Presently, the Ministry of Health (MOH) in Singapore is considering subsidising genetic testing of IVF embryos for patients at risk of transmitting specific congenital genetic defects, a procedure known as Preimplantation Genetic Diagnosis (PGD) or Preimplantation Genetic Testing - Monogenic Disorders (PGT-M).
Nevertheless, there has been no talk of extending similar subsidies to IVF patients whom are not carriers of genetic diseases, a slightly different procedure known as Preimplantation Genetic Screening (PGS) or Preimplantation Genetic Testing - Aneuploidy (PGT-A).
In fact, MOH still restricts PGS (PGT-A) to a tightly-regulated clinical trial in government hospitals, which enrols only patients with specific conditions such as recurrent miscarriages or repeated IVF failures, even though it is well-known that older women have increased risks of having a Down syndrome baby.
This is due to 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.
Genetic Testing: All You Need To Know
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Nevertheless, PGS (PGT-A) is often readily available to Singaporean patients at many 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 should be aware of, when embarking on IVF treatment abroad.
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.
"Older women and women with low ovarian reserves usually produce less embryos"
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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 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 consider more economical means of screening for birth defects"
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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 take note that there is a small risk 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, 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.