The Modern Laboratory · Room 5 of 8

Room 5

Testing an embryo

How patient hands learned to take a few cells from an embryo, and gave families with serious inherited conditions new hope.

Our embryo is now a blastocyst, a hollow ball of cells inside a clear shell called the zona pellucida. Some families come to IVF not because they cannot conceive, but because they carry a serious inherited condition and long for a child who will not suffer from it. For them, the laboratory can take a few cells from the embryo and read the instructions inside.

Jacques Cohen opened the shell. In the late 1980s, at Emory University in Atlanta, Jacques Cohen and his colleagues used the finest glass tools to make a small opening in the zona. They called it partial zona dissection, and they first used it to help sperm reach the egg when sperm alone could not get through; they reported their first results in 1988. In 1990 Cohen's team showed that a small opening could also help an embryo hatch out of its shell, so that more embryos implanted. This became known as assisted hatching. In New York, Jon Gordon's team had already opened the shell of mouse eggs with an acid solution in 1986, a method called zona drilling, and in 1988 used it to help sperm reach human eggs. Cohen went on to work at Cornell in New York and then at Saint Barnabas in New Jersey. Opening the shell safely made it possible, in time, to take a cell for testing.

Alan Handyside took the first step for families. At the Hammersmith Hospital in London, Alan Handyside worked with Robert Winston and colleagues on two couples at risk of passing on serious conditions that affect boys. They removed a single cell from each embryo at the six to eight cell stage, about three days after fertilisation, and used a new way of copying DNA to find out whether each embryo was a girl or a boy. Only girl embryos were transferred.

Two years later the same team reported the birth of a healthy girl after her parents, both carriers of cystic fibrosis, had their embryos tested for the condition itself. Preimplantation genetic testing, as it is now called, had begun.

Yury Verlinsky looked at the egg first. Born in Siberia and trained in Kharkiv, Yury Verlinsky built his life's work in Chicago. As an egg matures, it sets aside a tiny packet of chromosomes it does not need, called the polar body. In 1990 Verlinsky and his colleagues showed that this packet could be removed and tested, giving clues to the egg's own genes without touching the embryo. He went on to become the founding president of the Preimplantation Genetic Diagnosis International Society. He died in 2009.

Santiago Munné counted chromosomes. Working with Cohen at Cornell, Santiago Munné adapted a method that lights up chosen chromosomes in different colours, so they can be counted inside a single cell. In 1993 they reported checking five chromosomes at once in human embryos. Their work showed how often early embryos carry the wrong number of chromosomes, especially as women grow older.

From day three to day five. The first tests took one cell from a day-three embryo. In Oxford in 1990, a team showed that cells could instead be taken from the trophectoderm, the outer layer of a blastocyst that will become the placenta, leaving the inner cells that form the baby untouched. Blastocyst biopsy is now the usual approach. In 2013 a randomised trial found that taking a cell on day three lowered an embryo's chance of implanting, while blastocyst biopsy did not.

A test still being weighed. Today embryos are tested for single-gene conditions, for chromosome rearrangements carried by a parent, and for the number of chromosomes, known as aneuploidy testing. This last use is widespread, and its benefit is still debated. A large trial published in 2019 found similar pregnancy rates overall with and without it, and in 2024 the American Society for Reproductive Medicine said its value as a routine test for every patient has not been shown. Some studies suggest it may help in particular situations, and research continues.

For families who have watched a loved one live with a serious inherited illness, these few cells can mean everything.