Researchers may be closer to determining one of the reasons miscarriages happen

A study found that excess insulin can damage cells from the placenta. Prasit Rodphan/Shutterstock
  • A new study found that high levels of insulin are toxic to human placenta cells in test tubes, which could potentially cause miscarriages.
  • It’s long been known that women with insulin resistance, which can lead to higher levels of insulin in the body, also have higher rates of miscarriage, but the reasons why weren’t fully understood, the study’s author told INSIDER.
  • The small study suggests that high levels of insulin in the body could damage the placenta, which plays a critical role in establishing pregnancies.
  • If the research is replicated in human studies, it could offer an explanation for some cases of miscarriage or lead to solutions for lowering miscarriage risk.

A new study found that high levels of the hormone insulin are toxic to human placenta cells, and the discovery may lead scientists to a better understanding of miscarriages and infertility.

For the small study, published Tuesday in the journal Fertility and Sterility, researchers examined placenta cells called trophoblasts taken from three first-trimester pregnancies and exposed those cells to insulin.

Insulin in and of itself isn’t problematic, as it’s a hormone made by the pancreas that helps regulate blood sugar. But some people develop what’s known as insulin resistance, in which the body doesn’t respond well to insulin, sometimes acusing the pancreas to make more and more of the hormone.

And it’s been known for a while that women with insulin resistance also have higher rates of miscarriage, Dr. Zev Williams, director of Columbia University Fertility Center and an author of the study, told INSIDER. But the exact mechanism behind this link wasn’t fully understood.

In the study, placenta cells were damaged by insulin

Pregnant woman ultrasound
The placenta plays a ‘critical role’ in establishing pregnancies, the study’s author said. Joe Raedle/Getty Images

In the study, the isolated placenta cells and control cells were exposed to amounts of insulin simulating the real-life levels of people with insulin resistance. This led to “profound damage” in the placenta cells, Williams said.

“Usually insulin acts as a growth factor,” he added. “If we take a muscle cell, a liver cell, a skin cell, and we grow it in the presence of elevated levels of insulin, those cells love it. It helps the cells grow better. The only cell that seems to have the opposite effect is the trophoblast cell. The placenta almost seems exquisitely sensitive to toxic effects from insulin.”

Read more: Michelle Obama didn’t realise how common miscarriages were when she had hers – here’s what you should know

This finding relates to miscarriage because the placenta, the organ that develops in the uterus to deliver oxygen and nutrients to a foetus, is important for healthy pregnancies.

“The placenta, especially early in pregnancy, plays such a critical role in terms of establishing the pregnancy and establishing good nutrients and oxygen supply to the embryo,” Williams said.

In a separate experiment for the study, the researchers exposed a new set of placenta cells to both insulin and the drug metformin, which is used to treat type 2 diabetes. They found that pre-treating the cells with metformin blocked insulin’s damaging effects.

Even though it’s a diabetes drug, metformin is also used by people polycystic ovary syndrome(PCOS), a common hormonal imbalance disorder. Many people with PCOS also have insulin sensitivity, and metformin (though it’s not technically approved for PCOS treatment) is sometimes prescribed to help lower blood sugar and insulin levels. Metformin may also help PCOS patients with fertility, Verywell reported last year, though it’s not exactly clear how.

Some studies have shown that taking metformin can reduce rates of pregnancy lossin people with PCOS. Other studies suggest that metformin might improve pregnancy rates in PCOS patients, though others don’t show this benefit, the authors wrote in their paper.

If the findings are replicated in human studies, doctors could have new ways to address miscarriage

Doctor holding hands patient
Right now, the authors wrote, the findings need to be confirmed with additional studies. Andrei_R/Shutterstock

This research was performed on cells in test tubes, meaning the current results can’t be applied to humans. But if the findings hold true in vivo (a.k.a in living organisms), it could help doctors better address pregnancy loss and infertility in people with insulin resistance, Williams explained.

“I think, if the in vitro data is replicated in vivo, it would suggest that women who have insulin resistance … may be at risk for pregnancy loss,” he said. “Insulin resistance is not a rare condition. About one in three American women have insulin resistance, and so the impact that this potentially has on pregnancy loss is really significant. It’s not just an academic discovery [saying,] ‘Look, insulin has this effect.’ It naturally leads to interventions that can hopefully reduce rates of pregnancy loss. It provides both a possible explanation and possible therapeutic option.”

If the data is replicated in further studies, Williams added, doctors may be able to help patients with insulin resistance reduce risk of miscarriage by having them adopt lower-carb and lower-sugar diets that would promote fewer spikes in insulin, or by using metformin, though the medicine wouldn’t necessarily be appropriate for all people.

“Our study suggests it’s not a drug that you give to everyone and they will do well,” Williams said. “It would help only those women who have this very high insulin response.”

For now, of course, more research is needed, but Williams added that the discovery helps push scientists toward a better understanding of miscarriage.

“Pregnancy loss and infertility tend to have a stigma associated with them, and I think part of the reason for that is so much of it has historically been unexplained,” he said. “When there’s not really a good scientific or medical explanation for something, people will fill in things like self-blame. And one of the nice benefits of this type of research is it sort of points out that pregnancy loss and infertility don’t just happen, and there might be genuine medical underpinnings to why the losses are happening. It’s sort of incumbent on us to try and discover those.”


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