WHAT IS THE ‘IMPLANTATION WINDOW’ IN FERTILITY TREATMENT AND HOW TO IMPROVE IT?
SIGN UP AND GET ANSWERS LIVE >

Should I add PGT-A to my IVF cycle : A Genetic counsellor’s perspective

Claire Bascuñana, MSc., CCGC
Fertility Genetic Counsellor

Category:
Genetics PGS / PGT-A

SHOULD I ADD PGT-A TO MY IVF CYCLE-Claire-Bascuñana
From this video you will find out:
  • How does PGT-A work, and what are the key steps involved in the process?
  • What is the relationship between maternal age and the risk of aneuploidy in embryos?
  • How PGT-A can help identify aneuploid embryos and their potential impact on the success of an IVF cycle?
  • Who are the ideal candidates who can benefit the most from incorporating PGT-A into their IVF cycle?
  • What genetic analyses are performed on the biopsied embryos during PGT-A, and how is this information used to select embryos for implantation?
  • What are the potential outcomes and considerations when dealing with mosaic embryos in PGT-A?
  • What are the limitations of PGT-A?
  • How do genetic counselors assist patients in making informed decisions about whether to include PGT-A in their IVF cycle?

Should I add PGT-A to my IVF cycle : A Genetic counsellor’s perspective

During this webinar, Fertility Genetic Counsellor, Claire Bascuñana introduced the world of Preimplantation Genetic Testing for Aneuploidy (PGT-A). Claire explained how the PGT-A tool can be integrated into your IVF journey and its benefits, limitations, and potential impact on your fertility treatment.

Understanding PGT-A

To begin, for those who are not aware of what PGT-A is, it’s an add-on for an IVF cycle. PGT-A means pre-implantation genetic testing for aneuploidy. Aneuploidy means there is an abnormal number of chromosomes. We are supposed to have 2 copies of each chromosome, and when there is an extra copy or a missing copy of a chromosome, it can impact development, pregnancy, and health. Having an abnormal number of chromosomes is an important determinant of fertility success. That’s why PGT-A is used to screen for aneuploidy.

Why is PGT-A used? The initial objective is to increase the implantation rate per embryo transfer during an IVF cycle. It means we want to increase the likelihood of an ongoing pregnancy after transferring an embryo. The second goal is to decrease the likelihood of losing the pregnancy due to a miscarriage.  We want to reduce the risk that the pregnancy won’t reach full term. It’s also aimed at decreasing the time it takes to achieve an ongoing pregnancy, especially when a large number of aneuploid embryos are produced during the IVF cycle. The more aneuploid embryos you have, the more possibilities you have for transfer. However, if you do not transfer the embryos with the best likelihood of resulting in an ongoing pregnancy first, it may take more time to become pregnant. PGT-A aims to reduce this timing by directly selecting the embryos with the best likelihood of achieving an ongoing pregnancy.

Significance of aneuploidy and maternal age

All of these objectives are meant to increase the efficiency of IVF when compared to the standard method, which is just looking at the morphology of the embryo for selection. We now know that a good-looking embryo with good morphology is not enough to guarantee its viability. Sometimes, a very good-looking embryo with a high grade can have chromosomal issues that are not compatible with life. That’s the main reason why PGT-A was implemented in fertility clinics during IVF cycles. It’s important to understand the link between aneuploidy or chromosomal issues and maternal age. With an increase in maternal age, there is a higher proportion of abnormal embryos produced.

As a woman’s age increases, the proportion of embryos with abnormal chromosomes also increases. At 36 years old, it’s about half of the embryos produced are aneuploid, and half with chromosomal issues. Maternal age has a significant impact. Aneuploidy is one of the main causes of implantation failure and miscarriages. Understanding this, you can see why PGT-A could be useful in improving outcomes. There is a specific population of patients that can benefit from PGT-A.

Not all patients could benefit from PGT-A; it’s not a one-size-fits-all solution. The first population of patients that could benefit from it is patients with advanced maternal age. As we saw in the graph earlier, patients with advanced maternal age have a higher risk of producing abnormal embryos, which can lead to lower chances of an ongoing pregnancy due to chromosomal issues. For these women, PGT-A would allow the direct selection of embryos that are not affected by chromosomal issues, increasing the likelihood of an ongoing pregnancy.

The other two patient populations that could benefit significantly from PGT-A are patients with recurrent miscarriages or implantation failure. It’s essential to keep in mind that PGT-A won’t help if the miscarriages or implantation failures are not due to chromosomal issues. Sometimes there are other health factors involved, and PGT-A may not be the solution. It’s not a perfect test, and sometimes even with PGT-A, you can still have implantation failure or miscarriages, indicating that the cause might be something other than chromosomal issues.

PGT-A and maternal age

For women with advanced maternal age, PGT-A seems to eliminate the effect of maternal age on implantation, but it doesn’t significantly influence the outcomes for young patients with good prognoses. If you do not fall into these categories of patients, you may not benefit from PGT-A, and it could sometimes even be harmful.

Fertilization and biopsy

For fertilization, not all collected eggs will be fertilized. It’s estimated that only 60-70% of eggs will successfully fertilize. So, at each step of the process, there’s some loss of biological material. After fertilization, the embryos are left to develop for several days before the biopsy. The biopsy occurs at the blastocyst stage, which is typically on day five. The blastocyst has an internal cavity, a mass of cells for the future fetus, and a layer of cells for the future placenta. At this stage, about 50% of blastocysts naturally survive, representing a natural selection process. The biopsy of the embryo at day five requires expertise. Studies show that when done by a skilled lab, there is a similar pregnancy rate with or without biopsy. The biopsy itself does not seem to harm the future development of the embryo.

Mosaicism and genetic analysis

During the biopsy, only 5 to 8 cells are removed, which is a small fraction of the approximately 100 cells an embryo has at this stage. The cells biopsied are not from the inner cell mass, which becomes the future fetus. They come from the trophectoderm, which is the future placenta. This is an important point because it explains why PGT-A cannot be a perfect technique. The cells analyzed for the biopsy are not the ones that will form the future fetus. Most of the time, the cells from the future fetus and the future placenta are the same in terms of chromosomal and genetic content, but sometimes they differ. When there’s a discrepancy between the PGT-A result and the future fetus’s status, we encounter the concept of mosaicism.

After the biopsy, the cells are sent to the PGT-A lab, and the embryos are frozen at the fertility clinic, awaiting the results. The goal is to freeze all embryos, send the biopsy to the lab, and then select the healthiest embryo from this cycle for transfer.

The genetic analysis (PGT-A) is usually performed by a technique called Next Generation sequencing. The objective of the test is simply to determine how many copies of each chromosome the biopsy cells have. We want to see if each chromosome is present in two copies, as we are supposed to have one copy from the biological mother and one from the biological father. When we have more or fewer copies, we call that trisomy or monosomy, and this can impact the development of the embryo and the future pregnancy’s health, if there is a pregnancy.

 

PGT-A technique can assess a variety of factors, not just major chromosomal abnormalities, but also some smaller segmental anomalies. Segmental anomalies occur when there is only one piece of a chromosome that is missing or duplicated. However, PGT-A cannot detect microduplications or microdeletions, which are small pieces of chromosomes. It can only detect whole chromosomes or large segments.

It’s essential to note that PGT-A is not 100% accurate because it relies on analysing future placental cells, and it doesn’t provide information about future fetal cells. Therefore, even if PGT-A suggests that your embryo doesn’t have any chromosomal issues, prenatal recommendations are still necessary because it’s not a diagnostic test. It’s more like a screening of the embryo.

PGT-A results are not just a simple “yes” or “no” answer. They have various implications. The results determine whether you can transfer the embryo, the priority order for transferring embryos, and the likelihood of success based on the specific result. It’s recommended to discuss your PGT-A results with a genetic counsellor or your doctor to understand the impact of each type of result.

Additionally, it’s important to know that different labs performing PGT-A may have different thresholds for determining whether an embryo is euploid, aneuploid, or mosaic. Therefore, the lab itself can influence the type of result you receive.

Mosaicism

Mosaicism, where there is a mix of normal and abnormal cells in the embryo, was not always reported by many labs. However, it’s now advocated that some mosaic embryos can be transferred with proper genetic counseling and prenatal care.

In terms of the outcomes of transferring mosaic embryos, they have a lower implantation rate and a higher rate of miscarriages compared to euploid embryos. However, low-level mosaic embryos can have a similar ongoing pregnancy rate as euploid embryos, depending on the percentage of mosaic cells. The risk of having an affected pregnancy after transferring a mosaic embryo is around 1%, based on recent studies. It’s encouraging that studies have shown no significant differences in pregnancy complications, delivery types, birth age, Apgar scores, congenital anomalies, and chronic illnesses between mosaic embryo transfers and euploid embryos up to 3 years old.

Understanding abnormal PGT-A results

It’s important to know that abnormal PGT-A could mean a lot of different things. Sometimes, you don’t have any results; sometimes, you have a chaotic result with six different types of anomalies. Sometimes, you have a mosaic that is identified, and sometimes you just have what we call a segmental aneuploidy, meaning you have one part of the chromosome missing.

Sometimes, it’s the whole chromosome missing. All these specific situations, I don’t have the time to detail now, but they should be addressed by a genetic counselor if you have hesitations about whether you can transfer those embryos. Of course, it depends on the policy of the clinic you’re working with, but asking these questions can be very helpful for you to feel empowered throughout your fertility journey and to understand what those results mean.

Considerations before embryo transfer

Another thing to think about is that some clinics are very hesitant to transfer, for example, a mosaic embryo. But before PGT-A, if you don’t do PGT-A, you might transfer thousands of embryos blindly that are probably mosaic or aneuploid without knowing it. So, it’s something we need to consider when we restrict patients from using certain embryos.

The next step after receiving the results and deciding which embryos should be transferred is the actual embryo transfer. 99% of embryos survive the thawing process, and then we expect an implantation rate, which depends on the embryo’s status. Depending on the embryo status, we’ll have specific prenatal recommendations. Globally, when you transfer a euploid embryo, or any embryo with a biopsy through PGT-A, it’s recommended to have all the usual ultrasounds, including a first-trimester ultrasound with nuchal translucency measurement and a morphological ultrasound.

Regarding specific prenatal screening, it’s important to know that PGT-A has a similar detection rate as NIPT (non-invasive prenatal testing). So, because of that, serum marker screening is not recommended, as it has a lower detection rate compared to PGT-A. However, if a patient still wants additional screening, they can go privately for non-invasive prenatal testing.

For mosaic embryos that are transferred, ultrasound is still indicated, and it’s possible to go through various types of screening. However, most non-invasive prenatal screenings only look at the main chromosomes 21, 18, and 13, which are possibly viable during pregnancy. Sometimes, the type of mosaic you transfer may affect other chromosomes not included in the screening. Because of this, for all pregnancies resulting from a mosaic embryo transfer, there is a possibility to go through amniocentesis, like invasive prenatal diagnosis, to target the specific chromosome of the mosaic and make sure the fetus is not affected. There’s a 1% risk of having an abnormal prenatal diagnosis following a mosaic embryo transfer.

I would like to emphasize that many patients opt not to go through invasive testing even with the 1% risk, and it’s a personal choice.

 Key takeaways

PGT-A does not improve the cumulative success of your cycle; it only impacts the success per transfer. It cannot guarantee anything and does not screen for all genetic conditions or congenital defects.

Pregnancy resulting from embryos with a mosaic transfer might be a personal decision, and genetic counseling is essential to make informed choices. PGT-A is a useful tool in specific situations, but it’s important to understand its limits and implications. It’s not a one-size-fits-all approach, and the decision to pursue PGT-A should be based on individual circumstances.

In summary, consider PGT-A if it aligns with your specific situation, but keep in mind that research and knowledge in this field may continue to evolve in the coming years.

Related reading:

- Questions and Answers

If I end up with one embryo, should I take the risk to perform PGT-A on that one embryo?

If you end up with just one embryo, the decision to perform PGT-A is a personal one. Depending on factors such as your age, the reason for PGT-A, and the number of embryos, some might recommend transferring the single embryo without testing, while others might opt for testing to ensure it’s chromosomally normal. There is a chance it could still work, even if untested. It’s a complex decision that should be discussed with your doctor.

How can we do PGT-A on day-3 embryos?

PGT-A on day 3 embryos was done in the past, but day five biopsy is now the standard. Day 5 biopsy is preferred because it provides more accurate results with less mosaicism, and it minimizes harm to the embryo. While day 3 biopsy can still be technically possible in some cases, it’s not the current standard practice.  

‘m 36 with low ovarian reserve. I only got one to three blastocysts per cycle. I’ve had 5 FETs from 3 cycles. Some doctors say never to do PGT-A because we don’t make many embryos. Some say we should because of recurrent implantation failure. We feel very conflicted and confused. We are worried about discarding a good embryo with some bad cell samples.

I understand your situation is challenging. In cases like yours with recurrent implantation failure, it’s a complex decision. PGT-A could provide insights into why your transfers are failing, but it comes with the risk of discarding embryos based on their results. It’s essential to discuss this thoroughly with your doctor, considering your specific circumstances and the pros and cons of PGT-A.

Do you have any data about the percentage of successful pregnancies or live births after PGT-A and embryo transfer compared to non-PGT-A pregnancies or live births?

Success rates can vary widely between clinics and depend on various factors, including maternal age and embryo quality. It’s best to consult your fertility clinic or doctor for specific data related to your situation, as success rates are clinic-specific. PGT-A can offer insights into embryo health, but it’s not a guarantee of success.

Amniocentesis isn’t always recommended after PGT-A. Is this correct?

The recommendation for amniocentesis after PGT-A can vary and is determined on a case-by-case basis. It depends on the specific circumstances and risks associated with the pregnancy. Your doctor will consider factors like maternal age and the PGT-A results before determining whether amniocentesis is necessary.

Is PGT-A recommended for egg donation treatment or for women less than 25 years old?

There’s generally no significant reason to recommend PGT-A for women under 25 years old, as the proportion of embryos with chromosomal issues is expected to be low in this age group. PGT-A is typically recommended for women of advanced maternal age or those with a history of recurrent miscarriages.

Do you recommend PGT-A testing for a 33-year-old with no known illness who has had 2 cycle with 3 embryo transfers, all of which failed? The embryo morphology was 4A and 3B, 3C.

The decision to recommend PGT-A testing depends on various factors, including the reason for IVF, medical history, and the specifics of the case. In your situation, where there have been recurrent implantation failures, it’s essential to consider all relevant factors. The embryo morphology alone may not provide a complete picture. Consult with your fertility doctor to make an informed decision.

Does paternal age play a role in embryo quality? If so, would PGT-A be recommended for a young female less than 25 years old, but with an older male partner?

Paternal age definitely has a role in other types of genetic risks and the quality of the embryo due to various factors. However, for chromosomal issues, the risk of aneuploidy is not directly associated with paternal age. PGT-A specifically does not help with paternal age-related genetic diseases, which are not chromosomal but monogenic, involving genetic mutations that cannot be screened through pre-implantation genetic testing.
Understanding the Importance of Carrier Genetic Testing
Hysteroscopy before IVF:  can it improve outcomes?
Recurrent Pregnancy Loss challenges: causes and solutions
How to prepare for an embryo transfer to improve your chances: There’s more to consider than just the endometrium
Endometrial factor and recurrent failures in IVF: diagnosis and treatment
How old is too old for my IVF treatment?
Authors
Claire Bascuñana, MSc., CCGC

Claire Bascuñana, MSc., CCGC

Claire Bascuñanais a genetic counsellor certified in Canada who graduated from the Genetic Counselling Master Degree at University of Montreal (UdeM) in 2012. She previously got a Master degree in Biomedical Health in Montpellier, and a D.E.S.S in Bioethics at University of Montreal UdeM). After a practice in hospital environment in the field of oncogenetics and prenatal diagnosis, she developed an expertise in reproductive genetics for the past 5 years at the service of patients in a fertility clinic and is passionate about patient's empowerment for their reproductive choices. To enhance her empathetic patient-centered approach, she will soon complete a perinatal psychology certificate at University of Quebec in Montreal (UQAM). Concerned with making medical genetics accessible to the general population, she developed French-speaking vulgarized content on social media (YouTube, Facebook, Instagram, TikTok) under the name ''La Génétique en Clair''.
Event Moderator
Caroline Kulczycka

Caroline Kulczycka

Caroline Kulczycka is managing MyIVFAnswers.com and has been hosting IVFWEBINARS dedicated to patients struggling with infertility since 2020. She's highly motivated and believes that educating patients so that they can make informed decisions is essential in their IVF journey. In the past, she has been working as an International Patient Coordinator, where she was helping and directing patients on their right path. She also worked in the tourism industry, and dealt with international customers on a daily basis, including working abroad. In her free time, you’ll find her travelling, biking, learning new things, or spending time outdoors.
Have questions about what factors will affect your IVF success?
Join our live event to directly ask your questions to three IVF experts.