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AndrologyStandardLast updated 29 May 2026

Infertility

Infertility is the failure to achieve a clinical pregnancy after ≥12 months of regular unprotected intercourse. Cumulative pregnancy rates among couples who do conceive are ~75% by 6 months, ~85% by 12 months, and >90% by 24 months.

Definitions and Classification

  • Idiopathic infertility — no identifiable cause for an abnormal semen analysis; unexplained infertility — a normal semen analysis and normal partner evaluation with no clear reason.
  • Primary male infertility — the man has never initiated a clinical pregnancy; secondary — he has previously initiated one but now cannot.

Epidemiology

Prevalence is ~11% in Canada. Semen parameters peak after 1–2 days of abstinence, so a single day of abstinence is optimal for assessing bulk parameters, while daily intercourse around ovulation maximises the chance of pregnancy. The female partner's age is the single most important predictor of conception — fecundity falls almost 50% in the late 30s, so the infertility "clock" is 12 months under age 35 but 6 months over 35. A male factor is solely responsible in ~20% of couples and contributes in ~30–40%.

Etiology

The most common causes of male infertility are idiopathic (33%), varicocele (27%), obstruction (15%), and endocrinopathy (10%, usually hypogonadism). Causes are classified as pre-testicular, testicular, or post-testicular.

Pre-testicular (hypogonadotropic hypogonadism)

  • Congenital — Kallmann syndrome (X-linked recessive, deficient pituitary hormones, anosmia; treated by replacing LH with hCG, then FSH with recombinant FSH/hMG once testosterone normalises) and Prader-Willi syndrome (hypogonadism, small testes, dysmorphic facies, short stature, cognitive impairment).
  • Acquired — hyperprolactinemia, pituitary/suprasellar tumours or infiltrative disease, pituitary apoplexy (Sheehan's), pituitary surgery, head trauma, and exogenous androgens.

Testicular

  • Congenital primary hypogonadism (DUNKY XX): Down syndrome, Undescended testis, Noonan's, Klinefelter, Y-microdeletions, and XX-male.
    • Klinefelter syndrome — the most common known genetic cause of male infertility and the most common abnormality of sexual differentiation; few non-mosaic 47,XXY men have ejaculated sperm.
    • Y-chromosome microdeletion — the second most common genetic cause; the AZF region (long arm) has three subregions: AZFa or complete AZFb deletions abolish spermatogenesis (AZFa → Sertoli-cell-only; AZFb → maturation arrest), whereas AZFc deletions impair but do not necessarily abolish it (sperm may still be retrievable).
    • Cryptorchidism — after orchidopexy, paternity is ~96% if unilateral and ~70% if bilateral (repair ideally before age 10).
    • Sertoli-cell-only syndrome — normal LH/testosterone with low inhibin-B and therefore elevated FSH.
    • Androgen-receptor resistance — markedly elevated testosterone with impaired fertility, mildly elevated LH, and normal FSH.
  • Acquired — medications/toxins (finasteride 5 mg/day reduces semen volume; opioids suppress LH; antipsychotics/SSRIs affect libido/ejaculation), chemotherapy (sperm DNA damage detectable ≥2 years later — bank sperm early in testicular cancer), radiation >7.5 Gy, infections (viral orchitis → bilateral atrophy), increased scrotal temperature (normally 2–4 °C below body), and obesity (adipose aromatase raises estradiol, lowering the T:E2 ratio).
    • Exogenous testosterone/anabolic steroids cause an acquired hypogonadotropic hypogonadism (suppressed FSH/LH, atrophic testes, oligo-/azoospermia) and are the most frequent cause of profound hypogonadism in young men. Cease them first: recovery begins at 4–5 months (up to 2 years), with recovery probabilities of 67%, 90%, 96%, and 100% at 6, 12, 16, and 24 months, and can be accelerated with hCG ± FSH.

Post-testicular

  • Ejaculatory dysfunction — retrograde ejaculation (pharmacologic: α-blockers/psychotropics; neurogenic: SCI, RPLND, diabetic autonomic neuropathy, MS; anatomic: bladder-neck surgery/TURP) is confirmed on post-ejaculatory urinalysis and managed with sympathomimetics plus urine alkalinisation, induced ejaculation, or surgical sperm retrieval. Anejaculation follows SCI, MS, diabetes, or RPLND.
  • Lubricants impair sperm motility (Pre-seed does not), and saliva is toxic to sperm.
  • Cystic fibrosis (CFTR) — CFTR mutations are found in up to 80% of congenital bilateral absence of the vas (CBAVD), 20% of unilateral absence, and 21% of idiopathic epididymal obstruction (CFTR testing may follow surgical diagnosis). Kartagener syndrome (primary ciliary dyskinesia) causes infertility from absent ciliary/flagellar motility.

Self-Test

1. What is the definition of infertility, and of primary vs secondary infertility? Infertility is failure to achieve a clinical pregnancy after ≥12 months of regular unprotected intercourse. Primary — the man has never initiated a pregnancy; secondary — he has previously initiated one but now cannot.

2. List the causes of male infertility. Pre-testicular (hypogonadotropic hypogonadism — Kallmann, hyperprolactinemia, exogenous androgens); testicular (genetic — Klinefelter, Y-microdeletion; cryptorchidism; varicocele; toxins/chemotherapy/radiation; obesity); post-testicular (obstruction/CBAVD, ejaculatory dysfunction). The most common are idiopathic, varicocele, obstruction, and endocrinopathy.