Ovulatory disorders Flashcards
Describe a regular menstrual cycle
Lasts 28-35 days and has 2 phases:
• Follicular
• Luteal
Define oligomenorrhea?
Cycle >35 days
Define amenorrhea?
Absent menstruation of a cause:
• Primary
• Secondary
Symptoms of anovulation?
Oligomenorrhea and amenorrhea
Describe the HPO (hypothalamic-pituitary-ovarian) axis
Hypothalamus produces GnRH, which stimulates the pituitary gland to produce LH and FSH
These stimulate the ovaries to produce:
• Oestradol - -vely feedbacks to the pituitary gland
• Progesterone - -vely feedbacks to the hypothalamus
Production, release and function of GnRH?
Synthesised by neurons in the hypothalamus and is released in a pulsatile manner
Stimulates FSH (low frequency pulses) and LH (high frequency pulses) synthesis/release from the anterior pituitary gland
Functions of FSH?
Stimulates follicular development and thickens the endometrium
Functions of LH?
- Peak of LH stimulates ovulation
- Stimulates corpus luteum development
- Thickens endometrium
What does the ovulation predictor kit do and what is its downfall?
Detects LH surge (which occurs 36 hours before ovulation)
Beware: for 3/100 women, this is not reliable as LH is not always in the urine
Which hormones peak before and after ovulation?
Oestradiol - peaks before ovulation
Progesterone - peaks after ovulation (it is produced by the corpuc luteum)
Production and functions of oestrogen?
Secreted primarily by the ovaries (follicles) and the adrenal cortex; also secreted by the placenta during pregnancy
Functions:
• Stimulates endometrial thickening
• Responsible for fertile cervical mucous
• High oestrogen conc. inhibits FSH and prolactin secretion (-ve feedback) and stimulates LH secretion (+ve feedback)
Production and functions of progesterone?
Secreted by the corpus luteum, to maintain early pregnancy; also secreted by the placenta during pregnancy
Functions:
• Inhibition of LH secretion
• Responsible for infertile (thick) cervical mucous
• Maintains endometrial thickness
• Has a thermogenic effect (increases basal body temp)
• Relaxes smooth muscles
What does a regular cycle say about ovulation?
Very suggestive of ovulation and this can be confirmed with mid-luteal (day 21) serum progesterone measurements with 2 samples
> 30 nmol/L is normal
What does an irregular cycle say about ovulation?
Likely anovulatory and requires further hormone evaluation
WHO classification for the 3 groups of ovulatory disorders?
Group 1 - hypothalamic pituitary failure
Group 2 - hypothalamic pituitary dysfunction
Group 3 - ovarian failure
Consequence of hypothalamic pituitary failure?
Hypogonadotrophic hypogonadism - there are low FSH/LH levels
Features of hypothalamic pituitary failure (group 1)?
Oestrogen deficiency (progesterone challenge test is -ve)
Normal prolactin
Amenorrhea
Causes of hypothalamic pituitary failure?
Stress, excessive exercise (athletes), anorexia/low BMI
Brain/pituitary tumours and head trauma
Kallman’s syndrome
Drugs, e.g: steroids, opiates
Mx of hypothalamic anovulation
Stabilise weight (BMI >18.5 is the aim)
Pulsatile GnRH if they continue to have hypogonadotrophic hypogonadism
Gonadotrophin (LH + FSH) daily injections
Monitoring of hypothlamaic anovulation treatment?
Both of the treatment required USS monitoring of response (follicle tracking)
Risk with gonadotrophin (LH +FSH) daily injections?
Higher rate of multiple pregnancy
Features of hypothalamic pituitary dysfunction (group 2)?
Normal gonadotrophins OR there can be excess LH
Normal oestrogen levels
Oligo/amenorrhea
Most common cause of hypothalamic pituitary dysfunction?
Polycystic Ovarian Syndrome (PCOS)
Rotterdam criteria for the diagnosis of PCOS?
Oligo/amenorrhea
- Polycystic ovaries (USS appearance):
• 12/more 2-9mm follicles
• Increased ovarian volume (>10ml)
• Unilateral/bilateral - Clinical and/or biochemical signs of hyperandrogenism, e.g:
• Hirsutism
• Acne
Symptoms of PCOS?
Sub-fertility
Oligo/amenorrhea
Hirsutism
Obesity
Acne
Describe the insulin resistance in PCOS
They have a normal pancreatic reserve so they have hyperinsulinaemia
Some develop frank glucose intolerance or NIDDM
Effects of insulin in PCOS?
Acts as a co-gonadotrophin to LH
Also lowers SHBG (sex-hormone binding globulin) so there is increased free testosterone, leading to hyperandrogenism
What does Mx of PCOS depend on?
Depends on symptoms and patient needs
Pre-treatment of anovulation in PCOS?
Weight loss optimises results (BMI>30 = poor outcome)
Lifestyle modification (smoking and alcohol <5 units)
Folic acid 400mcg / 5mg daily
Check prescribed drugs
Ensure Rubella immunity
Ensure serum analysis is normal and that fallopian tubes are patent
Treatments that cause ovulation induction in PCOS?
- Clomifene citrate (days 2-6) is the 1ST-LINE treatment
- Gonadotrophin therapy (recombinant FSH) daily injections
- Laparoscopic ovarian diathermy
Alternatives to clomifene citrate?
Tamoxifen
Letrozole
Risks with gonadotrophin therapy?
Multiple pregnancy
Over-stimulation
Risks with laparoscopic ovarian diathermy?
Ovarian destruction
Options for those who do not ovulate on Clomifene?
Metformin (+ clomifene citrate) - can induce ovulation for those where clomifene citrate was not effective alone; it is used alongside lifestyle modifications
Gonadotrophic therapy (FSH injections)
Laparoscopic ovarian drilling
Assisted conception treatment
Effects of metformin in ovulation induction?
Improves insulin resistance, reduces androgen production and increases SHBG
Restores menstruation and ovulation
May increase pregnancy rate
IT DOES NOT AID WEIGHT LOSS
Risks with ovulation induction?
Ovarian hyperstimulation (most serious consequence) - formation of many follicles and the end result is fluid shift; risk increases if aged <35 years and if patient has PCOS
Multiple pregnancy (twins, etc)
May increase ovarian cancer risk
Types of ovarian hyperstimulation?
Mild - abdominal bloating/pain
Moderate - moderate abdominal pain, N&V, USS evidence of ascites, etc
Severe - clinical ascites, oliguria, etc
Critical - tense ascites, thromboembolism, ARDS, etc
Risks assoc. with multiple pregnancy for the mother?
Increased maternal pregnancy complications:
• Hyperemesis
• Anaemia
• Hypertension and pre-eclampsia
• Gestational diabetes (assoc. increase risk IUD / SB)
• Mode of delivery (caesarian) / PPH
• Post-natal depression / stress
Risks assoc. with multiple pregnancy for the neonate?
Increased risk of: • Early and late miscarriage • Low birth weight (<2.5kg) • Prematurity • Disability • Stillbirth / neonatal death • Twin-twin transfusion syndrome (TTTS) - affects identical twin pregnancies and causes unequal blood supply
Which types of twins have a higher peri-natal mortality?
Monochorionic (monozygotic and shared the same placenta) twins
NOTE: monoamniotic means that the twins shared the same amniotic sac
What sign on USS suggests a dichorionic pregnancy?
Lambda sign (twin peak) - triangular appearance of the chorion insinuating between the layers of the inter-twin membrane
What sign on USS suggests a monochorionic pregnancy?
T-sign - absence of a twin peak sign
Pathophysiology of twin-twin transfusion syndrome?
Unbalanced vascular communications within the placental bed
Recipient develops polyhydramnios (too much amniotic fluid)
Donor develops oliguria, oligohydramnios and growth restriction
Treatment options for twin-twin transfusion syndrome?
Laser division of placental vessels
Amnioreduction
Septostomy
Early problems that occur with prematurity?
Neonatal intensive care required, help with breathing and some suffer from neonatal respiratory distress syndrome
Long-term problems that occur with prematurity?
Higher risk of a child being affected with disability, e.g: cerebral palsy, impaired sight, congenital heart disease
Lower IQ
Attention Deficit Hyperactivity Disorder (ADHD) and long-lasting behavioural difficulties
Problems with language development
Another cause of hypothalamic pituitary dysfunction (group 2), other than PCOS?
Hyperprolactinaemia (raised serum prolactin >1000 iu/l on 2/more occasions)
Treatment of hyperprolactinaemia?
Dopamine agonist (cabergoline); these must be stopped when pregnancy occurs
Features of ovarian failure (group 3)?
High levels of gonadotrophins (raised FSH >30 iu/l with 2 samples)
Low oestrogen
Amenorrhea
Menopausal
What is premature ovarian failure?
Menopause before 40 years of age
Causes of premature ovarian failure?
Genetic:
• Turner syndrome (46 XO)
• XX gonadal agenesis
• Fragile X
Autoimmune ovarian failure
Bilateral oophrectomy
Pelvic radio/chemotherapy
Cause can be unclear
Treatment of premature ovarian failure?
HRT (hormone replacement therapy)
Egg/embryo donation (assisted conception)
Ovary/egg/embryo cryopreservation prior to chemo/radiotherapy where premature ovarian failure is anticipated
Counselling/support
Points to cover in a gynaecological history?
Details of menstrual cycle Amenorrhoea (do a pregnancy test) Hirsutism and acne Galactorrhea Headaches Visual symptoms PMH and DH
Biochemical tests for anovulation?
Mid-luteal progesterone (day 21)
In the early follicular phase (day 2-5): • Serum FSH, LH, oestradiol • Serum testosterone, SHBG • Prolactin • TSH (hypothyroidism)
Use of a progesterone challenge test?
Menstrual bleeding in response to a 5-day course of progesterone indicates normal oestrogen levels
Other Ix for anovulation?
USS scan
Karyotype
Auto-Ab screen
MRI of pituitary fossa
Bone density scan for BMD (risk of osteoporosis if oestrogen is low)
