On Jan. 21, 2026, a Johns Hopkins University-led team demonstrated robust connections between specific variations in a mother’s DNA and their risk of miscarriage. The findings shed new light on human reproduction and suggest pathways for developing treatments to lower the risk of pregnancy loss. The federally funded work is published in Nature.

By studying genetic data from nearly 140,000 IVF embryos, scientists have with unprecedented detail revealed why fewer than half of human conceptions survive to birth. The research uncovered the strongest evidence yet for how common genetic differences leave some individuals more vulnerable to pregnancy loss.

“This work provides the clearest evidence to date of the molecular pathways through which variable risk of chromosomal errors arises in humans,” said senior author Rajiv McCoy, a Johns Hopkins computational biologist focused on the genetics of human reproduction. “These insights deepen our understanding of the earliest stages of human development and open the door for future advances in reproductive genetics and fertility care.”

Pregnancy loss in humans is common, with about 15% of recognized pregnancies resulting in miscarriage and many more conceptions being lost at early stages without people realizing it. Scientists have long known that the main reason is extra or missing chromosomes. Down syndrome, caused by an extra copy of chromosome 21, for example, is one of the few chromosome abnormalities of this type that is survivable.

Most chromosome errors originate in the egg and increase in frequency with a mother’s age. More mysterious is how factors beyond age, such as genetic differences, may predispose a person to produce eggs with abnormal numbers of chromosomes in the first place. The strongest associations appear in genes that govern how chromosomes pair, recombine, and are held together during egg formation, including a gene (SMC1B) that encodes part of the ring-shaped structure that encircles and binds chromosomes, the team found. These rings are essential for accurate chromosome segregation and tend to break down as women age.

Strikingly, these same genetic variants that influence the risk of pregnancy loss are also associated with recombination, the genetic shuffling process that generates diversity when eggs and sperm are made, they found. “Our results demonstrate that inherited differences in these meiotic processes contribute to natural variation in risk of aneuploidy and pregnancy loss between individuals,” McCoy said.

The team is now studying rare variation in maternal and paternal genomes that may have larger effects on aneuploidy risk. They are also using new technologies to better understand how even smaller, poorly understood genetic changes contribute to pregnancy loss.