Subfertility / Infertility

Approximately 15% of couples will experience infertility. By definition, this is the failure to achieve pregnancy within 12 months of regular unprotected intercourse in a woman aged under 35 years or within six months in a woman aged over 35 years. Approximately 85% of couples conceive within the first 12 months of adequate, unprotected intercourse, with about 30% to 40% achieving pregnancy within the first 3 months.

Both partners are assessed together, not in sequence. Female factors account for about 50% of cases, male factors for 40%, and combined causes for the remainder.

Causes: ovulatory disorders, tubal or uterine disease, endometriosis, male factor, and unexplained. Approximately 15% to 30% of female infertility cases remain unexplained despite thorough evaluation and complete diagnostic workup.

When to assess

Assess after 12 months of trying if the woman is under 35, or after 6 months if she is over 35. Assess earlier when a risk factor is already apparent.

Factors that justify early assessment include oligomenorrhoea; amenorrhoea; known or suspected uterine, tubal or peritoneal disease; severe endometriosis; multiple surgeries to the ovary or loss of one ovary; and previous chemotherapy or radiotherapy treatment. Known or suspected male subfertility should also prompt evaluation.

Age is the most important determinant of female fertility. Age-related decline results from rising oocyte aneuploidy, which increases from 20% at age 30 to 60% at age 40. Other modifiable risk factors are smoking, moderate to high alcohol intake, high or very low BMI, and cannabis use.

History

Cover time trying to conceive, previous pregnancies in either partner, and the frequency and timing of intercourse.

Female: age, menstrual history, endometriosis symptoms (dysmenorrhoea, dyspareunia, dyschezia), cervical screening and HPV vaccination history, previous IUDs, previous STIs or PID, medications, and family history of infertility, miscarriage or prothrombotic disorders. Irregular cycles with more than a 7-day variation suggest ovulatory dysfunction, while amenorrhoea indicates hypothalamic dysfunction or primary ovarian insufficiency. A history of weight changes, stressors, hot flushes, visual disturbance, galactorrhoea or clinical hyperandrogenism may assist in delineating the cause of anovulation.

Male: age, pubertal history, post-pubertal mumps, testicular problems (cryptorchidism, torsion, trauma, surgery), erectile or ejaculatory dysfunction, androgen use, medical and surgical history, genetic conditions such as Klinefelter syndrome and cystic fibrosis, and medications, smoking and drugs.

Examination

The examination should include an assessment of body mass index and blood pressure, a focused examination of the thyroid and breasts, and auscultation of the heart sounds. An abdominal or pelvic examination may be indicated on the basis of the presenting history and to complete cervical or infectious screening.

Look for signs of hyperandrogenism — hirsutism, acne, obesity and acanthosis nigricans — which may reflect insulin resistance or PCOS, while a BMI below 18.5 kg/m² can indicate hypothalamic amenorrhoea. In men, examine the testes only if indicated by the history.

Investigations

Preliminary panel for both partners: day 2–4 FSH, LH and oestradiol; anti-Müllerian hormone; TSH; transvaginal pelvic ultrasound for antral follicle count, pelvic anatomy and features of deep infiltrating endometriosis; blood group and antibody screen; full blood examination; rubella and varicella IgG; hepatitis B, hepatitis C, HIV and syphilis serology; and genetic carrier screening if desired. Add prolactin and androgens where anovulation or PCOS is suspected.

Confirming ovulation. Ovulatory cycles are indicated by a history of regular cycle intervals of between 21 and 35 days with consistent characteristics and premenstrual molimina. Serum progesterone is not required to confirm ovulation when cycles are regular in frequency and character. Where there is doubt, a mid-luteal progesterone (seven days before the next expected menses) is confirmatory.

Ovarian reserve. Routinely performed markers include day 2–4 FSH and oestradiol, AMH, and antral follicle count on transvaginal ultrasound.

• An FSH concentration above 10 IU/L has high specificity for poor ovarian response to controlled ovarian hyperstimulation in women undergoing assisted reproduction.
• Serum AMH concentration is inversely related to female age and shows minimal variation both within and between cycles, so testing on any day of the menstrual cycle is appropriate.
• For women attempting spontaneous conception, AMH correlates poorly with fecundity — it predicts response to treatment, not natural chance of pregnancy.
• Antral follicle count above 15, or below 3 to 7, predicts hyper-response and poor ovarian response respectively, but correlates poorly with pregnancy.

Pelvic anatomy and tubal patency. Transvaginal ultrasound assesses uterine anatomy, polyps, fibroids, Müllerian anomalies, adenomyosis and endometriosis, and the mobility of pelvic organs. Tubal patency may be assessed using hysterosalpingography, hysterosalpingo-contrast sonography or hydrotubation at laparoscopy, and is generally considered after the preliminary investigations, including semen analysis, are back.

Semen analysis. Because approximately 40% of infertility cases involve a male factor, semen analysis remains a critical component of the initial workup. A normal semen analysis effectively excludes male infertility, allowing clinicians to focus on more extensive and costlier investigations of female reproductive factors. Contact the pathology provider beforehand for collection instructions — keep the sample warm, deliver it promptly, and abstain for about two days beforehand.

Preconception screening

Women presenting for assessment should have serology performed for rubella and varicella IgG at a minimum, so susceptible women can be vaccinated before pregnancy, deferring conception for at least 28 days post-vaccination. Add hepatitis B, hepatitis C, HIV and syphilis serology, which form part of the routine antenatal investigations anyway. Genetic carrier screening should also be discussed and offered to all women contemplating pregnancy.

Management

Lifestyle. Stop smoking, which reduces fertility in both partners. Limit alcohol, which is detrimental to semen quality, and caffeine. Aim for a healthy BMI — a 5–10% weight loss meaningfully improves fertility where BMI is above 28, and underweight women usually benefit from weight gain. Weight optimisation improves conception rates by 20% to 30%, while smoking and alcohol cessation increase IVF success by 15%.

Preconception care, including folate and iodine supplementation, applies to everyone at this point — see the pre-conception counselling page.

Intercourse timing. Sperm survive around 3 days and eggs 12–24 hours; ovulation occurs on days 11–16 of a 28-day cycle, so the fertile window is roughly the 5–6 days up to and including ovulation. Aim for intercourse every 2 days across that window.

Ovulation induction. Clomiphene citrate induces ovulation in approximately 80% of women, achieving a 40% pregnancy rate per cycle, with hot flushes in 10% and multiple gestation in 8%. Letrozole demonstrates superiority over clomiphene citrate in managing PCOS, offering higher ovulation, pregnancy and live birth rates. Metformin enhances ovulation in PCOS by improving insulin sensitivity. These are usually started in specialist care in Australia.

Prognosis. Women younger than 35 with ovulatory dysfunction achieve pregnancy in 70% to 80% of cases within 6 cycles. IVF live birth rates decline sharply with age.

Referral

Refer routinely to gynaecology for patients aged 18–43 with more than 12 months of infertility, more than 6 months if the woman is over 35, or any obvious fertility factor identified such as azoospermia or amenorrhoea. Fertility treatment itself is only available privately in most of Australia.

For a woman considering elective oocyte cryopreservation, the same history, examination and preliminary panel applies. The ideal age to freeze oocytes is prior to 35 years of age, as poorer pregnancy outcomes related to deteriorating egg quality are achieved from oocytes vitrified after the age of 35 years.