that causes the now ripe follicle to rupture.
This is ovulation.
What happens if embryo implantation occurs?
Rather than the corpus luteum involuting at the end of the cycle, the hCG produced by the trophoblast tissue acts on the corpus luteum to maintain oestrogen and progesterone production until the fetoplacental unit takes over at 8-10 weeks.
What investigations are used to detect ovulation?
Progesterone levels in the mid-luteal phase (day 21 of a 28 day cycle it peaks - basically 7 days before menstruation).
OTT urine predictor kits will indicate if the LH surge has taken place.
Temperature charts and US monitoring of follicles are methods but not used.
What is polycystic ovary?
This describes a characteristic transvaginal US appearance of multiple (12 or more) small follicles in an enlarged ovary.
There are no symptoms of the syndrome.
What is polycystic ovarian syndrome?
When 2 of the 3 criteria are met:
- PCO on ultrasound
- irregular periods (>35 days apart)
- Hirsutism (clinical - acne/excess body hair - or biochemical - raised testosterone)
What is the pathology of PCOS?
They have disordered LH production and insulin resistance and hence have higher circulating insulin levels.
Insulin and LH levels cause increased ovarian androgen production and insulin causes increased adrenal androgen production.
Increased ovarian androgens disrupt folliculogenesis, leading to excess small follicles and irregular/absent ovulation.
Raised peripheral androgens causes hirsutism.
What is the link between excess body weight and PCOS?
- Obesity can cause PCO to become PCOS
- Obesity increases insulin resistance and therefore increases peripheral androgen production from the adrenals –> hirsutism.
What hormones should be measured to exclude other diagnoses?
FSH
AMH
prolactin
TSH
What are the affects of ovarian failure, hypothalamic failure and PCOS on FSH?
Ovarian failure = FSH raised
Hypothalamic = FSH low
PCOS = FSH normal
What is the affect of PCOS on AMH levels?
Raised
What are the problems with PCOS and pregnancy?
Subfertility
Miscarriage
What are the complications of PCOS?
50% develop type 2 diabetes 30% develop gestational diabetes Endometrial cancer (due to unopposed oestrogen action)
What are the treatments for PCOS (not including fertility)
Weight loss - diet and exercise.
COCP to regulate menstruation and treat hirsutism - need at least 3 or 4 bleeds a year to protect endometrium.
Antiandrogens (spironolactone or cyproterone acetate) to treat hirsutism but conception should be avoided. Eflornithine is a topical antiandrogen used for facial hirsutism.
Metformin - sensitises to insulin and therefore reduces insulin levels and consequent androgen levels.
What are the causes of anovulation, other than PCOS?
Hypothalamic hypogonadism - anorexia, Kallmann’s syndrome (GnRH neurones don’t develop and they need GnRH pump to induce ovulation or HRT to protect bones).
Hyperprolactinaemia - excess prolactin production from the pituitary reduces GnRH release. Associated with PCOS, anti-psychotics, tumours, hypothyroidism.
Pituitary damage e.g. Sheegan’s syndrome after birth - production of GnRH is normal but FSH and LH are reduced.
Premature ovarian insufficiency
Gonadal dysgenesis
The luteinised unruptured follicle syndrome
Androgen producing tumour
Hypo- or hyperthyroidism
What is the treatment for hyperprolactinaemia?
Dopamine agonist (bromocriptine or cabergoline) because dopamine usually inhibits prolactin release.
What is premature ovarian insufficiency?
Failure of the ovaries results in no oestradiol and inhibin to inhibit FSH and LH, so theres are high.
AMH is low because there are so few small follicles in the ovary and US shows a low antral follicle count.
Need a donor egg for conception and pregnancy.
Bone protection and HRT is required for bone health.
What are the first and second line treatments for PCOS induction of ovulation? What happens if these fail?
First line:
Clomifene
Metformin
Second line:
Clomifene + metformin
Gonadotrophins
Ovarian diathermy
Fail? = IVF.
What does clomifene do?
It results in ovulation and live births in 70% and 40% respectively.
It is an anti-oestrogen, blocking oestrogen receptors in the hypothalamus and pituitary. This makes the pituitary think that there is no oestrogen and therefore produces more FSH and LH.
It is given days 2-6 and then the cycle is self-perpetuating.
Ovarian follicles are monitored - if no follicles develop then more is given the next time, and if 3 or more develop then less is given next time and the cycle is cancelled.
What is the hypothesised reason for clomifene’s ovulation rate being 70% but live birth being 40%?
Due to it’s action on the endometrium - it causes thinning.
For which women is clomifene better than metformin?
In those with BMI < 30, metformin is more efficacious. In those with a BMI > 30, clomifene works better.
Explain gonadotrophin induction of ovulation
Recombinant or purified urinary LH and FSH acts as a substitute for normal pituitary production.
Given as daily subcutaneous injections (small increases incrementally in PCOS to prevent multiple follicles).
Recombinant LH or hCG (similar to LH) is then injected to artificially kick-start ovulation.
