WHAT IS IT?

Preimplantation genetic testing for structural rearrangements (PGT-SR), previously referred to as chromosomal preimplantation genetic diagnosis (PGD), is a genetic test that assesses the chromosomal make-up of an embryo using an embryo biopsy sample. By doing this, euploid or balanced embryos can be prioritized for transfer to maximize your chances of a healthy pregnancy and drastically reduce the risks typically present for individuals who carry a chromosomal structural rearrangement.

WHO IS IT FOR?

PGT-SR is meant for any individual who carries a chromosomal structural rearrangement and thus is at high risk to have a miscarriage or a child with a chromosomal genetic disorder. The main types of structural rearrangements are reciprocal translocations, Robertsonian translocations, and inversions.

Reciprocal translocations occur when two distinct chromosomes exchange large segments of DNA, leading to derivative chromosomes that contain DNA from two different chromosome sources.

Robertsonian translocations are similar to reciprocal translocations in that there is an atypical exchange of DNA between different chromosomes, but in this case only acrocentric chromosomes are involved--these are chromosomes where the majority of the DNA is located on one section of the chromosome (referred to as the q arm) while the other section (the p arm) is very small and does not contain essential genetic material.

Inversions occur when there are two breaks within a single chromosome and the separated segment is reversed before it is reinserted within the chromosome. There are two types of inversions: pericentric and paracentric.

HOW DOES IT WORK?

If you decide to undergo IVF with PGT-SR due to a chromosomal rearrangement carried by you and/or your partner, the process is simple.

1

Your doctor’s office will send your genetic testing records to our laboratory before you begin your IVF cycle. We will review these records and ensure that our PGT-SR test can identify any chromosomal abnormalities in your embryos related to the structural rearrangement. We will notify your doctor’s office regarding whether or not we can accept your samples for testing within a few days.*

2

If the case is accepted, IVF will then be performed at your doctor’s laboratory to produce embryos.

3

Once your embryos reach the blastocyst stage (typically at Day 5 or Day 6 of development), an embryologist will biopsy a few cells from each embryo’s trophectoderm, the part of the embryo that goes on to form the placenta. Your embryos will be cryopreserved and stored safely at your doctor’s laboratory.

4

The embryo biopsy samples are sent to our genetic testing laboratory, where we use next generation sequencing (NGS) technology to analyze the DNA for aneuploidies related to the specific structural rearrangement of interest as well as those occurring sporadically.

5

Once testing is complete --within 1-2 weeks --a report is sent to your doctor’s office detailing the results of each embryo biopsy. Your doctor can then use those results to determine which embryos are suitable for transfer.

*Not all structural rearrangements can be detected with NGS, the technology our lab utilizes for PGT-SR, so the initial case review is very important to ensure NGS-based PGT-SR is the right test for you.

WHAT RESULTS CAN I EXPECT?

There are three types of results you can receive: 1) euploid, 2) aneuploid, or 3) mosaic.

EUPLOID

“Euploid” indicates that no chromosome abnormalities were identified in the biopsy sample. Euploid embryos have the highest chance of leading to a successful pregnancy and healthy baby. Thus, euploid embryos are the ones prioritized for transfer.**

ANEUPLOID

“Aneuploid” indicates that one or more chromosome abnormalities was identified throughout the biopsy sample. Aneuploidies that are expected to be related to the structural rearrangement are highlighted as such in the report. Aneuploid embryos are unlikely to result in a successful pregnancy or can lead to miscarriage or the birth of a child with a serious genetic disorder. Thus, the transfer of aneuploid embryos is not recommended.

MOSAIC

“Mosaic” indicates that one or more chromosome abnormalities was identified, but only in a portion of the biopsy sample--indicating that there is a mix of euploid and aneuploid cells in the biopsy due to an error in DNA division that occurred post-fertilization. While this result would not be expected for the segments involved in a structural rearrangement since those would be inherited from the egg or sperm directly, mosaic results can occur for sporadic aneuploidy. Mosaic embryos are known to implant less often and miscarry more often than euploid embryos, but they have led to the birth of apparently healthy children. There is a risk that a mosaic embryo could lead to the birth of a child with a genetic condition, though this risk appears to be small based on existing data. Given these risks, the transfer of mosaic embryos can be considered, though euploid embryos are typically prioritized. Approximately 15% of all samples are categorized as mosaic.

Though rare (<2% of samples), the results of PGT-SR can sometimes be inconclusive. This can occur due to a variety of reasons, including poor embryo or cell quality, degraded DNA, or technical failure. When this occurs, a re-biopsy of the embryo can be considered, as a second sample returns a conclusive result the vast majority of the time. However, the option of re-biopsy should be discussed in detail with your doctor and/or the IVF lab’s embryologist(s) to determine if it is a recommended procedure.

It is important to note that PGT-SR is not meant to replace standard prenatal care. Should a transfer be successful, you are encouraged to consider any prenatal genetic testing options presented to you by your OB/GYN.

**Existing NGS technology cannot differentiate between a truly euploid sample and a sample with a balanced rearrangement.