Female Infertility

Female infertility is failure to conceive after 12 months of regular unprotected intercourse (6 months if aged 35 or over), where the cause lies partly or wholly with the woman.

• Causes are ovulatory disorders (polycystic ovary syndrome, hypothalamic, hyperprolactinaemia, thyroid disease, premature ovarian insufficiency), tubal disease, uterine and cervical factors, endometriosis, and unexplained infertility.
• Both partners must be assessed together.
• Age is the strongest predictor of success.

Inability to conceive; irregular or absent menses, pelvic pain, previous pelvic infection, galactorrhoea, hirsutism, weight change or recurrent miscarriage.

• Findings include obesity or low weight, acne, hirsutism, thyroid enlargement, abnormal pelvic mass, or normal examination.
• Differential diagnosis: male factor infertility, infrequent intercourse, unexplained infertility.
• Complications: prolonged infertility, psychological distress, relationship strain, ectopic pregnancy and multiple pregnancy from treatment.

Diagnosis rests on history, examination and targeted tests.

• Menstrual history, body mass index and pelvic examination.
• Mid-luteal (day 21 of a 28-day cycle) serum progesterone for ovulation (above 30 nmol/L indicates ovulation); thyroid stimulating hormone; prolactin; FSH, LH and oestradiol on day 2 to 5; anti-Müllerian hormone.
• Pelvic ultrasound; hysterosalpingography or sonosalpingography; laparoscopy with dye test and hysteroscopy as indicated.
• Semen analysis for the partner; rubella immunity; HIV, syphilis and hepatitis B tests; cervical screening.

Management treats the cause and the couple together.

• Supportive: couple counselling; intercourse every 2 to 3 days across the cycle; folic acid 400 micrograms oral daily (5 mg daily in obesity, diabetes or epilepsy); stop smoking; limit alcohol and caffeine; body mass index 19 to 30; control chronic disease.
• Pharmacological:
  • Ovulation induction: letrozole 2.5 mg oral daily on days 3 to 7, increased by 2.5 mg per cycle to 7.5 mg (maximum), or clomifene citrate 50 mg oral daily on days 2 to 6, increased to 100 mg and then 150 mg (maximum).
  • Use ovulation induction for up to 6 ovulatory cycles.
  • Polycystic ovary syndrome with insulin resistance: metformin 500 mg oral daily with food, increased over 4 weeks to 1.5 to 2 g daily in divided doses.
  • Hyperprolactinaemia: cabergoline 0.25 mg oral twice weekly, increased by 0.25 mg twice weekly every 4 weeks to a maximum of 1 mg twice weekly.
  • Hypothyroidism: levothyroxine 1.6 micrograms/kg oral daily, adjusted to a thyroid stimulating hormone below 2.5 mIU/L.
  • Active infection: ceftriaxone 500 mg IM single dose plus doxycycline 100 mg oral 12-hourly for 7 days.
• Procedures: intrauterine insemination, in vitro fertilisation or intracytoplasmic sperm injection for tubal disease, male factor, unexplained infertility or failed induction; laparoscopic surgery for endometriosis, hydrosalpinx or adhesions; hysteroscopic resection of fibroids, polyps or septa.
• Special groups: in HIV-serodiscordant couples optimise antiretroviral treatment, use pre-exposure prophylaxis and timed intercourse, or sperm washing with assisted reproduction. In women aged 35 or over move early to assisted reproduction. Stop metformin and ovulation drugs once pregnancy is confirmed, except when specialist care continues them.
• Red flags: abdominal pain with a positive pregnancy test (ectopic), ovarian hyperstimulation symptoms (distension, vomiting, breathlessness), amenorrhoea with galactorrhoea and headache or visual change.
• Follow-up: review after each treatment cycle; refer to a fertility specialist after 6 ovulatory cycles without pregnancy or sooner if aged 35 or over.