Mitochondrial reproductive options

What are my options for having children if I have mitochondrial disease?

If you have a genetically confirmed mitochondrial disease diagnosis and are considering starting or extending your family, there are a number of reproductive options that can reduce the risk of passing the condition on to any future children.

The options vary considerably depending on what type of mitochondrial disease is present in your family.  For this reason, it’s important to seek reproductive advice from mitochondrial experts. It’s also important, where possible, for women with mitochondrial disease to consider their reproductive options early.

If you’d like to discuss your reproductive options, the Mitochondrial Reproductive Advice Clinic (MRA-C) is a clinic specifically for women of reproductive age who carry a genetic mistake in their mitochondrial DNA. It offers a comprehensive pathway of care for women with a personal or family history of mitochondrial DNA disease.

Below is a brief overview of the reproductive options currently available to people affected by mitochondrial disease. Some individuals may also choose to explore options such as adoption or may decide not to have children – all choices are valid and deeply personal.

Egg donation

Egg donation is a reproductive option that may be suitable for families with mitochondrial disease caused by a genetic mistake in the nuclear DNA or mitochondrial DNA.

Egg donation involves an IVF (in vitro fertilisation) procedure. It uses an egg from an unrelated donor that is fertilised in the lab using the father’s sperm. The fertilised egg is transferred to the woman with mitochondrial disease where it will hopefully establish a pregnancy. This is not guaranteed, however, and it’s important to note that the process may need to be repeated.

The child will be genetically related to the father but not the mother with mitochondrial disease. This means there is no risk to the child of mitochondrial disease.

Sperm donation

Sperm donation is an option for families with mitochondrial disease caused by a genetic mistake in the nuclear DNA.

Sperm donation also involves an IVF procedure. It uses an egg from the mother that is fertilised in the lab using donor sperm. The fertilised egg is then transferred to the mother where it will hopefully establish a pregnancy. Like egg donation, this isn’t guaranteed, and the process may need to be repeated.

The child will be genetically related to the mother but not the father with mitochondrial disease. This means there is no risk to the child of mitochondrial disease.

Prenatal testing

Prenatal testing can be used for some mitochondrial diseases caused by a genetic mistake in the nuclear or mitochondrial DNA.

Prenatal testing involves a couple conceiving naturally and then testing the baby in early pregnancy to determine the risk of mitochondrial disease. This can be done by chorionic villus sampling or amniocentesis. Both techniques involve collecting cells from the pregnancy which are tested in the lab to determine the risk.

The couple then need to make a decision (with specialist advice and counselling) to continue with the pregnancy or consider a termination based on the outcome of the test. This may be more complicated when testing for genetic mistakes in the mitochondrial DNA as the risk and/or severity of the mitochondrial disease may depend on the level of faulty mitochondrial DNA identified by the test.

Prenatal testing is only suitable for couples who would consider a termination of pregnancy. The prenatal test itself has a small risk of causing pregnancy loss (around 1%).

Preimplantation genetic testing

Preimplantation genetic testing, or PGT, is a test done on embryos during IVF where eggs are fertilised by sperm in a lab. Before any embryo is implanted in the womb, doctors test the embryos to see if they carry the genetic change that causes mitochondrial disease. It works in the following way:

1. Eggs are taken from the woman and fertilised with sperm in the lab.
2. The embryos are allowed to grow for about three days.
3. Each embryo is then tested for the mitochondrial DNA mutation that is causing disease. This testing takes about two days and the embryos continue to develop during that time.
4. On day five, embryos that have low levels of the mitochondrial DNA mutation are chosen to be implanted. Only one embryo is returned to the womb, but if other embryos are suitable then they can be frozen for use in the future.

A slightly different, more straightforward, form of PGT is available for nuclear genetic causes of mitochondrial disease and is widely available. PGT for mitochondrial DNA disease is only available in a few international centres. It’s suitable only for those women where there’s a realistic chance of having eggs with low levels of the disease-causing mitochondrial DNA mutation. It’s NOT suitable for women with high levels of the mitochondrial DNA mutation and this is where the new technique of mitochondrial donation can be helpful.

Mitochondrial donation

Some forms of mitochondrial disease are passed down through mitochondrial DNA, which is inherited only from the mother. For these women, a reproductive option can be mitochondrial donation.

This is a newer technique designed for women who have a high risk of passing on faulty mitochondrial DNA. It uses healthy mitochondria from a donor to create an embryo with the mother’s and father’s DNA, but the donor’s healthy mitochondria.

The goal is to keep the mother’s and father’s genes (from the nucleus) but replace the faulty mitochondria using something called Pronuclear Transfer, or PNT. The technique works as follows:

1. Both the mother’s egg and the donor’s egg are fertilised with the father’s sperm, creating embryos.
2. Before the embryos start developing, the mother’s embryo has the nuclear DNA removed and placed into the donor embryo (which had its own nuclear DNA removed but has healthy mitochondria).
3. The embryo with the parents’ DNA but donor mitochondria is implanted into the mother’s womb.

The resulting child ends up with DNA from their mother and father (from the nuclear DNA) and the mitochondrial DNA from the donor. It’s important to remember that the mitochondrial DNA does not control any of the characteristics of the person, it only controls the mitochondria.

To find out more about mitochondrial donation, watch our video explainer.