This tab covers genetic testing, imaging, the work-up of recurrent pregnancy loss, and fertility preservation before gonadotoxic therapy.
Genetic Testing
- Karyotype + Y-microdeletion — indicated for primary infertility with azoospermia/severe oligozoospermia (<5 million/mL) and elevated FSH, testicular atrophy, or presumed impaired sperm production.
- CFTR (including the 5T allele) — indicated for vasal agenesis/abnormalities, idiopathic obstructive azoospermia, or a carrier female partner.
Karyotype abnormalities (e.g. Klinefelter) are the most common known genetic cause of male infertility (an abnormal karyotype in ~6% of infertile men). Y-microdeletion is the second most common — perform it in azoospermia before surgical sperm extraction: complete AZFa and/or AZFb deletions should not undergo TESE (no sperm), whereas AZFc (and smaller partial AZFa/AZFb) deletions may or may not yield sperm. For a man with a CFTR mutation, test the female partner: the risk of an affected child is 25% if both are carriers and up to 50% if the man has mutations in both alleles and the partner is a carrier.
Imaging
- Renal ultrasound — indicated for congenital absence of the vas (regardless of CFTR status), because the Wolffian duct forms both the vas and the kidney's connection; ipsilateral renal anomaly/agenesis occurs in ~26–75% of unilateral and ~10% of bilateral vasal agenesis.
- Transrectal ultrasound (TRUS) — not initial; used to assess for ejaculatory-duct obstruction when there is low semen volume with azoospermia and palpable vasa, low volume with significant asthenospermia, or painful ejaculation. (Semen is ~10% testicular, ~20% prostatic, ~70% seminal-vesicle fluid; obstruction of the alkaline SV contribution gives acidic semen (pH <7.0).) EDO findings: seminal-vesicle AP diameter >1.5 cm, ejaculatory-duct caliber >2.3 mm, dilated vasal ampulla >6 mm, or a prostatic cyst. TRUS does not help in CBAVD.
- Scrotal ultrasound — assesses testicular size and varicoceles (US varicocele = veins >3 mm with flow reversal on Valsalva), but is not routine (treating non-palpable varicoceles does not improve outcomes); a routine work-up of an isolated right varicocele is unnecessary unless it is new-onset, non-reducible, or large.
- Brain MRI — for secondary hypogonadotropic hypogonadism (a pituitary tumour); the 2018 AUA testosterone guideline advises MRI if total testosterone <150 ng/dL with low/low-normal LH, regardless of prolactin.
- Testicular biopsy — not routine to distinguish obstructive from non-obstructive azoospermia (predicted clinically: FSH >7.6 IU/L with testis <4.6 cm → 89% spermatogenic failure; FSH <7.6 with testis >4.6 cm → 96% obstruction) — reserve it for intermediate values, and cryopreserve any sperm found (spermatogenesis can be focal).
Recurrent Pregnancy Loss
Defined as ≥2 failed pregnancies and distinct from infertility; most miscarriages reflect fetal abnormalities. Causes include genetic (translocations), uterine anatomic, infectious, immunologic, and endocrine factors, plus a male contribution — the commonest male etiologies being karyotypic abnormalities and sperm DNA fragmentation. The male work-up is karyotype, sperm DNA fragmentation, and sperm aneuploidy testing.
Gonadotoxic Therapy and Fertility Preservation
Discuss the effects on sperm production and encourage sperm banking (multiple specimens) before treatment — recovery depends on spermatogonial stem-cell survival.
- Radiation — recovery takes months to years above 1 Gy, and >10 Gy usually causes permanent azoospermia (fractionated radiation is more harmful than a single dose).
- Chemotherapy — alkylating agents (cyclophosphamide, ifosfamide, procarbazine) and cisplatin target stem cells and most often cause permanent azoospermia; most other agents target differentiating germ cells and cause transient suppression with recovery in 3–6 months.
- Onco-TESE — for an azoospermic man with an intratesticular tumour, cryopreserve testicular tissue at orchiectomy.
- RPLND — counsel about aspermia/retrograde ejaculation (the ejaculatory sympathetic fibres, T10–L2, lie near the dissection) and offer banking; recovery of antegrade ejaculation can take 12–24 months, and aspermia persisting at 24 months is likely permanent.
- After treatment — advise avoiding pregnancy for ≥12 months, and defer a semen analysis until 12 (preferably 24) months afterward; TESE is an option for persistent azoospermia.
Self-Test
1. What are the genetic tests in male infertility, and when are they indicated? Karyotype and Y-microdeletion — for primary infertility with azoospermia/severe oligozoospermia and elevated FSH, testicular atrophy, or presumed impaired sperm production (Y-microdeletion before surgical sperm retrieval). CFTR testing (with the 5T allele) — for vasal agenesis, idiopathic obstructive azoospermia, or a carrier partner.