Embryo screening: How a high-tech new fertility intervention is fueling debate

An American tech company is offering in-depth embryo screening to maximise the chance of a healthy baby. But Irish fertility specialists warn about the potential for social engineering and point to established tests which screen for genetic conditions

American technology company Orchid Health claims it can help parents maximise the chances of their children being born healthy by using a process called whole genome sequencing on embryos.

Ask anyone who is expecting a baby if they are hoping for a boy or girl and the response you get is almost always the same — their prime concern is that it doesn’t matter as long as the baby is healthy.

American technology company Orchid Health claims it can help parents maximise the chances of their children being born healthy by using a process called whole genome sequencing on embryos.

This is a form of pre-implantation genetic testing and here’s how it works. The first step is IVF, which starts with women taking daily hormone injections to stimulate their ovaries to produce eggs. 

These eggs are then extracted and fertilised with sperm to create embryos. Five days later, the surviving embryos are either transferred into the woman’s uterus or frozen for future use.

But just before this step, Orchid’s test screens each embryo’s genetic predisposition for some 1,200 health conditions. These include birth defects, neurodevelopmental disorders, chromosomal abnormalities, various cancers, diabetes, epilepsy and mental illnesses. Hopeful parents are then given genetic risk scores for each embryo to help decide which to implant.

To date, pre-implantation genetic testing has been used to screen embryos for a limited number of genetic or chromosomal conditions. 

But whole genome sequencing represents a major leap forward, according to a spokesperson speaking on behalf of Orchid, because it means there is no limit to the number of conditions that can be checked.

Dr John Waterstone questions reliability of the whole genome sequencing test.

In a country where 3% of babies are born with birth defects and where the ‘Growing Up in Ireland’ report published in 2019 found that 7% of 20-year-olds had mental, behavioural or neurodevelopmental disorders, Dr John Waterstone, medical director of Waterstone Clinic, can understand the attraction of such a test.

“No parent would wish for their child to be born with a serious illness or for their life to be limited by disability,” he says. “This test appears to offer the possibility of reducing or even eliminating the possibility of that.”

It’s no wonder that Orchid reports a high demand for its test. Orchid patients include those who have genetic conditions in their families they don’t want to pass on, older couples who are worried that their age might impact their children’s health, and parents who have already had a child with a disability and want to reduce the risk of that happening again.

While Orchid’s test seems to provide parents with the ultimate reassurance, Waterstone questions its reliability. “It’s uncertain whether the predictions made by tests like Orchid’s are accurate,” he says. “And even if they are, the results are always shades of grey rather than black and white.”

Take diabetes, for example. “There is a genetic component but there’s more than one gene involved, and environment plays a role too,” says Waterstone. “This means prospective parents are presented with test scores that are difficult to interpret.

“And then there’s the cost. Orchid charges $2,500 per embryo on top of the IVF fee. It’s expensive. It’s as of yet unproven. Pragmatically, one has to ask is it worth it.”

Dystopian nightmare?

Orchid’s screening test has been certified by the College of American Pathologists and Clinical Laboratories Improvements Amendments in the US, but it has not been approved for commercial use on this side of the Atlantic.

“The European Society of Human Reproduction and Embryology regards the polygenic screening offered by Orchid as unethical and rejects its use in clinical care,” says Waterstone.

Orchid argues that, while its interpretation of whole genome sequencing may not be 100% accurate, it provides more accuracy than any other currently available methods.

“In the case of polygenic conditions that involve multiple genes, it’s never black or white,” says the Orchid spokesperson. 

“But genetic counsellors explain this to patients. Orchid’s role is to provide prospective parents with as much information as possible and to place that information in context so they and their IVF doctor can decide on the best embryo to implant.”

Dr John Kennedy fears new test could lead tosocial engineering.

Dr John Kennedy, medical director of Thérapie Fertility, worries that such tests could lead to the social engineering of children.

“It feels like the start of a dystopian nightmare or the movie Gattaca made real,” he says. “In that movie, they screen embryos and then go one step further, fixing what’s wrong with them. We’re very far from being able to do that, but there are concerns to be considered here. What will parents do with these test results?”

In the short term, he imagines these results will likely affect how parents treat their children. “Would you not be anxious around a child that was born from an embryo that showed an elevated risk of schizophrenia?” he asks. “Would you tell that child about that risk or withhold it from them? The information could be wrong but could have ramifications for your child’s life, regardless. It’s a potential quagmire.”

Orchid takes a different viewpoint. “Parents might treat children differently but likely in a way that would help them,” says the spokesperson. “They would get them checked for those particular conditions regularly and get the help, support and treatment they might need earlier than they might otherwise have done.”

Brave new world

Genetic testing has been available in Ireland since 2012, with three main offerings.

The first test is the PGT-M or pre-implantation genetic testing for single-gene defects. “It is offered to prospective parents who have an inherited genetic condition such as cystic fibrosis that they don’t want to pass on to their children,” says Dr Ahmed Omar, medical director of Beacon Care Fertility.

This test has been a game-changer for couples identified as being at risk of having a child with a genetic condition, according to Waterstone. 

“In the past, they had two options: do no testing and take a chance or have an amniocentesis to check for the condition 15 weeks into the pregnancy,” he says. “Then, if their child had the condition, they would have to make the horrendous decision of whether or not to terminate the pregnancy.”

The second test is PGT-A.

“Pre-implantation genetic testing for aneuploidy screens for chromosomal abnormalities such as one too few or one too many chromosomes, which allows for the selection of chromosomally normal embryos for transfer,” says Omar.

Dr Ahmed Omar points to existing tests that enhance chances of a successful pregnancy.

Kennedy explains that embryos with one too few or too many chromosomes aren’t usually compatible with life. “They typically result in miscarriage,” he says.

Consequently, PGT-A is often offered to women over 35 or women who have already experienced recurrent pregnancy loss. “It significantly enhances the chances of a successful pregnancy,” says Omar.

Too few or too many chromosomes can also lead to children being born with Down syndrome, for example. “PGT-A testing allows us to screen for this and to reduce the risk of babies being born with a congenital condition that could greatly impact their health,” says Omar.

The third test is PGT-SR, which examines the chromosomal structure of embryos for segments that may have been deleted, duplicated or inverted.

None of these tests come cheap, with IVF plus genetic testing costing couples up to €15,000. However, it is hoped that funding for PGT-M and PGT-SR will eventually be included under the new HSE funding for IVF.

Couples also have the option of testing post-conception. “A simple blood test that costs between €200 and €300 can be carried out on the mother,” says Waterstone. 

“It’s currently used to screen for Down syndrome and is being expanded to screen for other single-gene disorders like cystic fibrosis.”

He points out that screening post-conception comes with a potentially greater emotional toll than screening embryos. “If you find out the baby you are carrying has a condition, can you be completely sure of the impact it will have on their lives,” he asks. “Deciding what to do in that case is a massive ethical question.”

While Waterstone is aware of thousands of families in Ireland who cherish children born with serious genetic conditions, he thinks we’re inching our way towards what he calls “a brave new world” in which these conditions no longer exist. As for Orchid, Kennedy’s verdict is that it is overpromising. 

“With traditional genetic screening like PGT-M and PGT-A, we can screen for single-gene conditions and chromosomal abnormalities and advise patients accordingly,” he says. “But it’s harder to steer patients in one direction or another with Orchid’s test. I don’t think it’s ready to be used commercially yet.”

Rather than prospective parents subjecting themselves to the difficulty of interpreting Orchid’s risk scores, Waterstone says they might be better advised to use tried-and-tested methods, one of which is expanded carrier screening pre-conception. “This involves screening the man and woman who are planning to have a child together to see if they both happen to be carriers of a harmful mutation in the same gene,” he says.

 “Couples who turn out to be at risk can then opt for PGT-M to have a child safely. It’s a simple blood test that costs approximately €700. It’s much more targeted than the scattergun approach of Orchid and the results are more black and white. I predict it will become the norm for all couples planning a pregnancy.”

Waterstone doubts whether science will ever eliminate the risks involved in conception and pregnancy.

“Couples who have no family history of certain conditions can have babies with those conditions,” he says. “I don’t know if we’ll ever be able to prevent the genetic mutations that can arise as a baby is formed.

“Then there are conditions like bipolar and ADHD that aren’t entirely determined by genetics. Having a baby and raising it to adulthood will always involve some unpredictability.”

Yet it’s to be expected that scientists will continue to push the limits of embryo screening, which is why Kennedy thinks we should confront its potential implications.

“The screening options we have now, and what’s purportedly being offered by Orchid, were but pipedreams when I first started out in fertility medicine,” he says. 

“We need to talk about what they mean for us. It’s obviously helpful to be forewarned about serious conditions but do we benefit from knowing about more subtle and non-life-threatening ones? Or is such information likely to confuse parents and make the process of parenthood even more fraught with anxiety? Now is the time to have these conversations.”

In our own words

Three women share their experience of embryo screening:

Sabrina Tadim lives in Carlow. The 33-year-old has been pregnant three times, but has yet to have a baby.

“After my third pregnancy, we found out I have a chromosomal issue called balance translocation,” she says. “It doesn’t affect me, but there’s a 50/50 chance it will affect my child and result in miscarriage or such severe disability that the baby dies in early childhood.”

She could throw the dice and conceive naturally again. “But it’s so hard,” she says. “Only one of our pregnancies ended in miscarriage. We had to travel to England to terminate the other two, as our situation isn’t covered under Irish abortion law. I don’t want to go through that again.”

Instead, she and her husband are about to embark on IVF and PGT-SR. “We will screen for the chromosomal condition and only implant healthy embryos,” says Tadim. “We don’t meet the criteria for the funded IVF scheme, as we have no problems getting pregnant, so it will cost us up to €15,000. It’ll be worth it if we get to hold our baby in our hands this time next year.”

While Tadim is starting her genetic screening journey, Alison Lynch, from Wicklow, is in the middle of hers. She decided to try to become a mother, using donor sperm, at the age of 40.

“I got pregnant for the first time aged 41,” says Lynch, who is now 46. “But a scan at 25 weeks showed that my baby boy’s brain and bones weren’t developing properly. I made the heartbreaking decision to terminate that pregnancy.” It took six fertility treatments for her to become pregnant again, at the age of 43, but once more, there were abnormalities. “I continued with that pregnancy, and my little boy lived for about 45 minutes,” she says.

Dr Sam Doyle, the National Maternity Hospital’s clinical geneticist, became involved at that stage. “She discovered that I carry a pathogenic variant of the orofacial digital gene OFD1,” says Lynch. “If I pass that on to my baby and that baby is a boy, it’s fatal.”

Since realising this, Lynch has had four IVF cycles with PGT-M testing, but has yet to become pregnant. “Finding out I had this genetic issue massively stacked the odds against me becoming a mother to a living child and I’ve since had to take huge gambles financially, physically, and mentally,” she says. “I have two embryos left, neither of which has the pathogenic variant of the gene, but which do show chromosomal abnormality. With so many improvements being made in genetic screening and fertility treatments, I hope there’s still a chance for me.”

Claire* and her husband are at the end of their journey. In 2016, they were worried that any children they conceived naturally might have Huntington’s disease.

“This incurable neurodegenerative disease is in my husband’s family and we didn’t want to take the risk of our children inheriting it from him,” she says.

Having confirmed that he was a carrier, they underwent IVF and PGT-M screening.

“We were lucky,” says Claire. “We got eight embryos and three made it to day five, so they could be tested. One had Huntington’s, but the other two didn’t. We returned on two occasions for embryo transfers and both resulted in healthy babies. That process cost us approximately €12,000.”

• *Name has been changed