Aaron and Lisa Christy was a happily married couple with a young son and another on the way. But unlike their firstborn who was born healthy, their second son, Ben was diagnosed with Wilms’ tumour (a rare inherited form of kidney cancer) when he was merely 18 months old. “When Aaron was a child, the doctors had diagnosed him with the very same kind of tumour. Thankfully, chemotherapy and surgery saved his life. But we never expected our child to have this cancer as we were told that it couldn’t be passed on to the next generation,” Lisa explains in an interview with Perth Now. While Aaron survived, the same couldn’t be said for Ben. After two years of anti-cancer therapy, he finally succumbed to the aggressive cancer.

Despite their loss, Aaron and Lisa were still adamant to have more kids, as they had always wanted a large family. But they now knew that it would come with risks. “If we decided to get pregnant naturally, there was a significant risk that our baby would have Wilms’ tumour. We didn’t want to put ourselves through that painful experience ever again,” Lisa says.

With this in mind, they turned to genetic experts at a Sydney hospital who referred them for a procedure known as pre-implantation genetic testing whereby Lisa’s embryos were screened for genes carrying the Wilms’ tumour to determine which ones were healthy and which weren’t. Five of the embryos were found to carry the cancer gene, only three were unaffected. “The results just drove home the fact that if we had gotten pregnant naturally, we would have been playing Russian roulette.” One of the three unaffected embryos was then implanted in her womb – to great success. “Now, we have a totally healthy baby girl and couldn’t be happier. I wasn’t prepared to gamble with my child’s life so I underwent the procedure – and I’m glad I did.”

Maximising your chances

The Christy couple is not the only one who has to deal with the fear of passing on flawed genes to their offspring. Many couples share the same predicament. Fortunately, thanks to advances in fertility treatments such as pre-implantation genetic testing (PGT), their dreams of having a healthy baby can now become a reality.

But it isn’t just couples with a history of inherited disorders who are seeking out PGT, healthy couples are also opting for this screening method according to Pre-implantation Genetic Testing Scientist Mr Aaron Chen. “These couples have no history of inherited illnesses. They just want to increase their chances of having a baby via IVF. By choosing only healthy embryos for implantation, the higher the success rate of the pregnancy,” he explains. “Therefore, PGT can be for everyone.”

Lifting the curtain on…

Pre-implantation genetic testing

“Basically, PGT refers to the technique used for identifying genetic defects in embryos via IVF. It acts as an alternative to post-conception diagnostic procedures like chorionic villus sampling and amniocentesis (amniotic fluid test). For some couples, these tests yield unfavourable results which can put them in the difficult predicament of deciding whether to keep their baby or not.”

Elaborating further, he explains, “We can break PGT down into a number of steps.”

• Step 1: The woman undergoes IVF so we can collect and fertilise her eggs.
• Step 2: The embryos (fertilised eggs) are grown in the lab for 2-3 days. By now, the cells would have divided and each embryo should consist of eight cells.
• Step 3: One of the cells (a blastomere) is removed from the embryo.
• Step 4: This cell is tested to see if the embryo from which it originated has a genetic or chromosomal anomaly.
• Step 5: An embryo, which is found to be healthy, is implanted in the womb while unhealthy embryos are discarded.
• Step 6: The remaining healthy embryos can be stored for future use. 

Pre-implantation genetic diagnosis

“PGT is actually divided into two types,” Mr Chen continues. “Firstly, we have pre-implantation genetic diagnosis (PGD) which is used to determine practically any inheritable disorder where a particular gene is known to cause that disorder. When one or both parents have a genetic abnormality, the embryos are subjected to PGD to see if they carry that same abnormality. Only genetically normal embryos are chosen.”

As of now, PGD is capable of testing for more than 250 inheritable disorders including:

• Sex-linked diseases like haemophilia, which are usually inherited by the son from the mother who is a carrier.
• Single-gene defects like thalassaemia, which results from a single gene abnormality.

Chromosomal disorders like Fragile X syndrome.

Mr Chen strongly recommends PGD to couples who are at risk of passing on inheritable disorders to their future children. Aside from couples with the aforementioned genetic conditions, potential PGD candidates are:

• Couples with affected children.
• Women who have had more than one failed fertility treatment.
• Women aged 35 and above.
• Women with a history of recurrent miscarriages.

Pre-genetic implantation genetic screening

“On the other hand, pre-implantation genetic screening (PGS) is where embryos from parents who are presumed to have chromosomally normal genes are tested for aneuploidy (chromosomal abnormalities). Aneuploidy occurs when a cell has an abnormal number of chromosomes such as 45 or 47 chromosomes, instead of the normal 46. Aneuploidy can result in disorders such as Down syndrome,” Mr Chen says.

Delving into the benefits which PGS offers, Mr Chen says, “Aneuploidy is the most common factor in IVF failure. By choosing chromosomally normal embryos, PGS helps to:

• reduce the risk of spontaneous miscarriage
• enhance implantation, pregnancy and live birth rates
• allow single- or double-embryo transfers (subsequently, reducing the number of high-risk multiple pregnancies).

He recommends PGS to couples with:

• A female partner who is advanced in age
• A male partner who has severe male factor infertility
• recurrent pregnancy losses (both naturally and via IVF).

“A decreasing live birth rate is a growing issue for couples who decide to wait till later in life to have kids. This is because late maternal age embryos are more likely to be chromosomally abnormal. This is why we suggest older couples to undergo PGS,” he stresses. “To sum it up, PGS is an effective tool in fertility treatment as it significantly lowers the risk of transferring chromosomally abnormal embryos into the mother.”

“Couples can rest assured, PGS has evolved over the years. In 2007, PGS used the Fluorescence In-situ Hybridization (FISH) technology which could only test 5-12 chromosomes and had a 9.1% error rate. Now, we have Next Generation Sequencing (NGS) which enables us to comprehensively screen all 24 chromosomes and has only a 1.9% error rate. It’s a great breakthrough.”

There’s always hope

Mr Chen concludes, “While genetic testing doesn’t guarantee that all clinical failures are eliminated, it delivers what it promises to do: significantly increases your chances of having a smooth pregnancy, a healthy baby and finally, a happy family. We like to call it the ‘Holy Grail’ of IVF.”

References:

1. American Pregnancy Association. Available at http://americanpregnancy.org/infertility/preimplantation-genetic-diagnosis/

2. Fertility Centers of New England. Available at www.fertilitycenter.com/fertility_cares_blog/the-difference-between-pgd-and-pgs/

3. Genesis Genetics. Available at http://genesisgenetics.org/pgs/ngs/

4. Human Fertilisation & Embryology Authority. Available at www.hfea.gov.uk/preimplantation-genetic-diagnosis.html

5. Medscape. Available at http://emedicine.medscape.com/article/273415-overview#a4

6. Penn Medicine. Available at www.pennmedicine.org/fertility/patient/clinical-services/pgd-preimplantation-genetic-diagnosis/

If you like this article, do subscribe here.