Ovulation Disorders

Spectrum of conditions that affect a woman's endocrine system, which controls her hormones and her patterns of ovulation

Aetiology

Group I: hypothalamic pituitary failure

  • Account for 10% of ovulatory disorders
  • Amenorrhoea
  • Low levels of FSH/LH
  • Oestrogen deficiency - negative progesterone challenge test
  • Hypogonadotrophic hypogonadism
Causes
  • Stress
  • Excessive exercise
  • Anorexia/low BMI
  • Brain/pituitary tumours
  • Head trauma
  • Kallman's syndrome
  • Drugs (steriods, opiates)

Group II: hypothalamic pituitary dysfunction

  • Accounts for 85% of ovulatory disorders
  • Oligo/amenorrhoea
  • Normal gonadotrophins/excess LH
  • Normal oestrogen levels
  • Nearly always PCOS
    • 10-20% amenorrhoea
    • 80-90% oligomenorrhoea

Group III: ovarian failure

  • Accounts for 5% of ovulatory disorders
  • Amenorrhoic patients who are menopausal
  • High levels gonadotrophins - raised FSH>30 IU/l x 2 samples
  • Low oestrogen levels
Premature ovarian failure
  • Defined as menopause before 40 years
  • Causes include genetic e.g. Turner syndrome, autoimmune ovarian failure, bilateral oophrectomy, pelvic radio/chemotherapy

Hyperprolactinaemia

  • Should also be considered

Pathophysiology

  • Menstrual bleeding usually lasts < 5 days
  • Ovulatory disorders are associated with oligomenorrhea and amenorrhea
    • Oligomenorrhoea: cycles > 42 days (< 8 periods/year)
    • Amenorrhea: absent mentration, can be primary (never mentruated) or secondary (mentruation started then stop)

Investigations

Assessing ovulation

  • Regular cycles are highly suggestive of ovulation - confirm by midluteal (D21) serum progesterone (> 30 nmol/l) x 2 samples
  • Irregular cycles are probably anovulatory - needs hormone evaluation (FSH, LH, TSH, prolactin, oestragiol, testosterone, SHBG, FAI)

Progesterone challenge test

  • Involves administration of progesterone to induce a period - provera 5mg BD x 5 days
  • Withdrawal bleed usually within 7-10 days after progesterone, this would indicate that oestrogen levels are normal
  • If no bleeding - low oestrogen levels, uterine/endometrial abnormality or cervical stenosis

Ultrasound

  • Transvaginal
  • Examines pelvic anatomy - uterus, PCOS
  • Scans to look for follicular growth/monitor ovulation induction

Others

  • Karyotype
  • Autoantibody screen
  • MRI of pituitary
  • Bone density scan

Management of infertility caused by ovulation disorders

Pre-fertility treatment

  • Stabilise weight - BMI >18.5 and <30
  • Lifestyle modification - smoking, alcohol
  • Folic acid 400 mcg daily, 5mg daily if BMI over 30
  • Check prescribed drugs
  • Check rubella immunity
  • Normal semen analysis
  • Patent fallopian tube

Management of type I anovulation

  • Stabilise weight (BMI > 18.5)
  • Pulsatile GNRH (SC/IV pump worn continuously) OR gonadrotrophin (FSH + LH) daily injections
    • Gonadrotrophin daily injections have higher multiple pregnancy rates
  • Both need ultrasound monitoring of response (follicle tracking)

Management of type II anovulation (PCOS)

  • Lifestyle - 90% of women with PCOS are obese, only induce ovulation when BMI under 30
  • First line - clomifene citrate (PO)
    • Alternatively - tamoxifen, letrozole
  • In patients who do not respond to clomifene citrate, consider metformin - reduces insulin resistance and androgens so can restore mentruation/ovulation; may increase pregnancy rate and may improve sensitivity to clomifene
  • If fails: gonadotrophin therapy - daily recombinent FSH injections
    • Risk of multiple pregnancy or overstimulation
  • If fails: laparoscopic ovarian diathermy
    • Mainly singleton pregnancies
    • Risks: risks associated with general anaethetic and laparoscopic procedures, ovarian destruction
  • Last line: IVF

Management of premature ovarian failure

  • Hormone replacement therapy
  • Egg/embryo donation
  • Ovary/egg/embryo cryopreservation prior to chemo/radiotherapy where POF anticipated
  • Counselling/support network