Researchers explore genetic roots of unexplained infertility
A recent PET event brought together clinicians and researchers to discuss how genetic testing is uncovering causes of previously unexplained infertility. Speakers noted that genetic variants can contribute to infertility, and diagnostic panels are expanding to include hundreds of genes. The event highlighted both opportunities and limitations of reproductive genetics.
The FMR1 gene, already used in clinical testing for primary ovarian insufficiency, represents just one of hundreds of genes now being incorporated into diagnostic panels. A 2023 systematic review catalogued 395 genes and 466 gene-disease relationships associated with female infertility, though only 105 had at least moderate supporting evidence.
Researchers are addressing the rarity of these variants through data-sharing initiatives. The European Society of Human Reproduction and Embryology runs the Female Reproductive Genetics Initiative, while the International Male Infertility Genomics Consortium covers the male equivalent. However, expanded panels risk surfacing variants of uncertain significance that complicate clinical interpretation.
This research could reshape how unexplained infertility is diagnosed and managed. Patients may gain clearer prognoses and more targeted treatment options, while clinicians face the challenge of interpreting ambiguous genetic findings. The expansion of testing may also raise questions about which variants warrant clinical action, potentially affecting reproductive decision-making for individuals and couples. As panels grow, the balance between diagnostic yield and actionable results will likely influence how widely such testing is adopted.