The role of genetics in fertility

Conventional chromosome analysis can detect major changes in the number (numerical abnormalities) and structure (structural abnormalities) of chromosomes that may be responsible for fertility problems.

Chromosomal abnormalities are relatively common in humans and are among the most frequent genetic causes of infertility, recurrent miscarriages and birth of affected offspring.

The Y chromosome contains genes essential for spermatogenesis and proper development of the male gonads. Microdeletions on the Y chromosome are the leading genetic cause of infertility, with a prevalence of 10-15% in cases of non-obstructive azoospermia and 5-10% in cases of severe oligospermia.

There are three regions on the long arm of the Y chromosome (Yq) that have been defined as ‘spermatogenesis loci’: AZFa, AZFb and AZFc. Complete deletions in the AZFa region are associated with the absence of germ cells, deletions in the AZFb region result in a blockage of spermatogenesis in primary spermatocytes, and deletions in the AZFc region present a more variable phenotype.

Sperm DNA fragmentation may be behind fertility problems such as low fertilisation and pregnancy rates, low embryo quality and an increase in miscarriage rates (even in those cases in which the other parameters analysed in the semen sample are normal).

At Genosalut we have the Comet test and the sperm chromatin dispersion test.

The most frequent mutations in individuals with fertility problems are those affecting the CFTR gene. These mutations are responsible for cystic fibrosis, and one of its manifestations is the absence of vas deferens in the testicles. Between 60 and 90% of infertile patients with absent vas deferens are carriers of this mutation.

Mutations in the AR gene, located on the X chromosome, cause a variety of defects collectively known as androgen insensitivity syndrome. Its product, the androgen receptor, plays an important role in meiotic progression and, possibly, in the formation of round spermatids. Mutations in AR cause azoospermia and affect 2% of the infertile patient population.

In case of early ovarian failure or juvenile menopause due to low ovarian reserve, the FMR1 gene is analysed, as 20% of women with a premutation in this gene have premature ovarian failure.

Complete exome or genome analysis to identify the causes of infertility in women and men. We analyse the results based on extensive research in the scientific literature and our own experience. We take into account common and rare genetic causes of infertility.