Embryo screening in IVF: everything you need to know

On this page:

What is embryo screening?

Understanding embryo chromosomes

Types of embryo screening

Preimplantation Genetic Testing for Aneuploidy (PGT-A)

Preimplantation Genetic Testing for Monogenic Diseases (PGT-M)

Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR)

Why is embryo screening important?

How does embryo screening work?

Embryo screening debate

What PGT-A does not do

Questions to ask your doctor about embryo screening

What is embryo screening?

Embryo screening is a scientific process that allows embryologists to check for genetic and/or chromosomal abnormalities in the embryos created through IVF.

Understanding embryo chromosomes

An embryo is created when a sperm fertilises an egg in the fallopian tube. The fertilised embryo travels down the fallopian tube and implants into the lining of the uterus.

Now a healthy embryo has 46 chromosomes—23 supplied from the sperm and 23 from the egg. These chromosomes carry the genetic material needed for normal growth and development.

But, according to Dr. Vladimiro Silva, Scientific Director of Ferticentro, “sometimes, during the fertilisation process, an embryo can end up with too many chromosomes, too few, or chromosomes that are damaged”.

In some cases, embryos may also carry inherited genetic conditions or structural chromosomal issues.

These problems can cause:

• Failed implantation (when the embryo does not successfully attach to the lining of the uterus, preventing the pregnancy from progressing)
• Miscarriage
• Genetic conditions, such as Down’s Syndrome or Turner’s Syndrome, or inherited disorders like cystic fibrosis.

“Embryo screening helps identify these problems early, before the embryos are placed in the uterus for implantation,” said Dr. Silva.

Types of embryo screening

While PGT-A is the most common and widely recognised form of embryo screening, there are actually three distinct types. Let’s explore each of them.

Preimplantation Genetic Testing for Aneuploidy (PGT-A):

Preimplantation genetic testing for aneuploidy (PGT-A) checks for issues in the number of chromosomes in embryos. These issues are typically related with female age, and are more common in women above 35 years old.

How do embryos end up with the wrong number of chromosomes?

1.   Errors during egg or sperm formation:

• Eggs and sperm are produced through a process that involves a stage called  meiosis, which occurs in the ovaries and testes.
• During meiosis, cells divide and reduce their chromosome number by half, resulting in gametes (eggs or sperm) with 23 chromosomes each.
• These gametes combine during fertilisation to form an embryo with the full set of 46 chromosomes.
• If meiosis goes wrong, the egg or sperm can end up with too many or too few chromosomes.

.    Errors during fertilisation:

• When the egg and sperm combine to form an embryo, mistakes can occur in how chromosomes are distributed.
• This can lead to an embryo with an abnormal number of chromosomes (aneuploidy).

3.   Errors during early cell divisions:

• After fertilisation, the embryo begins to divide into more cells.
• Errors during these early divisions can cause some cells in the embryo to have the wrong number of chromosomes.

In some cases, we have what we call mosaicism (where some cells are normal, and others are not).

Conditions that can result from chromosomal abnormalities:

1.   Trisomies (extra chromosome):

• Down’s syndrome (Trisomy 21): Caused by an extra copy of chromosome 21.
• Edwards syndrome (Trisomy 18): Caused by an extra copy of chromosome 18. Often leads to severe developmental issues and is usually life-limiting.
• Patau syndrome (Trisomy 13): Caused by an extra copy of chromosome 13. It often causes severe physical and intellectual disabilities and is also life-limiting.

2.   Monosomies (missing chromosome):

• Turner syndrome (Monosomy X): Occurs when a female has only one X chromosome instead of two. It can cause short stature, infertility, and other physical and developmental issues.

3.   Sex chromosome abnormalities:

• Klinefelter syndrome (XXY): Males have an extra X chromosome, which can cause infertility, reduced testosterone, and learning difficulties.
• Triple X syndrome (XXX): Females have an extra X chromosome, which can sometimes cause tall stature and learning difficulties.
• XYY syndrome: Males have an extra Y chromosome, which may lead to increased height and sometimes mild learning difficulties.

4.   Mosaicism:

o   This is when some cells have the correct number of chromosomes, and others do not. The effects depend on which cells are affected and the specific chromosomes involved.

5.   Pregnancy-related outcomes:

• Miscarriages: Many chromosomally abnormal embryos fail to develop and result in early pregnancy loss.
• Failed IVF cycles: Embryos with chromosomal abnormalities often fail to implant in the uterus or stop developing after implantation.

6.   Structural chromosomal issues:

• Translocations, deletions, inversions or duplications can also affect an embryo’s viability and development, potentially leading to miscarriage or congenital conditions.

Who should consider PGT-A testing?

1.   Women of advanced maternal age:

• Women aged 35 or older are at a higher risk of producing eggs with chromosomal abnormalities (aneuploidy).
• PGT-A can help identify embryos with the correct number of chromosomes, reducing the risk of miscarriage or implantation failure.

2.   Couples with a history of recurrent pregnancy loss:

• Repeated miscarriages are often caused by chromosomal abnormalities in the embryo.
• PGT-A can identify chromosomally normal embryos for transfer, lowering the likelihood of another miscarriage.

3.   Couples with a history of failed IVF cycles:

• Embryos with chromosomal abnormalities are a leading cause of failed implantation in IVF.
• PGT-A can help select the most viable embryos, increasing the chances of successful implantation.

4.   Couples experiencing infertility for unexplained reasons:

• Chromosomal abnormalities in embryos may be an underlying cause of unexplained infertility.
• PGT-A can provide insights into embryo quality and improve the chances of a successful pregnancy.

PGT-A helps identify embryos with the correct number of chromosomes, increasing the likelihood of a healthy pregnancy and reducing the risk of complications.

Preimplantation Genetic Testing for Monogenic Diseases (PGT-M)

Sometimes called preimplantation genetic diagnosis (PGD), Preimplantation Genetic Testing for Monogenic Diseases (PGT-M) is a procedure used during in vitro fertilization (IVF) to test embryos for specific genetic disorders caused by mutations in a single gene.

A gene is a specific segment of DNA on a chromosome that contains the instructions for making proteins or regulating biological processes.

PGT-M allows doctors and genetic specialists to identify embryos that do not carry the inherited genetic condition, ensuring that only unaffected embryos are implanted into the uterus.

When is PGT-M used?

PGT-M is recommended for individuals or couples who:

1. Are known carriers of a genetic condition:
   If one or both parents carry a mutation in a specific gene linked to a monogenic disorder (a disorder caused by mutations in a single gene), PGT-M can help reduce the risk of passing it on to their child.
2. Have a family history of a genetic disorder:
   Families with a known history of monogenic conditions can use PGT-M to screen for the same condition.
3. Have a child affected by a genetic condition:
   If a couple already has a child with a genetic condition, PGT-M can help them identify embryos that are unaffected for future pregnancies.
4. Wish to avoid passing on a recessive or dominant genetic condition:
   PGT-M is especially useful when both parents carry mutations for recessive conditions or when one parent has a dominant mutation.

Examples of monogenic disorders detectable with PGT-M:

1. Autosomal Recessive Conditions (both parents need to carry the mutation):
   • Cystic fibrosis
   • Sickle cell anaemia
   • Tay-Sachs disease
   • Thalassemia
2. Autosomal Dominant Conditions (only one parent needs to carry the mutation):
   • Huntington’s disease
   • Marfan syndrome
   • Polycystic kidney disease
3. X-Linked Conditions (gene mutations carried on the X chromosome, often passed from mothers to sons):
   • Duchenne muscular dystrophy
   • Haemophilia
   • Fragile X syndrome

Why are these considered monogenic?

These conditions arise specifically because of changes (mutations) in one gene. PGT-M is designed to detect these changes, allowing for the identification of embryos that do not carry the mutation before implantation.

PGT-M reduces the risk of passing on serious genetic conditions, helps parents have a child free of the specific genetic disorder they carry, and increases the likelihood of a healthy pregnancy and baby.

Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR)

Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR) is a test during IVF that checks for structural chromosome issues, like missing, duplicated, swapped, or inverted segments. It helps find embryos with normal chromosomes, improving pregnancy success and reducing the risk of miscarriage or genetic problems.

What are structural rearrangements?

Structural rearrangements involve changes in the physical structure of chromosomes. They can occur in the following ways:

1. Translocations:

• Balanced translocations: Parts of one chromosome are swapped with parts of another without any loss or gain of genetic material. The individual may have no symptoms but can pass on unbalanced chromosomes to their offspring.
• Unbalanced translocations: There is a loss or gain of genetic material during the rearrangement, which can lead to genetic disorders or pregnancy complications.

2. Deletions:
   A segment of a chromosome is missing, leading to a loss of genetic material.
3. Duplications:
   A segment of a chromosome is duplicated, resulting in extra genetic material.
4. Inversions:
   A segment of a chromosome is flipped in reverse order. While this might not affect the individual, it can cause problems during reproduction.
5. Insertions:
   A segment of one chromosome is inserted into another chromosome.

Who should consider PGT-SR?

PGT-SR is particularly useful for Individuals with known chromosomal rearrangements, like balanced translocations, inversions, or duplications. 

What conditions can PGT-SR help prevent?

PGT-SR reduces the risk of:

1. Pregnancy complications:

• Recurrent miscarriages.
• Failed implantation during IVF.

2. Genetic disorders in children:

• Certain chromosomal disorders caused by unbalanced rearrangements, such as partial monosomies or trisomies.

3. Birth defects or developmental issues:

• Structural rearrangements can sometimes cause conditions that lead to physical or intellectual disabilities.

Why is embryo screening important?

Embryo screening provides insights into potential issues that may prevent a pregnancy from progressing.

Chromosomal abnormalities, such as aneuploidy, are a leading cause of failed IVF cycles and miscarriages.

By identifying these issues early, doctors and patients can avoid transferring embryos unlikely to result in a successful pregnancy, saving time, money, and emotional energy.

How does embryo screening work?

The process is similar for PGT-A (testing for chromosomal issues), PGT-M (testing for single-gene disorders), and PGT-SR (testing for structural rearrangements):

• Creating embryos through IVF: Eggs and sperm are combined in a lab to create embryos.
  
• Biopsy: A few cells are gently taken from the outer layer of a 5- or 6-day-old embryo (blastocyst). The embryo is then vitrified (frozen) and is kept in our containers while waiting for the genetic testing results (that typically takes from 4 to 6 weeks).
• Genetic analysis:
  • For PGT-A: Cells are tested for chromosomal abnormalities, such as missing or extra chromosomes.
  • For PGT-M: Cells are analysed for specific single-gene mutations linked to inherited conditions.
  • For PGT-SR: Cells are checked for structural chromosome issues like translocations or inversions.

• Embryo transfer: Healthy embryos are selected and transferred to the uterus.

This process does not harm the embryo and helps identify the ones most likely to lead to a successful pregnancy.

What happens during the biopsy?

During a biopsy, a specialist uses a fine tool to remove several cells from the trophectoderm, the outer layer of the blastocyst. These cells will become the placenta, not the baby. This method ensures that the embryo’s development is not harmed.

Embryo screening debate

The use of PGT-A in IVF has been a topic of controversy in reproductive medicine.

While other types of preimplantation genetic testing (like PGT-M and PGT-SR) are well-established, some experts have expressed concerns about the widespread promotion of PGT-A to IVF patients without fully explaining its limitations.

The truth is that PGT-A is a powerful tool that can provide valuable insights into chromosomal abnormalities, helping many people achieve successful pregnancies.

However, in regions like the United States, where regulations are limited, some clinics promote it to all IVF patients, even when it is not necessary.

While PGT-A can be especially beneficial for women over 37, who are more likely to produce embryos with chromosomal abnormalities, it is not suitable for everyone.

The fact is, PGT-A is not for everyone. It is most helpful for:

• Women aged 37 or older, as the risk of chromosomal problems increases with age (By age 40, over 50% of embryos may have chromosomal issues)
• People with repeated miscarriages.
• Those who have had failed IVF cycles.
• Couples with known genetic issues or chromosomal problems.

If you are younger and do not have these risk factors, you might not need PGT-A.

What PGT-A does not do

While PGT-A has many benefits, it is not perfect. Here are some limitations:

• • No guarantees: PGT-A can improve the odds, but it cannot promise a pregnancy or a healthy baby.
  • Not for all: PGT-A may not be helpful for younger women or those without risk factors.
  • Limited scope: PGT-A focuses on chromosomal issues and cannot detect all genetic problems.

• Not improve quality: If an embryo is healthy, it is already viable. If it has a genetic issue, testing will not change that. But what PGT-A can do is help you get pregnant faster. More importantly, it gives you and your medical team clearer information to make the best decisions about your treatment and any further testing.

Questions to ask your doctor about embryo screening

If you are thinking about embryo screening, ask your doctor:

• Is embryo screening right for me?
• What are the chances of success for someone my age?
• What are the risks and limits of this test?
• How will embryo screening affect my IVF plan?
• What happens if no embryos pass the test?
• What happens to embryos that are not chosen?

Final thoughts

Embryo screening is an important step for many people going through IVF. It helps identify embryos with chromosomal or genetic issues, improving the chances of a healthy pregnancy.

While it is not needed for everyone, it can make a big difference if you are over 37, have faced repeated miscarriages, failed IVF cycles, or carry genetic conditions.

By understanding how it works and asking the right questions, you can decide if it is the right option for your journey to parenthood.

If you are considering embryo screening as part of your IVF journey, our team at Ferticentro is here to guide and support you. Contact us today to book your appointment and speak with one of our fertility specialists.