Objective: We investigated the clinical characteristics and pregnancy outcomes of patients with zona pellucida (ZP) gene variants undergoing assisted reproductive technology (ART) treatment, to identify variants associated with female infertility.
Design: Retrospective study.
Setting: University-based reproductive medicine centre.
Population: Twelve patients in whom only empty follicles or degenerated oocytes were retrieved after controlled ovulation stimulation and for whom no successful pregnancies were achieved after ART treatment.
Methods: Next-generation sequencing (NGS) and Sanger sequencing were performed on DNA obtained from peripheral blood of the patients. The VCF files generated by the Genome Analysis Toolkit were functionally annotated using SnpEff with reference to the refSeq, gnomAD, dbSNP, InhouseSNP, ClinVar and dbNSFP databases.
Main outcome measures: American College of Medical Genetics and Genomics (ACMG) annotation of the SnpEff results was performed using InterVar.
Results: We identified 14 ZP variants, including eight novel variants. These included heterozygous variants in ZP1, ZP2 and ZP3. These findings contribute to the understanding of ZP gene variants and their roles in the diagnosis of an abnormal ZP.
Conclusions: ZP gene variants are associated with female infertility, which can potentially affect ART outcomes. Therefore, ZP gene variant screening should be performed in female patients experiencing ART failure with pertinent clinical and laboratory indicators to guide personalised treatment and enhance fertility outcomes. However, further research is required to confirm the functional impact of these variants.
Keywords: genetic variants; infertility; zona pellucida.
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