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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Subfertility = failure to conceive after 12 months of regular UPSI. Investigate after 12 months (<36 years) or 6 months (≥36 years or known risk factors)
- Causes: male factor ~30%, ovulatory disorders ~25%, tubal damage ~20%, unexplained ~25%
- Male: semen analysis (x2 if abnormal). Female: day 2–5 FSH/LH/oestradiol, day 21 progesterone (ovulation), tubal patency test, pelvic USS
- Ovulatory disorders: PCOS most common. Treat with weight loss, clomifene citrate (anti-oestrogen → stimulates ovulation), or letrozole
- Tubal damage: HSG or laparoscopy + dye test. IVF bypasses tubal factor
- IVF: offered on NHS after 2 years if <43 years. Up to 3 cycles depending on local commissioning
Overview
Subfertility is defined as failure to conceive after 12 months or more of regular unprotected sexual intercourse. It affects approximately 1 in 7 couples in the UK. The terminology "subfertility" is preferred over "infertility" as most couples have reduced rather than absent fertility. Causes are broadly categorised as male factor (30%), female factor (ovulatory 25%, tubal 20%, other), combined (20%), and unexplained (25%). A systematic investigation of both partners should begin after 12 months of trying, or sooner if the woman is ≥36 years or there are known risk factors for subfertility.
Epidemiology
Subfertility affects approximately 1 in 7 couples (about 3.5 million people in the UK). Female fertility declines progressively after age 30, more sharply after 35, and substantially after 40. The most common cause of female subfertility is anovulation (usually due to PCOS). Tubal factor subfertility is most commonly due to previous PID (chlamydia). Male factor subfertility is most commonly due to idiopathic abnormalities in sperm count, motility, or morphology. Lifestyle factors affecting fertility include obesity, smoking, alcohol, recreational drugs, and excessive heat exposure to testes.
Clinical Features
Symptoms
Failure to conceive despite regular unprotected intercourse for ≥12 months
Irregular or absent periods (suggests anovulation — PCOS, hypothalamic amenorrhoea)
Dysmenorrhoea and deep dyspareunia (suggests endometriosis)
Previous PID, STI, or pelvic surgery (suggests tubal damage)
Galactorrhoea (hyperprolactinaemia)
Male: history of undescended testes, testicular surgery, mumps orchitis, chemotherapy, varicocele
Signs
BMI: obesity (anovulation, reduced sperm quality) or underweight (hypothalamic amenorrhoea)
Hirsutism, acne, acanthosis nigricans (PCOS)
Galactorrhoea (hyperprolactinaemia)
Visual field defects (pituitary tumour)
Testicular examination: size, varicocele, absence
Investigations
First-line
Semen analysis (male)First-line male investigation. If abnormal → repeat at 3 months. WHO criteria: volume ≥1.5 mL, count ≥15 million/mL, motility ≥40%, morphology ≥4% normal. Two abnormal samples required for diagnosis
Mid-luteal progesterone (day 21 in 28-day cycle)Serum progesterone ≥16 nmol/L confirms ovulation. >30 nmol/L = adequate ovulation. If cycles irregular, time according to cycle
Hormonal profile (day 2–5)FSH, LH, oestradiol (baseline ovarian function). Raised FSH suggests diminished ovarian reserve. Raised LH:FSH ratio suggests PCOS
Pelvic USSAssess ovarian morphology (polycystic ovaries), antral follicle count, uterine pathology (fibroids, polyps)
Second-line
Tubal patency testHSG (hysterosalpingography): outpatient X-ray with contrast through cervix — shows tubal fill and spill. OR HyCoSy (hystero-contrast sonography) — USS-based alternative
AMH (anti-Müllerian hormone)Marker of ovarian reserve. Low AMH predicts poor response to IVF stimulation. Can be tested on any day of cycle
Prolactin, TFTsExclude hyperprolactinaemia and thyroid dysfunction as causes of anovulation
Rubella immunityCheck and vaccinate if non-immune before assisted reproduction
Specialist
Laparoscopy and dye testGold standard for tubal patency. Also assesses peritoneal disease (endometriosis, adhesions). Consider if HSG abnormal or endometriosis suspected
Testicular USSIf azoospermia or severe oligospermia — exclude obstruction or testicular pathology
KaryotypeIf azoospermia (Klinefelter syndrome 47,XXY) or POI (Turner syndrome 45,X)
1
Lifestyle advice
- Optimise BMI (18.5–29.9) — both partners. Obesity reduces fertility and IVF success
- Stop smoking — both partners. Smoking reduces sperm quality and ovarian reserve
- Limit alcohol (<14 units/week for women, avoid binge drinking)
- Advise regular intercourse every 2–3 days throughout the cycle (not just around ovulation)
- Folic acid 400 mcg daily for women. Reduce caffeine to <200 mg/day
2
Anovulatory subfertility
- PCOS (WHO group II — most common): weight loss if BMI >30 (even 5–10% loss can restore ovulation)
- Clomifene citrate 50–150 mg (days 2–6): anti-oestrogen → stimulates FSH release → ovulation. First-line medical treatment. Max 6 cycles. USS monitoring to reduce multiple pregnancy risk
- Letrozole (aromatase inhibitor): increasingly used as alternative to clomifene, particularly in PCOS
- Gonadotrophins (FSH injections): if clomifene fails. Requires specialist supervision and USS monitoring
- Laparoscopic ovarian drilling: second-line for PCOS if clomifene fails — creates small holes in ovarian cortex
3
Tubal subfertility
- Mild tubal disease: tubal surgery (laparoscopic adhesiolysis, salpingostomy) may be offered
- Severe tubal damage: IVF is the treatment of choice (bypasses tubes)
- Hydrosalpinx: clip or remove (salpingectomy) before IVF — improves success rates
4
Male factor subfertility
- Mild male factor: IUI (intrauterine insemination) may be offered
- Moderate-severe male factor: IVF with ICSI (intracytoplasmic sperm injection)
- Azoospermia: surgical sperm retrieval (PESA/TESA) + ICSI, or donor sperm
5
Assisted reproduction — IVF
- NHS funding: up to 3 full cycles offered to women <43 years after 2 years of trying (varies by local commissioning)
- Process: ovarian stimulation (gonadotrophins) → egg retrieval → fertilisation in laboratory → embryo transfer
- ICSI: sperm injected directly into egg — used for male factor
- Live birth rate per cycle: ~25–30% (age-dependent: higher <35, significantly lower >40)
- Risks: ovarian hyperstimulation syndrome (OHSS), multiple pregnancy (mitigated by single embryo transfer policy), ectopic pregnancy
Complications
- Ovarian hyperstimulation syndrome (OHSS): From gonadotrophin/IVF treatment — ovarian enlargement, ascites, pleural effusions, VTE risk. Mild (common), severe (rare but life-threatening)
- Multiple pregnancy: Risk with clomifene (~10% twins) and IVF. Mitigated by single embryo transfer
- Psychological impact: Significant emotional distress, relationship strain, depression, anxiety. Offer psychological support
- Ectopic pregnancy: Slightly increased risk with IVF and with tubal disease
UKMLA Exam Tips
- 1Investigate after 12 months of regular UPSI. Earlier (6 months) if ≥36 or known risk factor
- 2Semen analysis is the FIRST male investigation. TWO abnormal samples needed (3 months apart)
- 3Day 21 progesterone: ≥16 nmol/L = ovulation occurred. This is for a 28-day cycle — adjust for longer cycles
- 4Clomifene = first-line for anovulatory subfertility (PCOS). Anti-oestrogen that stimulates FSH
- 5PCOS is the most common cause of anovulatory subfertility
- 6Tubal damage from previous PID/chlamydia → IVF bypasses the tubes
- 7AMH = ovarian reserve marker. Low AMH = poor IVF response. Can be tested any day
- 8Hydrosalpinx reduces IVF success — clip or remove before treatment
practicetest your knowledge on subfertilityApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — obstetrics and beyond.
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