IVF linked to higher mutations than natural conception in mice

Researchers compared genome sequences of laboratory mice conceived naturally with those conceived through assisted reproductive technologies, including hormone treatments, in vitro fertilisation and embryo transfer.

Fertility-treated pups had about 30 per cent more single-nucleotide variants, tiny one-letter DNA changes.

The Jackson Laboratory team found these mutations were spread across the genome rather than clustered in specific genes.

Single-nucleotide variants can occur when cells replicate their genetic material.

Beth Dumont, a geneticist who led the study, said: “What we are seeing is a true biological signal, but we cannot make an apples-to-apples comparison relative to what happens in a clinic.

“Still, the fact that we see this trend in mice does argue for additional research investigating this possibility in humans.”

The mutations observed appear unlikely to cause harm. Scientists estimate fewer than 2 per cent of new mutations arising in a genome are deleterious or affect an individual’s characteristics or disease susceptibility.

“Even though we see an increase in mutation rate, most of these mutations are peppered across the genome, and they are neutral mutations that have no impact overall on the organism’s phenotype.” said Dumont.

Because it is not a large rise in mutation rate, the risk that any one new mutation would be deleterious is very small, almost negligible.

For roughly every 50 mice conceived with assisted reproduction, researchers expect one additional harmful DNA change compared with natural conception.

This is one problematic change among the mouse genome’s 2.7 billion DNA letters.

The effect is comparable to what would be expected if the male parent’s age increased by about 30 weeks, since paternal age significantly influences mutation rates in mammals.

The biological mechanisms remain unclear. Possible factors include hormone treatments that stimulate ovaries to restart meiosis, a cell-division stage prone to errors.

Physical handling of embryos or laboratory culture conditions might also contribute.

“Nothing in our study directly speaks to the potential of mutations in human IVF, but there have been associations in the literature suggesting some steps in IVF might induce genetic changes. That is clearly worth studying to ensure patients are maximally informed.” said Dumont.