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PGT-SR

PGT-SR (Preimplantation Genetic Testing for Structural Rearrangements) is a type of genetic test performed on embryos during in vitro fertilization (IVF) to detect structural chromosomal rearrangements. Structural rearrangements include conditions like translocations, deletions, duplications, and inversions of large segments of chromosomes, which can affect fertility or lead to miscarriages and congenital disabilities.Key aspects of PGT-SR:

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Purpose:

  • To screen embryos for chromosomal abnormalities due to structural rearrangements in one or both parents, which can increase the risk of implantation failure, miscarriage, or offspring with chromosomal imbalances.

Who may need it:

  • Couples with a history of recurrent miscarriages.
  • Individuals with known chromosomal rearrangements (such as balanced translocations).
  • Those who have previously had a child with chromosomal imbalances.

How it works:

  • After embryos are created via IVF, a few cells from each embryo are biopsied. These cells undergo genetic testing to assess whether the embryo has a balanced or unbalanced chromosomal structure. Only embryos with normal or balanced chromosomal structures are typically selected for implantation.

Benefit:

  • Helps reduce the risk of miscarriage and increases the chances of having a healthy baby.
  • Improves pregnancy success rates in individuals or couples with known structural chromosomal issues.

How PGT-SR is Performed:

IVF Procedure:

  • PGT-SR begins with the standard in vitro fertilization (IVF) process. This involves stimulating a woman’s ovaries to produce multiple eggs, retrieving them, and fertilizing them with sperm in a laboratory to create embryos.

Embryo Biopsy:

  • On the fifth or sixth day after fertilization (blastocyst stage), a small number of cells (usually around 5-10) are carefully removed from the outer layer of the embryo, known as the trophectoderm. This biopsy does not harm the embryo’s development and allows the remaining embryo to be frozen for later use.

Genetic Testing:

  • The biopsied cells are analyzed using advanced genetic techniques, such as Next-Generation Sequencing (NGS), array Comparative Genomic Hybridization (aCGH), or Fluorescent In Situ Hybridization (FISH). These tests look for structural rearrangements, such as balanced translocations, duplications, deletions, and inversions in the chromosomes. The goal is to differentiate between embryos with normal, balanced, or unbalanced chromosomal structures.

Selection of Embryos:

  • Only embryos that have normal or balanced chromosomal structures are considered for transfer to the uterus. Embryos with unbalanced chromosomal rearrangements, which can lead to miscarriage or birth defects, are not selected.

Embryo Transfer:

  • Once the genetic results are available, one or more healthy embryos are thawed and transferred into the woman’s uterus. This is usually done in a subsequent IVF cycle after the embryos have been tested and found to be viable.

Follow-Up:

  • A pregnancy test is performed about 10-12 days after the embryo transfer to determine if the implantation was successful. Ongoing prenatal care monitors the pregnancy to ensure the health of the baby.

Success Rates of PGT-SR:

Increased Pregnancy Success:

  • For couples or individuals with structural rearrangements, the use of PGT-SR can significantly increase the chance of having a successful pregnancy and a healthy baby. It helps avoid embryos that may result in miscarriage or serious chromosomal abnormalities.

Decreased Miscarriage Risk:

  • Studies have shown that PGT-SR reduces the risk of miscarriage by allowing only chromosomally balanced embryos to be transferred. For couples with balanced translocations, the risk of miscarriage can drop from as high as 60-70% to 10-20%.

Live Birth Rates:

  • The live birth rate following PGT-SR is dependent on several factors, including maternal age and embryo quality, but is generally improved for couples with chromosomal rearrangements. For individuals with known translocations, the live birth rate with PGT-SR is around 40-50% per embryo transfer, which is comparable to standard IVF for people without chromosomal issues.

Considerations:

  • While PGT-SR greatly improves the chances of a healthy pregnancy for people with structural chromosomal issues, it doesn’t guarantee success. Some embryos may still fail to implant, or pregnancy complications may arise for other reasons unrelated to chromosomal status.

Ethical Considerations:

Selection of Embryos:

  • Since PGT-SR involves selecting which embryos to transfer, some ethical concerns arise around the potential discrimination against embryos with chromosomal abnormalities. For instance, some people question whether this might lead to a preference for embryos with certain traits, raising concerns about eugenics.

Embryo Discarding:

  • Embryos that are found to have unbalanced chromosomal rearrangements are typically discarded, raising concerns for individuals who believe life begins at conception. For these people, discarding embryos could be seen as morally problematic.

Equity and Access:

  • Access to PGT-SR is expensive, meaning it’s primarily available to those who can afford it. This raises concerns about inequity in access to advanced reproductive technologies.

Psychological Impact:

  • The process can be emotionally taxing for couples, especially if PGT-SR reveals that many or all embryos have chromosomal abnormalities. The waiting period for genetic results, as well as the potential need for multiple IVF cycles, can create a significant emotional burden.

Alternative Options to PGT-SR:

Natural Conception with Prenatal Diagnosis:

  • Some couples choose to conceive naturally and rely on prenatal testing (such as amniocentesis or chorionic villus sampling) during pregnancy to check for chromosomal abnormalities. If the fetus is found to have a significant chromosomal abnormality, couples may consider the option of pregnancy termination. This route avoids the high costs and complexities of IVF, but involves making decisions later in pregnancy, which can be emotionally difficult.

Egg or Sperm Donation:

  • If one partner has a known chromosomal rearrangement, couples may opt for donor eggs or sperm. This eliminates the risk of passing on structural chromosomal issues but may carry emotional and identity-related concerns for some couples.

Adoption:

  • Some couples who face challenges with fertility and genetic conditions opt to pursue adoption. Adoption offers the opportunity to become parents without undergoing fertility treatments, but involves its own set of challenges and requirements.

Living with Risk:

  • Some couples choose not to pursue PGT-SR or other forms of genetic testing, accepting the possibility of miscarriage or the birth of a child with chromosomal abnormalities. For some, this choice aligns with personal or religious beliefs.

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