This tab covers the initial approach to the infertile male — the goals of evaluation, timing and counselling, the 2020 AUA testing algorithm, and the history and physical examination.
General Principles
Both partners should be assessed concurrently (maternal age is the strongest predictor of outcome in couples undergoing therapy, and many couples have more than one issue). The male work-up is a reproductive history, physical examination, and basic tests, with referral to a male-reproduction specialist for abnormal results. The goals are to identify: (1) potentially correctable conditions; (2) irreversible conditions amenable to ART with the partner's sperm; (3) irreversible conditions needing donor sperm/adoption; (4) life- or health-threatening conditions underlying the infertility (e.g. testicular cancer, pituitary tumour); and (5) genetic or lifestyle/age factors affecting the patient or offspring. After failed ART or recurrent pregnancy loss (≥2), evaluate the male and consider sperm DNA fragmentation and karyotype testing.
Timing and Counselling
Evaluate after 6 months of trying if the female partner is over 35 (otherwise 12 months). Counsel that abnormal semen parameters carry an increased risk of testicular cancer and mortality (1–6% of men have an undiagnosed medical disease at evaluation), and that advanced paternal age (≥40) raises the risk of adverse offspring outcomes (sperm aneuploidy, miscarriage, pre-eclampsia, preterm birth) — genetic counselling may be appropriate.
2020 AUA Testing Algorithm
After history, examination, and at least two semen analyses a month apart (parameters are highly variable — up to 35% of non-obstructive azoospermia men have sperm on a repeat SA without intervention):
- Serum FSH + morning total testosterone if there is azoospermia, oligozoospermia (concentration <10 million/mL), impaired libido, ED, atrophic testes, or a hormonal abnormality on exam. If testosterone is <300 ng/dL, add repeat total/bioavailable testosterone, free testosterone, LH, estradiol, and prolactin.
- Karyotype + Y-microdeletion if primary infertility and one of: azoospermia/severe oligozoospermia (<5 million/mL) with elevated FSH, testicular atrophy, or presumed impaired sperm production.
- CFTR testing (including the 5T allele) if there is vasal agenesis, idiopathic obstructive azoospermia, or a carrier female partner.
- Renal ultrasound if vasal agenesis; TRUS if low semen volume with azoospermia and palpable vasa, low volume with significant asthenospermia (total motility <40% or progressive <32%), or painful ejaculation.
History
Document the duration of infertility and whether it is primary or secondary (secondary infertility focuses on exposures since the last pregnancy), prior treatments, and risk factors (pre-/testicular/post-testicular). Stop any gonadotoxic agent and retest semen in 3–6 months, and retest at least 3 months after recovery from a serious illness or reproductive-tract infection. Review the sexual history (libido, function, lubricants), comorbidities, prior reproductive-tract surgery (vasectomy reversal may be more cost-effective than IVF), and family genetic history.
Physical Examination
- General — body habitus (obesity raises estradiol via adipose aromatase, lowering testosterone and SHBG), virilisation, and gynecomastia (a possible marker of endocrine disorder).
- Testis — size correlates with sperm production (a long axis <4.6 cm or volume <20 mL is low). Normal-sized testes with indurated epididymides ± absent vas suggest obstructive azoospermia, whereas soft, atrophic testes with FSH >7.6 IU/L suggest spermatogenic failure. Examine for masses (testicular cancer).
- Vas deferens — confirm presence to exclude agenesis. Unilateral absence implies failed Wolffian-duct development on that side (with possible ipsilateral renal agenesis, since the vas and ureteral bud share a Wolffian origin). Bilateral absence (CBAVD) warrants CFTR testing (mutations in up to 80% of CBAVD, most commonly ΔF508); both partners should be tested, and a CBAVD man is assumed to be a CFTR carrier even with a negative test. CBAVD semen is typically low-volume and acidic (seminal-vesicle hypoplasia); CAVD men without a CF mutation need renal US (absent ipsilateral kidney in 26% of unilateral and 11% of bilateral cases).
- Epididymides — induration/dilation or cysts/spermatoceles suggest obstruction.
- Varicocele — contributes to infertility via hyperthermia, hormonal imbalance, reactive oxygen species, and hypoperfusion; large varicoceles impair semen quality more than small ones.
- DRE — midline prostatic cysts or dilated seminal vesicles suggest ejaculatory-duct obstruction.
(Embryologic recall: the Wolffian (mesonephric) ducts form the epididymal body/tail, vas, seminal vesicles, and ejaculatory ducts; the Müllerian remnants are the appendix testis and prostatic utricle; the urogenital sinus forms the prostate and bulbourethral glands.)