A new study uses a special genetic sequencing technique to detect chromosomal abnormalities in couples with recurrent miscarriage. The findings are published in The American Journal of Human Genetics.
For about 40 to 60 percent of couples with recurrent miscarriage (RM), the condition remains unexplained. Chromosomal abnormalities -- rearrangements of large chunks of DNA -- in the genomes of one or both individuals trying to conceive are thought to be one of the major genetic causes of RM. Routine chromosome analysis can currently detect these abnormalities in about 1 in 50 couples, according to Science Daily.
This new study was conducted by investigators from Brigham and Women's Hospital, Shandong University and The Chinese University of Hong Kong and it uses a special genetic sequencing technique known as low-pass genome sequencing (GS) to look for chromosomal abnormalities in couples with RM. Low-pass GS revealed additional chromosomal abnormalities in more couples than traditional testing, increasing detection to 1 in 9 couples.
According to co-author Cynthia Morton, PhD, the director of cytogenetics at the Brigham, "RM carries an underappreciated psychological and financial burden for affected couples. It's often difficult to know how to treat or counsel couples when the cause of their infertility remains unknown." She adds that there are couples who have chromosomal rearrangements that can't be seen by classical methods and the technique they used increases detection in the number of couples who are at risk.
The investigators analyzed samples from 1,090 couples who had two or more pregnancy losses. Couples were enrolled from RM clinics at the two universities. Investigators performed chromosome analysis and low-pass GS. The team detected 127 chromosomal abnormalities using low-pass GS, accounting for approximately 12 percent of the couples and about 50 more couples than traditional chromosomal analysis detected.
"This a perfect example of the fundamental role that genetics can serve to help patients with infertility," said co-author Raul E. Piña-Aguilar, MD, a postdoctoral fellow in the Morton lab. "We have found that additional RM couples have chromosomal rearrangements. Undoubtedly, these couples are the ones who will benefit most from personalized intervention."
A technique known as pre-implantation genetic testing (PGT) can help couples with genetic abnormalities conceive through in vitro fertilization. Such approaches are expensive and until now, it's been unclear which patients with RM would benefit most from genetic testing of their embryos. The results suggest that applying low-pass GS could help identify a larger subgroup of patients at increased risk of subsequent miscarriage who might take advantage of pre-implantation genetic testing.