Why assessing the genetic normality of IVF embryos by AI is a better option – Dr. Alexis Heng Boon Chin

With the rapid economic growth and urbanization in Malaysia over the past few decades, women are increasingly likely to delay marriage and childbearing as they now enjoy better education and employment opportunities.

However, with advancing maternal age, there is an increasing likelihood that a woman’s eggs will have an extra chromosomal copy, which in turn increases the chances of spontaneous birth defects in their offspring.

Besides Down syndrome caused by an extra copy of chromosome 21, older women are also at increased risk of Edwards syndrome (extra copy of chromosome 18), Patau syndrome (extra copy of chromosome 13) and Klinefelter (additional X chromosome).

Graphic courtesy of Dr. Alexis Heng Boon Chin.

Although such genetic defects in fetuses can be accurately diagnosed in pregnant women by non-invasive prenatal testing (NIPT), they face the agonizing dilemma of whether or not to abort their unborn child, after obtaining a diagnosis. positive.

To avoid the moral dilemma and emotional trauma of abortion, it might be best for older women undergoing IVF (in vitro fertilization) to screen their embryos for genetic abnormalities, before transferring them to their uterus.

This can be done by a very expensive and invasive procedure known as preimplantation genetic screening (PGS) or preimplantation genetic testing – aneuploidy (PGT-A).

Typically, PGS (PGT-A) increases total IVF medical costs by around 40-50%, so it would be a lucrative business model for fertility clinics to encourage more patients to add this expensive procedure. to their IVF treatment.

Nevertheless, patients should be wary of aggressive sales pitches and marketing gimmicks that could be used against them.

One example is how the concept of relative risk can be twisted 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 then to 4% at age 45, another way to present the data would be to say that the risk of trisomy 21 is increased tenfold between 20 and 40 years old and forty times between 20 and 45 years old.

Thus, by sneaky manipulation of words and numbers, the risks of genetic malformations can be “exaggerated” for patients who are not familiar with medical statistics.

PGS (PGT-A) is also very invasive, as it involves drilling a hole in the shell of the embryo (Zona Pellucida) and extracting cells from the embryo for genetic testing (biopsy), which is potentially harmful and may harm its development.

Many experts have pointed out that studies claiming no adverse effects on embryos are often based on PGS (PGT-A) of healthy and robust embryos of excellent quality rather than embryos more “delicate” who could suffer more.

Therefore, if an IVF patient only has one or two embryos, it may not be worth the risk. Regardless of the training of the laboratory personnel (embryologist) performing 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.

Graphic courtesy of Dr. Alexis Heng Boon Chin.

Another deficiency of PGS (PGT-A) is that it involves the extraction and sampling of cells from the outer embryonic layer (Trophectoderm, TE) which gives rise to the placenta and umbilical cord.

It is not representative of the inner embryonic layer (inner cell mass, ICM) that forms the actual embryo, which gives birth to the baby.

Graphic courtesy of Dr. Alexis Heng Boon Chin.

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 misdiagnosis and rejection of mosaic embryos, which have been shown to be capable of giving birth to a normal, healthy baby.

Graphic courtesy of Dr. Alexis Heng Boon Chin.

There is scientific evidence that mosaic embryos are able to “self-correct” which increases the chances of a normal birth. This “self-correcting” mechanism involves pushing the genetically abnormal cells back into the outer layer of the embryo, which gives rise to the placenta and the umbilical cord.

Older women with low ovarian reserves have significantly fewer embryos during IVF. Therefore, excluding or rejecting mosaic embryos that can potentially give birth to a normal baby would actually significantly reduce their chances of success in IVF. Some older women may not have any more embryos to transfer after genetic testing.

Indeed, in neighboring Singapore, PGS (PGT-A) is still not approved as a mainstream clinical treatment, due to ambiguous results and a high attrition rate of 72% in local clinical trials, such as the reported the Singapore Ministry of Health in 2021.

Recently, a much cheaper and less invasive alternative to PGS (PGT-A) was announced, with groundbreaking results from an international study published in the reputable journal human reproduction log.

A new artificial intelligence (AI) algorithm called “Life Whisperer Genetics” has been successfully developed by US healthcare company Presegen to accurately assess the genetic normality of embryos, based solely on microscopic images.

Interestingly, Alpha IVF in Malaysia has been a major collaborative partner in the development of this new reproductive technology platform, which is non-invasive, inexpensive and delivers results instantly, and therefore far preferable to the expensive, time-consuming and invasive. PGS technique (PGT-A).

According to Dr. Sonya Diakiw, Director of Medical Sciences at Presagen, this AI screening technique based solely on microscopy images may not be as accurate as PGS (PGT-A) itself, which involves actual sequencing of DNA.

Nevertheless, a relatively high accuracy rate of 77.4% was reported in human reproduction.

This doesn’t compare too badly with the results of the PGS technique (PGT-A), which themselves can be variable, due to their small sample size.

Typically, PGS (PGT-A) only tests about five cells out of a total of about 200 cells in a blastocyst-stage embryo, so it is not always representative of the whole embryo.

Therefore, there is a risk of misdiagnosis of false positives and false negatives, especially with mosaic embryos.

In contrast, Life Whisperer Genetics’ AI algorithm is a whole embryo genetic integrity assessment that does not require any invasive procedures, which can be used to prioritize embryos for use in IVF procedures.

Graphic courtesy of Dr. Alexis Heng Boon Chin.

Since instant results can be achieved with AI screening, unlike time-consuming PGS (PGT-A) which takes at least a few weeks, there is no requirement to freeze the entire batch of IVF embryos tested, pending test results.

This could be beneficial for some patients with a few weak embryos who could be harmed by the freeze-thaw process.

Graphic courtesy of Dr. Alexis Heng Boon Chin.

However, a current shortcoming of this new technological platform is its inability to reveal the sex of the embryo, unlike conventional genetic testing with PGS (PGT-A).

It is possible that this will be corrected in the near future, with the development of new AI algorithms that could identify the sex of IVF embryos with some degree of accuracy through microscopic imaging.

Given the much lower costs and reduced risk of harming the embryo, although somewhat less precision and inability to perform sex selection, it may be more attractive and cost-effective for patients to do a AI-based screening of IVF embryos, rather than actual genetic testing with PGS (PGT-A).

Ultimately, it is up to patients to decide which technique will give them the best value for money, based on their individual analysis of risks, costs and benefits.

Dr. Alexis Heng Boon Chin, originally from Singapore, is an associate professor of biomedical sciences at Peking University, China.

  • This is the personal opinion of the author or publication and does not necessarily represent the views of code blue.

Comments are closed.