Scientists Identify Genetic Factors Linked To Miscarriage Risk And Chromosomal Errors

Pregnancy loss is a widespread yet often silent issue. Around 15 percent of confirmed pregnancies end in miscarriage, although the real figure is likely higher because many losses occur before a pregnancy is detected. New research now suggests that part of this risk may be shaped before a woman herself is born.

In a large genetic study, scientists identified inherited factors that influence aneuploidy, a condition in which embryos have too many or too few chromosomes. Aneuploidy is one of the leading causes of early miscarriage. The findings deepen understanding of how subtle DNA differences affect the earliest stages of human development.

Large Embryo Study Reveals Patterns

Researchers examined clinical data from pre-implantation genetic testing of in vitro fertilization embryos. They analyzed 139,416 embryos from 22,850 sets of biological parents, looking for chromosomal errors and links to parental genetics. In total, they identified 92,485 aneuploid chromosomes in 41,480 embryos.

The unusually large dataset gave the team the statistical power needed to detect small but meaningful effects. Many traits related to survival and reproduction are strongly shaped by evolution, meaning only genetic variants with modest effects tend to remain common in the population. Detecting these subtle influences therefore requires very large sample sizes.

Key Genes Tied To Egg Cell Errors

The strongest associations were found in genes involved in controlling how chromosomes pair, exchange segments, and separate during meiosis, the specialized type of cell division that forms eggs and sperm.

One variant of the gene SMC1B, which encodes a protein that helps hold chromosomes together, was associated with fewer crossovers and higher rates of maternal aneuploidy.

The analysis also highlighted genes such as C14orf39, CCNB1IP1, and RNF212, all of which are involved in crossover recombination. These same genes have been studied for decades in mice and worms, where they are known to play crucial roles in recombination and chromosome cohesion. The new study shows that similar mechanisms also operate in humans.

Risk May Begin Before Birth

Female meiosis begins before birth, when chromosomes pair and exchange segments in the fetal ovaries. The process then pauses for years before resuming later during ovulation and fertilization.

Genetic variants that weaken chromosome cohesion or reduce crossover events may make chromosomes more likely to separate incorrectly when meiosis restarts later in life.

This vulnerability may help explain why chromosomal abnormalities in eggs become more common with maternal age. Over time, the structures that hold chromosomes together can gradually weaken, especially if they were already more fragile because of inherited genetic variants. This combination may increase the likelihood of embryos developing missing or extra chromosomes.

Implications For Miscarriage And Fertility Care

About half of clinically recognized miscarriages during the first or second trimester are linked to chromosomal abnormalities.

The new study suggests that inherited differences in meiotic processes contribute to why some individuals face higher or lower risks of pregnancy loss. However, the authors stress that genetics represents only one part of a much more complex picture.

Factors such as maternal age, environmental exposures, health conditions, and paternal genetics also influence pregnancy outcomes. Predicting miscarriage risk for any individual person therefore remains difficult, and the study does not provide a simple clinical test for future pregnancy loss.

Instead, researchers say the findings provide an important framework for future studies.

Over time, understanding the molecular pathways involved in aneuploidy could help guide new fertility treatments or identify drug targets aimed at improving egg quality and embryo survival. The findings may also improve how clinicians interpret embryo testing results during IVF, helping patients make more informed decisions about fertility treatment options.

The research was published in the journal Nature and adds to growing evidence that some aspects of reproductive risk are established long before adulthood. An earlier version of the study was reported in February 2026, but the updated analysis expands and clarifies the genetic links involved.