Pregnancy loss affects up to 25% of all pregnancies, with most losses occurring in the first trimester. About half of these early losses result from genetic or chromosomal abnormalities. When pregnancy loss happens three or more times, clinicians classify it as recurrent pregnancy loss (RPL). Despite advanced testing, the cause often remains unclear for many individuals and families.
New Studies Offer Hope Through Advanced Genome Analysis
Two new studies presented at the Association for Molecular Pathology (AMP) 2025 Annual Meeting & Expo in Boston highlight promising ways to uncover hidden causes of recurrent pregnancy loss. Both studies used optical genome mapping (OGM)—a high-resolution technology that detects structural genome variations often missed by traditional methods such as karyotyping or chromosomal microarray analysis.
Optical Genome Mapping Reveals Hidden Structural Abnormalities
Researchers at Dartmouth–Hitchcock Medical Center evaluated whether OGM could identify harmful chromosomal changes in patients with a personal or family history of recurrent pregnancy loss. These patients had already undergone standard genetic testing, allowing direct comparison across methods.
After analyzing the data, researchers observed an average of 40 structural changes per genome. They then examined 238 genes linked to RPL. OGM identified:
- Two cases where four key genes tied to RPL and infertility were directly affected
• One case involving a hidden chromosomal rearrangement impacting genes not previously associated with RPL
As reported by medicalxpress, these findings indicate that OGM can uncover subtle genomic changes that routine tests frequently miss. As a result, the authors suggest that OGM, when used alongside conventional testing, can significantly improve the diagnostic evaluation of recurrent pregnancy loss and strengthen clinical decision-making.
This work was led by Debopriya Chakraborty, Ph.D., under the supervision of Wahab A. Khan, Ph.D., FACMG, and colleagues in the Clinical Genomics and Advanced Technology section at DHMC. Dr. Chakraborty presented the findings during a poster session on Nov. 14 at the Thomas M. Menino Convention and Exhibition Center in Boston.
Rare Fragile Chromosome Site Implicated in Pregnancy Loss
Chromosomal regions known as fragile sites are particularly vulnerable to breaks, gaps, or constrictions when DNA undergoes stress. Although fragile sites contribute to genomic instability, researchers have not extensively explored their role in recurrent pregnancy loss.
A second study led by investigators at Queen’s University’s Kingston Health Sciences Center and the University of Ottawa examined a 33-year-old patient who experienced three consecutive early pregnancy losses. Traditional chromosome testing revealed breaks at the rare fragile site FRA16B in nearly one-third of her cells.
Using OGM, the research team detected an abnormally large repeated DNA segment at FRA16B, confirming genomic instability that may contribute to recurrent pregnancy loss. These findings suggest that fragile sites like FRA16B may play an underrecognized role in reproductive challenges.
Moreover, combining karyotyping with optical genome mapping offers a more detailed and accurate view of fragile sites, improving the ability to detect overlooked genetic contributors to pregnancy loss.
This work was overseen by Amira Othman, M.D., Ph.D., a diagnostic and molecular pathology resident at Kingston Health Sciences Center, Queen’s University.
Conclusion
Together, these studies underscore the value of optical genome mapping in identifying previously hidden genetic causes of recurrent pregnancy loss. By pairing OGM with traditional cytogenetic testing, clinicians may gain a clearer understanding of genomic factors and offer more informed guidance to affected individuals and families.