The 'Three Parents' Baby and the Future of Genetic Medicine

Approximately one in every 5,000 newborns is affected by mitochondrial diseases, serious pathologies resulting from mutations transmitted exclusively through the maternal lineage. For women carrying these mutations, natural conception presents a dilemma: while some children may be born healthy, others inevitably inherit progressive and often fatal diseases. It was precisely to mitigate this risk that science developed in vitro fertilization with mitochondrial donation, a revolutionary technique that recently gained media attention with the birth, in the United Kingdom, of the first baby with genetic material from three people.

This is possible through the donation of mitochondria, which are small, energy-producing structures found in the cytoplasm of our cells and are exclusively maternally transmitted. This means that mitochondria always pass through the egg. This technique is performed in very few countries, with the United Kingdom being one of those where it is regulated, unlike Portugal, where mitochondrial donation does not yet have a regulatory framework.

The process allows genetically altered mitochondria to be replaced with healthy mitochondria from a donor, resulting in an embryo that, in addition to the genetic heritage of the parents (derived from the egg and sperm), also incorporates a small fraction of the donor's mitochondrial DNA.

This birth of the first baby with genetic material from three people undoubtedly represents a historic milestone in reproductive medicine and an extraordinary advance in the fight against inherited mitochondrial diseases. However, modern medicine already has a diverse arsenal of genetic tests and preconception diagnostic strategies that allow for risk assessment, guidance on reproductive decisions, and prevention of the transmission of serious diseases that have a significant impact on quality of life.

I'm talking about tests whose main objective is to enable a successful pregnancy when the high risk of miscarriage or the birth of a child with a serious genetic disease is already known. These tests are used in assisted reproduction and are performed on embryonic cells. In recent years, these tests have not only gained significant attention but have also been legally accepted in Portugal and several other countries.

They can be used to detect chromosomal alterations when one of the partners carries a balanced alteration (translocation, inversion) that causes a high risk of repeated miscarriages or malformed fetuses, called PGT-SR; when one of them has a serious monogenic disease (which involves a gene), such as Huntington's disease, familial amyloid polyneuropathy, among others, and they want to avoid passing it on to their children, or even when the couple is healthy but carries a specific genetic disease, such as cystic fibrosis or spinal muscular atrophy, a test called PGT-M.

There is also another approach, PGT-A, which allows assessing whether embryos have the correct number of chromosomes (euploidy), permitted in Portugal when there are recurrent implantation failures or in couples with recurrent miscarriages without a specific cause, or in situations where IVF is necessary and the woman is 37 years of age or older or has had a previous pregnancy with a chromosomal anomaly.

For all these assessments to be carried out properly, monitoring by a medical genetics specialist is essential, as their intervention makes sense at multiple stages of the couple's reproductive journey and throughout the IVF process. Clinical genetics consultation is particularly recommended in situations of identifiable genetic risk, namely when there is consanguinity between the parents – a factor that significantly increases the likelihood of recessive genetic diseases, which can be detected through preconception screening. Equally important is evaluation when there is a family or personal history of genetic disease, allowing not only to confirm the diagnosis through specific tests, but also to quantify the risk of transmission, explore available reproductive options, and assess potential implications for other family members.

Genetic counseling is also essential when some of the tests performed during the IVF process reveal significant alterations, as well as in the context of pre-implantation genetic testing, whether to assess its feasibility or to guide possible alternatives. Ultimately, the main goal is to help couples identify specific risks, ideally before fertilization procedures, so they can make informed decisions about family planning and maximize the likelihood of having a healthy baby.

In this area, scientific progress has been remarkable and offers increasingly personalized and effective options, in a path where prevention and diagnostic accuracy go hand in hand to ensure the birth of healthy children and provide peace of mind to families.