PGS / PGT-A in Singapore - High attrition rate of 72% reported by Ministry of Health (MOH) - Why?

[Angelica Cheng]

The Ministry of Health in Singapore has reported that the pilot trial of PGS / PGT-A in Singapore suffers from a high attrition rate of 72%.

The question is Why?

Please see:

Rahayu Mahzam on pre-implantation genetic screening

A pilot study on pre-implantation genetic screening (PGS) has had a high attrition rate of about 72 per cent and more data is needed to determine its clinical effectiveness, said Parliamentary Secretary for Health Rahayu Mahzam in Parliament on Tuesday (Mar 2). She said MOH will try to support...

www.channelnewsasia.com

MP Rahayu Mahzam on pre-implantation genetic screening

02 Mar 2021 10:48AM (Updated: 02 Mar 2021 05:27PM)

A pilot study on pre-implantation genetic screening (PGS) has had a high attrition rate of about 72 per cent and more data is needed to determine clinical effectiveness, said Parliamentary Secretary for Health Rahayu Mahzam in Parliament on Tuesday (Mar 2). She said the Ministry of Health will try to support as many patients as possible to participate, but must proceed carefully as there is some risk to the embryo. Ms Rahayu was answering an MP’s questions on whether MOH could allow any patient regardless of prognosis to take part in the study and whether full subsidies could be considered.

Could there be a problem with the PGS / PGT-A technique itself? Please see the following previous threads:

New scientific evidence dispute the beneficial effects of PGS / PGT-A in IVF treatment

Many fertility clinic websites claim that PGS can improve IVF success for older women and patients with multiple IVF failures or recurrent miscarriages. However, there has recently been increasing contradictory information from different sources, which dispute the beneficial claims of PGS in IVF...

singaporemotherhood.com

Latest news on PGS / PGT-A (embryo genetic testing), which cast doubts on the usefulness and effectiveness of this technique for older women

Here are the latest news on Preimplantation Genetic Screening (PGS / PGT-A), which cast doubts on the usefulness and effectiveness of this technique for older women undergoing IVF / ICSI : Prominent Physicians and Scientists Criticize Continued Utilization of Preimplantation Genetic Testing for...

singaporemotherhood.com

What Singaporean patients should know before doing PGS (embryo genetic testing) when going for IVF overseas

There are plenty of arguments against doing preimplantation genetic screening - PGS / PGT-A, and it’s up to you to decide if they outweigh the pros… https://theduff.co.uk/pgs-testing-ivf/ Argument 1 against PGS: it’s expensive Paying an extra $5,000 (ish) per cycle – on top of the $10,000 or...

singaporemotherhood.com

Is PGS (PGT-A) useful for older women at risk of Down Syndrome, or patients with low ovarian reserves?

Relevant Q & A on the Quora website: https://www.quora.com/Why-may-it-be-unnecessary-for-older-women-undergoing-IVF-or-ICSI-to-do-pre-implantation-genetic-screening-PGS-PGT-A/answer/Alexis-Heng https://www.quora.com/How-can-I-do-preimplantation-genetic-screening-PGS-or-PGT-A-in-Singapore-1...

singaporemotherhood.com

Video podcasts that explain the Preimplantation Genetic Screening (PGS or PGT-A) procedure. What are the limitations and risks of PGS / PGT-A?

Here are some excellent video podcasts that introduce and explain the Preimplantation Genetic Screening (PGS or PGT-A) procedure to patients:

singaporemotherhood.com

 

[Angelica Cheng]

Recently, some Australian patients even filed a class-action lawsuit against PGS / PGT-A:

 

[Angelica Cheng]

Singapore Today - Get the latest Singapore & World news from Business, Money, Technology, Health, Auto & Other Sectors

Singapore News: Catch all the latest news from Singapore and World, news from Business, Money, Technology, Auto, Health on Singaporenewslive.com.

singaporenewslive.com

Genetic testing of IVF embryos (PGS / PGT-A) – what Singaporean patients should know

Recently, Ms Rahayu Mahzam, Parliamentary Secretary of Ministry for Health — reported that the pilot trial of genetic testing of IVF (In Vitro Fertilization) embryos in Singapore suffers from a high attrition rate of 72% (2nd March 2021). She stressed the need to proceed carefully as there is some risk to the embryo during testing.

This procedure, also known as Preimplantation Genetic Screening (PGS) or Preimplantation Genetic Testing – Aneuploidy (PGT-A), involves screening the embryos of IVF patients whom are not known to be carriers of genetic diseases, unlike the closely-related Preimplantation Genetic Diagnosis (PGD) technique, which specifically tests for known genetic defects carried by prospective parents. Hence, the pertinent question that arises is why is there such a high attrition rate?

Yet at an earlier parliamentary session on 25th February 2021, MP Cheng Li Hui, called for less restrictions to make PGS (PGT-A) more widely available to IVF patients, on the basis that this procedure screens for the correct number of chromosomes to improve the chances of conception.

Hence, Singaporean IVF patients should be made aware of the widespread controversy and accumulating scientific evidence against the medical effectiveness of PGS (PGT-A) in improving the outcome of fertility treatment in patients, whom are non-carriers of genetic diseases.

Currently, PGS (PGT-A) is readily available to Singaporean patients at most foreign fertility clinics, particularly those from neighbouring countries. Indeed, many Singaporean patients who travel abroad for fertility treatment, often end up choosing to do genetic testing of their IVF embryos, not only for sex-selection, but also to eliminate the risks of Down Syndrome in older women and improve success rates.

This is due in large part to aggressive marketing of this technique by foreign fertility clinics, which substantially increases the costs of fertility treatment from 30% to 50%. Hence, it is imperative to highlight the controversial issues surrounding this expensive technique, which Singaporean patients and healthcare policymakers should be aware of.

Currently, there is good evidence that the PGS technique is fraught with false positive misdiagnoses due to the frequent occurrence of ‘mosaic’ embryos in IVF treatment. These are embryos that have a mixture of genetically abnormal and normal cells. Recent studies have shown that such ‘mosaic embryos’ can often give rise to healthy normal babies.

To understand why this is so, imagine the human embryo as containing multiple layers of cells, with the inner layers giving rise to the baby itself, while the outer layers give rise to the placenta and umbilical cord. Indeed, many studies of normal births often detect genetic abnormalities in the placenta and umbilical cord.

This is because nature has an amazing way of correcting genetic defects during the course of normal embryo development, by gradually pushing and segregating genetically abnormal cells to the outer layers that give rise to the placenta and umbilical cord, whilst preserving the genetic integrity of the inner layers that will eventually form the baby itself.

The problem with the PGS technique is that it only extract cells from the outer layers (Trophectoderm) for genetic testing, because sampling cells from the inner layers (Inner Cell Mass that forms the baby)
incurs too much risk of damaging the embryo. Hence the high incidence of false positive misdiagnoses associated with PGS, which often lead to discarding of ‘mosaic’ embryos, many of which can in fact give rise to a normal healthy baby.

Consequently, some studies have reported that PGS in fact reduces rather than improve the cumulative chances of IVF success. Because older women and women with low ovarian reserves usually produce less embryos during each IVF treatment cycle, the discarding of ‘mosaic’ embryos could in fact have a more devastating impact on their chances of success.

For such patients with very few available embryos, every single embryo (including mosaic ones) is more ‘valuable’, and would count more to their chances of reproductive success. Just recently in Australia, a class action lawsuit was launched by patients against Monash IVF for misdiagnosis by the PGS (PGT-A) technique, which led to discarding of their viable embryos that could have otherwise led to healthy births.

Although the PGS technique is often touted to be useful for avoiding birth defects such as Down syndrome in older women, patients must be aware that it is not a foolproof means of screening for genetic defects despite its high cost.

Usually, PGS screens only for a panel of common genetic defects, which excludes many rarer genetic diseases. It is also useless for detecting more complex genetic conditions that involve interaction of multiple genes with various factors within the birth environment, such as Autism Spectrum Disorders (ASD).

Patients should also be aware that the vast majority of genetically-abnormal embryos often fail to implant upon transfer to the womb during the IVF procedure; and even those genetically abnormal embryos that do implant often spontaneously abort at very early stages e.g. biochemical pregnancy.

Hence, patients should consider more economical means of screening for birth defects, such as the new generation of Non-Invasive Prenatal Testing (NIPT), that can screen for genetic defects in fetal DNA extracted from the pregnant mother’s blood sample.

Additionally, patients must also be wary of the aggressive sales pitch and marketing gimmicks routinely used to coax patients to undertake PGS during IVF treatment abroad.

One example is how the concept of relative risks is being misrepresented to patients, to play on their fears of birth defects. For example if the risk of Down syndrome is 0.1 % at age 20, and increases to 1% at age 40 and subsequently to 4% at age 45; then another way of presenting the data would be to say that the risk of Down syndrome increases 10-folds from age 20 to 40, and 40-folds from age 20 to 45.

Hence, through a sly manipulation of words and figures, the risks of genetic defects can be ‘exaggerated’ to patients who are unfamiliar with medical statistics.

Another dubious and ethically-questionable marketing tactic is to manipulate and play on the patient’s biased preference for either a boy or girl child, which may be helped by the fact that PGS is currently the most accurate and reliable embryo sex selection technique that is available in the market.

Last but not least, patients should also be aware of the risks of damaging the embryo during the ‘highly-delicate’ PGS procedure, which involves extracting cells from the embryo after drilling a hole through the embryo shell (Zona pellucida).

The smooth performance of this technique is often highly dependent on the skill and training of the laboratory staff (Embryologist). Even with high levels of training and accreditation, there is still a possibility of human error, particularly in a very busy laboratory that handles several such cases a day.

In conclusion, there is increasing scientific evidence that cast doubts on the medical benefits of PGS (PGT-A). There are certainly good reasons why the PGS technique is so stringently regulated by the MOH here in Singapore at the present moment, which is exercising due diligence to protect the welfare of patients.

Singaporean patients traveling abroad for IVF treatment should be cautious not to be ‘pushed’ into undertaking PGS unnecessarily, by asking themselves why this technique is so severely restricted in their own country, even if it is deemed to be so beneficial by profit-driven private fertility clinics abroad.

 

[Angelica Cheng]

Avoiding the moral dilemma and emotional trauma of Down syndrome abortions by mainstreaming IVF genetic testing for older women - Singaporenewslive.com

by Dr Alexis Heng Boon Chin Down syndrome is a genetic condition caused by an extra copy of chromosome 21, which is characterized by impairment of mental and physical development, together with increased predisposition to certain medical conditions such as congenital heart defects, diabetes, and...

singaporenewslive.com

Avoiding the moral dilemma and emotional trauma of Down syndrome abortions by mainstreaming IVF genetic testing (PGS/PGT-A) for older women

Down syndrome is a genetic condition caused by an extra copy of chromosome 21, which is characterized by impairment of mental and physical development, together with increased predisposition to certain medical conditions such as congenital heart defects, diabetes, and Alzheimer’s disease (after the age of 40).

It has a worldwide prevalence rate of approximately 1 to 800 live births, and occurs throughout all ethnicity and social classes. Although the link between older mothers and Down syndrome is well-established, it must be noted that most babies with Down syndrome are born to women below 35 years of age, due to the much higher fertility rates of younger women.

In recent years, there have been a number of local media reports of pregnant women deciding to keep their Down syndrome baby after prenatal testing. Undoubtedly, couples undergo much emotional trauma upon learning the results of prenatal testing, and face an agonizing dilemma of whether to proceed with abortion.

The conscientious objection of some women against abortion should be commended, given the many unique challenges and sacrifices that they face in raising a Down syndrome child.

Highly contentious issue overseas

Currently, this is a highly contentious issue overseas, as evidenced by some recent high-profile court cases.

In the United States, an appellate court ruling upheld Ohio state law prohibiting abortion of Down syndrome fetuses.

In Britain, a review of abortion law relating to Down syndrome is set to be heard at the High Court after vigorous campaigning by pro-life groups.

In India, a legal precedent was set in 2020 by a landmark supreme court ruling that permitted abortion of a 25 week-old fetus diagnosed with Down syndrome; whereas previously, abortion was permitted only for fetuses less than 20 weeks-old.

Difficult moral choices to expectant parents

Undoubtedly, continuous improvements in the accuracy of prenatal screening technology now present difficult moral choices to expectant parents faced with a positive diagnosis, who have to weigh the heavy financial, emotional and physical toll of raising a Down syndrome child, with their conscience, as well as personal and religious beliefs on abortion.

On one hand, there is right-to-life of the unborn child and respect for the dignity of disabled people. On the other hand, there are grave concerns on the happiness and quality-of-life for the child and themselves, together with the nagging fear that they would be unable to cope with the heavy burden of raising a special needs child.

Additionally, there are also risks to the mental, physical, and reproductive health of the patient to consider, when aborting a Down syndrome fetus.

The incidence of Down syndrome rises with increasing maternal age, which is particularly significant for Singapore, given the increasing trend of late marriages and parenthood.

For older women undergoing IVF (in vitro fertilization) treatment, there is a way of avoiding this abortion dilemma and emotional quagmire by genetic screening of IVF embryos prior to transfer into the womb, a procedure known as Preimplantation Genetic Testing – Aneuploidy (PGT-A) or Preimplantation Genetic Screening (PGS).

This is designed for IVF patients without any known heritable genetic disorders.

PGT-A (PGS) service in Singapore

To date, PGT-A (PGS) is still not approved as mainstream clinical service in Singapore, and is restricted to a pilot clinical trial at public IVF centers, in contrast to genetic testing of IVF embryos for patients with known genetic disorders, which was recently approved as mainstream clinical service.

The criteria for participation in this pilot PGT-A trial are that the female patient must be at least 35 years old, or have experienced at least two miscarriages or two failed IVF cycles.

A recent article in Channel NewsAsia (‘So near, yet so far: Aspiring parents and their embryos separated by the pandemic‘, 23 May) reported on local women traveling overseas to do IVF with PGT-A, because this procedure is much more readily available and less strictly regulated abroad, compared to Singapore.

Hence, based on compassionate grounds, to avoid future abortion dilemmas and emotional trauma for older women undergoing IVF, whom are at increased risk of Down syndrome, the Ministry of Health (MOH) should approve PGT-A as mainstream clinical service specifically for such older patients.

Nevertheless in doing so, MOH should ensure rigorous counseling to inform patients of the various downsides and risks of PGT-A.

In particular, patients should be advised to think carefully on the cost-benefit aspect of this expensive procedure that may increase the cost of IVF treatment by up to 50 per cent.

By contrast, prenatal testing for Down syndrome and other genetic defects is much cheaper, albeit the risks of needing to consider aborting an abnormal fetus.

Given the uncertain outcome and high costs of IVF, it may be preferable for some patients with limited funds to cut costs by not doing PGT-A, so as to save money for future IVF attempts.

After all, more than one IVF attempt is usually needed to achieve reproductive success, and it would be financially exhausting to do PGT-A for each and every IVF treatment cycle.

Risk of Down syndrome for women

According to published medical statistics, the risk of Down syndrome for women in their late 30’s, around 37 to 39 years old, hovers around 0.5 per cent.

Even at age 40, the risk of Down syndrome increases to about 1 per cent, and then to around 3.5 per cent at age 45.

Hence, for almost the entire span of a woman’s reproductive life, the risks of Down syndrome are in fact relatively low, at less than 4 per cent.

Ultimately, it is up to patients with limited financial resources to decide whether it is worthwhile taking a calculated risk of avoiding this highly-expensive procedure, to get more shots at IVF.

 

[Angelica Cheng]

Utilization of public funding to detect and prevent Down syndrome in older female IVF patients

Unlike subsidizing the genetic testing of IVF patients with known heritable disorders, which is currently being considered by MOH, the utilization of public funding to detect and prevent Down syndrome in older female IVF patients by PGT-A is neither economical, cost-efficient nor politically-justifiable in the long term.

First, there is the issue of personal choice and responsibility for late motherhood, unlike the case of heritable genetic disorders, which is involuntary.

Second, heritable genetic disorders are relatively rare, and represent only a tiny fraction of IVF patients, as compared to the much larger numbers of older female IVF patients, which would mean that subsidies would cost much more.

Third, there is a much cheaper, yet accurate and reliable alternative to detect Down syndrome, in the form of Non-Invasive Prenatal Testing (NIPT), albeit the risks of abortion after positive diagnosis.

Lastly, it would be highly cost-inefficient to subsidize PGT-A for all older women undergoing IVF, given that the risks of Down syndrome do not exceed 4 per cent for almost the entire female reproductive lifespan (20 to 45 years old).

Additionally, patients should beware that PGT-A is prone to false-positive misdiagnosis, leading to discarding of some of their viable embryos that can otherwise give rise to healthy births.

This is because PGT-A sample cells only from the outer embryo layer (Trophectoderm) that generates the placenta and umbilical cord, which is not representative of the inner embryo layer (Inner Cell Mass) that gives rise to the baby itself.

Mosaic embryos containing a mixture of genetically normal and abnormal cells, have demonstrated ability to self-correct and give rise to healthy births. Recently, a class-action lawsuit was filed by Australian patients against misdiagnosis by PGT-A that led to discarding of their viable embryos and consequent loss of chance at parenthood.

Another note of caution is that at a recent parliamentary debate, MOH reported a relatively high attrition rate of 72 per cent for the pilot trial of PGT-A at public IVF centers in Singapore; and consequently voiced the need to proceed carefully, because there are some risks of damaging the embryo by this procedure.

Earlier in 2019, a large international multi-centre clinical trial involving more than 600 patients in the USA, Canada, UK and Australia, reported no significant improvements in pregnancy rates from PGT-A, despite utilizing the latest next-generation sequencing assay for aneuploidy testing.

More choices to circumvent the moral dilemma and emotional trauma of aborting a Down syndrome fetus

In conclusion, by mainstreaming PGT-A for older female IVF patients at higher risks of Down syndrome, this would confer them with more choices to circumvent the moral dilemma and emotional trauma of aborting a Down syndrome fetus.

The primary responsibility of MOH is to ensure that patients make an informed decision, via proper and thorough counseling on the cost-effectiveness and risks of utilizing PGT-A for this particular purpose.

It is also imperative that MOH enact stringent safeguards to prevent aggressive marketing tactics by private fertility clinics that exaggerate risks and exploit patients’ fear of Down syndrome.

 

[Angelica Cheng]

Is it worthwhile doing IVF genetic testing (PGS / PGT-A) to prevent birth defects in older women?

"IVF genetic testing to prevent birth defects in older women"

In conversation with Dr. Alexis Heng Boon Chin, Associate Professor, Peking University, China

www.biospectrumasia.com

With an increasing trend of late motherhood, many women across Asia and worldwide are choosing to postpone childbearing while prioritizing lifestyle and career objectives. Nevertheless, the risks of conceiving a baby with genetic (chromosomal) abnormalities increase with older maternal age, the most common and well-known of which is Down syndrome. Worldwide, more than 90% of Down syndrome fetuses are routinely aborted upon positive diagnosis by prenatal testing. However, there are serious risks to the mental, physical and reproductive health of the patient to consider, when aborting a fetus diagnosed with Down syndrome or other genetic abnormalities.

For older women undergoing assisted reproduction treatment, there is a way of avoiding this abortion quagmire by genetic screening of IVF embryos before transferring into the womb, a highly expensive procedure known as Preimplantation Genetic Testing - Aneuploidy (PGT-A) or Preimplantation Genetic Screening (PGS). Hence, the pertinent question that arises for older women undergoing assisted reproduction treatment, is whether it is worthwhile and cost-effective to utilize expensive PGT-A (PGS) for screening and excluding genetically abnormal embryos, as compared to standard prenatal testing techniques that are much cheaper.

What are the different types of genetic abnormalities that occur in older mothers?

Due to a lack of proper separation of chromosomes during egg development in older women, they are at higher risks of genetically abnormal births.

The most common genetic abnormality in older mothers is Down syndrome, caused by an extra copy of chromosome 21. Additionally, increasing maternal age is also associated with elevated risks of Edwards syndrome (extra copy of chromosome 18), Patau syndrome (extra copy of chromosome 13) and Klinefelter syndrome (extra X chromosome - 47,XXY). Among these, only babies with Down and Klinefelter syndromes usually survive to adulthood. The life expectancy of Patau syndrome is around 7-10 days, with 90% dying in the first year of life.

Similarly, the average lifespan for Edwards syndrome is 3 days to 2 weeks, with only 5% to 10% of afflicted infants surviving for over a year. Down syndrome is characterized by a substantial reduction in lifespan to about 60 years, severe impairment of mental and physical development, together with increased predisposition to certain medical conditions such as congenital heart defects, type II diabetes and Alzheimer’s disease (after the age of 40). In contrast, for Klinefelter syndrome (47, XXY), there is only a very slight reduction in lifespan by about 2 years compared to the normal male population (46, XY). Although individuals with Klinefelter syndrome usually have normal intelligence, they suffer from infertility and have small underdeveloped male sex organs, poor motor coordination and weak muscles, reduced facial and body hair, breast growth, and low sex-drive.

According to published medical statistics, the risks of conceiving a genetically abnormal baby for women in their late 30's, around 37 to 39 years old, is approximately within the 0.8% to 1.2% range. By age 40, the risk of genetic abnormalities increases to about 1.5%, and then to around 4.8% at age 45.

Can genetic testing potentially harm IVF embryos?

IVF genetic testing involve drilling a hole through the embryo shell (Zona Pellucida) and extracting cells from the embryo, which is potentially harmful, and can impair it’s development. Experts have pointed out that studies claiming no ill effects to embryos are often based on PGS of excellent-quality, healthy, robust embryos rather than more “delicate” embryos that might suffer more. If you have just one or two embryos, you might decide it is not worth the risk. No matter how well-trained is the lab staff (embryologist) doing this procedure, there is still a risk of human error. The more busy the IVF lab is, the greater the risk of human error, as lab staff are under pressure to complete procedures as fast as possible.


What are the challenges associated with IVF genetic testing?

There are several aspects to be considered towards genetic testing in IVF treatment.

• IVF genetic testing involve extracting and sampling cells from the outer embryo layer that gives rise to the placenta and umbilical cord. This is not representative of the inner embryo layer that goes on to form the actual embryo proper, which gives rise to the baby.
• Mosaic embryos, which are embryos with a mixture of genetically normal and abnormal cells occur quite frequently and commonly among woman undergoing IVF. Genetic testing often leads to the misdiagnosis and discarding of mosaic embryos, which have been shown to be capable of giving rise to a normal and healthy baby. Recently in 2020, a class-action lawsuit was filed by Australian patients against misdiagnosis by IVF genetic testing, which led to discarding of their viable embryos and consequent loss of chance at parenthood.
• There is scientific evidence that Mosaic embryos are able to “self-correct”, which increases the chances of normal birth. This “self-correction” mechanism involve pushing out the genetically abnormal cells into the outer embryo layer, which gives rise to the placenta and umbilical cord.
• Older women with low ovarian reserves have much fewer embryos during IVF. Therefore excluding or discarding of mosaic embryos that can potentially give rise to a normal baby, would in fact substantially reduce their chances of IVF success. Some older women may have no embryos left to transfer after genetic testing.

Are there alternative methods to IVF genetic testing for preventing birth defects in older women?

Yes, there is an alternative method that is much cheaper than PGT-A (PGS). This is known as Non-Invasive Prenatal Testing (NIPT), in which the DNA of fetal cells within the expectant mother’s blood circulation is extracted and tested for genetic abnormalities. Nevertheless, the downside is that NIPT can only be performed after getting pregnant, so the patient has to be mentally and emotionally prepared to abort a genetically abnormal fetus. Additionally, ultrasound can also be used to some extent for detecting Down syndrome, even though the results are not as accurate and determinative as NIPT.


How cost-effective is IVF genetic testing for older women?

Given the uncertain outcome and high costs of IVF treatment, it may be preferable for some patients with limited funds to cut costs by not doing genetic testing, so as to save money for future attempts at IVF treatment, given that cheaper alternative prenatal testing methods are available. After all, more than one IVF attempt is usually needed to achieve reproductive success, and it would be financially exhausting to do genetic testing for each and every IVF treatment cycle. As mentioned earlier, given that the risks of genetic abnormalities do not exceed 5% for almost the entire female reproductive lifespan (20 to 45 years old), it may be highly cost-inefficient to utilize such an expensive procedure for all older women undergoing IVF, In particular, the incidence of genetic abnormalities is typically less than 1.5% for women below 40 years old, so that utilizing PGT-A would be superfluous more than 98.5% of the time. Ultimately, it is up to patients with limited financial resources to decide whether it is worthwhile taking a calculated risk of avoiding highly expensive genetic testing, to get more shots at IVF.


Can you elaborate on the principles and regulations of IVF genetic testing in Singapore?

Singapore healthcare policies allow IVF genetic testing only for mainstream clinical treatment for patients who are sufferers or carriers of known genetic diseases (PGT-M & PGT-SR). Routine genetic screening of IVF embryos of older women (PGS or PGT-A), who are at increased risks of Down syndrome is still not approved as mainstream clinical treatment but is restricted to a tightly regulated clinical trial at government hospitals. To participate in this clinical trial, women have to be 35 years old or older, or have suffered two recurrent miscarriages, or have two failed IVF attempts. Also, there are inadequate and doubtful results from the current clinical trial of IVF genetic testing in Singapore, which was reported to suffer from a high attrition rate of 72%.