Category: Health

In Fertility Specialist Dr Wong Pak Seng’s line of work, he is always up to date on the constantly evolving genetic screening technology. These days, there are machines that can help detect any number of mutated or abnormal genes present in one’s DNA, even the very rare ones.

Dr Wong believes that pre-conception genetic screening should be recommended for people with a family history of inheritable. “These are the high-risk groups, so they should go for screening,” he says. For other couples hoping to conceive and have no family history of such conditions, he recommends going for pre-implantation genetic screening and prenatal screening instead.

The following are couples who may benefit from pre-conception genetic screening:

• With a family history of an inheritable conditions, birth defect, mental handicap as well as cancer.
• Has a previous child with genetic condition, birth defect or mental handicap.
• Have a history of two or more pregnancy losses, stillbirth or babies who died unexpectedly.

Accurate? While the list of conditions that can be screened for grows longer as technology evolves rapidly with time, not every condition can be tested, and the results of testing may not always be clear either. This is because there are still limitations to what current genetic testing methods can do. Therefore, a result indicating that everything is normal may not guarantee that the child will be healthy.

Why should you get screened? According to Dr Wong, many couples who have a family history of a condition that may be passed on to a child will find the results useful to help them decide whether they want to proceed with fertility treatments. And if they decide to go ahead, they can also look up options and plan in advance as to what they should do if their child is found to have an inheritable disorder.

What is the process like? Before fertility treatment such as in-vitro fertilization (IVF) can begin, the fertility specialist will review the couple’s family history thoroughly. Dr Wong explains that, should the specialist believe that there is a need for pre-conception genetic screening, the specialist will discuss this with the couple. The couple can also be referred to a genetic counsellor for advice as well as emotional support.

Once the couple agree to the screening, a blood sample will be extracted and sent to the laboratory for further analysis. How soon the results will be available depends on the specific gene mutation being analysed – rarer ones may require the sample to be sent to specialized labs out of Malaysia, for example, as their analysis may require special chemicals and/or equipment.

If you like this article, do subscribe here. 

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. 

After the anxious and often stressful weeks of undergoing fertility tests and in-vitro fertilization (IVF), it must surely be a joyous moment when the fertilized egg is successfully implanted and both husband and wife are now proud parents-to-be.

However, for couples who are considered to be of high risk when it comes to passing down genetic disorders to their children, it may be worth considering one more round of genetic screening to make sure that their baby is fine.

Dr Wong Pak Seng, a fertility specialist with years of experience and success stories under his belt, says that prenatal genetic screening is still worth considering because no genetic screening is 100% accurate.

Prenatal genetic screening can offer the parents-to-be more peace of mind. Even if the test comes back with unhappy news, the parents-to-be may appreciate having the opportunity to make special arrangements in advance. The parents-to-be also have time to prepare themselves emotionally and make necessary research on how to best provide a special needs child with tender loving care. 

Such screening is recommended for:

• Parents-to-be with a family history of genetic disorders and birth defects.
• Parents-to-be who are aged 40 years or older, especially the mother-to-be, as the risk of having a child with Down syndrome  and other conditions caused by chromosomal disorders is higher.
• Mothers-to-be with abnormal ultrasound findings.
• Mothers-to-be with a history of miscarriages or previous children with birth defects, mental handicap or genetic disorders.

The ‘Old school’ invasive ways

In the past, prenatal genetic screening was done through either amniocentesis or chorionic villi sampling (CVS). Both methods involve the use of needles or other devices to extract samples from the mothers-to-be – hence, the description of these methods as ‘invasive’!

Both methods can cause a certain degree of discomfort and even pain in some mothers-to-be. Furthermore, there is a very small risk of miscarriage, infection and other undesirable complications associated with these procedures. While such complications occur only very rarely, the fact that they can happen drives the medical industry to look for better, less invasive ways to perform prenatal genetic screening.

Fortunately, in the recent years we have developed the technology and method for a less invasive method for prenatal genetic screening. This method is called, appropriately enough, non-invasive prenatal screening test, or NIPST for short.

NIPST – A less invasive solution

Dr Wong explains that, during a NIPST, the doctor only needs to obtain blood sample from the mother-to-be. There are two NIPST services commonly offered by fertility centres in Malaysia.

Non-invasive prenatal diagnosis (NIPD)

When a woman is pregnant, some of her child’s DNA finds its way into her bloodstream. NIPD analyse this DNA for birth defects and genetic disorders such as Down syndrome, Edwards syndrome and Patau syndrome, as well as chromosomal disorders such as Turner syndrome, Klinefelter syndrome and Triple X syndrome.

• When to do it? NIPD can be done from as early as week 9 of one’s pregnancy, but please consult a gynaecologist or fertility specialist for the best time to take this test.
• Accuracy. NIPD is considered to be more accurate than the other available prenatal genetic screening methods available at the moment.
• Risks. Because NIPD only requires a small amount of blood from the mother-to-be, usually extracted from the arm, there is no risk to the mother or the baby she is carrying.
• Expensive? NIPD costs a bit more than many other available methods, as it requires specialised equipment and chemicals to perform the analysis. Currently, fertility centres in Malaysia that offer this service send the blood samples to laboratories abroad for analysis.

First trimester screening (FTS)

FTS is actually a combination of several tests that include ultrasound and blood analysis. It can screen for Down syndrome and heart defects.

• When to take it? FTS is usually performed between week 11 and 14.   
• The procedure. An ultrasound exam will be performed to check the size of the clear space in the tissue found at the back of the baby’s neck (nuchal translucency). Blood tests will be taken and analysed for the levels of two substances: pregnancy-associated plasma protein-A (PAPPA) and human chorionic gonadotropin (HCG).
• Getting the results. The results of the above procedures, along with the age of the mother-to-be, will be used to determine the risk of the child having Down syndrome.
• Risks. There is no known risk associated with FTS.
• Expensive? FTS costs less than NIPD, but its scope of detection is narrower and is slightly less accurate than NIPD. However, it is still a powerful genetic screening procedure worth considering for couples who find NIPD above their budget.

Dr Wong reminds us that these screening tests are not 100% accurate. A low-risk result will not guarantee that the baby will be free from genetic disorders, just like how a high-risk result does not necessarily mean that the child will have a genetic disorder. In some cases, the gynaecologist or fertility specialist may recommend follow-up screening tests to verify the results of these tests.

At the end of the day, the choice to go for genetic screening lies ultimately in the hands of the couple, says Dr Wong. If the couple does not wish to proceed with genetic screening, they are certainly free to do so. The genetic counsellor is always available to offer advice and support if the couple encounter difficulties in making a decision.

If you like this article, do subscribe here. 

Although a woman’s average menstrual cycle is 28 days, it is normal to have a cycle that is between 21 and 35 days. A cycle can also change due to hormonal changes caused by age, certain medical conditions and lifestyle factors. This does not necessarily mean there is an underlying serious problem. Even so, changes and irregularities in a woman’s menstrual cycle needs to be observed, especially when her period suddenly stops.

Maybe baby?

The most common cause for missing periods is pregnancy. Sexually active women who experience delays in their period can do a home pregnancy test to find out, using a pregnancy test kit that can be purchased at a pharmacy. The most common type of pregnancy test kit is one which uses a test strip or dipstick to detect the presence of a pregnancy hormone, called the human chorionic gonadotropin (hCG) in urine samples. When the kit is used exactly as instructed, a home pregnancy test has more than 99% accuracy, similar to results of a urine test in a doctor’s office. However, if done too early into the pregnancy, there may be insufficient hCG in the urine to be detected. Check the details on the package of the pregnancy kit for the best time to take a test.   

Should you be worried?

If you have been on birth control, changes in your menstrual cycle, and even skipping a period or two, is normal. But if you are not pregnant and on taking contraceptives, there may be other factors that could be responsible for your period stopping, including:

• Prolonged emotional stress
• Physical stress from extreme exercising or crash dieting
• Unexplained drastic weight loss or weight gain Polycystic ovary syndrome (PCOS); a common endocrine system disorder among women of reproductive age, characterised by enlarged ovaries that contain small collections of fluids.
• Medical problems that causes hormonal imbalances, such as thyroid problems and celiac disease
• Recently stopped use of birth control
• Early menopause

Changes to your cycle can be a harmless short-term condition, or it can be a sign of a more serious health issue. Whatever the case may be, missed periods are not to be taken lightly. So, consider making an appointment with a gynaecologist to set your mind at ease.

References:

Mayo Clinic. Available at www.mayoclinic.org

WebMD. Available at www.webmd.com

If you like this article, do subscribe here.