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Detecting chromosome rearrangements in embryos

The Foundation for Embryonic Competence (FEC) offers chromosome rearrangement testing for individuals who are carriers of chromosome rearrangements. The testing is designed to detect chromosomal rearrangements in an embryo prior to transfer during an in vitro fertilization (IVF) cycle.

 


Isolating embryos with extra or missing DNA

A chromosome rearrangement refers to chromosomal material that is arranged in a different order than is usual. There are different types of chromosome rearrangements.  For example:

  • Reciprocal translocation, i.e., chromosome material from two different chromosomes switch places (Fig. A)
  • Inversions, i.e., a segment of chromosomal material is “flipped over” within a chromosome (Fig. B)
  • Robertsonian translocation, i.e., two chromosomes are attached together (usually involving chromosomes 13, 14, 15, 21, and 22)

Chromosome rearrangements can be balanced or unbalanced. Chromosome rearrangements are considered balanced if they do not cause a loss or gain of genetic material. Hence, an individual with a balanced chromosome rearrangement has all of the usual chromosomal material, just arranged in a different order.

Embryos without a gain or loss of genetic material have a better chance of resulting in a health pregnancy and baby.

 

reciprocal-translocation-300x300

chromosome-inversion-300x300

 

 

Individuals who are carriers of a balanced rearrangement generally do not experience any health problems related to the chromosome rearrangement; however, they may pass on extra or missing genetic material to their embryos. As a result, these individuals have an increased risk of reproductive problems such as infertility, miscarriage, or the birth of a child with health problems associated with extra or missing genetic material. These health problems may include birth defects and intellectual disability.

The FEC’s chromosome rearrangement testing identifies embryos with extra or missing genetic material. Embryos without a gain or loss of genetic material have a better chance of resulting in a health pregnancy and baby.

Our testing is greater than 98% accurate in screening for chromosome rearrangements and has the ability to detect unbalanced chromosomal material at a much higher resolution than standard aneuploidy screening.1 This allows you and your doctor to make an informed decision about which embryo(s) should be considered for transfer in your IVF cycle.

Talk to your doctor, nurse, or genetic counselor about chromosome rearrangement testing.

 


Reference: 1. Treff NR, Northrop LE, Kasabwala K, Su J, Levy B, Scott RT Jr. Single nucleotide polymorphism microarray-based concurrent screening of 24-chromosome aneuploidy and unbalanced translocations in preimplantation human embryos. Fertil Steril. 2011;95(5):1606-1612.e1-2.

The latest in embryonic testing from the FEC

Chromosome rearrangement testing uses microarray, which is designed to detect large chromosomal imbalances associated with parental chromosomal rearrangements. At the FEC, chromosome rearrangement testing is greater than 98% accurate and detects unbalanced chromosomal material at a much higher resolution than standard aneuploidy screening.1

Chromosome rearrangement testing uses SNP-based array to determine copy number. Genetic material obtained from an embryo biopsy is analyzed on a gene chip that contains specific probes designed to pinpoint different areas along a chromosome. Analysis of this pattern along the chromosome helps determine the number of copies of genetic material corresponding to each location and, as a result, identify deletions and duplications of whole or partial chromosomes. The criterion for clinically significant DNA copy losses or gains in the translocated segments is a dosage change covering the entire predicted unbalanced region with a minimum total size of 5Mb.

Greater than 98% accuracy in screening and ability to detect unbalanced chromosomal material at a much higher resolution than standard aneuploidy screening.1

Truly balanced chromosome rearrangements, polyploidy, deletions or duplications below the resolution criteria stated above and low-level mosaicism or abnormalities involving gains of the Y chromosome (ie, XYY) will not be detected by this analysis.

The chromosome rearrangement testing process

To initiate chromosome rearrangement testing, patients must complete two phases: the validation (work-up) phase and the biopsy phase.

Validation phase

The ability to do preimplantation genetic diagnosis testing for chromosome rearrangements is different for each patient and depends on the location of the specific chromosome breakpoints identified in each patient. For this reason, during the validation phase we request that copies of the karyotypes or cytogenetic reports for both patient and partner, so that the FEC can assess whether the analysis can be done by microarray. The lab will perform a size analysis to ensure our array platform has sufficient coverage for the regions of the chromosomes affected by the rearrangement. Once we are certain that microarray can detect the particular rearrangement, we require bloodwork from the patient and the partner.

Biopsy phase

Once validation is complete, the biopsy phase can begin. Chromosome rearrangement testing using microarray requires a trophectoderm embryonic biopsy. Upon receipt of the biopsy sample, the FEC will test the embryo for extra or missing chromosomal material that could result from the chromosome rearrangement in the family. Additionally, all embryos will receive aneuploidy screening to identify extra or missing chromosomes not related to the familial rearrangement. By the end of this process, you and your patients can make better decisions about which embryos should be considered for IVF transfer based on their genetic makeup. All microarray testing results are available within 3 weeks of samples arriving at the FEC.

 

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Reference: 1. Treff NR, Northrop LE, Kasabwala K, Su J, Levy B, Scott RT Jr. Single nucleotide polymorphism microarray-based concurrent screening of 24-chromosome aneuploidy and unbalanced translocations in preimplantation human embryos. Fertil Steril. 2011;95(5):1606-1612.e1-2.