Ovulation disorders Flashcards
Recall the female HPG axis
What are ovulatory disorders associated with ?
Ovulatory disorders associated with oligomenorrhea and amenorrhea
Define what oligomenorrhoea is
menses at intervals > 35 days (infrequent periods)
What can amenorrhoea be subdivided into ?
Primary & secondary amenorrhoea
Define primary amenorrhoea
Failure to start menstruating
Define secondary amenorrhoea ?
Absence of menstruation for > 6months, other than that caused by pregnancy
For women who are concerned about their fertility what should be asked about their menstrual cycle and what advice should be given?
- They should be asked about the frequency and regularity of their menstrual cycles
- Women with regular menstrual cycles should be informed they are likely to be ovulating
- Women with irregular menstrual cycles are likey to be anovulatory
For women with regular menstrual cycles who are undergoing assessment for infertility how should ovulation be confimed?
Confirm by midluteal (D21 of a 28 day cycle) serum progesterone (>30 nmol/L) X 2 samples
For women with irregular menstrual cycles being assessed for infertility, what should be done to assess ovulation ?
- Women with prolonged irregular menstrual cycles - measure serum progesterone. Depending upon the timing of menstrual periods, this test may need to be conducted later in the cycle (for example day 28 of a 35-day cycle) and repeated weekly thereafter until the next menstrual cycle starts.
- Women with irregular menstrual cycles should be offered a blood test to measure serum gonadotrophins (FSH & LH)
What is the WHO classification of ovulatory dysfunction ?
- Group I – hypothalamic pituitary failure
- Group II – hypothalamic pituitary dysfunction
- Group III – ovarian failure
Other causes- Hyperprolactinaemia
What is Class I hypothalamic pituitary failure ?
- It is essentially where there is failure to secrete GnRH ==> failure to secrete FSH and LH ==> hypogonadism
- Called hypogonadotropic hypogonadism
What are the biochem results which indicate hypogonadotrophic gonadism ?
- Low levels FSH / LH
- Oestrogen deficiency - Negative progesterone challenge test (this tests to see if there is normal oestrogen levels - withdrawl bleeding within 10 days of progesterone challenge diagnoses anovulatory cycle)
- Normal prolactin
What does hypothalamic pituitary failure result in ?
Amenorrohea
What are the main causes of hypogonadotrophic gonadism (hypothalamic pituitary failure) ?
- Stress
- Excessive exercise
- Anorexia / low BMI
- Hypothyroidism
- Brain / pituitary tumours
- Head trauma
- Kallman’s syndrome
- Drugs (steroids, opiates)
What should be done prior to ferility treatment for someone with hypothalamic pituitary failure (Hypogonadotrophic hypogonadism)?
- Stabilise weight (BMI >18.5)
- Life style modification: smoking, alcohol
- Folic acid 400 mcg daily
- Check prescribed drugs
- Check patinet is Rubella immune
- Check there is normal semen analysis & Patent fallopian tubes
What specific fertility treatment should be given to women with hypothalamic pituitary failure (hypogonadotrophic hypogonadism)
Pulsatile GnRH or Gonadotrophin (FSH+LH) daily injections (2nd option has higher multiple preg rates)
Both need US monitoring of response
What is biochem features of hypothalamic pituitary dysfunction ?
- Normal gonadotrophins/excess LH
- Normal oestrogen levels
What is the result of hypothalamic pituitary dysfunction ?
Oligomenorrohea/amenorrhoea
What is the most common hypothalamic pituitary dysfunction disease ?
Polycystic ovarian syndrome
What is the key diagnostic criteria of polycystic ovarian syndrome ?
Is a condition where at least two of the following occur and often all three:
- At least 12 tiny cysts (follicles) develop in your ovaries.
- Clinical or biochemical signs of hyperandrogenism (such as hirsutism, acne, or male pattern alopecia), or elevated levels of total or free testosterone.
- You do not ovulate each month. Some women do not ovulate at all (oligo/amenorrhoea)
What is the US appearance of PCOS ?
- 12/more 2-9mm follicles
- Increased ovarian volume
- >10ml
- Unilateral / bilateral
What do people with polycystic ovarian syndrome often have ?
Insulin resistance - there is normal pancreatic insulin reserves so the resistance to insulin results in hyperinsulinaemia
- Insulin acts as co-gonadotrophin to LH
- Insulin lowers SHBG (sex hormone binding globulin) levels – increased free testosterone leads to hyperandrogenism
What are the general clinical features of PCOS ?
- Excess hair growth (hirtiuism) mainly on the face, tummy and chest
- Acne
- Thinning of hair on scalp (male pattern baldness)
- Weight gain
- Depression
- Irregular or light periods, or no periods at all.
- Infertility
What diagnostic investigations can you do to clarify a diagnosis of PCOS ?
US to look for polycystic ovaries
Blood tests:
- To measure LH and FSH levels - LH levels rasied but FSH levels normal (distinguishes from premature ovarian failure)
- Also measure total testosterone - this may be raised >5
What does the management of PCOS depend on ?
Depends on patient symptoms / needs -
- Subfertility: Ovulation Induction
- Oligo- / Amenorrhoea
- Hirsutism
- Obesity
- Acne/ Alopecia
What is recommened for obesity in PCOS ?
Simply weight loss
If a women with PCOS required contraception what should be used and why ?
COC pill - may help regulate her cycle and induce a monthly bleed
What is the management of hirtuism and acne in someone with PCOS?
- 1st line = COC pill (either 3rd gen. or co-cyprindiol)
- 2nd line = topical eflornithine
What is the initial management of someone with PCOS presenting with infertility ?
- Weight loss to optimise results (BMI >30 poor treatment outcome)
- Life style modification: smoking, alcohol
- Folic acid 400 mcg / 5mg daily
- Check prescribed drugs
- Check women is Rubella immune
- Check normal semen analysis & Patent fallopian tube
What is the management of PCOS?
Depends on the needs of the patient:
Weight loss and lifestyle modification to optimise treatment
For ovulation induction:
- 1st line - Clomifene citrate
- 2nd line = Gonadotrophin therapy (FSH injections) OR combined treatment with clomifene citrate and metformin
- 3rd line = Laparoscopic ovarian drilling
- Assisted conception treatment
What are the risks of ovulation induction ?
- Ovarian hyperstimulation
- Multiple pregnancy - greater risk of complications
- Risk of ovarian cancer
What additional risk is there when doing laproscopic ovarian drilling ?
Ovarian destruction
List the things there is an increased risk of in multiple pregnancies
- Hyperemesis
- Anaemia
- 4 x hypertension / 3 x pre-eclampsia
- 3 x risk gestational diabetes in turn has associated increase risk IUD / SB
- Mode of delivery / PPH
- Postnatal depression / stress
- Increased risk early and late miscarriag
- Increased risk low birth weight (<2.5kg)
- Increased risk prematurity
- Increased risk disability
- Increased risk stillbirth / neonatal death
- Twin-twin transfusion syndrome (TTTS)
What is premature ovarian failure ?
Menopause before age 40y
What are the main causes of premature ovarian failure ?
- Usually idiopathic
- Pelvic radiotherapy, chemotherapy
- Autoimmune ovarian failure
- Turner Syndrome (46XO)
- XX gonadal agenesis
- Fragile X
- Bilateral oophorectomy
- Gene mutations – FH receptor/LH receptor
What are the clinical features of turners syndrome ?
- Short stature
- shield chest, widely spaced nipples
- webbed neck
- bicuspid aortic valve (15%), coarctation of the aorta (5-10%)
- primary amenorrhoea
- cystic hygroma (often diagnosed prenatally)
- high-arched palate
- short fourth metacarpal
- multiple pigmented naevi
- lymphoedema in neonates (especially feet)
- gonadotrophin levels will be elevated
- hypothyroidism is much more common in Turner’s
- horseshoe kidney: the most common renal abnormality in Turner’s syndrome
What are the clinical features of premature ovarian failure ?
- Amenorrhoea
- Infertility
- Features of menopause (refer to O&G notes)
What are the biochem results indicating premature ovarian failure ?
- High FSH and LH
- Low oestradiol
How is premature ovarian failure (menopause) confirmed ?
2 measurements showing Raised serum FSH>30IU/L taken 1 month apart
What is the treatment of premature ovarian failure ?
- Hormone replacement therapy
- Egg or embryo donation – assisted conception treatment
- Ovary / egg / embryo cryopreservation prior to chemo/radiotherapy where premature ovarian failure is anticipated
What test should you always remember to do in someone with amenorrhoea ?
A pregnancy test!
What are the causes of hyperprolactinaemia ?
- Prolactinoma
- Pregnancy
- Oestrogens
- Physiological: stress, exercise, sleep
- Acromegaly: 1/3 of patients
- PCOS
- Primary hypothyroidism (due to thyrotrophin releasing hormone (TRH) stimulating prolactin release)
- Drugs - metoclopramide, domperidone, phenothiazines, haloperidol, SSRIs & opioids (very rarely for these two)
What are the presenting features of hyperprolcatinaemia ?
- Men: impotence, loss of libido, galactorrhoea
- Women: amenorrhoea, galactorrhoea, infertility
If large enough may have a visual field defect
What are the biochem results indicating hyperprolcatinaemia?
- Normal FSH/LH
- Low oestrogen
- Raised serum prolactin >1000 iu/l on 2 or more occasions
- TFT’s normal
What is the main cause of hyperprolactinaemia and how is it diagnosed ?
Prolactinoma - MRI used to diagnose
What is the treatment of hyperprolactinaemia (& therefore infertility caused by it) ?
1st line = dopamine agonist - carbegoline (best) alternative is bromocriptine (less effective tho)
What is turners syndrome caused by?
- It is a chromosomal disorder caused by either the presence of only one sex chromosome (X) or a deletion of the short arm of one of the X chromosomes.
- Turner’s syndrome is denoted as 45,XO or 45,X.
