Overview

Genetic abnormalities are found in ~15% of men with severe infertility. In the GCC, where consanguineous marriages are more common, the prevalence of recessive genetic conditions affecting fertility is higher. Identifying genetic causes is critical for treatment planning and genetic counselling — as some conditions can pass to children.

Common Conditions

• Klinefelter Syndrome (47,XXY) — affects ~1 in 600 males; extra X chromosome; small testes, testosterone deficiency, usually azoospermia; some sperm retrievable by micro-TESE
• Y-chromosome microdeletions — AZFa/b deletions usually mean no sperm retrievable; AZFc deletions most common, sperm often retrievable; all male offspring inherit the deletion
• CBAVD — absent vas deferens from CFTR mutations; sperm production normal; obstructive azoospermia
• Kallmann syndrome — GnRH failure; absent puberty; sperm production often stimulable with gonadotropins
• Chromosomal translocations — cause recurrent miscarriage or embryo abnormalities

Diagnosis

• Karyotype — blood test analysing all 46 chromosomes
• Y-chromosome microdeletion analysis — for all men with <5 million/mL or azoospermia
• CFTR gene mutation testing — for CBAVD
• Genetic counselling — essential before fertility treatment

Treatment

• IVF with ICSI — primary treatment
• Micro-TESE — for Klinefelter or AZFc deletions with no ejaculated sperm
• Gonadotropin therapy — for Kallmann syndrome
• PGT-M and PGT-A — to screen embryos before transfer
• Testosterone replacement — for androgen deficiency; must stop before sperm retrieval

Concerned about genetic causes? Book a consultation today