How Does Screening my Frozen Embryos Work

Using Orchid requires a small sample of cells to be collected from an embryo - this is called a biopsy. If your embryo is frozen it will need to be thawed, and a sample of cells can be taken for additional genetic testing. The embryo then needs to be re-frozen while the testing on those cells is underway.

Why Consider Testing Frozen Embryos

1. You did not choose to have embryo screening completed previously 

• You may have chosen to not perform any screening at the time the embryos were previously created and frozen. 

2. Inconclusive Initial Results

• Sometimes an embryo’s original biopsy did not provide  an informative result. This can happen for many reasons including:
  • The sample was not successfully transferred to the test tube 
  • The genetic material was poor quality 
  • Unknown reasons. These embryos are typically reported as having an “Indeterminate” result and another sample (rebiopsy) can help to clarify an embryo’s result to inform decisions for transfer.

3. New Genetic Information 

• Occasionally parents may learn about a new genetic condition in themselves or their family members after they created and did basic PGT on their embryos. This can lead to stress and anxiety as not only are they potentially navigating new health information for themselves, but they may be left wondering “what about my embryos?” A rebiopsy may be available to perform targeted testing for the new genetic condition through a process called PGT-M - this can help parents learn which of their remaining embryos might be at risk for the condition and help in making informed decisions about embryo selection

4. More testing becomes available

• Because genetics is such a rapidly evolving field, its possible there are new forms of PGT that might not have been readily available at the time of original biopsy. Traditional embryo screening essentially counts the number of chromosomes through PGT-A, whereas newer options may provide additional information on single gene disorders (monogenic screening), complex multifactorial conditions (PGT-P), and whole genome sequencing (PGT-WGS). Parents may wish to consider a rebiopsy of their embryos to access these services.

What is the Process to Test a Frozen Embryo

1. Embryo Thawing: Carefully thaw the previously biopsied and frozen embryo
   1. Embryos are typically frozen after being allowed to grow and develop for 5-7 days after initially being created. At this point they are called a ‘blastocyst’ 
2. Cell Sampling: Remove a small number of cells from the trophectoderm
   1. The trophectoderm refers to the outer ring of cells in a blastocyst that will eventually form the placenta, not the baby
3. Genetic Analysis: The biopsy is sent to the PGT lab where the genetic testing is conducted

What are the Risks and Considerations

Procedural Risks

• Minor risk of embryo damage during the biopsy - generally speaking, the embryo biopsy procedure is associated with minimal risk with most clinics quoting a 1-5% risk for the embryo to stop growing after biopsy. You can read more here.
• Potential reduction in embryo viability - most studies suggest that embryo survival rates after rebiopsy are very high, with this study finding a 96.7% survival rate.
  • We spoke with the renowned ‘Egg Whisperer’ Dr. Aimee Eyvazzadeh who shared further insights. Dr. Aimee states when considering a rebiopsy, the embryo quality and grading are key considerations. While each center will likely quote their own risks, in her experience, high quality embryos typically have minimal risk for damage during the procedure, while low-medium quality embryos can see up to a 15% reduction in implantation rates. Additionally, the vast majority (>99%) of embryos typically survive the initial thaw, with ~5% of embryos being lost during overnight culture that might be required for rebiopsy. 

Genetic Considerations

• Regardless of what type of testing you’re considering on a rebiopsy, its important to keep in mind that not all genetic conditions can be detected. While advances in embryo screening like PGT-WGS offer unprecedented amounts of genetic information, there is no single test that screens for every disease and a successful outcome can never be guaranteed. 
• When considering the rebiopsy of embryos that have already completed some level of genetic screening, there is also a possibility of receiving different results on the second test. This can occur because of differences in the tests themselves (ie, how much and what they are screening for), as well as differences throughout the embryo. Since each biopsy relies on a different cluster of cells for the testing, it is possible that the genetics within those cells might be different (ie some may appear to have normal chromosomes, while others may have abnormal) - this is commonly referred to as mosaicism. Its important to discuss with your physician how these new, possibly different, results may impact embryo selection and transfer decisions.

So…should I rebiopsy my embryo(s)

This is ultimately a deeply personal decision to be made between you and your fertility clinic. While it is possible from a technical standpoint, there are numerous considerations to take into account including:

• What specific tests will be performed?
• What are the potential outcomes?
• How will results impact embryo selection?
• What are the success rates?

Its important to balance the benefits and risks associated with the rebiopsy specific to your family’s situation. Discussing options with your fertility specialist can help you to understand what may be possible at your clinic, and Orchid’s genetic counseling team is available to answer any questions you might have about PGT-WGS!

‍

References: 

‍

1. Danilo Cimadomo, Laura Rienzi, Valeria Romanelli, Erminia Alviggi, Paolo Emanuele Levi-Setti, Elena Albani, Ludovica Dusi, Letizia Papini, Claudia Livi, Francesca Benini, Antonella Smeraldi, Cristina Patassini, Filippo Maria Ubaldi, Antonio Capalbo, Inconclusive chromosomal assessment after blastocyst biopsy: prevalence, causative factors and outcomes after re-biopsy and re-vitrification. A multicenter experience, Human Reproduction, Volume 33, Issue 10, October 2018, Pages 1839–1846, https://doi.org/10.1093/humrep/dey282

‍