Key takeaways:
- Optical genome mapping identified chromosomal abnormalities often missed by traditional methods, offering improved detection of factors linked to pregnancy loss.
- Dartmouth–Hitchcock researchers found an average of 40 structural genome changes among patients evaluated for recurrent pregnancy loss.
- Hidden chromosome rearrangements and fragile sites, including the rare FRA16B, were detected and linked to genomic instability and pregnancy loss.
- Combining traditional testing with optical genome mapping may help clinicians better understand the genetic causes of miscarriage.
- IVF-based embryo genetic testing continues to reduce miscarriage risk by identifying and avoiding embryos with chromosomal abnormalities.
Data presented at the Association for Molecular Pathology 2025 Annual Meeting & Expo has indicated increased odds of pregnancy loss following chromosome changes, providing a potential opportunity for predicting pregnancy loss.1
The studies utilized optical genome mapping to evaluate the structure of genomes and identify abnormalities often missed when using traditional sequencing methods. This provides an opportunity to detect genetic or chromosomal issues linked to approximately 50% of pregnancy loss cases.
Key gene disruptions
Investigators from Dartmouth–Hitchcock Medical Center evaluated the efficacy of optical genome mapping toward identifying negative chromosomal changes among patients at risk or with a family history of recurrent pregnancy loss. Comparisons were made with prior traditional genetic testing given to these patients, such as karyotyping or chromosomal microarray analysis.
There were 238 genes evaluated, all of which were associated with recurrent pregnancy loss. The team reported a mean of 40 structural changes in the genome. Four genes linked to recurrent pregnancy loss were influenced by these changes, alongside being tied to infertility.
When examining another case, researchers found genes not linked to recurrent pregnancy loss were disrupted by a hidden chromosome rearrangement. Therefore, they concluded that genetic changes missed by standard tests may be identified through optical genome mapping. This can help give clinicians a deeper understanding of potential genetic causes.
Fragile sites and their emerging role in pregnancy loss
Alongside this study, the presentation covered research about the association between fragile sites and recurrent pregnancy loss. Fragile sites are parts of human chromosomes more likely to develop gaps, breaks, or constrictions, especially during DNA replication or repair.
“While fragile sites are known to contribute to genomic instability, their connection to recurrent pregnancy loss is not well studied,” wrote the authors.
The evaluation was performed on a woman aged 33 years with 3 consecutive cases of early pregnancy loss. The rare fragile site FRA16B was identified in approximately one-third of the patients’ cells using traditional chromosomal testing, and this observation was confirmed through optical genome mapping, which indicated an unusually large, repeated DNA segment at FRA16B.
This observation confirmed a potential association between instability and pregnancy loss. Therefore, investigators concluded that implementing optical genome mapping could help identify missed cases, highlighting the opportunity to improve detection through a combination of traditional testing and optical genome mapping.
Advances in genetic testing for miscarriage prevention
The efficacy of genetic testing for preventing miscarriage has previously been reported in a study by Daniel Potter, MD, FACOG, medical director at HRC Fertility.2 In an interview with Contemporary OB/GYN, Potter noted that complex biological, genetic, and environmental factors often make miscarriage unpredictable.
To address these hurdles, HRC Fertility clinicians have performed embryo testing by creating embryos through in vitro fertilization, biopsying them, and identifying chromosomal abnormalities through DNA assessment. This method decreases miscarriage risk by helping to eliminate embryos with aneuploidy.
This method also increases the identification of embryos that are likely to lead to successful pregnancies. Alongside preventing miscarriage, this reduces the risks of abnormal live births and genetic disorders such as Down syndrome, Turner syndrome, and Edwards syndrome.
“Genetic diagnosis is really the most significant advance in reproductive medicine in the last 30 years… It’s a very powerful technique, and it can be used to screen embryos prior to transfer to reduce the rate of miscarriage,” said Potter.
