Can genetic tests for IVF potentially detect birth defects in a fertilized embryo?

Is it worth doing genetic testing for IVF (PGS / PGT-A) to prevent birth defects in older women; In conversation with Dr Alexis Heng Boon Chin, Associate Professor, Peking University, China

With an increasing trend towards late motherhood, many women in Asia and around the world are choosing to postpone motherhood while prioritizing their lifestyle and career goals. However, the chances of conceiving a baby with genetic (chromosomal) abnormalities increase with maternal age, the most common and well-known being Down syndrome. Globally, more than 90% of fetuses with Down syndrome are systematically aborted after a positive diagnosis by prenatal test. However, there are serious risks to the mental, physical and reproductive health of the patient to be aware of, when having an abortion of a fetus diagnosed with Down syndrome or other genetic abnormalities.

For older women undergoing assisted reproduction treatment, there is a way to avoid this abortion quagmire by genetic testing of IVF embryos before they are transferred to the uterus, a very expensive procedure known as preimplantation genetic testing – Aneuploidy (PGT-A) or preimplantation genetic screening (PGS). Therefore, the relevant question for older women undergoing assisted reproduction treatment is whether it is useful and cost effective to use expensive PGT-A (PGS) for the screening and exclusion of genetically embryos. abnormal, compared to standard prenatal testing techniques which are much cheaper.

Dr Alexis Heng Boon Chin, Associate Professor, Peking University, China share more ideas in this perspective with Biospectrum Asia.

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 a higher risk of genetically abnormal births.

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

Likewise, the average lifespan for Edwards syndrome is 3 days to 2 weeks, with only 5% to 10% of affected infants surviving more than a year. Down syndrome is characterized by a substantial reduction in lifespan up to about 60 years, severe impairment of mental and physical development, as well as an increased predisposition to certain medical conditions such as congenital heart defects, diabetes. type II 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 of about 2 years compared to the normal male population (46, XY). Although people 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 libido.

According to published medical statistics, the chances of conceiving a genetically abnormal baby for women in their late thirties, between the ages of 37 and 39, are approximately 0.8% to 1.2%. At age 40, the risk of genetic abnormalities increases to about 1.5%, then to about 4.8% at age 45.

Can genetic testing potentially harm IVF embryos?

Genetic testing for IVF involves drilling a hole in the shell of the embryo (Pellucide Zone) and extract cells from the embryo, which is potentially harmful and may interfere with its development. Experts pointed out that studies claiming that there were no harmful effects on embryos are often based on PGS of excellent quality, healthy and robust embryos rather than on more “delicate” embryos which could suffer more. If you only have one or two embryos, you might decide it’s not worth the risk. No matter how well trained the laboratory staff (embryologist) in this procedure, there is always a risk of human error. The busier the IVF lab, the greater the risk of human error, as lab staff are under pressure to complete procedures as quickly as possible.

What are the challenges associated with genetic testing for IVF?

There are several aspects to consider for genetic testing in the treatment of IVF.

  • Genetic IVF testing involves extracting and removing cells from the outer layer of the embryo that gives rise to the placenta and umbilical cord. It is not representative of the inner layer of the embryo which forms the actual embryo, which gives birth to the baby.
  • Mosaic embryos, which are embryos with a mixture of genetically normal and abnormal cells, occur quite frequently and commonly in women undergoing IVF. Genetic testing often leads to the misdiagnosis and elimination of mosaic embryos, which have been shown to be able to give birth to a normal, healthy baby. Recently, in 2020, a class action lawsuit was filed by Australian patients against a misdiagnosis by genetic IVF testing, which led to the disposal of their viable embryos and a consequent loss of chance of parenthood.
  • There is scientific evidence that Mosaic embryos are able to self-correct, which increases the chances of a normal birth. This “self-correction” mechanism involves expelling genetically abnormal cells into the outer layer of the embryo, resulting in the placenta and umbilical cord.
  • Older women with low ovarian reserves have significantly fewer embryos during IVF. Therefore, excluding or rejecting mosaic embryos that could potentially give birth to a normal baby would in fact greatly reduce their chances of successful IVF. Some older women may not have more embryos to transfer after genetic testing.

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

Yes, there is a much cheaper alternative method than PGT-A (PGS). This is called the non-invasive prenatal test (NIPT), in which DNA from fetal cells in the pregnant woman’s bloodstream is extracted and tested for genetic abnormalities. However, the downside is that NIPT can only be performed after pregnancy, so the patient must be mentally and emotionally prepared to abort a genetically abnormal fetus. Additionally, ultrasound can also be used to some extent to detect Down syndrome, although the results are not as precise and conclusive as NIPT.

What is the Cost-Effectiveness of Genetic IVF Testing for Older Women?

In view of the uncertain results and the high costs of IVF treatment, it may be preferable for some patients with limited funds to reduce costs by not doing genetic tests, in order to save money for future IVF attempts. IVF treatment, as 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 draining to do genetic testing for each cycle of IVF treatment. As mentioned earlier, since the chances of genetic abnormalities do not exceed 5% during most of the reproductive lifespan of women (20 to 45 years), it can be very unprofitable to use such an expensive procedure for all. older women undergoing IVF. In particular, the incidence of genetic abnormalities is generally less than 1.5% for women under 40, so the use of PGT-A would be unnecessary more than 98.5% of the time. Ultimately, it is up to patients with limited financial resources to decide whether it is worth taking a calculated risk of avoiding very expensive genetic testing, to get more IVF vaccines.

Can you clarify the principles and regulations of genetic testing for IVF in Singapore?

Singapore’s health policies allow genetic testing for IVF only for the traditional clinical treatment of patients with or carriers of known genetic diseases (PGT-M and PGT-SR). Routine genetic screening of older female IVF embryos (PGS or PGT-A), who are at increased risk for Down syndrome, is still not approved as general clinical treatment, but is limited to a strictly clinical trial. regulated in public hospitals. To participate in this clinical trial, women must be 35 years of age or older, or have suffered two repeated miscarriages, or have two unsuccessful IVF attempts. In addition, there are insufficient and questionable results from the ongoing clinical trial of genetic IVF testing in Singapore, which reportedly suffered from a high attrition rate of 72%.

Hihaishi C Bhaskar

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