Infertility
Exam Tips
- Use the UK cause split in exams: male 30%, ovulatory 25%, tubal 20%, uterine/peritoneal 10%, unexplained ~25%, and remember combined factors are common.
- Classify ovulatory infertility by WHO groups (I low gonadotrophins/low oestrogen, II axis dysfunction e. g. PCOS, III ovarian failure with high gonadotrophins).
- Always assess both partners at the outset; one abnormal test does not exclude additional factors.
- PID history is high-yield: repeated episodes markedly increase tubal damage risk and future ectopic pregnancy risk.
- In management stations, include safety: counsel on multiple pregnancy and OHSS with ovulation induction, and document contraindications before prescribing.
Definition
Infertility is a reproductive disorder in which a couple does not achieve pregnancy despite regular unprotected intercourse for at least 12 months, prompting formal assessment and treatment planning. It is described as primary when there has never been a prior conception and secondary when conception has occurred previously (with the same or a different partner).
Pathophysiology
Infertility results from failure at one or more steps of reproduction: gamete production, transport, fertilisation, implantation, or early embryo development. In UK practice, major contributors are male factor (~30%), ovulatory dysfunction (~25%), tubal damage (~20%), and uterine/peritoneal pathology (~10%), with unexplained infertility in about a quarter of couples and mixed male/female factors common. Female ovulatory disorders are often framed by WHO groups: Group I (hypothalamic-pituitary failure; low gonadotrophins and low oestrogen), Group II (hypothalamic-pituitary-ovarian axis dysfunction, commonly PCOS or hyperprolactinaemia), and Group III (ovarian failure; high gonadotrophins with low oestrogen). Tubal infertility commonly follows pelvic infection (especially PID due to Chlamydia trachomatis, Neisseria gonorrhoeae, and anaerobes), with cumulative risk after repeated infection episodes; endometriosis can impair fertility through adhesions/tubal distortion and inflammatory cytokine effects on sperm, oocyte, and embryo function.
Risk Factors
- Increasing female age (reduced ovarian reserve and oocyte quality)
- Previous pelvic inflammatory disease or recurrent sexually transmitted infection
- History of appendicitis/diverticulitis with pelvic sepsis
- Endometriosis
- Previous tubal surgery or sterilisation reversal
- PCOS and other ovulatory disorders (including hyperprolactinaemia)
- Hypothalamic amenorrhoea (low BMI, excessive exercise, stress)
- Primary ovarian insufficiency
- Thyroid disease, Cushing syndrome, congenital adrenal hyperplasia
- Chronic systemic illness (e. g. poorly controlled diabetes, severe renal disease, malignancy)
- Male factors: impaired spermatogenesis, testicular pathology, varicocele, endocrine disturbance
- Smoking, excess alcohol, obesity, and anabolic-androgenic steroid exposure
Clinical Features
Symptoms
- Failure to conceive after 12 months of regular unprotected intercourse
- Irregular, infrequent, or absent periods (suggesting oligo-/anovulation)
- Pelvic pain, dysmenorrhoea, or dyspareunia (possible endometriosis/PID sequelae)
- Galactorrhoea, headache, visual symptoms (possible hyperprolactinaemia/pituitary pathology)
- Male sexual dysfunction, reduced libido, ejaculatory problems, or history suggestive of genital infection
Signs
- BMI extremes (underweight or obesity)
- Hirsutism, acne, androgenic alopecia, acanthosis nigricans (hyperandrogenism/insulin resistance)
- Thyroid signs (goitre, tremor, bradycardia, dry skin depending on disorder)
- Pelvic tenderness/adnexal abnormalities or fixed retroverted uterus (endometriosis/adhesions)
- Male signs: small testes, varicocele, gynaecomastia, absent vas deferens, or epididymal induration
Investigations
Management
Lifestyle Modifications
- Advise regular intercourse every 2-3 days throughout the cycle
- Smoking cessation, reduce alcohol, optimise weight (both partners), and address recreational/anabolic drug use
- Preconception folic acid for women trying to conceive (400 micrograms once daily; 5 mg once daily if high-risk indications such as previous neural tube defect, diabetes, or anti-epileptic therapy)
- Treat comorbid endocrine/systemic disease (thyroid dysfunction, diabetes, hyperprolactinaemia) and review medicines affecting fertility
- Early referral if red flags (amenorrhoea, known tubal disease, severe male factor, age-related urgency)
Pharmacological Treatment
Ovulation induction (specialist care)
- Letrozole 2.5 mg orally once daily for 5 days (typically cycle days 2-6), may increase stepwise in later cycles
- Clomifene citrate 50 mg orally once daily for 5 days (usually cycle days 2-6), increased in later cycles up to 150 mg daily if needed
Used for anovulatory infertility (commonly PCOS). Exclude pregnancy first. Risks include multiple pregnancy; monitor response. Letrozole/clomifene are specialist-initiated in fertility pathways.
Insulin-sensitising therapy in PCOS
- Metformin immediate-release 500 mg once daily with food, titrated over weeks to 1.5-2 g/day in divided doses as tolerated
Can improve ovulation in selected women with PCOS, especially with metabolic features; gastrointestinal adverse effects are common.
Gonadotrophin therapy (specialist fertility units)
- Follitropin alfa or beta 75 IU subcutaneously once daily initially, adjusted by ovarian response
- Human menopausal gonadotrophin 75 IU subcutaneously once daily initially, titrated by ultrasound/estradiol monitoring
- HCG trigger (e. g. choriogonadotropin alfa 250 micrograms subcutaneously once) when follicle criteria reached
Requires close monitoring to reduce ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy risk; contraindicated in pregnancy and in untreated hormone-dependent malignancy.
Hyperprolactinaemia treatment
- Cabergoline 0.25 mg twice weekly initially, titrated according to prolactin response
- Bromocriptine 1.25 mg at night initially, gradually increased (commonly 2.5 mg once to twice daily)
Dopamine agonists restore ovulation in prolactin-mediated infertility; monitor for postural hypotension, nausea, and impulse-control/psychiatric adverse effects.
Surgical / Interventional
- Laparoscopic treatment of endometriosis/adhesiolysis in selected patients
- Hysteroscopic polypectomy, septum resection, or submucous fibroid resection when cavity distortion is present
- Tubal surgery in selected proximal/distal disease (case-dependent outcomes)
- Assisted reproductive techniques: IVF for tubal factor, prolonged unexplained infertility, or failed ovulation induction; ICSI for severe male factor
Complications
- Psychological morbidity (anxiety, depression, relationship strain)
- Ectopic pregnancy risk, particularly with prior tubal disease/PID
- Multiple pregnancy following ovulation induction
- Ovarian hyperstimulation syndrome during gonadotrophin/ART treatment
- Adverse obstetric outcomes linked to underlying conditions (e. g. obesity, endocrine disease)
Prognosis
Prognosis depends strongly on maternal age, infertility duration, underlying diagnosis, and semen quality. Treatable endocrine and ovulatory causes often have good outcomes, whereas severe tubal disease, diminished ovarian reserve, and severe male factor reduce spontaneous conception rates; assisted reproduction improves cumulative live-birth chances but does not eliminate age-related decline.
Sources & References
🏥BMJ Best Practice(3)
✅NICE Guidelines(1)
- Infertility[overview]