Genetic matching helps identify whether 2 people — a patient and donor — carry mutations in the same gene that could lead to inherited diseases in their children. In this insightful session, Dr Antonio Urbano Carrillo, Clinical Geneticist at Nuuma Genetics, explains how carrier screening and Next Generation Sequencing (NGS) are revolutionising fertility care — reducing genetic risks, guiding donor selection, and helping couples make informed choices before IVF or donor conception.
Genetic matching is a process used in assisted reproduction to ensure that both reproductive partners — whether a couple or a patient and a gamete donor — are genetically compatible.
It identifies whether they carry pathogenic variants in the same gene that could be passed to a child, potentially causing severe inherited diseases.
This process is based on carrier screening, a test that looks for mutations in genes responsible for autosomal recessive and X-linked disorders. While both partners may appear healthy, if they carry mutations in the same gene, their offspring could inherit two defective copies — leading to serious conditions.
Dr Antonio Urbano Carrillo, Clinical Geneticist and Technical Director at Nuuma Genetics, explains that nearly 3 out of every 1,000 newborns are affected by severe genetic diseases.
Even among healthy couples with no family history, about 1 in 40 carry mutations that increase the risk of having an affected child.
These genetic conditions can be life-limiting or untreatable, including disorders such as cystic fibrosis, spinal muscular atrophy, or beta-thalassemia.
Genetic matching allows fertility specialists to identify at-risk combinations before conception, preventing emotional and medical complications later.
Genetic conditions can be inherited in several ways:
Autosomal Recessive Disorders:
Both parents carry one faulty copy of the same gene. Each child has a 25% chance of inheriting the disease, a 50% chance of being a healthy carrier, and a 25% chance of being unaffected.
Autosomal Dominant Disorders:
Only one faulty gene copy can cause disease, even if the other copy is healthy. These are often already known within the family.
X-linked Disorders:
These are carried on the X chromosome. Because males have one X chromosome, they are more likely to be affected, while females may be carriers without symptoms.
Understanding these inheritance patterns helps clinicians assess risk and guide appropriate matching and counselling.
Both partners undergo genetic testing using Next Generation Sequencing (NGS) technology. This powerful method screens hundreds of genes associated with severe hereditary diseases.
Results from both individuals are compared.
If no shared mutations are found, the couple is considered genetically compatible.
If shared mutations occur in the same gene, the couple is labelled high-risk, and genetic counselling is recommended.
For high-risk couples, options include:
Choosing a different donor who doesn’t carry the same mutation.
Preimplantation Genetic Testing (PGT-M) — to select embryos free from the specific mutation.
Informed family planning and alternative reproductive options.
Genetic matching should ideally be performed before conception or before starting IVF treatment.
It’s particularly relevant for:
Couples planning pregnancy through IVF or ICSI.
Donor-assisted reproduction (sperm, egg, or embryo donation).
Consanguineous couples (those related by blood).
Couples with family histories of genetic diseases.
Performing the test before gamete donation ensures that donors and recipients are genetically compatible — reducing the likelihood of inherited disease in donor-conceived children.
While no genetic test can reduce risk to absolute zero, expanded carrier screening combined with genetic matching can lower the risk of serious inherited conditions by 50–90%.
This is due to what specialists call residual risk — the small chance that some genetic variants remain undetected, or that new mutations occur spontaneously.
However, genetic matching remains one of the most effective preventive tools in modern reproductive medicine.
In donor-assisted reproduction, matching the donor’s genetic profile with that of the recipient is essential.
If both the donor and recipient share a mutation in the same gene, there is a high chance of passing the disease to the offspring, even though both are healthy.
Therefore, reputable egg and sperm banks now perform genetic carrier screening for all donors and use the same testing panels for patients.
If incompatibility is detected, another donor is selected to ensure maximum genetic safety.
Modern matching uses Next Generation Sequencing (NGS) to test hundreds of genes simultaneously.
While it’s technically possible to analyse the entire genome, specialists recommend focusing on genes that are clinically relevant and actionable — those linked to severe, childhood-onset, and untreatable diseases.
Professional bodies like the American College of Medical Genetics and Genomics (ACMG) recommend including around 200–500 genes, balancing accuracy, clinical value, and cost.
Even with advanced sequencing, certain limitations remain:
Not all disease-causing variants are yet known.
Some genetic regions are difficult to analyse.
New mutations (de novo mutations) can arise spontaneously.
As Dr Urbano notes:
We can never achieve zero risk, but with comprehensive screening, we can get as close to zero as possible.
Both before and after testing, couples should receive genetic counselling to understand their results and options.The
counsellor can explain:
What it means to be a carrier.
How inheritance works for specific conditions.
What reproductive options are available if a shared mutation is found?
This guidance helps couples make informed, confident reproductive decisions.
Genetic matching raises important ethical and practical questions — such as how much testing is appropriate, or how to balance risk reduction with cost. Experts recommend a personalised approach, focusing on clinically significant, severe, and well-understood conditions, rather than attempting to test every known gene.
The key principle is actionability: tests should identify risks that can be managed or prevented.
Genetic matching is one of the most significant advancements in assisted reproduction.
It empowers couples to make informed decisions, protects the health of future generations, and improves IVF and donor program outcomes.
While no test can eliminate risk, comprehensive screening combined with expert counselling brings couples closer than ever to achieving genetically safe, healthy pregnancies.
Genetic matching transforms IVF and donor-assisted reproduction into safer, personalised journeys.
By combining advanced technology with thoughtful counselling, it gives hopeful parents the power to reduce genetic risks — before conception even begins.
Genetic matching in assisted reproduction requires that both members of the couple undergo the same carrier screening panel. This is extremely important.
If, for example, one partner has carrier screening performed at one centre and the other partner has a different screening at another centre, the panels may not be comparable. If a pathogenic variant is identified in one partner, it is straightforward to check the same gene in the other partner, but only if the same genes were analysed.
If different panels are used, one panel may include genes that were not studied in the first test. This creates a situation where testing has to start again, potentially requiring three different panels instead of two.
If identical panels cannot be used, it is essential to ensure that the new panel is fully compatible with the first one. One possible approach is to analyse only the gene found to be altered in the first partner, but this risks overlooking other relevant conditions.
There are many carrier screening panels on the market, some analysing hundreds or even thousands of genes. In my opinion, this is excessive. In Spain, we are legally limited in which conditions we can act upon using PGT-M. There are conditions for which embryo selection is not permitted, so it does not make sense to include genes that cannot be acted upon.
More is not always better. I strongly support the use of a basic, targeted panel, typically around 15 conditions, selected according to clinical relevance.
Yes, it is time-consuming, and this must be planned properly. There are two separate tests involved, and the minimum turnaround time is usually two weeks, but it can take up to six weeks.
This is why genetic matching should be discussed during the first reproductive consultation. At the very first visit to a fertility centre, patients should be informed that this testing exists, and blood samples should be taken immediately.
The earlier the testing is started, the less impact it has on treatment timelines.
I would like to emphasise again that there is no single best carrier test. Most carrier screening tests available on the market are good tests.
What is most important, whenever possible, is to have a pre-test consultation with a genetic counsellor. This ensures that patients understand what is being tested, what the results may mean, and how those results can or cannot be acted upon.
