Comprehensive genetic testing for female and male infertility using next-generation sequencing

Area of Science:

• Genetics
• Reproductive Medicine
• Molecular Diagnostics

Background:

• Genetic factors significantly impact female and male infertility.
• Current genetic testing for infertility often involves multiple, separate assays.
• Assisted reproductive technology (ART) requires accurate genetic assessment for effective treatment planning.

Purpose of the Study:

• To develop a unified genetic testing panel for female and male infertility.
• To support clinical decision-making within ART protocols.
• To enhance the efficiency and reduce the cost of genetic infertility diagnostics.

Main Methods:

• Development of a next-generation sequencing (NGS) panel encompassing 87 genes, including regulatory regions and introns.
• Simultaneous analysis of sex chromosome aneuploidies and Y chromosome microdeletions within the same NGS panel.
• Analytical validation using 118 genomic DNA samples with known infertility-related variants.

Main Results:

• The NGS panel demonstrated high analytical accuracy (>99%), with excellent sensitivity for single-nucleotide variants (SNVs) (>98%) and insertions/deletions (indels) (>91%).
• Clinical sensitivity reached 100% for SNVs, indels, CFTR IVS8-5T variants, sex chromosome aneuploidies, and copy number variants (CNVs).
• The comprehensive NGS assay showed potential cost savings compared to traditional multi-assay approaches.

Conclusions:

• A single, comprehensive NGS panel provides an accurate and efficient method for genetic infertility assessment in both sexes.
• This integrated approach simplifies the testing process for healthcare providers, reducing turnaround times.
• The developed NGS panel offers a cost-effective solution for genetic evaluation in infertility cases undergoing ART.