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Waiting safely

How scientists learned to pause a life at minus 196°C, and to wake it again.

Not every embryo goes back to its mother straight away. Some wait for a later month, a calmer body, or a little brother or sister years from now. Eggs can wait too. They rest in liquid nitrogen at minus 196°C, where time almost stands still. Learning to freeze them, and to bring them back unharmed, took decades of patient work.

It began with mice. In 1972 David Whittingham, Stanley Leibo and Peter Mazur reported in Science that mouse embryos could survive being frozen to minus 196°C, and even to minus 269°C, if they were cooled and warmed slowly enough. Living embryos could be stopped and restarted.

Alan Trounson and Linda Mohr brought it to people. At Monash University in Melbourne they worked out how to freeze human embryos at the four and eight cell stages. In 1983 they reported in Nature the first pregnancy from a human embryo that had been frozen, stored in liquid nitrogen for four months, thawed and transferred. That first pregnancy was lost at 24 weeks to an infection, a heartbreak recorded plainly in their paper. But the method worked, and the Melbourne team kept going.

A few months later, in July 1984, a baby boy was born in Rotterdam from a frozen embryo, cared for by the team of Zeilmaker and colleagues at Dijkzigt University Hospital. Within a year, two countries on opposite sides of the world had shown that a frozen embryo could become a healthy child.

Christopher Chen froze the egg itself. An egg is far harder to freeze than an embryo. It is a single, very large cell, full of water, with delicate structures inside. Working in Adelaide, where he had been recruited by Flinders University to lead research into infertility, Christopher Chen reported in The Lancet in 1986 the first pregnancy, a twin pregnancy, from human eggs that had been frozen and thawed.

Then came a new idea: no ice at all. Ice crystals are the great danger to a frozen cell. In 1985 William Rall and Gregory Fahy showed in Nature that mouse embryos could survive in a solution so concentrated that, when cooled, it set into a clear glass with no ice. This is vitrification, from the Latin word for glass.

Faster and smaller. Vitrification works best when cooling is very fast and the drop of fluid is very small. In 1998 Gábor Vajta and colleagues in Denmark described the open pulled straw: a straw heated and drawn out until very thin, holding embryos in a tiny volume and plunged straight into liquid nitrogen, cooling at more than 20,000°C per minute. They first proved it with cattle eggs and embryos. In Tokyo, Masashige Kuwayama took the idea further. In 2005, with Vajta, Leibo and a colleague, he vitrified human eggs in a droplet of less than a tenth of a microlitre resting on a fine strip. Nine in ten eggs survived warming, and healthy babies followed.

Zsolt Peter Nagy built a bank of hope. Born in Hungary, Peter Nagy graduated in medicine in Budapest in 1986 and from 1989 worked at Brussels University, in the team that brought intracytoplasmic sperm injection into the world in the early 1990s. In 2002 he became Scientific and Laboratory Director at Reproductive Biology Associates in Atlanta. There his team used vitrification to freeze eggs from donors, so that the eggs could wait in a bank until a family needed them. In 2009 they reported that 15 of 20 recipients using vitrified donor eggs had ongoing pregnancies. By 2020, data from this national donor egg bank, studied with Emory University, described 989 recipients and 856 transfers that ended in a live birth. It became one of the first large frozen donor egg banks in the United States, and it changed how donor eggs reach families.

And the waiting can be very long indeed. In July 2025 a baby boy was born in Ohio from an embryo frozen in May 1994, more than 31 years before. Somewhere in the cold, the embryo had simply waited, safe, for its moment.