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Lowering the oxygen levels that embryos are exposed to during IVF improves fetal and placental development, according to a study in mice. This is thought to be due to low oxygen levels better mimicking the conditions of the reproductive tract.

This is a 鈥渓andmark paper that we will cite for decades to come鈥�, says at the University of Iowa, who wasn鈥檛 involved in the research.

from about 8700 in 2000 to 20,700 in 2023. This is a safe and well-established procedure; however, IVF has been linked .

IVF attempts to replicate the changing oxygen levels in the reproductive tract 鈥� which 2 per cent in the uterus 鈥� via specialised incubators that provide the right mix of different gases. 鈥淗istorically, people would do IVF at atmospheric oxygen levels 鈥� about 20 per cent鈥�, says at the University of Pennsylvania.

These days, to limit damage caused by oxidative stress, an imbalance of molecules called free radicals and antioxidants. But some studies suggest .

To test this, Bartolomei and her colleagues cultured mouse embryos at either 2 per cent or 5 per cent oxygen, before transferring them into mice鈥檚 uteruses, like with regular IVF. They then followed the offspring for 12 weeks after birth. 鈥淢ost studies looking at altering oxygen concentration and its impact on embryo development have stopped at the termination of embryo culture,鈥� says Sparks. 鈥淭his goes so far beyond.鈥�

The researchers found that the embryos cultured at 2 per cent oxygen more closely mimicked a third group of naturally conceived embryos than those cultured at 5 per cent oxygen. This included similarities in their epigenetic reprogramming, which describes how the chemical tags that switch genes on or off are reset to allow embryo development before implantation. Many of the enzymes involved in this process are sensitive to oxygen.

The team also observed that the embryos cultured at 5 per cent oxygen had more trophectoderm cells, which help form the placenta, when in their blastocyst stage, when IVF-cultured embryos are transferred to a uterus. Too many of these cells may explain why the placenta can be , which has been , says Bartolomei. The mice born in the 5 per cent group had a lower birth weight than the 2 per cent group.

Our fertility window could be extended by making ovaries softer

A drug that softens the ovaries helped mice and rats conceive more easily at an older age, and produce more pups

Although it is unclear how lower oxygen levels may improve outcomes, Bartolomei says they could allow embryos to use energy in a way that more closely resembles development inside the uterus, where a blastocyst embeds in early pregnancy. Another possibility is that oxygen levels affect epigenetic reprogramming, she says. 鈥淥ur idea is that [the enzymes involved] overshoot the mark [at higher oxygen levels]. They become too active.鈥�

Sparks hopes the study 鈥渨ill encourage others to do quite a bit of research in this area鈥�. at the Karolinska Institute in Stockholm, Sweden, says this should be in larger animals, such as cows and pigs, whose reproduction more closely resembles that of people.

The mice in the 2 per cent oxygen group didn鈥檛 experience any known side effects from the intervention. However, it needs to be tested for safety, as well as efficacy, in people. If these tests are successful, lowering oxygen levels in IVF shouldn鈥檛 be too difficult, says Bartolomei. 鈥淚t鈥檒l be costly in the sense that [clinics] have to change their incubators and gases. But compared to how much IVF costs, it really isn鈥檛 very costly.鈥�