The story of Bojana Mirosavljević and her two healthy daughters, aged four and 10, is a testament to the power of modern reproductive medicine and the work of researchers like Greek fertility specialist Dr Aspasia Destouni and Estonian molecular biologist Dr Ants Kurg.
After losing her eldest daughter Zoja to a devastating genetic disorder, Mirosavljević found hope in preimplantation genetic testing (PGT), a technique developed in the 1990s and perfected, among others, by EU-funded researchers.
By analysing her daughters’ DNA while they were still five-day-old embryos, doctors confirmed they did not carry flawed copies of the gene TPP1. This gene’s malfunction can cause CLN2, a deadly disease that impairs physical movements and skills, as well as mental development. As a result, they were deemed safe for implantation into their mother’s womb.
“Genetic testing helped save my family,” said Mirosavljević, who had previously gone through 27 rounds of in-vitro fertilisation (IVF).
She lives in Novi Sad, Serbia, and is today an active member of EURORDIS, a non-profit alliance of rare disease patients, and founder of the LIFE Association for Rare Diseases in Children – a support and advocacy group for patients and their families.
Safe prenatal checks
Infertility in Europe is a growing concern. According to a report from the World Health Organization, it affects one in six couples in Europe. The highest rates are found in the eastern and southern regions.
Thanks to intensive research over the last three decades, PGT is now routinely offered to at-risk women in many – but not all – European countries. For instance, Spain, the Netherlands and the UK have excellent track records in providing access to PGT. By contrast, Ireland, Greece and Germany offer a less comprehensive service.
“
In Europe, women are often delaying motherhood, so we need to finetune our fertility solutions.
EU-backed researchers in Europe are determined to expand the reach of PGT and other pioneering reproductive services across the continent. The goal is to ensure that patients like Mirosavljević are given the best possible chance to overcome fertility issues and give birth to children free from genetic diseases.
Networking for excellence
Destouni is a researcher in reproductive genomics at the Aristotle University of Thessaloniki in Greece, currently on secondment at the University of Tartu in Estonia.
She is the co-principal investigator of a three-year EU-funded project called NESTOR. It aims to establish a Greek network of researchers and innovators working with those from Estonia and Maastricht University in the Netherlands. The NESTOR team focuses on turning discoveries in the lab into real-life solutions.
The team aims to improve PGT, non-invasive prenatal testing (NIPT), female reproductive health and methods for predicting fertility.
Estonia, in particular, is proving a great inspiration.
“They have a fantastic model,” said Destouni. “For instance, they’ve created the Estonian Biobank, which collects and stores genetic and health data from 20% of the country’s adult population, which is used to support research, personalised medicine and public health.”
Knowledge sharing
Estonia’s successes can be traced back to the EU’s Widening initiative, a broad EU-funded research programme that started in 2014 and continues today.
Its aim is to transfer ideas, expertise and training from established research centres to those in Widening countries, meaning those that lag behind, and create networks between research teams.
In terms of fertility problems, the underlying idea is to guarantee that all 27 EU Member States can equally contribute to and benefit from scientific advancements in reproductive medicine.
At the time of the initiative’s inception, Estonia and Greece were among the 15 European countries classified as Widening countries.
Much of the progress Estonia has since made can be traced back to a clinic that opened at the University of Tartu in 2016.
In setting it up, Estonian scientists collaborated closely with fertility researchers from KU Leuven in Belgium and the University of Oxford, UK.
This collaboration was brought about through an offshoot of Widening, a three-year EU-funded research programme called WIDENLIFE, which ended in 2018.
Kurg, a professor of molecular biotechnology at the University of Tartu and principal investigator of WIDENLIFE, says sharing expertise between Belgium, the UK and Estonia has helped many Estonian couples achieve normal pregnancy and deliver healthy babies.
Before WIDENLIFE, pre-implantation testing for IVF embryos was limited and costly in Estonia, as was prenatal genetic testing.
“Samples had to be sent abroad and there would be a two- to three-week wait for results, which is much longer than you’d want,” said Kurg.
The collaboration with Belgian researchers was one of the cornerstones of the project, according to Kurg. Thanks to this, they were able to bring the necessary technology to Estonia so that all testing could be done there.
The system developed by WIDENLIFE uses a combination of single cell analysis and software algorithms to analyse the likelihood of successful implantation and development of an embryo, which helps those undergoing IVF therapy.
NESTOR builds upon the success of WIDENLIFE, and the hope is that it will strengthen the collaborative innovation activities between Estonia, Greece and the Netherlands.
Closing the gap
Destouni singled out age as the most critical determinant of a woman’s fertility.
“In Europe, women are often delaying motherhood, so we need to finetune our fertility solutions to make them effective for the population we are treating.”
Since the establishment of the Tartu clinic, many women in Estonia have also benefited from improved access to PGT for single-gene diseases, such as late infantile type CLN2 Batten disease – the condition that claimed Zoja’s life.
Experts estimate there are between 7 600 and 10 000 diseases caused by mutations to a single gene. These disorders affect up to 10 in 1 000 people and include cystic fibrosis, sickle cell disease, thalassemia and haemophilia.
PGT is also valuable for women over 35, as the likelihood of carrying a child with a genetic abnormality increases and the success of IVF decreases with age. PGT can also be beneficial for women with a history of miscarriages, multiple failed IVF cycles, or for couples experiencing infertility.
“
Genetic testing helped save my family.
One very concrete success of WIDENLIFE is the advancement of another class of fertility tests, known as non-invasive prenatal testing (NIPT), which have greatly improved in Estonia.
This method is used to assess the risk of a foetus having certain genetic abnormalities, such as Down’s Syndrome.
The test – conducted after 10 weeks of pregnancy – analyses small fragments of foetal DNA present in the mother’s blood. It is safer than the older and better-known amniocentesis test, which involves extracting amniotic fluid that surrounds the foetus through a needle.
Incredibly accurate tests
Scientists from the University of Tartu have further developed NIPT, in partnership with Celvia, an Estonian company and research institution, to create an even more accurate technique for detecting chromosomal abnormalities non-invasively.
Known as Niptify, it is today widely offered to pregnant women in Estonia, subsidised by the Estonian national health care system. The objective is to enable parents to make an informed decision about continuing or ending the pregnancy.
“Niptify is an incredibly accurate way to detect foetal chromosomal abnormalities. It is offered to every pregnant woman over the age of 35 in Estonia,” said Kurg, adding that “the technology behind it continues to be improved”.
In Greece, however, the reproductive medicine landscape is very fragmented, Destouni said, and some tests are not done in public health institutions, which means they are not readily available to the broadest population.
“The most innovative tests are generally offered by the private sector, which adopts mature technologies from foreign biotech companies,” she said. “This is not ideal, because it de-incentivises research and innovation efforts and allows the loss of valuable genomic data from the Greek population.”
“Everything needs improving, from research and data collection to fertility treatment and birthing services.”
The hope is that, with European networking and collaboration among researchers, things will indeed improve.
Research in this article was funded by the EU’s Horizon Programme. The views of the interviewees don’t necessarily reflect those of the European Commission. If you liked this article, please consider sharing it on social media.
