Factors associated with euploid survival after thaw

Researchers in a 2021 study examined the factors associated with euploid survival after thaw, highlighting contributors such as day 7 embryos, fully hatched embryos, and poor quality embryos.

Most embryos (and eggs!) are frozen by vitrification these days. Vitrification is a process where the embryo is cooled to very low temperatures quickly to prevent ice crystal formation. Embryos that are vitrified have high survival rates – typically 95%+!

With more and more people performing PGT-A, it isn’t clear what factors can influence thaw survival in biopsied embryos.

Check my complete guide to PGT-A to get more background on PGT-A (aka PGS testing).

Oliva et al. (2021), in their retrospective, single-center study, looked at thaw survival in over 6000 euploid embryos between 2010 and 2019.

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They used 50% as the cut-off for embryo survival after thaw. So if more than 50% of the cells were viable after thawing then it survived. Viability can be estimated based on the % of dark (dead) cells in an embryo. You can see what this would look like from this image by Richter et al. (2016) (I don’t have permission to share the image, so I need to share the link).

Of the 6167 euploid embryos thawed in their study, 2.8% (175) didn’t survive. The study focused on these 175 embryos that didn’t survive and what separated them from the euploid embryos that did survive. So what were the biggest factors associated with reduced euploid thaw survival?

The number of oocytes retrieved. Embryos were less likely to survive in women who had a higher number of eggs collected during their retrieval (19.6 eggs vs 17.5 eggs). This may be due to reduced egg quality with a higher number retrieved.

Day of embryo development at biopsy/freeze. More embryos frozen on Day 7 died (8.2%) compared to embryos frozen on Day 6 (3.9%) or Day 5 (1.9%). Embryos on Day 7 take longer to develop, which is often associated with reduced quality.

Expansion of the embryo at biopsy/freeze. More embryos died with an expansion of “6” (fully hatched blast, 9.0%) compared to a “5” (hatching blast, 2.2%) or a “4” (expanding blast, 1.7%). A fully hatched blastocyst might be more fragile to the biopsy (or freezing) process.

Quality of the ICM at biopsy/freeze. More embryos did not survive with a C quality grade (5.5%) compared to B quality (2.6%) and A quality (2.6%). Lower quality embryos may have a harder time tolerating the biopsy/freezing process.

Number of biopsies performed. More embryos died that were twice biopsied compared to once biopsied (8.2% vs 2.7%). Repeat biopsies might damage the embryo and it may not survive another round of freezing/thawing.

The factors that had no influence on thaw survival:

• Cell number at cleavage stage and % of fragmentation.
• Number of times frozen and thawed.
• Male and female embryos.
• Fertilization method (conventional vs ICSI).
• Ovarian stimulation method (GnRH antagonist, GnRH agonist downregulation, microdose GnRH agonist).

This study found quite a few interesting things! It’s not perfect though. The sample size they’re basing this data from is relatively small (175 euploid embryos that didn’t survive the thaw vs nearly 6000 that did survive). So there could have been some more interesting factors that they didn’t uncover because of the small size.

Still, I wanted to summarize this study because I think it gives some answers to what causes biopsied embryos to die after thaw. You might be tempted to draw conclusions and say that this applies to unbiopsied embryos, but don’t! There might be carryover from the biopsy procedure itself that can influence the embryo’s survival after thaw.

Reference

Oliva, M., Briton-Jones, C., Gounko, D. et al. Factors associated with vitrification-warming survival in 6167 euploid blastocysts. J Assist Reprod Genet 38, 2671–2678 (2021). https://doi.org/10.1007/s10815-021-02284-0

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About Embryoman

Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.

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