Ovulation Disorders Flashcards
How long do regular menstrual cycles last?
28-35 days
What is day one of the menstrual cycle?
When bleeding starts = bleeding typically lasts 3-8 days
What are the phases of the menstrual cycle?
Follicular and luteal phases = defined by ovulation
What are ovulatory disorders associated with?
Oligomenorrhoea = cycle >35 days Amenorrhoea = absent menstruation
What produces GnRH?
Synthesised by neurons in the hypothalamus
How is GnRH released?
Pulsatile release = low frequency pulses stimulate FSH release, high frequency pulses stimulate LH release
Where are FSH and LH secreted from?
The anterior pituitary
What are the functions of FSH?
Stimulates follicular development and thickens endometrium
What triggers ovulation?
LH surge (peak LH levels)
What are the functions of LH?
Stimulates corpus luteum development and thickens endometrium
What do ovulation predictor kits detect?
The LH surge = 36hrs before ovulation, successful in 97%
When does oestradiol peak?
Before ovulation
When does progesterone peak?
Following ovulation
Where is progesterone produced?
By the corpus luteum to maintain early pregnancy (also by placenta during pregnancy)
Where is oestrogen secreted from?
Primarily by the ovaries (follicles) and adrenal cortex (and the placenta during pregnancy)
What is the function of oestrogen?
Stimulates the thickening of the endometrium and is responsible for the fertile cervical mucus
What do high oestrogen levels cause?
Inhibits secretion of FSH and prolactin (by negative feedback)
What are the functions of progesterone?
Inhibits secretion of LH, responsible for infertile (thick) cervical mucus, maintains thickness of endometrium and relaxes smooth muscle
How does progesterone have a thermogenic effect?
Increases basal body temperature
What are regular cycles very suggestive of?
ovulation = confirm by midluteal (D21) serum progesterone (>30nmol/L) x 2 samples
What are some methods not recommended for assessing ovulation?
BBT, cervical mucus and ovulation predictors
What are irregular cycles suggestive of?
Anovulatory cycles = needs further hormone evaluation
What is the WHO classification of ovulatory disorders?
Group 1 = hypothalamic pituitary failure
Group 2 = hypothalamic pituitary dysfunction
Group 3 = ovarian failure
How common is hypothalamic pituitary failure
Account for 10% of ovulatory disorders = often hypogonadotrophic hypogonadism
What are some features of hypothalamic pituitary failure?
Low levels of FSH/LH, normal prolactin, oestrogen deficiency (negative progesterone challenge test), amenorrhoea
What are some causes of hypothalamic pituitary failure?
Stress, excessive exercise, anorexia/low BMI, brain/pituitary tumours, head trauma, Kallman’s syndrome, steroids/opiates
What is used to treat hypogonadotrophic hypogonadism?
Pulsatile GnRH = SC or IV, pump worn continuously, pulsatile administration every 90mins, 90% ovulation rate
How should hypothalamic pituitary failure be treated?
Stabilise weight (BMI >18.5) Gonadotrophin (FSH/LH) daily injections = higher multiple pregnancy rates
How is response to treatment for hypothalamic pituitary failure monitored?
Using ultrasounds (follicle tracking)
How common are hypothalamic pituitary dysfunctions?
Accounts for 85% of ovulatory disorders (includes PCOS)
What are some features of hypothalamic pituitary dysfunction?
Normal gonadotrophins/excess LH, normal oestrogen levels, oligo/amenorrhoea
How common is polycystic ovary syndrome (PCOS)?
Affects 5-15% of women of reproductive age = 10-20% have amenorrhoea, 80-90% have oligomenorrhoea
What is the Revised Rotterdam diagnostic criteria for PCOS?
Presence of 2 of = oligo/amenorrhoea, clinical and/or biochemical signs of hyperandrogenism (acne/hirsutism), polycystic ovaries on US
What is the appearance of polycystic ovaries on US?
12 or more 2-9mm follicles, increased ovarian volume >10ml, unilateral/bilateral
How common is insulin resistance in PCOS?
Seen in 50-80% = normal pancreatic reserve (hence hyperinsulinaemia), 20% have frank glucose intolerance or type 2 diabetes
How does insulin affect sex hormones?
Acts as co-gonadotrophin to LH = 60% have elevated LH, 95% have altered LH/FSH ratios
Lowers SHBG levels = increased free testosterone leads to hyperandrogenism
What does the management of PCOS depend on?
The patient’s symptoms and needs (ie subfertility should be treated with ovulation induction)
What are some symptoms of PCOS?
Oligo/amenorrhoea, hirsutism, obesity, acne, alopecia
What are the pre-treatment interventions for PCOS?
Weight loss to optimise results (BMI <30), stop smoking and alcohol, folic acid 400mcg/5mg daily, check prescribed drugs, rubella immunity
What are some ways to cause ovulation induction in patients with PCOS?
Clomifene citrate, gonadotrophin daily injections, laparoscopic ovarian diathermy
What are some features of clomifene citrate?
First line, 50/100/150mg orally, days 2-6, 70% ovulate, 40-60% conceive alternatively on tamoxifen/letrozole (all three are anti-oestrogens)
What are some features of gonadotrophin daily injections?
Recombinant FSH, 80% ovulate, 60-70% conceive
Risks = multiple pregnancies, overstimulation
What is the risk of laparoscopic ovarian diathermies?
Ovarian destruction
What are alternative treatments for patients resistant to clomifene citrate?
15-20% of cases = metformin, gonadotrophin injections, laparoscopic ovarian drilling, assisted conception treatment
What must metformin be used alongside?
Lifestyle modifications
What are the effects of metformin as a treatment for PCOS?
Improves insulin resistance, reduces androgen production, restores menstruation and ovulation, doesn’t help weight loss, may increase pregnancy rate
What are the risks of ovulation induction?
Ovarian hyperstimulation, multiple pregnancies, risk of ovarian cancer
What are some features of ovarian hyperstimulation?
Affects 10% of IVF patients, ranges from mild to severe, increased risk in PCOS or if age<35
What maternal pregnancy complications do multiple pregnancies increase the risk of?
Hyperemesis, anaemia, pre-eclampsia, hypertension. gestational diabetes, postnatal depression
What are some risks associated with multiple pregnancies?
Early/late miscarriage, low birth weight (<2.5kg), prematurity, disability, stillbirth/neonatal death, twin-twin transfusion syndrome (TTTS)
What is chorionicity?
Refers to type of placentation = number of membranes that surrounds babies in a multiple pregnancy
What are some features of chorionicity?
Lambda sign on US for dichorionic, T sign on US for monochorionic, monochorionic twins 3x risk of perinatal mortality compared to dichorionic twins
How common is twin-twin transfusion syndrome?
Complicates 10-15% of MCDA twin pregnancies, responsible for 15-17% of all perinantal mortality in twins
What is twin-twin transfusion syndrome?
Unbalanced vascular communications within placental bed
What occurs in twin-twin transfusion syndrome?
Recipient develops polyhydramnios, donor develops oliguria, oligohydramnios and growth restrictions, 80-100% fatal if untreated
What are the treatment options for twin-twin transfusion syndrome?
Laser division of placental vessels, amnioreduction, septosectomy
What are some early problems caused by prematurity?
40-60% require neonatal intensive care, 8% need help with breathing, 6% suffer from respiratory distress syndrome
What are some late problems caused by prematurity?
Lower IQ, ADHD, behavioural difficulties, language development problems
What is the history of hyperprolactinaemia?
Amenorrhoea, galactorrhoea, current medication important
Examine visual fields
What do investigations for hyperprolactinaemia show?
Normal FSH/LH, low oestrogen, raised serum prolactin (>1000iu/L on 2 or more tests), TFT normal, MRI (to diagnose micro/macroprolactinoma)
How are dopamine agonists used to treat hyperprolactinaemia?
Longer acting = cabergoline twice weekly
Conventional treatment with bromocriptine
Should be stopped when pregnancy occurs
How common is ovarian failure?
5% of ovulatory disorders
What are the features of ovarian failure?
High levels of gonadotrophins (raised FSH >30iu/L x 2 samples), low oestrogen levels, amenorrhoea
What is premature ovarian failure?
Menopause before age 40
What are some causes of premature ovarian failure?
Turner syndrome (46X0), XX gonadal agenesis, Fragile X, autoimmune ovarian failure, bilateral oophorectomy, pelvic radio/chemotherapy
How can premature ovarian failure be treated?
Hormone replacement therapy, assisted conception treatment, freezing of ovum before chemo/radiotherapy where POF anticipated
What should be included in a gynaecological history?
Details of menstrual cycle, amenorrhoea, hirsutism, acne, galactorrhoea, headaches, visual symptoms, PMH, drug history
What are some biochemical tests that can be done to investigate ovarian disorders?
Midluteal progesterone (day 21), progesterone challenge tests, early follicular phase testing (days 2-5)
What is tested for during the early follicular phase (days 2-5)?
Serum FSH/LH/oestradiol, serum testosterone/SHBG, prolactin, TSH
What result of a progesterone challenge test indicates normal oestrogen levels?
Menstrual bleed in response to a five day course of progesterone
How are ultrasounds used to investigate ovulatory disorders?
Transvaginal US, routine part of infertility consultation, examines normal pelvic anatomy, look for follicular growth and monitor ovulation induction
What are some other tests that can be done to investigate ovulatory disorders?
Karotypes, auto-antibody screen, MRI of pituitary fossa, bone density scan
