Genetic Abnormalities in Early Miscarriages: New Research and Testing Method

Much more often than previously thought, early miscarriages involve genetic abnormalities in the embryo. Abnormalities in the numbers of chromosomes, the carriers of hereditary material, occur in almost 70 percent of miscarriages in the first three months of pregnancy, according to research by geneticist Masoud Zamani Esteki and his team at Maastricht UMC+.

Thanks to a refined testing method, the Maastricht team was able to better map the genetic abnormalities. The researchers hope to use this technique to improve the accuracy of the so-called NIPT, a blood test used in pregnant women to detect genetic abnormalities in the unborn child. The study appeared Thursday in the medical scientific journal Nature Medicine.

At least one in ten recognized pregnancies ends in a miscarriage, and early miscarriages are especially common: about 90 percent of miscarriages occur in the first three months of pregnancy.

Biobank of Tomsk

Researching the cause of early miscarriages is difficult. They often happen out of the sight of a doctor. Sometimes the pregnant woman does not even recognize such an early miscarriage as such. For this study, the researchers used 1,745 tissues from a unique biobank at Russia’s Tomsk University, in which tissues from early miscarriages have been collected for 35 years – both the early embryo, the amniotic sac and the placenta.

Studies to date have shown that abnormal chromosome numbers are the cause of more than half of early miscarriages. This study shows that number is higher. But the researchers also discovered that not every chromosomal abnormality necessarily leads to a miscarriage. “If the mistakes are in the early embryo, it almost always leads to a miscarriage,” says research leader Zamani Esteki. “But if the chromosome abnormalities are in tissue that forms the placenta, a normal pregnancy can sometimes occur.”

The team used a self-developed method (haplarithmisis), which can be used to find out in which of those tissues genetic errors occur and at what point in embryonic development.

Embryo selection

The new method could improve embryo selection in in vitro fertilization (IVF) and the non-invasive prenatal test (NIPT). This is a blood test that pregnant women have been able to have done since 2017 to detect genetic abnormalities in the unborn child, in particular the chromosomal abnormalities in Down, Edwards and Patau syndrome. If an abnormality is discovered, a chorionic villus sampling or amniocentesis is performed, in which some tissue or amniotic fluid is removed from the abdomen with a needle. These procedures also carry a small risk of miscarriage.

The NIPT examines DNA from the placenta that occurs in the mother’s blood. But the Maastricht discovery shows that chromosomal abnormalities in the placenta do not always have consequences for the embryo. “The NIPT incorrectly indicates an abnormality in 2 percent, a false positive result,” says Zamani Esteki. “If we can reduce the risk of this, it means less invasive tests and associated risks.”

In 2021, just over half of all pregnant women did a NIPT. Of these, 0.5 percent were told that there was a chromosomal abnormality, a total of 506 pregnant women.

The team now wants to further investigate what causes the remaining 30 percent of early miscarriages. Zamani Esteki: “That could have to do with smaller mutations, with the receptivity of the uterus.”

Zamani Esteki hopes with his insights to take away the feeling among women who have a miscarriage that there is something wrong with them, or that they have done something wrong. “A miscarriage is the result of a natural selection process, there is nothing you can do about that.”

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2023-11-27 14:25:03
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