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

by The Online Citizen
25/05/2021
in Commentaries, Health, Opinion
Reading Time: 8 mins read
0
Avoiding the moral dilemma and emotional trauma of Down syndrome abortions by mainstreaming IVF genetic testing (PGS/PGT-A) for older women

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 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.

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.

Dr Alexis Heng Boon Chin is a native Singaporean who is working as an Associate Professor at Peking University, China. He had previous worked in the field of IVF research in Singapore. 

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