Female and male infertility

Overview

Subfertility means a couple has not conceived after 12 months of regular unprotected intercourse. It affects about 1 in 7 couples.

• Primary: the couple has never conceived together.
• Secondary: they have conceived before (even if it ended in miscarriage or ectopic).

It is always a couple problem: assess and treat both partners together.

Natural conception

• A healthy couple has about a 15-20% chance of conceiving in any one cycle.
• Cumulative: about 70% by 6 months, 80% by 12 months, 90% by 24 months.
• Female age is the strongest factor: fertility drops after 35 and further after 40, because egg number and quality fall. Semen quality falls in men over 50.
• Intercourse 2-3 times a week through the cycle is best; three times a week gives about three times the conception rate of once a week.
• The egg lives about 12-24 hours; sperm up to about 72 hours. For a 28-day cycle the most fertile days are about days 12-15.
• Harmful factors: smoking, very high or very low BMI (either partner), stress, excess alcohol.
• Pre-pregnancy advice: folic acid 400 micrograms daily until 12 weeks (5 mg if high risk: previous neural tube defect, antiepileptic drugs, diabetes), and vitamin D 10 micrograms daily.

Causes

Female causes

• Hydrosalpinx: a blocked, fluid-filled tube with a thin or thickened wall, flattened lining and adhesions; often after chlamydia.
• A tube can be open but still not work: no test measures tubal function.
• Intramural and subserosal fibroids have not been clearly shown to reduce fertility; submucosal ones do.
• In Pakistan, ask about past tuberculosis; genital TB can damage the tubes and endometrium and is an important local cause to consider.

Male causes

History and examination

When to investigate

• After 1 year of trying in most couples.
• Sooner if: woman over 35, amenorrhoea or oligomenorrhoea, past PID, known low ovarian reserve, or a known male problem.

Female investigations

Male investigations

• Semen analysis is the only routine test. Abstain 2-4 days before the sample.
• If abnormal, repeat after 3 months (a full cycle of sperm production); a fever or illness can temporarily lower the count.
• With very low count or azoospermia: FSH, LH, testosterone, karyotype (Klinefelter) and cystic fibrosis screen; Y microdeletion testing in selected men.
• High FSH with azoospermia and small testes = testicular failure; normal FSH and normal testes with azoospermia suggests obstruction.

Semen analysis: lower reference limits (WHO, as given in Ten Teachers)

Management

Treatment depends on the cause; it may be expectant, medical, surgical or assisted conception.

Ovulation induction

Clomiphene citrate

• An anti-oestrogen (selective oestrogen receptor modulator). It blocks oestrogen receptors in the hypothalamus, so the brain senses low oestrogen and releases more GnRH, FSH and LH; more follicles grow.
• About 70% ovulate; pregnancy about 15-20% per cycle.
• Risk of multiple pregnancy (about 12%); monitor follicles by ultrasound.
• Side effects: hot flushes; thin endometrium and poor cervical mucus (anti-oestrogen effect at the uterus).
• Needs an intact hypothalamic-pituitary axis: useless in hypothalamic amenorrhoea.

Letrozole (aromatase inhibitor): lowers oestrogen so FSH rises; now first-line in anovulatory PCOS.

Metformin: added in insulin-resistant PCOS.

Gonadotrophins (injected FSH ± LH): for hypothalamic anovulation and clomiphene failure; risk of OHSS and multiples. Pulsatile GnRH is an option in hypothalamic amenorrhoea.

Laparoscopic ovarian drilling: for clomiphene-resistant PCOS.

Dopamine agonists for hyperprolactinaemia.

Surgery

• Laparoscopic treatment of endometriosis and adhesions.
• Removing or clipping hydrosalpinges before IVF improves IVF success.
• Tubal surgery for selected blockages; hysteroscopic removal of submucosal fibroids, polyps, septum and adhesions; myomectomy for large fibroids.

Intrauterine insemination (IUI)

• Prepared sperm placed in the uterus through a fine catheter, timed with an hCG trigger (hCG acts on the LH receptor like the LH surge).
• Used for mild male factor, mild endometriosis, couples unable to have intercourse, donor sperm (single women, same-sex couples). Success 10-20% per cycle.

In vitro fertilisation (IVF)

• Indications: tubal disease, endometriosis, unexplained subfertility, failed ovulation induction or IUI, male factor (with ICSI), donor eggs.
• Success is very age-dependent: about 40-45% per cycle under 35, under 15% over 40.
• Surgical sperm retrieval (from epididymis or testis) with ICSI for azoospermia.
• Donor eggs for POI or poor reserve; surrogacy if no uterus or pregnancy is unsafe.
• Pre-implantation genetic testing lets carriers of genetic disease transfer unaffected embryos.

Ovarian hyperstimulation syndrome (OHSS)

• The most serious risk of IVF: 1-3% of cycles. Driven by hCG; VEGF from large stimulated ovaries makes capillaries leak.
• Severe OHSS: enlarged multicystic ovaries, ascites, pleural effusion, haemoconcentration, low urine output, thrombosis (even arm or neck veins), pulmonary oedema.
• Admit and manage under a strict protocol: fluid balance, thromboprophylaxis, drainage of ascites.
• Prevention: low-dose stimulation, GnRH antagonist protocol, GnRH agonist trigger instead of hCG, freezing all embryos.

Fertility preservation

• Before chemotherapy or radiotherapy: sperm banking, egg or embryo freezing; ovarian or testicular tissue freezing is still experimental.

Pakistani practice note

Fertility treatment is largely private and expensive in Pakistan, so careful basic work-up (ovulation, tubes, semen) and correction of simple causes matter. Do not forget the male partner: semen analysis is simple and should be done early. Follow current national and professional guidance.

Quick revision

• Subfertility after 12 months; 1 in 7 couples; 80% conceive by 1 year, 90% by 2.
• Male 30%, female 30%, unexplained 25%, both 15%.
• Ovulation: mid-luteal progesterone 7 days before the period.
• Reserve: AMH (any day), AFC, early follicular FSH.
• Tubes: HSG/HyCoSy (low risk); laparoscopy and dye (high risk, gold standard).
• Semen: 1.5 mL, 15 million/mL, 32% progressive, 4% normal forms; repeat in 3 months.
• Clomiphene: hypothalamic ER block; 70% ovulate; 12% multiples.
• IVF: downregulate → stimulate → hCG → collect at 36 h → IVF/ICSI → transfer → progesterone.
• OHSS: ascites, haemoconcentration, thrombosis.

Written by The House Job from standard references (Gynaecology by Ten Teachers; Guyton and Hall Textbook of Medical Physiology).

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