Fertility Flashcards
What is the definition of subfertility?
If conception has not occurred after 12 months of regular unprotected intercourse
Primary - female has never conceived
Secondary - previous conceived even if it resulted in miscarriage or termination
What conditions are required for pregnancy?
Egg must be produced (30%)
Adequate sperm release (25%)
Sperm must reach egg/fallopian tube blockage (25%)
Fertilised egg must implant (30%)
What causes the decline in female fertility?
Reduced genetic quality of remaining oocytes
What occurs during ovulation?
High levels of FSH cause maturation of several follicles which produce more oestrogen
Intermediate oestrogen has negative feedback effect so less LH and FSH are produced
Maturing follicles compete for stimulating hormone and only dominant follicle has enough gonadotrophin receptors to continue
Increased oestrogen causes positive feedback so more FSH and LH -> rupture of follicle
How is ovulation detected?
Spotting/discharge/mittelschmerz
What are cases of anovuation?
PCOS Hypothalamic hypogonadism Hyperprolactinaemia Thyroid disease - reduce fertility Androgen secreting tumours - cause virilisation
What is a polycystic ovary?
Characteristic transvaginal USS appearance of multiple small follicles in an enlarged ovary
20% of all women
Majority have normal cycles
What is polycystic ovarian syndrome?
Women with PCO who put on weight
5% of women
80% of anovulatory infertility
What are the diagnostic criteria for PCOS?
PCO on USS Irregular periods (>35 days apart) Hirsutism: clinical (acne, excess body hair) or biochemical (raised testosterone)
What is the pathology of PCO?
Disordered LH production and peripheral insulin resistance
Increased LH and insulin act on PCO causing increased adrenal androgen production and reduced hepatic production of steroid hormone binding globulin
Therefore increased free androgens
What does increased androgens cause in PCOS?
Disrupt folliculogenesis -> excess small ovarian follicles and irregular ovulation
Hirsutism
What is the link between body weight and androgen levels in PCOS?
Increased body weight leads to increased insulin resistance therefore increased insulin -> androgens
How does PCOS present?
Obesity Acne Hirsutism Oligo/amenorrhoea Increased miscarriage
How is PCOS investigated?
Blood tests
- normal FSH
- normal prolactin
- normal TSH
- raised testosterone
- raised LH
USS
- PCO
Other
- screen for diabetes and abnormal lipids
How does the level of FSH differentiate causes of anovulation?
Raised in ovarian failure
Low in hypothalamic disease
Normal in PCOS
What are complications of PCOS?
50% develop type II diabetes
30% develop gestational diabetes
Endometrial cancer - unopposed oestrogen action
How is PCOS treated?
Diet and exercise
COCP will regulate menstruation and treat hirsutism - need 3-4 bleeds/year
Antiandrogens (cyroterone acetate or spironolactone)
Metformin - reduces insulin therefore androgens and hirsutism
What is hypothalamic hypogonadism?
Reduction in GnRH production reduced stimulation of pituitary, reduces FSH and LH levels and reduces oestrogen
ANOREXIA NERVOSA
Diets
Athletes
Stress
What is Kallmann’s syndrome?
GnRH secreting neurones fail to develop
What causes prolactinaemia?
Benign tumour (adenoma) Hyperplasia of pituitary cells PCOS Hypothyroidism Psychotrophic drugs
How does prolactinaemia present?
Reduces GnRH so cascade is reduced Oligo/amenorrhoea Galactorrhoea - milky discharge from nipples Headaches Bitemporal hemianopia
How is prolactinaemia treated?
Dopamine agonist
Bromocriptine
Cabergoline
How does pituitary damage affect ovulation?
Reduces FSH and LH release
Can result from pressure from tumour or infarction following PPH (Sheehan’s syndrome)
What are ovarian causes of anovulation?
PCOS
Premature ovarian failure
Luteinised unruptured follicle syndrome - follicle develops but isn’t released
How is ovulation induced in PCOS?
Clomifene - use for 6 months
Antioestrogen - blocks receptors in hypothalamus and pituitary so oestrogen cannot inhibit release of FSH and LH
Given days 2-6 of cycle to cause follicle to mature
Monitor via transvaginal USS to check endometrium doesn’t thin
Can cause multiple pregnancies
Increase up to 150mg/day
What are second line treatments for PCOS?
Metformin - used with clomifene to increase effectiveness
If continued during pregnancy, decreases risk of early miscarriage and gestational diabetes
What is the treatment ladder for inducing ovulation?
Weight loss and lifestyle changes Clomifene Metformin Gonadotrophins Ovarian diathermy IVF
How does surgery improve anovulation?
Each ovary is diathermied for a few seconds and tubal patency tested at same time
How are hormones used to improve anovulation?
Recombinant FSH +/- LH are given in step up doses every 5-7 days
USS of ovaries and when large enough, hCG is given
What are side effects of ovulation induction?
Multiple pregnancy - with clomifene or gonadotrophins
Ovarian hyperstimulation syndrom
Ovarian and breast carcinoma
What stimulates spermatogenesis?
LH stimulates production of testosterone in Leydig cells of testis
FSH and testosterone control Sertoli cells which synthesis and transport sperm
What is normal semen analysis?
> 1.5ml volume
15 million/ml sperm
32% progressive motility
What causes an abnormal sperm analysis?
Smoking Alcohol Drugs Chemicals Inadequate cooling Varicocoele Antisperm antibodies
How is male subfertility investigated?
Semen analysis is repeated after 12 weeks
Blood test - FSH, LH, testosterone, prolactin, TSH, cystic fibrosis
What causes disorders of fertilisation?
Tubal damage - infection, endometriosis, adhesions
Cervical problems
Sexual problems
How are disorders of fertilisation treated?
Laparoscopic addhesiolysis and salpingostomy
How are problems with fertilisation detected?
Laparoscopy and dye test
Hysterosalpingogram
What are indications for assisted conception?
Failure of other methods Unexplained subfertility Male factor subfertility Tubal blockage Endometriosis
What is intrauterine insemination?
Washed sperm are injected into uterus
Done after urine LH test or gonadotrophin ovulation induction
What is IVF?
Embryos are fertilised outside uterus and then transferred back
What hormones are given before IVF?
2 weeks of daily sub-cut gonadotrophin injections
Then hCG or LH given and 35 hours later egg is collected
What is ICSI?
Intracytoplasmic sperm injections
IVF plus sperm is injected into oocute
How does OHSS present?
Hypovolaemia Electrolyte disturbances Ascites Thromboembolism Pulmonary oedema
How is OHSS treated?
Intravascular volume restoration Electrolyte monitoring Analgesia Thromboprophylaxis Drain ascites fluid
What is OHSS?
Gonadotrophins (LH + FSH) overstimulate follicles
Cause large and painful
What are risk factors for OHSS?
Age less than 35
PCO
