Can you explain what PGS is?

Pre-implantation Genetic Screening or PGS, is an assisted reproductive treatment where we undertake the genetic analysis of the embryo and replace a genetically normal embryo back into the womb.

This is also commonly referred to as comprehensive chromosomes screening or CCS. As part of the treatment, the patients have to go to an IVF treatment process which will involve taking the fertility drugs, going to the egg collection, and once the eggs have been collected and inseminated, the embryos will become cultured up to blastocyst or day-five stage.

After blastocyst stage, we will then take a few cells from the embryo and these cells will then be subjected to the genetic analysis using the next generation sequencing platform. We will then assess which of these embryos are genetically normal. After the genetic analysis has been performed, we will then start another cycle for yourself and this genetically normal embryo – one or two – would be replaced back into the womb in a frozen embryo replacement cycle.

This intervention is of more relevance to patients, for example, women trying for pregnancy may be over 38 or 40 way there is a higher incidence of the genetic errors in the embryo leading to the reduction the fertility rates and a higher incidence of genetic problems in babies such a Down’s Syndrome. This can also be of relevance to patients with repeated treatment failures because repeated treatment failures can either be related to the failure of the implantation or to the embryo health.

Assessing the embryo health is only one aspect that we understand as of now and is a little bit more about the genetics. So by testing the embryos for genetic normality, we are trying to correct one of the potential factors that might be contributing to the treatment failures or preimplantation failures.

The other group of patients would be repeated miscarriages. if patients have multiple miscarriages which have been less than 12 weeks of gestation, sixty percent of these miscarriages could be genetic in nature. So by doing PGS and replacing a genetically normal embryo back, we are hoping to correct the problem leading to an ongoing pregnancy and childbirth.

We also offer pre-implantation genetic diagnosis. Pre-implantation genetic diagnosis is of relevance to the patients with single gene disorders or maybe double gene disorders. Largely it is for single gene disorders. Generally, for these cases, NHS funding for the treatment should be available, and if you would want to explore those then it would require an initial assessment of the genetic condition, involvement of a clinical geneticist, and then planning your treatment. These are some of the other genetic services that we offer at the clinic.

What you should know about expanded genetic carrier screening?

A recent study published in the Journal of American Medical Association (JAMA), looked into the possibility of routine screening of all couples for a single recessive gene carrier status. This is irrespective of their family history.

Between 2012 and 2015 more than 300,000 individual were tested for 94 profound or severe genetic conditions. They observed that around 94 to 392 fetuses for every 100,000 would have at least one of these conditions. This varied for different ethnic groups. The study highlighted that by using the expanded carrier screening panels, many more fetuses are likely to be identified than with the current screening guidelines.

The challenge is that the couples have to make a difficult decision. They have to decide if ending the pregnancy or having a child who may have a recessive single gene defect. This has consequences for the child, parents and healthcare systems. This study has started a new dialogue. It will be important to confirm these findings in larger studies before such tests are available.

In my opinion, the test should be a part of preconception counselling or services. This will inform the couples of the risk and prevent the birth of children who may have these genetic conditions. There has been a progression in genetic diagnostic testing since genome sequencing. This has expanded the number of conditions that specialists can diagnose.

This progression also increased the diagnostic efficiency and significantly dropped the costs. Expanded carrier screening for recessive conditions was first made available in 2009. It is noteworthy that one in four individuals are carriers of at least one of the ninety-six serious/profound single gene recessive conditions. To inherit a recessive condition, both parents should be carriers of the faulty gene.

The future of expanded genetic carrier screening

In such cases, the chance of the child inheriting the condition is almost one in four. Hence, most parents who are carriers will be offered preimplantation genetic diagnosis or PGD. This will prevent the transmission of the genetic condition to the next generation. Usually, such couples either have had an affected child or have a family history. Preimplantation genetic diagnosis or PGD involves couples going through IVF treatment.

When the embryos have been created, they are biopsied and screened for the faulty gene. Only those embryos that do not carry the faulty gene are then transferred or frozen for future use. The current practice is to screen the pregnant mother for certain genetic conditions. These screening methods are based on the prevalence of the genetic conditions. In particular, ethnic groups or family history. Your specialist will assess at the initial antenatal visits for any extra screening.

I think that the expanded genetic carrier screening is offered to couples as part of the preconception counselling rather antenatal (or prenatal) care. We are in an information age and deal with billions of pieces of information each day.

In my experience, most potential parents try to avoid any genetic conditions that can affect the next generation. When counselling patients, I am commonly asked if the unborn child will be absolutely healthy and free of genetic conditions. This will never be possible, but there is a potential to reduce the risk of a child being born with recessive genetic conditions.

Obviously, the consequence will be the rise in the number of healthy couples with no family history seeking PGD. They prefer this process instead of what would have been a natural conception. As PGD involves an IVF treatment, couples will risk many complications of IVF treatment. This may avoid the long term risk of having a child affected with the single gene recessive condition. Besides the risks of IVF, this also causes a sense of anxiety and referral to clinical geneticists.

Currently, some of the European fertility clinics are using these expanded carrier screening tools. In particular, screening egg donors before matching to the potential egg recipient couples. In such fertility clinics, the egg donor has a blood test. Specialists control her for few hundred autosomal recessive genetic conditions.

If she is a carrier, then the partner of the egg recipient lady undergoes the test. This is necessary to confirm that he is not the carrier of the any of these genetic conditions to which the donor has been screened. If the partner of the egg recipient and the egg donor have a positive screen for the same condition, then specialists match the couple to a different egg donor.

Some of the clinics are offering these services as a routine practice, whereas others are considering on a case by case basis. In the UK, such practice of screening egg donors using expanded genetic carrier screening does not exist. This is because there are fewer donors available. By screening the egg donors, the number of available donors will be even more limited.

This is an interesting study that has opened a new chapter of routine expanded genetic carrier screening of the pregnant mothers. I wait for larger studies to explore this in greater depth before offering this to our patients as part of preconception counselling. I think this may be the start of new era in our quest of a perfectly healthy child.

What Should you Know Before Deciding About Comprehensive Chromosome Screening ( CCS ) Or Preimplantation Genetic Screening ( PGS )?

CCS or PGS is a scientific intervention that some patients may consider for a variety of reasons. This is different from Preimplantation Genetic Diagnosis ( PGD ). In PGD, the scientists are looking for a specific defect in the genetic material that has resulted in a genetic disorder in the family.

Whereas, in PGS or CCS we are checking for the amount of genetic material in the embryos. Too little or too much genetic material ( chromosomes ) can result in an abnormal or aneuploid embryo. This may result either in a failed IVF treatment or a miscarriage or a birth of an abnormal child. It is possible to use different technologies for testing embryos. Historically, we used the FISH (Fluorescent in situ Hybridisation) technique. Later, specialists developed new techniques such as array CGH (comparative genomic hybridization). Other methods are SNP ( Single Nucleotide Polymorphism ) microarray and NGS ( Next-Generation Sequencing ).

Who needs PGS or CCS?

Patients who are reflecting on pregnancy at a later age, such as over 38 years, can consider PGS or CCS. Also, patients with repeated IVF treatment or recurrent implantation failures can consider it. Sometimes, IVF treatment may fail because of a genetical abnormality in the transferred embryo. Without doing genetic testing of the embryo (or embryos), there is no way of knowing for sure it is genetically normal or not.

This is the case even if the embryo developed well and looked healthy on the day of embryo transfer. Other patients such as those with recurrent pregnancy loss or repeated miscarriages can also think of having PGS or CCS. Almost one percent of women of reproductive age may experience repeated miscarriages. This is defined as loss of three or more pregnancies.

Almost sixty percent of these early miscarriages (before twelve weeks of pregnancy) are due to genetically abnormal embryos. Hence, testing the embryos and replacing them with genetically normal embryos is necessary. It may improve the chances of such couples having a successful ongoing pregnancy and childbirth. Some patients with male factor infertility may also consider it.

Does PGS or CCS guarantee a genetically healthy child?

PGS or CCS is looking into the amount of the genetic material or chromosomes. When the cells are dividing, the genetic material should split equally between the two resultant cells. But, sometimes this might not be the case. Some cells may have a higher number of chromosomes and the other may have fewer than desired. Depending on the technology used for testing, the results have a reliability of around 97 % to 98%.

Also, it does not test for the genetic codes that are responsible for expressing different traits in the child. So, even if the tested cells have a normal chromosome number or amount of genetic material, the embryos may still carry an abnormal gene or genetic code. Sometimes, this may result in the birth of an abnormal child. So, PGS or CCS cannot guarantee a genetically healthy child.

Do I have to have antenatal screening even if a genetically normal embryo has been transferred?

Yes, as I mentioned earlier, the reliability of the results is around 97 – 98% even with the latest next-generation sequencing (NGS) technology. So, there is a chance that the transferred embryo may have tested falsely negative. So, all patients having PGS or CCS are still advised to avail of the antenatal screening tests.

Do I have to take fertility drugs?

All patients thinking of PGS or CCS must go through an IVF treatment. This will involve taking fertility drugs just like any other IVF patient. You will also go through the minor surgical procedure of egg collection. Once the genetic test results are available then you will go through the embryo transfer procedure. So, you will go through all the steps and processes of an IVF treatment cycle. Your specialist will discuss all the pros and cons of the treatment before you decide to go for PGS or CCS.