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

Angelica Cheng

Active Member
Relevant Q & A on the Quora website:

The risk of Down syndrome for a woman in their late 30's, around 37 to 39 years old, hovers around 0.5% or 1 in 200, according to the attached tables and charts. Hence, women in this age group have to be really unlucky to have a Down Syndrome baby, which is like hitting the jackpot.

At the same, it is highly expensive to do PGS / PGT-A. It roughly costs about 50% of an IVF / ICSI cycle. Hence, if the treatment cycle was to cost $10,000, adding PGS or PGT-A would bring the costs up to $15,000.

Is it worthwhile taking a calculated risk of not doing PGS / PGT-A to cut costs and save money for further IVF attempts? After all, more than one IVF attempt is usually needed to achieve success, and it would be financially exhausting to do PGS for every IVF cycle.

I am of the opinion that the Ministry of Health (MOH) in Singapore considers PGS / PGT-A not cost-efficient. Or else why are they currently being so restrictive on allowing the widespread application of PGS / PGT-A in Singapore?

After all, one can always do much cheaper prenatal testing after getting pregnant to check for Down syndrome.

Non-invasive prenatal testing (NIPT) is now available. This is much cheaper than PGS / PGT-A and involves sampling of the baby's cells within maternal blood of a pregnant woman, with minimal risks to the unborn child. Please refer to the following websites:

What Does NIPT Test For and How Accurate Are Results?

I would love to hear your opinion.


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Angelica Cheng

Active Member
Is PGS (Preimplantation Genetic Screening) or PGT-A (Preimplantation Genetic Testing - Aneuploidy) useful for older women, or women with low ovarian reserves? Here are interesting videos that discuss this issue:


Angelica Cheng

Active Member
False positives during PGS / PGT-A may arise because of mosaic embryos that contain a mixture of genetically abnormal and normal cells. There have been many reports that these mosaic embryos can give rise to normal healthy births. So the cumulative chance of success may not increase by PGS / PGT-A and may even decrease by excluding "mosaic" embryos, that could have developed into a healthy normal baby. As seen in the attached diagram of a blastocyst stage embryo, the ICM gives rise to the embryo, while the TE gives rise to the placenta and yolk sac. Testing a few cells from the TE only gives you a probability about what's going on in the ICM. An embryo with abnormal (aneuploid) TE but normal ICM most likely will still make a healthy baby.

Please click on the following website link:


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Angelica Cheng

Active Member
Latest scientific news - mosaic embryos can self-correct and give rise to normal births ! PGS / PGT-A may not even be necessary !

Here are some relevant articles:

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Angelica Cheng

Active Member
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:

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 it because there is some problem with the PGS / PGT-A technique itself? Please see the following previous threads:
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Angelica Cheng

Active Member

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

Recently, the Parliamentary Secretary for Health, 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.


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Angelica Cheng

Active Member

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

Active Member
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.