Two studies presented at the Association for Molecular Pathology (AMP) 2025 Annual Meeting & Expo describe how optical genome mapping (OGM) may support the diagnostic evaluation of recurrent pregnancy loss by identifying chromosomal abnormalities that are not detected with standard cytogenetic methods.
Pregnancy loss affects up to one in four pregnancies, with genetic or chromosomal factors contributing to about half of first-trimester losses. When pregnancy loss occurs three or more times, it is classified as recurrent pregnancy loss (RPL). Despite established testing options – such as karyotyping and chromosomal microarray analysis – the underlying cause often remains unclear, leaving many patients without definitive answers.
The first study, conducted at Dartmouth–Hitchcock Medical Center, assessed whether OGM could detect structural chromosomal variants in individuals undergoing evaluation for RPL who had already received traditional genetic testing. According to the report, OGM identified an average of 40 structural genomic changes per case after full data review. The investigators focused on 238 genes associated with RPL. In two patients, OGM revealed structural disruptions affecting four genes linked to both infertility and pregnancy loss. Another case showed a previously undetected chromosomal rearrangement involving genes not previously associated with RPL. These findings suggest that OGM can identify structural abnormalities not captured by karyotyping or microarrays and may complement existing diagnostic workflows.
A second study, from Queen’s University’s Kingston Health Sciences Centre and the University of Ottawa, examined the potential role of chromosome fragile sites in RPL. Fragile sites are genomic regions prone to breaks or gaps under conditions of replication stress. Although known contributors to genomic instability, their involvement in pregnancy loss has not been extensively studied.
The team evaluated a 33-year-old patient who experienced three consecutive early pregnancy losses. Standard chromosome analysis showed breaks at the rare fragile site FRA16B in about one-third of examined cells. OGM revealed an unusually large repeated DNA segment at FRA16B, supporting the presence of structural instability that may have contributed to the losses. The authors note that fragile sites such as FRA16B may represent an under-recognized category of chromosomal contributors to early pregnancy loss. They suggest that combining cytogenetic testing with OGM may offer higher resolution assessment of these regions.
Together, these studies highlight how OGM may help clarify complex chromosomal changes in cases of unexplained RPL, supporting more detailed genomic assessment when conventional approaches yield inconclusive results.
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