Pregnancy loss affects up to 25% of all pregnancies, with most miscarriages occurring in the first trimester and about half linked to genetic or chromosomal abnormalities. However, when pregnancy loss occurs three or more times, determining the cause becomes far more difficult and often remains unclear.
Two new studies presented at the Association for Molecular Pathology (AMP) 2025 Annual Meeting & Expo in Boston suggest that optical genome mapping (OGM) may help identify genetic factors missed by traditional testing methods, offering families new avenues for answers.
Researchers at Dartmouth-Hitchcock Medical Center evaluated whether OGM could detect chromosomal changes in patients with a family history or risk of recurrent pregnancy loss who had previously received standard genetic testing such as karyotyping or chromosomal microarray analysis. On average, the team identified around 40 structural genome changes after detailed review. Focusing on 238 genes associated with recurrent pregnancy loss (RPL), they found two cases where four key RPL-related genes—also linked to infertility—were directly affected. Another case revealed a concealed chromosome rearrangement disrupting additional genes not tied to RPL. According to the authors, the findings indicate that OGM can detect genetic alterations often missed by conventional tests and can improve diagnostic evaluation when used alongside standard methods.
The study was led by Debopriya Chakraborty, Ph.D., a clinical postdoctoral fellow at Dartmouth-Hitchcock Medical Center, under the supervision of Wahab A. Khan, PhD, FACMG, and the Clinical Genomics and Advanced Technology team.
A second study explored the role of fragile chromosome sites in recurrent pregnancy loss. Fragile sites are regions prone to breaks, gaps, or constrictions, especially under DNA replication or repair stress, but their connection to RPL is not well understood. Researchers at Queen's University’s Kingston Health Sciences Centre and the University of Ottawa examined a 33-year-old patient who had three consecutive early pregnancy losses. Traditional chromosome testing detected breaks at the rare fragile site FRA16B in about one-third of her cells. Using OGM, they found the repeated DNA segment at FRA16B to be unusually large, confirming instability that may be associated with pregnancy loss.
The authors note that fragile sites like FRA16B may be overlooked contributors to reproductive challenges. They say combining traditional cytogenetic testing with OGM can offer a more precise understanding of fragile sites and help identify previously undetected causes of recurrent pregnancy loss.