A groundbreaking study has identified genetic variants associated with chromosomal abnormalities that may contribute to pregnancy loss. This research highlights a significant relationship between maternal genetics and the risk of producing aneuploid embryos, which are linked to about half of all first-trimester pregnancy losses.
Approximately 10% to 20% of clinically recognized pregnancies end in miscarriage, but estimates suggest that around 50% of all conceptions may be lost before birth, often in the early stages of development. The study, published in the journal Nature in January, involved clinical genetic testing data from over 139,000 embryos created through in vitro fertilization (IVF) and analyzed the genetic profiles of 22,850 mothers aged between 20 and 56 years, with an average age of 36.
According to Rajiv McCoy, an associate professor of biology at Johns Hopkins University, previous research lacked well-characterized associations between maternal genetic variations and the occurrence of aneuploid embryos. The study aimed to fill this gap by employing genome-wide association studies to explore statistical links between the mothers’ genetic variants and the incidence of aneuploidy.
The researchers identified significant associations with specific versions of the SMC1B gene, which encodes a protein that plays a critical role in holding chromosomes together during cell division. Another important gene linked to the study was C14orf39, which facilitates interactions between chromosomes during cell division.
By examining the process of “crossover recombination,” the researchers discovered that errors in this mechanism, which involves the exchange of DNA segments during egg or sperm cell formation, contribute to aneuploidy. The study found that a lower number of crossovers correlated with a higher incidence of aneuploid embryos, reinforcing prior findings that errors in chromosome separation during cell division lead to increased aneuploidy risk.
McCoy noted, “The same machinery that’s influencing recombination is the machinery that’s influencing the risk of producing these aneuploidies.” This revelation marks a significant advance in understanding the genetic factors that may influence fertility and pregnancy outcomes.
Despite the promising findings, the researchers caution that the genetic variants linked to aneuploidy explain only a small portion of an individual’s overall risk. Therefore, it is premature to apply these results directly to patient diagnostics or treatments. Nonetheless, McCoy believes that advancements in understanding these genetic mechanisms could pave the way for future therapies to reduce pregnancy loss.
The insights from this study not only enhance the understanding of genetic factors affecting pregnancy but also underscore the importance of crossover recombination in ensuring the viability of pregnancies. Shai Carmi, a professor of computational and statistical genetics at the Hebrew University of Jerusalem, emphasized the significance of identifying risk factors associated with aneuploidy, stating, “What are the risk factors that make some women have more aneuploidy and, therefore, lower fertility?”
As research continues to evolve, the implications of these findings may lead to improved predictions regarding pregnancy risks and potentially inform future fertility treatments. McCoy expressed a broader perspective on the importance of this research, stating, “It’s helping us understand who we are as humans.”
The study represents a crucial step in unraveling the complex relationship between genetics and pregnancy outcomes, offering hope for future advancements in reproductive health.
