Recurrent First Trimester Miscarriage: Genetic Etiology, Diagnosis and Prevention

Professor CHOY Kwong-wai, Richard

Department of Obstetrics and Gynaecology, CUHK

Recurrent miscarriage is a global health issue, affecting millions of couples across the world. The contribution of genetic defects remains elusive. Understanding and pinpointing the underlying genetic defects enable effective and personalized treatment options for the suffering couples and improves the chances of successful pregnancy through assisted reproductive options.

Herein, we aim to investigate and identify the spectrum of a wide range of causative genetic aberrations including aneuploidies, copy number variants, balanced chromosomal abnormalities, and single nucleotide variants using our in-house low-pass whole genome sequencing in a trio-based setting. Also, we will employ third generation sequencing to further optimize and improve our variant detection bioinformatics algorithms for subsequent analysis in a prospective cohort. Our hypothesis is, through in vitro fertilization and preimplantation genetic testing for the detected genetic aberrations, pregnancy rates will be improved and subsequent miscarriage rates will be reduced. As such, we propose our study in obtaining a genetic diagnosis contributory to recurrent miscarriage enables personalized clinical intervention (selection of genetically unaffected embryos for implantation). We are confident that the findings of our collaborative study will increase knowledge on the genetic etiologies of recurrent miscarriage and lead to improved treatment strategies.

復發性早期流產：遺傳學病因，診斷與干預

香港中文大學婦產科學系 蔡光偉教授

復發性流產影響全球數百萬對夫婦。理解和闡明其遺傳性的病因可為患者提供更有效的治療方案。

我們已研發低覆蓋度高通量全基因組測序技術，以檢測可能導致復發性流產的各類遺傳變異。我們亦會優化第三代測序技術和檢測變異的生物信息學算法。我們將研究體外受精和胚胎植入前遺傳學檢測的方法能否有效提高妊娠率並降低再次流產的比例。

我們深信，該研究成果有助實現對患者的個性化臨床干預，如只植入不含遺傳學變異的胚胎。