Two studies show the advanced technique can identify chromosomal abnormalities missed by traditional genetic testing methods.
Optical genome mapping (OGM) can reveal genetic changes that contribute to recurrent pregnancy loss but are often missed by standard genetic testing methods, according to two studies presented at the Association for Molecular Pathology 2025 Annual Meeting & Expo.
The cutting-edge technique allows researchers to study genome structure at high resolution to detect abnormalities that traditional genetic sequencing methods cannot identify. Both studies focused on patients experiencing recurrent pregnancy loss, which affects up to 25% of all pregnancies and is defined as when pregnancy loss happens three or more times.
Researchers at Dartmouth-Hitchcock Medical Center investigated whether OGM could detect harmful chromosomal changes in patients with a family history or risk of recurrent pregnancy loss who had previously undergone traditional genetic testing, including karyotyping or chromosomal microarray analysis.
The team found an average of 40 structural changes in the genome after reviewing the data. The study focused on 238 genes known to be linked to recurrent pregnancy loss. In two cases, four important genes related to both recurrent pregnancy loss and infertility were directly affected by structural changes. Another case showed a hidden chromosome rearrangement that disrupted other genes not tied to pregnancy loss.
The authors say that, used alongside standard genetic tests, OGM can enhance the diagnostic evaluation of recurrent pregnancy loss, helping clinicians better understand potential genetic causes.
Fragile Chromosome Sites May Contribute to Pregnancy Loss
A second study examined the connection between chromosome fragile sites and recurrent pregnancy loss. Fragile sites are parts of human chromosomes that are more prone to developing breaks, gaps, or constrictions, especially when DNA is under stress during replication or repair.
Researchers at Queens University’s Kingston Health Sciences Centre and the University of Ottawa studied a 33-year-old patient referred after three consecutive early pregnancy losses. Traditional chromosome testing found breaks at the rare fragile site FRA16B in about one-third of her cells. Using OGM, researchers discovered that the repeated DNA segment at FRA16B was unusually large, confirming instability that may be linked to pregnancy loss.
Fragile sites such as FRA16B may be underappreciated contributors to reproductive issues, and incorporating OGM could help identify previously missed causes. Combining traditional cytogenetic testing (such as karyotyping) with OGM provides a clearer, more precise understanding of fragile sites.
The researchers noted that combining traditional cytogenetic testing such as karyotyping with OGM provides a clearer, more precise understanding of fragile sites.
Both studies suggest that OGM could serve as a valuable complement to existing genetic testing methods for patients experiencing recurrent pregnancy loss, potentially uncovering genetic causes that remain unknown with current diagnostic approaches.
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