Strategies for Addressing Recurrent Pregnancy Loss (Virtual Symposium)-HANDOUT: 07-Thacker-Genetics

HANDOUT: 07-Thacker-Genetics

Pdf Summary

Dr. Mili Thakur, a reproductive endocrinologist and medical geneticist, focuses on genetic testing for recurrent pregnancy loss (RPL), defined as two or more consecutive clinical pregnancy losses. Genetic causes, particularly chromosomal abnormalities, contribute to up to 60% of early pregnancy losses. The evaluation of RPL aims to identify treatable causes and provide prognostic information.<br /><br />Standard genetic testing includes parental karyotyping to identify balanced structural chromosomal abnormalities, which occur in 2-5% of couples with recurrent miscarriage, and chromosomal analysis of pregnancy tissue or products of conception (POC). Techniques include karyotype analysis, fluorescence in situ hybridization (FISH), chromosomal microarray, and next-generation sequencing (NGS). Karyotyping detects large chromosomal anomalies, with a 99% detection rate but requires fresh dividing cells, while microarray identifies copy number variants and uniparental disomy. POC testing helps determine whether a loss was random and can offer psychological benefit, though risks include maternal tissue contamination.<br /><br />Common sporadic cytogenetic abnormalities causing miscarriage include trisomy 16 and other aneuploidies, mostly due to meiotic errors influenced by maternal age. For balanced translocation carriers, miscarriage risk is elevated (20-30%), and reproductive options include natural conception with prenatal testing, IVF with preimplantation genetic testing for structural rearrangements (PGT-SR), donor gametes, adoption, or no children, with live birth rates for IVF/PGT-SR around 31-35% per cycle.<br /><br />Emerging approaches include whole genome sequencing (WGS) of POC and parent samples to detect a broad spectrum of genetic variants, supported by NIH-funded research projects (e.g., HOPE and GPRPL studies) aiming to uncover novel genetic causes of unexplained RPL. A clinical case highlighted successful identification of a parental balanced translocation using SNP microarray and FISH, with subsequent PGT enabling a healthy ongoing pregnancy.<br /><br />Dr. Thakur advocates informed decision-making and pre-test genetic counseling to guide personalized reproductive care incorporating advanced genomic technologies.

Keywords

Recurrent Pregnancy Loss

Genetic Testing

Chromosomal Abnormalities

Parental Karyotyping

Products of Conception Testing

Preimplantation Genetic Testing

Whole Genome Sequencing

Balanced Translocation

Trisomy 16

Genetic Counseling