Male-factor infertility — structured SAQ (15 marks)

(a) Semen analysis and examination interpretation (3 marks)

One mark per point, maximum three. [1][3]

• Semen analysis vs WHO 6th-edition (2021) lower reference limits — volume 1.0 mL (below 1.4 — ABNORMAL); pH 7.5 (normal); concentration 18 M/mL (above 16 — normal); total motility 50% (above 42% — normal); progressive motility 35% (above 30% — normal); vitality 60% (above 54% — normal); morphology 5% (above 4% — normal). The only abnormal parameter is the volume. Low volume raises the possibility of incomplete collection, retrograde ejaculation (check post-ejaculate urine), or absent/reduced seminal vesicles.[1]
• Examination findings — normal testicular volumes (normal 15 to 25 mL each) suggest intact spermatogenesis; bilaterally palpable vas deferens argues against CBAVD; no varicocele means the abnormal semen cannot be attributed to a clinical varicocele.[2]
• Single abnormal sample is NOT diagnostic — repeat the semen analysis in 3 months (the spermatogenic cycle is around 74 days); also repeat the post-ejaculate urine to exclude retrograde ejaculation if the volume remains low.[3]

(b) Endocrine panel (3 marks)

One mark per hormone with rationale. [2]

• FSH — low FSH with normal volume and testicular size suggests hypogonadotropic hypogonadism; elevated FSH suggests primary testicular failure (Sertoli/germ-cell damage).
• LH — low LH with low testosterone suggests hypogonadotropic hypogonadism; elevated LH suggests primary Leydig-cell failure.
• Testosterone (morning, before 10:00) — for the circadian rhythm; below 8 nmol/L is clearly low; assess for hypogonadism with the LH/FSH pattern.
• Prolactin — when libido is low or there are galactorrhoea or visual symptoms; very high or with visual field defect or low testosterone suggests a macroadenoma (image the pituitary).
• TSH — to exclude thyroid dysfunction (alters SHBG and sex-hormone metabolism); broadly mirrors the female workup.[2]

(c) Genetic cascade for severe male factor (5 marks)

One mark for the principle that the cascade is phenotype-driven; one mark per test with indication. [3][5][6]

• The cascade is phenotype-driven, not population-wide. Severe male factor is defined as azoospermia, severe oligozoospermia (under 5 million/mL), or unexplained abnormal semen on two samples after treatable causes have been excluded.[3]
• Karyotype — for idiopathic azoospermia (10 to 15% have Klinefelter 47,XXY); consider for concentration under 5 million/mL; identifies autosomal translocations relevant for miscarriage and ART counselling.[6]
• Y-chromosome microdeletion (AZFa, AZFb, AZFc) — for severe oligozoospermia or idiopathic azoospermia (concentration under 1 to 5 million/mL); AZFc is the most favourable (retrieval often works; ALL male offspring inherit the deletion); AZFa or AZFb complete deletion predicts retrieval failure — counsel towards donor sperm.[5]
• CFTR screen — for idiopathic obstructive azoospermia or congenital bilateral absence of the vas deferens; autosomal recessive — SCREEN THE PARTNER too; if both carry mutations, the risk of an affected child (cystic fibrosis) is 25% per pregnancy — offer preimplantation genetic testing for monogenic disease (PGT-M).[6]
• Genetic counselling — before any ART for an identified genetic defect — transmission risk, reproductive options, PGT-M availability.[6]

(d) Pre-ICSI counselling in Klinefelter syndrome (4 marks)

One mark per point, maximum four. [3]

• Klinefelter syndrome — what it is — a 47,XXY karyotype, the commonest genetic cause of non-obstructive azoospermia, due to a sex chromosome nondisjunction. Phenotype: tall stature, gynaecomastia, small firm testes, primary testicular failure with elevated FSH and LH. Mosaic (46,XY/47,XXY) forms exist with milder phenotype.[2][3]
• Micro-TESE outcomes — sperm retrieval in roughly 30 to 50% of men with 47,XXY; better outcomes in younger men; the procedure carries a small risk of testicular damage and is performed by an experienced andrologist.[3]
• Embryo aneuploidy risk — some retrieved sperm may carry the extra X chromosome; the resulting embryos have a higher rate of sex chromosome aneuploidy. Offer preimplantation genetic testing for aneuploidy (PGT-A) to identify euploid embryos for transfer; this reduces miscarriage and improves live birth per transfer.[3]
• Offspring health — most children fathered by men with non-mosaic Klinefelter are chromosomally normal, but there is a small increased risk of sex chromosome aneuploidy in offspring. Long-term health surveillance of the offspring is appropriate. Donor sperm is an alternative pathway if micro-TESE fails or the couple declines the aneuploidy risk.[3][6]