What is embryo compaction?

This post goes over “embryo compaction,” or “embryo collapse,” which occurs naturally as a blastocyst develops and after thawing a blastocyst, and how this relates to success rates.

A “compacted” embryo is what embryologists call a blastocyst that is squished up into a tight wad of cells. It can also be referred to as a “collapsed” or “contracted” blastocyst. When a blastocyst looks like this, it can be hard to identify the ICM and trophectoderm structures that are used to grade the blastocyst.

For more background on blastocysts, check out my complete guide to embryo grading and success rates.

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Embryo compaction is a natural part of development

So what causes blastocysts to become compacted?

Blastocysts contain a cavity called a “blastocoel” that’s filled with water, and when they lose this water the blastocyst deflates like a balloon would — causing it to become compacted/collapsed. Sticking with this balloon analogy, the outer surface of a blastocyst is the trophectoderm, similar to how the outer layer of a balloon is made of rubber. Inside the trophectoderm is the blastocoel, a fluid-filled cavity, much like the water inside a water balloon. When the blastocoel loses water, the blastocyst shrinks and collapses, just like a water balloon would if you let the water out.

As part of their normal development, embryos go through rounds of expansion and contraction. They take up water and get bigger (expand) until they can’t anymore and they begin to deflate (collapse). These cycles of expanding/contracting might help to break down the zona so they can hatch and implant (Kovacic 2017).

This system is manipulated in the IVF lab to artificially collapse a blastocyst before freezing.

Why are embryos artificially compacted or collapsed?

When freezing, water can form sharp ice crystals that can puncture the cells of the embryo, which isn’t good! Darwish 2016 found that embryos that were artificially collapsed before freezing had:

• higher survival rates after thaw (97.28% vs 74.90%)
• higher clinical pregnancy rates (67.21% vs 39.12%)
• and higher implantation rates (41.08% vs 24.48%)

Blastocysts can be collapsed in the lab in different ways, but usually a laser pulse is used to make a tiny hole between two trophectoderm cells for the water to escape. After collapsing, the embryo deflates and is ready for freezing within a few minutes. Here’s a video of an embryo that is collapsing after pulsing with a laser:

After thawing, an embryo is usually still compacted and needs time to take up water and re-expand. That’s why blastocysts photographed shortly after thawing in the lab usually look compacted. Timing can vary between labs, but embryologists often take a picture right after thawing, before the embryo has had much time to re-expand. If another photo is taken closer to transfer, the embryo might look more expanded by then.

After an embryo collapses, it needs to re-expand

In order to re-expand, the hole made by the laser needs to be closed so the blastocoel can take up and retain water. The process of sealing the hole and re-expanding can happen quickly, but it can take longer in some cases, possibly due to damage from freezing or the trophectoderm layer is compromised in some way (Kovacic 2017).

Now let’s look at a few videos, all from Iwasawa et al. (2019, CC by 4.0).

1) Here’s a collapsed blastocyst that re-expands and hatches:

2) Here’s a video of a collapsed blastocyst that re-expands, then collapses, then re-expands, etc. without actually hatching. This is sometimes called spontaneous collapse. You can imagine that hatching from the zona requires a certain amount of force, and embryos that fail to meet this threshold won’t hatch but will continue to collapse.

3) Here’s a video of a collapsed blastocyst that can’t re-expand, despite its best efforts:

Embryos that don’t re-expand quickly, or don’t re-expand at all, might have a lower chance of success (discussed in detail below). Poor quality blastocysts and day 7 blastocysts are less likely to re-expand after thaw (Cimadomo et al. 2018). Whether the embryo is euploid also seems to have an impact — Huang et al. (2019) showed that euploid embryos (after PGT-A) re-expanded 52.6% more quickly than aneuploid embryos.

Embryologists can use tools to measure the % re-expansion:

Multiple studies have shown that re-expansion is linked to improved IVF success rates:

• Caprell 2019: women who transferred embryos that had fully re-expanded between thaw and transfer had a higher chance of pregnancy.
• Kinzer 2011: embryos that re-expanded more than 40% within two hours post thaw had a higher chance of implanting (~36% implantation vs ~10%).
• Ahlstrom 2013 stated that “degree of re-expansion is the most significant post-thaw morphological predictor of live birth” with live birth rates increasing from 27.8% (at 70% re-expansion) to 51.2% (at 100% re-expansion).
• Hershko-Klement et al. (2022) measured blastocyst re-expansion two hours after thaw, finding that embryos that didn’t re-expand had the lowest clinical pregnancy rate (18.9%), with embryos that expanded slightly or more having higher rates (27%, 51.2%).
• Shu et al. (2009) compared pregnancy outcomes for blastocysts with <50% or ≥50% re-expansion 2-4 hours after thaw, finding that embryos with ≥50% re-expansion had higher pregnancy rates (37.1% vs 16.8%).
• Ito et al. (2023) found that blastocysts with ≥90% re-expansion after 9-11 minutes post-thaw had higher live birth rates (26.1% vs 10.2%)

A more recent study also evaluated blastocysts 9-11 minutes after thaw (with a ≥90.2% re-expansion threshold) and showed that these embryos had a higher chance of live birth (28.6% vs 14.1%). The authors also noted that evaluating embryos for quick re-expansion 9-11 minutes after thaw can be useful for deciding if another embryo should be thawed. I discuss this study in detail in my post Blastocysts that re-expand quickly after thaw linked to higher IVF success rates.

 

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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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