Exome Sequencing to Identify Novel Variants Associated with Secondary Infertility in Infertile Couples

Background: Secondary infertility, the inability to conceive after a previous successful pregnancy, affects about ۱۰% of women aged ۲۰–۴۴. Although environmental and physical factors are well-studied, genetic causes remain underexplored. Advances in whole-exome sequencing (WES) have improved the identification of pathogenic mutations in infertility. Objective: This study aimed to investigate the role of WES in detecting causative variants associated with secondary infertility. Methods: WES was performed on couples with unexplained secondary infertility, followed by quality control, variant filtering, annotation, and in silico and bioinformatic pathogenicity prediction. Candidate variants were prioritized by population frequency and pathogenicity, and validated by Sanger sequencing. Results: Pathogenic or likely pathogenic variants were detected in three women: These included ZFP۳۶L۲:c.۹۲۲T>G (maturation defect ۱۳), PATL۲:c.۱۳۳۸del (oocyte maturation defect ۴), and PSMC۳IP:c.۱۳۵C>CA (ovarian dysgenesis ۳). All variants were confirmed by Sanger sequencing. Conclusion: Our findings demonstrate the role of whole exome sequencing (WES) in identifying novel variants in genes critical for oocyte maturation and ovarian function, highlighting its value in diagnosing secondary infertility and guiding genetic counseling.

کلیدواژه ها:

Secondary infertility ، Whole-exome sequencing ، Secondary female infertility ، Genetic variants ، Oocyte maturation defect ، Ovarian dysfunction