Genetic Variants Linked to Chromosome Errors May Explain Pregnancy Loss

A new study has identified specific genetic variants linked to an increased risk of chromosomal abnormalities in embryos, a key factor contributing to pregnancy loss. Published in January 2026 in the journal Nature, the research offers a deeper understanding of the biological mechanisms underlying early pregnancy failure and may pave the way for improved fertility treatments, and diagnostics.

Approximately half of all first-trimester pregnancy losses are attributed to aneuploidy, a condition where cells have an abnormal number of chromosomes. Research indicates that aneuploidy is significantly more common in egg cells than in sperm cells, and its incidence rises with a woman’s age. While maternal age is a well-established risk factor, this new study focuses on genetic differences that may predispose individuals to produce eggs with chromosomal abnormalities, independent of age.

“I think that’s a big blind spot for our field,” said Rajiv McCoy, an associate professor of biology at Johns Hopkins University. McCoy and his team sought to address this gap in knowledge by analyzing clinical genetic testing data from over 139,000 embryos created through in vitro fertilization (IVF). The dataset included information from 22,850 mothers, with ages ranging from approximately 20 to nearly 56 years old, with an average age of around 36.

The researchers performed genome-wide association studies, searching for statistical links between genetic variations carried by the participants and the occurrence of aneuploidy in their embryos. They also analyzed the transcriptome – the collection of RNA molecules within cells – to gain insights into gene activity. This approach allowed them to identify genes that are actively involved in the processes leading to chromosomal abnormalities.

The strongest association identified was with variations in the SMC1B gene, which provides instructions for making a protein crucial for maintaining chromosome structure. Another significant link was found with the C14orf39 gene, involved in chromosome interactions during cell division. These findings suggest that variations in these genes can disrupt the delicate processes necessary for accurate chromosome segregation during egg development.

The study also sheds light on the relationship between aneuploidy and crossover recombination, a natural process where chromosomes exchange genetic material during the formation of egg and sperm cells. The researchers observed that crossover count was lower in aneuploid embryos, supporting previous research linking errors in crossover recombination to an increased risk of aneuploidy. However, the new research goes further, demonstrating that the genetic variants associated with aneuploidy risk are also involved in regulating crossover recombination.

“The same machinery that’s influencing recombination is the machinery that’s influencing risk of producing these aneuploidies,” McCoy explained. This suggests a shared genetic basis underlying both processes, highlighting the importance of proper crossover recombination for ensuring accurate chromosome number in eggs.

Shai Carmi, a professor of computational and statistical genetics at the Hebrew University of Jerusalem, who was not involved in the study, emphasized the significance of these findings. “This helps us understand how all of these traits are tied together. What are the risk factors that make some women have more aneuploidy and, lower fertility?”

Pregnancy loss is a common experience, affecting an estimated 10 to 20% of clinically recognized pregnancies. However, researchers believe that as many as half of all conceptions are lost before birth, often very early in development. Understanding the underlying causes of these losses is crucial for improving reproductive health.

While the identified genetic variants each explain only a small portion of an individual’s overall risk, the study represents a significant step forward in understanding the complex interplay of factors contributing to pregnancy loss. McCoy cautions that it is currently too early to apply these findings directly to patient care, but he believes they could eventually lead to better risk prediction and potentially, new therapies. “That doesn’t mean that it’s not possible, in the future, to get better predictions of people’s risk. And this provides one clue as to what we should be looking for.”

The researchers emphasize that this study provides fundamental insights into the biological mechanisms underlying pregnancy loss, which is valuable in itself. “I personally think that the value of this study is more fundamental,” McCoy said. “It’s helping us understand who we are as humans.”