More women in work-obsessed Singapore, which has raised the age limit of elective egg freezing from 35 to 37 years, are known to travel overseas to clinics such as this fertility center in Kuala Lumpur in Malaysia to get their eggs frozen. (Photo: AFP / UCAN files)
As Singapore raises the age limit of elective egg freezing from 35 to 37 years, the question that will be on many older women's minds is the risk of genetic abnormalities in their frozen eggs.
It is well known that birth defects such as Down syndrome occur more frequently in older women.
Besides Down syndrome, caused by an extra copy of chromosome 21, the frozen eggs of older women are also at higher risk of Edwards syndrome (an extra copy of chromosome 18), Patau syndrome (extra copy of chromosome 13), and Klinefelter syndrome (an extra X chromosome).
For women who want to use their frozen eggs later for fertility treatment, there is a highly expensive technique for genetic screening of IVF embryos, known as Preimplantation Genetic Testing — Aneuploidy (PGT-A) or Preimplantation Genetic Screening (PGS), which typically increases the costs of IVF treatment by 20 percent to 30 percent.
Although Non-invasive Prenatal Testing (NIPT) is much cheaper and equally accurate, this is carried out after pregnancy, so the patient has to consider abortion upon a positive diagnosis of Down syndrome and other genetic defects.
Nevertheless, costs would likely be a secondary issue for women using their frozen eggs for IVF treatment. Because the limited number of frozen eggs would represent their last chance of having a child, they would not mind spending extra money on genetic testing to avoid complications such as abortion of a Down syndrome fetus.
Indeed, many egg-freezing patients would consider doing highly-expensive PGT-A as money well-spent to ensure a normal healthy child, rather than undergoing abortion or wasting more money on the healthcare and special education of a Down syndrome child that would ultimately be a burden to society and embarrassment to themselves and their families.
Knowing the psychology and mindset of such older women intending to use their frozen eggs for IVF treatment, fertility clinics can easily put up an aggressive sales pitch to hard-sell PGT-A to egg-freezing patients by playing on their fears of birth defects such as Down syndrome.
Herein lies the fallacy and contradiction of PGT-A, because if this technique is really so useful and necessary, why does the Singapore Ministry of Health (MOH) still not approve it as mainstream clinical treatment?
Currently, in Singapore, PGT-A is still an experimental technique under evaluation by a pilot clinical trial conducted at government-funded IVF clinics. As reported to the Singapore Parliament in 2021, the results of this pilot clinical trial are still uncertain and very much in doubt, with a high attrition rate of 72 percent.
Hence, before adding the expensive PGT-A technique to their IVF treatment, egg-freezing patients must understand its various flaws and drawbacks, which disqualify it as mainstream clinical treatment in Singapore.
First, patients should be aware that the risks of Down syndrome do not exceed 0.5 percent at the age of 37 years, which is the upper age limit for egg freezing in Singapore.
Hence, the question is whether PGT-A is really worthwhile and cost-effective, given such a relatively low risk of less than 1 in 200 chance of having Down syndrome, for women aged 37 years and younger. Should patients not consider much cheaper and equally accurate prenatal testing such as NIPT?
Second, patients must beware that genetic testing with PGT-A can potentially damage their embryo. The technique is highly invasive, involving drilling a hole through the embryo shell (Zona Pellucida) and extracting cells from the embryo for genetic testing (biopsy), which is potentially harmful and can impair its development.
Many experts have pointed out that studies claiming no ill effects of PGT-A on embryos are often based on testing of excellent high-quality embryos rather than more ‘delicate’ lower-quality embryos that might suffer more. Because older women with frozen eggs tend to have weaker lower-quality embryos, these may be more prone to damage upon PGT-A testing.
Third, patients should be wary that genetic testing with PGT-A is prone to misdiagnosis, which could result in patients discarding viable embryos that can give rise to a healthy baby. This is because PGT-A testing involves extracting cells only from the outer embryo layer that produces the placenta and umbilical cord (trophectoderm), 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 the ability to self-correct and produce a healthy birth. This “self-correction” mechanism involves pushing out the genetically abnormal cells into the outer embryo layer, which gives rise to the placenta and umbilical cord.
Older women with frozen eggs have a limited number of embryos during IVF. Therefore, excluding or discarding mosaic embryos that can potentially give rise to a normal baby, would in fact substantially reduce their chances of IVF success. Some older egg-freezing patients may have no embryos left to transfer after genetic testing.
Fourth, patients must be aware that PGT-A requires a second freezing of IVF embryos after initial egg freezing. It takes time to obtain the results of genetic testing after extracting cells from IVF embryos, which must therefore be frozen and cannot be transferred to the patient immediately. The detrimental effects of multiple freeze-thawing on the weaker lower-quality embryos of older women are still unknown.
Last, patients must also beware that several large-scale clinical studies published in reputable medical journals have demonstrated conclusively that PGT-A does not improve IVF success rates.
In 2019, a large multi-center randomized clinical trial (STAR trial ) involving 34 IVF clinics in the United States, Canada, United Kingdom, and Australia and including 661 patients aged between 24 and 40 years, found no significant overall improvement in IVF success rates with PGT-A.
Subsequently, in 2021, another large multi-center clinical trial conducted in China, involving 14 IVF clinics and a total of 1212 patients aged between 20 to 37 years, reported similar unfavorable results that were published in the prestigious New England Journal of Medicine (NEJM).
Hence, based on the latest scientific and clinical data, serious doubts about the medical benefits of PGT-A have emerged.
For many egg-freezing patients, especially those already past the age of menopause, their frozen eggs represent their last chance of getting pregnant. They should therefore think twice before choosing this highly expensive and invasive genetic testing technique, which risks damaging their embryos and possibly lowering their chances of conception through misdiagnosis and discarding of mosaic embryos.
*The views expressed in this article are those of the author and do not necessarily reflect the official editorial position of UCA News.
