New genetic tool reveals chromosome changes linked to pregnancy loss: Study

Maryland [US], November 16 : Pregnancy loss affects up to 25 per cent of all pregnancies, with most miscarriages occurring in the first trimester and roughly half caused by genetic or chromosomal abnormalities. But when pregnancy loss occurs three or more times, identifying the underlying cause becomes significantly more challenging, and often remains unknown.

Now, two new studies presented at the Association for Molecular Pathology (AMP) 2025 Annual Meeting & Expo in Boston suggest that a cutting-edge technology known as optical genome mapping (OGM) may uncover genetic factors missed by traditional methods, offering new hope for families seeking answers.

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, such as karyotyping or chromosomal microarray analysis, allowing direct comparison between methods.

On average, researchers found about 40 structural changes in the genome after carefully reviewing the data. The study focused on 238 genes known to be linked to recurrent pregnancy loss (RPL). In two cases, four important RPL-related genes that also play a role in infertility were directly affected by these structural changes. Another case showed a hidden chromosome rearrangement that disrupted other genes not tied to RPL. These results show that optical genome mapping (OGM) can reveal genetic changes that standard tests often miss.

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.

This work was led by Debopriya Chakraborty, Ph.D., a clinical postdoctoral fellow at Dartmouth Hitchcock Medical Center and overseen by Wahab A. Khan, PhD, FACMG and colleagues in the Clinical Genomics and Advanced Technology section at DHMC.

Certain parts of human chromosomes, known as fragile sites, are more susceptible to developing breaks, gaps, or constrictions, particularly when DNA is under stress during replication or repair. While fragile sites are known to contribute to genomic instability, their connection to recurrent pregnancy loss is not well studied.

Researchers at Queens University's Kingston Health Sciences Centre and the University of Ottawa investigated the connection between fragile sites and recurrent pregnancy loss. A 33-year-old patient was referred to them 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 optical genome mapping (OGM), they discovered that the repeated DNA segment at FRA16B was huge, 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.

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