Karyotype Analysis, Y-Chromosome Microdeletions (Y-Microdeletions), FISH, CFTR Mutation Analysis and other specialised genetic investigations.

Genetic testing is performed to identify chromosomal abnormalities and genetic mutations that may underlie severe male infertility, including azoospermia and severe oligozoospermia. A comprehensive genetic evaluation may include karyotype analysis, Y-chromosome microdeletion testing, CFTR gene mutation analysis, and Fluorescence In Situ Hybridisation (FISH), depending on the clinical indications.

Karyotype Analysis

Karyotype analysis is a fundamental cytogenetic test that evaluates the number and structure of an individual’s chromosomes. The analysis is performed on cells obtained from a blood sample using specialised cytogenetic techniques and microscopic examination, allowing the detection of both numerical and structural chromosomal abnormalities.

Karyotype analysis plays an important role in the investigation of male infertility, as certain chromosomal abnormalities are recognised causes of severe oligozoospermia, azoospermia, recurrent pregnancy loss and unsuccessful assisted reproductive treatment.

One of the most common findings is Klinefelter syndrome (47,XXY), which is associated with impaired sperm production and represents one of the leading genetic causes of male infertility. Karyotype analysis can also identify balanced chromosomal rearrangements, such as translocations and inversions, which may affect fertility, embryo development and reproductive outcomes.

The results provide valuable information for accurate diagnosis, genetic counselling and personalised fertility management, helping clinicians recommend the most appropriate treatment or assisted reproductive strategy for each patient.

Sperm FISH Testing

Sperm FISH (Fluorescence In Situ Hybridisation) is an advanced cytogenetic test performed directly on sperm cells. It is designed to detect the proportion of sperm carrying numerical chromosomal abnormalities (aneuploidies) in specific chromosomes that are most commonly associated with impaired fertility and abnormal embryo development.

The test typically evaluates chromosomes 13, 16, 18, 21, 22, X and Y, as abnormalities affecting these chromosomes have been linked to reduced fertilisation potential, implantation failure, recurrent pregnancy loss and an increased risk of chromosomal abnormalities in the offspring.

Sperm FISH provides valuable information about the genetic quality of sperm and can help guide fertility management, particularly in men with severe male factor infertility, recurrent IVF or ICSI failure, recurrent miscarriage, or when a chromosomal abnormality is suspected. The results assist fertility specialists in recommending the most appropriate reproductive strategy and, where indicated, appropriate genetic counselling or preimplantation genetic testing (PGT).

Y-Chromosome Microdeletion Testing

This test detects microdeletions within the AZFa, AZFb and AZFc regions of the Y chromosome, which are closely associated with impaired sperm production. It is particularly important in men with azoospermia (absence of sperm in the ejaculate) or severe oligozoospermia.

The results can provide valuable information for clinical decision-making, including the likelihood of retrieving sperm through Testicular Sperm Extraction (TESE) or microTESE, and help guide the management of men with severe spermatogenic failure.

Y-chromosome microdeletions are identified using PCR-based molecular analysis performed on DNA extracted from a simple blood sample.

This test is recommended for men with:

• Severe oligozoospermia.
• Confirmed azoospermia before undergoing TESE or microTESE.
• Structural abnormalities involving the Y chromosome.

CFTR Mutation Analysis (Cystic Fibrosis Screening)

Mutations in the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene are among the most common inherited genetic disorders in many populations and represent an important cause of male infertility.

The CFTR gene is responsible for producing a protein that regulates the movement of salt and water across cell membranes. Mutations in this gene can impair the function of several organs, particularly the lungs and digestive system, and are also strongly associated with Congenital Bilateral Absence of the Vas Deferens (CBAVD), a condition responsible for obstructive azoospermia in otherwise healthy men.

CFTR mutation analysis is recommended for men with obstructive azoospermia, congenital absence of the vas deferens, or when there is a personal or family history of cystic fibrosis. The results are also important for reproductive counselling, as carrier testing of the female partner may be recommended before attempting pregnancy or assisted reproductive treatment.