OGM, combined with standard genetic tests, can improve diagnosis of recurrent pregnancy loss and reveal hidden genetic causes.
Pregnancy loss is more common than many realize, affecting up to 25% of all pregnancies. The majority of these losses happen during the first trimester, and roughly half are linked to genetic or chromosomal abnormalities.
Recurrent Pregnancy Loss: Understanding the Hidden Causes and Challenges
When pregnancy loss occurs three or more times, it is classified as recurrent pregnancy loss (RPL). For many experiencing RPL, the underlying cause remains elusive, adding emotional and medical uncertainty to an already difficult situation.
Recent research, however, is shedding new light on this complex issue. Two studies presented at the Association for Molecular Pathology (AMP) 2025 Annual Meeting & Expo, held Nov. 11–15 in Boston, have made important advances in understanding the genetic factors behind pregnancy loss.
Both studies employed a state-of-the-art technique called optical genome mapping (OGM), which enables scientists to examine the structure of genomes with unprecedented resolution.
This method can detect genetic abnormalities that are often missed by conventional sequencing approaches, offering hope for more accurate diagnoses and better-informed treatment options for those affected by recurrent pregnancy loss.
Dartmouth–Hitchcock Study Explores OGM for Detecting Hidden Genetic Risks in RPL
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.
Some parts of human chromosomes, known as fragile sites, are more prone to developing breaks, gaps or constrictions, especially 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.
Uncovering Hidden Causes: How OGM and Fragile Sites Impact Reproductive Health
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 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.
Source-Eurekalert