Understanding recurrent miscarriage: new research to explore metabolic and immune health in pregnancy

There’s a whole lot that needs to go right in pregnancy. A sperm fertilises an egg, an embryo develops and then implants into the wall of the uterus. Later, the placenta is established, and the fetus develops and grows to form a baby.

Recurrent miscarriage is a devastating form of infertility where the early steps in a pregnancy do take place, but then something goes wrong. For many couples this happens over and over again, with no apparent explanation.

Now a new program of research will explore aspects of women’s health that are linked with recurrent miscarriage: metabolism and immunology.

“The immune system is really important in fighting infections – but we also know it is vital in supporting pregnancy success,” says Dr Lachlan Moldenhauer, Senior Research Associate at the Robinson Research Institute, University of Adelaide.

From an immunological perspective, implantation and survival of an embryo requires the establishment of a tolerant environment in which the tiny ball of cells is recognised and not rejected by the woman’s body.

Something appears to be going wrong immunologically in some women who experience multiple miscarriages.

“We also have data showing that in women with recurrent miscarriage, a high proportion have dysregulated metabolic health; for example, high insulin levels,” Dr Lachlan Moldenhauer says.

Insulin is a hormone that helps regulate blood sugar levels – but when it’s high, it can also be linked with immune system dysfunction. What makes the situation more complex is, that most of the affected women are fit and healthy and completely unaware that they have altered glucose and insulin metabolism, which currently makes finding a cause for their losses difficult.

“In this new research, we’re going to bring those components together and explore the links between metabolic health, immunological activity and miscarriage,” says Lachlan.

“We hope our studies will enable us develop a more personalised approach to managing recurrent pregnancy loss in patients – and perhaps help more women achieve a healthy and sustained pregnancy.” 

Titled Recurrent Miscarriage – defining clinical subtypes based on immune-metabolic dysfunction, the new project was awarded $1,612,205 over four years through the Ideas Grant program from the National Health and Medical Research Council (NHMRC).

Finding answers for women

Working with Professor Louise Hull and other colleagues at Robinson Research Institute and the University of Adelaide, Dr Moldenhauer says the new program of research will expand on a preliminary study.

“For around half of all women experiencing repeated miscarriages, at the moment we can’t give them any answers,” Dr Lachlan Moldenhauer says.

“In our new study we’ll work with a larger group of women to see if we can identify patterns of metabolic and the immune factors that are linked with high risk of multiple miscarriages.”

“With better data, perhaps we can help more women better understand their pregnancy losses.”

“In the longer term, we’re aiming to work towards creating treatment options to support pregnancy, and that can be tailored to support women based on their profile of metabolic and immune health,” says Lachlan.

Measuring metabolic and immune health will involve taking blood samples and looking at factors such as blood insulin and glucose levels, nutritional factors, markers of inflammation, immune cell activity and more.