Mitochondrial Reproductive Options

If you have a genetically confirmed mitochondrial disease 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 is important to seek reproductive advice from mitochondrial experts.  It is also important for women with mitochondrial disease to consider their reproductive options early.

If you would like to discuss your reproductive options, the Newcastle Mitochondrial Reproductive Clinic (NMRC) 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. To find out more, including how to get a referral to the NMRC, please see the information provided at the end.

The video below was created by the Wellcome Centre for Mitochondrial Research at Newcastle University and outlines the reproductive options available for women who carry a genetic mistake in their mitochondrial DNA.

The reproductive options currently available for people affected by mitochondrial disease are explained briefly below. Other options that can be considered (but are not listed) include voluntary childlessness or adoption.

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 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 is 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 of mitochondrial disease.

 

Sperm Donation

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

Sperm donation involves an IVF procedure. It uses an egg from the mother that is fertilised in the lab using donor sperm. The fertilised egg is transferred to the mother where it will hopefully establish a pregnancy.  This is not guaranteed, however, and it is important to note that 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 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 to continue with the pregnancy or consider a termination based on the outcome of the test (with specialist advice and counselling). 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 Diagnosis (PGD)

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

PGD involves an IVF procedure. It uses eggs from the mother that are fertilised in the lab using the father’s sperm.  This means that any future child will be genetically related to both parents.  

The embryos that develop in the lab are tested to determine the risk of mitochondrial disease. If a suitable embryo is identified that has no risk (or a lower risk), this can be transferred to the woman where it will hopefully establish a pregnancy.  This is not guaranteed, however, and it is important to note that the process may need to be repeated.

The results for genetic mistakes in the nuclear DNA may be easier to interpret as the faulty gene will either be present or absent from an embryo, making the choice of embryo for transfer relatively straightforward. 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 in the embryo. PGD will not be suitable if a woman has only faulty mitochondrial DNA in her eggs (referred to as ‘homoplasmy’).

 

Mitochondrial Donation

Mitochondrial donation is a relatively new reproductive option that may be suitable for families with mitochondrial disease caused by a genetic mistake in the mitochondrial DNA.

Mitochondrial donation is a novel IVF procedure. It uses eggs from both a healthy donor and a woman with mitochondrial disease. The nuclear DNA is removed from the donor egg and replaced with the nuclear DNA from the egg containing faulty mitochondrial DNA.  The egg is then fertilised in the lab using the father’s sperm.  This means that any future child will have the nuclear DNA from both parents (and so be genetically related to both the mother and father) but with a much lower risk of mitochondrial disease due to the healthy mitochondrial DNA from the donor egg. It is this combination of DNA from three people that led to the term ‘three-person baby’ that is often used to describe the technique.

The law was changed in the UK in March 2015 to allow the use of mitochondrial donation. The Lily Foundation, along with mitochondrial patients and their families, were instrumental in this law change. For more information on the history of mitochondrial donation, click here

The use of mitochondrial donation is highly regulated in the UK and requires that every person who wishes to use the technique is granted approval by the Human Fertilisation and Embryology Authority (HFEA).  The Newcastle Fertility Clinic at Life (Newcastle Hospitals NHS Foundation Trust) is currently the only fertility clinic in the UK that is licensed to perform the technique. Please contact your own clinician who can discuss the possibility of a referral to the Newcastle Mitochondrial Reproductive Clinic.

Upon receipt of a clinical referral, an appointment will be made to attend the Newcastle Mitochondrial Reproductive Clinic, undertaken by Prof Gráinne Gorman (Consultant in Mitochondrial Medicine) & Catherine Feeney (Nurse Consultant in Mitochondrial Medicine) at the Royal Victoria Infirmary, Newcastle. This clinic will review and confirm the genetic diagnosis, assess fitness for pregnancy from a mitochondrial disease perspective and offer psychological support and advice regarding reproductive options for IVF-based techniques, including preimplantation genetic diagnosis (PGD) and mitochondrial donation. Once assessed in this clinic, and if considered appropriate, couples will be referred to the Mitochondrial Assisted Reproductive Technologies (Mito-ART) Clinic at Newcastle Fertility Clinic at Life.

General enquiries can be made via:

Bernadette Caygill ([email protected])                             

Direct Dial:  0191 2824876                                                                  

Fax:  0191 282 4373    

For mitochondrial donation, is it crucial that healthy women aged between 18-34 years and living in the North-east of England consider donating their eggs.  This will allow some women with mitochondrial disease to use the technique to have a healthy child.