Some children conceived by a common method of IVF could be carrying chunks of bacterial DNA in their chromosomes, according to a study in mice. The researchers who conducted the work say that such accidental genetic modification would be very rare, but they argue that fertility doctors should take more precautions to exclude it.
Intracytoplasmic sperm injection, or ICSI, is used to help would-be fathers with very low sperm counts or sperm that cannot swim normally. Rather than mixing sperm and eggs in a culture dish as in conventional IVF, technicians take individual sperm and inject them into a woman’s eggs. ICSI has been growing in popularity since its debut in 1991, and now accounts for around half of the IVF procedures in many countries, including the UK and the US.
Over the past five years, researchers have experimented with using ICSI to make genetically modified animals by mixing DNA with sperm before injecting the cells into eggs. For large DNA sequences, which would be difficult to transfer by other techniques, it turns out to be an efficient method.
So Pedro Nuno Moreira and his team at INIA, the Spanish agricultural research agency in Madrid, decided to investigate the possibility that children’s DNA could be accidentally modified if a sperm sample was contaminated with bacteria. They mixed samples of mouse sperm with Escherichia coli containing a gene that codes for a fluorescent protein, and then used the sperm in ICSI. For fresh sperm “washed” by spinning in a centrifuge, to separate them from the other components of semen, 12 per cent of newly fertilised embryos contained the fluorescence gene, although it was not found in embryos that implanted in female mice. For samples of sperm that had been frozen but not washed in this way, 19 per cent of newly fertilised embryos and 6 per cent of those that implanted contained the gene.
ICSI experts stress that Moreira used high concentrations of bacteria, which would typically be spotted under the microscope by IVF technicians. “I don’t think there is any need to alarm patients or to change procedures for the moment,” says Maryse Bonduelle of the Flemish Free University of Brussels (VUB) in Belgium, who is studying the health of several hundred children conceived by ICSI who are now around 10 years old.
But Moreira points out that sperm samples are frequently contaminated with skin bacteria carried by the donor. He argues that IVF clinics conform to different standards, and many should take more precautions to eliminate the possibility of accidental genetic modification, such as treating sperm with antibiotics. “It’s better to be sure that no children will inherit these problems,” he says.
One worry is that bacterial DNA could disrupt genes that suppress cancer. Bonduelle thinks this unlikely, adding that the children in her study seem to be healthy. But she concedes that the consequences of accidental genetic modification might emerge later in life. “It is one more reason to continue the follow-up over a long time,” says Bonduelle.
The Human Fertilisation and Embryology Authority, which regulates IVF in the UK, says it will review Moreira’s study to see if any guidelines need to be changed.