Genetic Causes of Infertility and When Testing Is Offered

Genetic causes of infertility fall into three groups. Chromosomal conditions such as Turner syndrome in women and Klinefelter syndrome in men affect how the ovaries or testes develop. Y chromosome microdeletions affect sperm production in men and are one of the more common genetic causes of a very low or absent sperm count. Single-gene conditions can affect either partner. Testing is generally offered where no sperm is found in the semen, where there is early loss of ovarian function, after recurrent miscarriage, or where there is a relevant family history.

Chromosomal conditions

Turner syndrome

Occurs in women where one X chromosome is missing or altered. It affects ovarian development and commonly causes premature ovarian insufficiency, so fertility is affected from an early age. Our article on premature ovarian failure covers that condition.

Klinefelter syndrome

Occurs in men with an additional X chromosome (XXY). It affects testosterone and sperm production, and commonly causes a very low sperm count or azoospermia, meaning no sperm in the ejaculate. Published research covers the effect of these conditions on fertility.

Importantly, azoospermia does not always mean no sperm is being produced anywhere. Sperm can sometimes be retrieved directly from the testicle through TESA, PESA or TESE and used with ICSI.

Y chromosome microdeletions

Small missing segments of the Y chromosome, particularly in the azoospermia factor (AZF) regions, can severely affect sperm production. Deletions in the AZFc region are associated with severely reduced sperm counts or azoospermia.

Which region is affected matters practically, because it bears on whether surgical sperm retrieval is likely to find sperm. This is why the test is done before that decision rather than after, and it is also why the result has implications for a son conceived through ICSI, who would inherit the same deletion. That is part of what genetic counseling covers.

Single-gene conditions

Mutations in individual genes can affect reproduction in both sexes. Mutations in the NR5A1 gene, for example, have been linked to reduced sperm production in men and premature ovarian insufficiency in women.

Where a specific inherited condition is known in a family, preimplantation genetic testing for that condition (PGT-M) can be used to identify unaffected embryos. This is distinct from PGT-A, which counts chromosomes as a screen; PGT-M tests for something already identified, and the evidence for the two is not the same. Our article on the difference between the PGT types covers this.

When is genetic testing offered?

• Azoospermia or a severely low sperm count.
• Premature ovarian insufficiency, or early menopause in the family.
• Recurrent miscarriage, where a chromosomal rearrangement in a parent may be found.
• A known genetic condition in either family.
• Consanguinity, or membership of a population with a higher carrier rate for a specific condition.

Genetic testing raises questions beyond fertility, including implications for other family members. Ask whether genetic counseling is available alongside the test rather than only the result.

We at Millennium IVF Clinic will advise whether genetic testing applies in your case. You can arrange a consultation with our team.

Frequently asked questions

Does a genetic cause mean I cannot have children?

Not necessarily. Some genetic causes can be worked around, for example by retrieving sperm surgically and using ICSI. What it does mean is that the cause is identified, which changes what treatment makes sense.

Will a genetic condition be passed to my child?

It depends on the condition. Some are inherited, some arise by chance. This is exactly what genetic counseling is for, and it should happen before treatment rather than after.

Should both partners be tested?

It depends on the finding. Where recurrent miscarriage is being investigated, both partners are usually tested, because a balanced rearrangement in either can be responsible.

Is this the same as PGT-A?

No. Testing described here looks at the parents. PGT tests embryos, and PGT-M tests them for a specific condition already identified in the family.