Male infertility: diagnosis & work-up
Initial work-up, WHO 2021 semen analysis, hormones/genetics, and referral to ART
Last updated: October 2026 — Sources: Cochrane / EAU / ESHRE / WHO / CDC
Key takeaways
Male work-up starts with strict semen analysis + exam + selective hormones, then genetics only for severe oligo/azoospermia. EAU 2025, AUA/ASRM 2024 and WHO 2025 agree: don't rush every patient to ART; timing with female partner age is decisive.
Read semen by WHO 6th (2021): vol 1.4 mL, conc 16M/mL, total mot 42%, progressive 30%, morph 4% — but 5th centile of fertile men, not fertile/infertile cutoff; now use decision limits.
Krausz 2023 updates Y-deletion testing: sY1064 replaces sY83 for AZFa, sY1192 for AZFb — most commercial kits haven't updated.
Hormones (FSH/LH/T + prolactin if low libido) and karyotype/CFTR are selective, not routine for every infertility.
Referral to IUI vs IVF/ICSI depends on partner age, duration, and severity of oligozoospermia, not a single semen number.
When to evaluate?
- Infertility >12 mo (or 6 mo if partner >35) — evaluate both partners together.
- Abnormal semen confirmed on repeat after 2–4 w with 2–7 d abstinence.
- Azoospermia or <5M/mL → karyotype + AZF deletion (Krausz) + CFTR if obstructive.
What not to do?
- Don't order SDF/ROS routinely — EAU limits to RPL/ART failure/unexplained only.
- Don't treat every low motility with antioxidants — Cochrane very low certainty, no general WHO 2025 endorsement.
- Don't panel hormones for every man with normal semen and exam.
Healthcare-professional notice
This hub is independent of NPF products and does not promote them. It is informational only and does not replace individual clinical judgment. Surrogate outcomes (SDF, motility, HOMA, IIEF) are never converted into pregnancy/cure promises, and GRADE certainty is quoted as published.
Binding rule: surrogate outcomes are never converted into patient outcomes. Every certainty grade and limitation is quoted as published.
Deep dive
WHO 6th: what changed?
Limits now from 5th centile of men who conceived in 12 mo + 5 new studies — not diagnostic cutoffs. New: decision limits (normal/borderline/pathological) at conc. 20/10M.
Added Extended tests: SDF & oxidative stress as add-ons without thresholds — each lab sets local reference.
Genetics: when & how?
Krausz 2023: mandatory multiplex PCR + confirm sY1064/sY1192. Complete AZFa precludes TESE; AZFc commonest 70–80% with retrieval possible.
Current kits non-compliant — ask lab which markers before sending.
Evidence in this domain
Each study broken into five questions: why it was run, who was studied, how it was done, the finding, and why it came out that way — then the clinical takeaway and limits, as published.
FAQ
Is one semen enough?
No — repeat in 2–4 w. Day-to-day variation and abstinence change results.
When to refer to genetics?
Azoospermia/severe oligo <5M, small testes, or family history — with counselling before TESE.
Notice: this reference is informational only and not a substitute for medical advice. Consult your doctor before making any treatment decision.