What are in vitro-derived gametes?

In vitro-derived (IVD) gametes are egg and sperm cells created in a laboratory by reprogramming other cells, such as embryonic stem cells or skin cells, to become functional egg and sperm cells. This process is known as in-vitro gametogenesis (IVG). The laboratory created eggs and sperm can then be used to create embryos.

What is happening in current scientific research?

Over the last decade, there have been significant developments in the creation of IVD egg and sperm cells in mice models as researchers seek to identify the causes of infertility and to find possible solutions. These developments have mainly been led by researchers in Japan who, in 2016, derived the first functional female egg cells from reprogrammed mouse skin cells. By using IVF techniques, the team was able to produce healthy mouse offspring from the laboratory created eggs.

Earlier in 2016, a team of researchers from China published a paper in the journal Cell Stem Cell, claiming that they had created male sperm-like cells from mouse embryonic stem cells. However, these claims were contested and it was not until 2021 that a team from Japan announced the creation of the first functional IVD mice sperm cells, which were successfully used to produce live offspring.

At the Third International Summit on Human Genome Editing in March 2023, one of the lead Japanese researchers, Professor Katsuhiko Hayashi, announced the creation of mice with two biological fathers. This is the first time that viable IVD eggs have been generated from male cells.

Most recently, an alternative IVG approach to creating eggs has been developed at the Centre for Embryonic Cell and Gene Therapy in Oregon. The researchers there used Somatic Cell Nuclear Transfer (a form of cloning) to create an egg by replacing the nucleus from a donor mouse egg with a nucleus taken from a mouse skin cell. 

The scientific advances in the creation of IVD egg and sperm cells in mice are not proving as easy to replicate with human cells. This is largely because the precise mechanisms by which human cells differentiate into egg and sperm cells and how they develop naturally in the embryo is still not fully understood.

Scientists have, however, been making progress toward the development of human IVD gametes. For example, in 2015, a research team at the University of Pennsylvania successfully created an early-stage human sperm cell using male blood cells and has, more recently, produced the precursor to sperm, spermatogonia. Researchers from Japan have cultured human cells to the stage before they become eggs.

In June 2024, there was a breakthrough in the creation of human IVD gametes. It was reported in Nature that human cells that were originally skin cells had been reprogrammed into early-stage sperm and egg precursors. This means that scientists are almost at the stage where IVD sperm and immature egg cells are possible.

Despite this breakthrough, the creation of functional, mature IVD human gametes has not yet been achieved and there are still a number of regulatory and technical challenges that need to be overcome.

However, if research on human IVD gametes does achieve the same results as the research on mice, it will open up new reproductive possibilities. IVD gametes will, for example, make it possible for individuals and couples, who are unable to produce viable gametes due to congenital anomalies or after certain medical treatments (e.g. for cancer), to create genetically-related gametes for reproduction from their own skin or stem cells. This will allow those who have previously only been able to reproduce using donor gametes to conceive and birth children who are genetically related to them.

If human gametes can be created in a laboratory, this may also disrupt various social and biological reproductive norms by enabling, for example, same sex couples to both be genetically related to their offspring; transgender women to contribute eggs and transgender men to contribute sperm; and post-menopausal women to continue to reproduce. These possibilities raise complex issues and questions which need to be addressed before scientists do manage to create human IVD gametes in the laboratory.

What issues/questions do IVD gametes raise?

• Are there any moral differences between an IVG embryo, an IVF embryo and an embryo created through biological reproduction? If so, what are they?
• Should children created through IVD gametes have a right to know how they were created?
• Given the existence of alternative routes to parenthood, such as adoption and surrogacy, are the costs and risks associated with these new technologies worth incurring?
• Should IVD gametes be publicly funded in countries with public healthcare systems?
• Does the development of IVD gametes perpetuate damaging pro-natalist and genetic essentialist stereotypes regarding the ideal of parenthood and the social acceptability of infertility?

For a more in-depth discussion about IVD gametes, read about our IVG Policy Briefing Workshop, in collaboration with the Nuffield Council on Bioethics, here.