Transfer of day 7 embryos a viable option

Researchers in a 2022 study showed that extending embryo culture to day 7 increases the number of useable blastocysts, particularly for older women.

After insemination, a fertilized egg becomes a blastocyst in about 5 days. In some cases, this can take longer, and most IVF clinics will culture embryos to day 6. Some clinics may extend culture further to day 7, although this isn’t common.

A recent review and meta-analysis by Corti et al. (2021) found that day 7 embryos had reduced clinical pregnancies, live birth rates, and euploidy rates compared to day 5 and 6 embryos. Despite this, they concluded that “the decision to discard blastocysts that develop beyond day 6 is not reasonable”, as these embryos still represented a chance at a baby.

Giulia et al. (2022) wanted to add to these studies and compared the outcomes of 1966 blastocysts (from 681 patients) that were tested for PGT-A at their Italian IVF center between 2013 and 2020. The average age was 38.3.

For more background on this post, you can check my Complete Guide to Embryo Grading and Success Rates and my Complete guide to PGT-A (PGS testing).

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In this study they defined a Day 7 embryo as any blastocyst that developed after 144 hours post-ICSI (this equals 6 days). They defined it in this way because embryos are checked, for the most part, the morning of and any embryo that isn’t eligible for biopsy is put back in the incubator until the following morning. Here are the different times for reference:

• 120 h = day 5
• 120 – 144 h = day 6
• 144 – 168 h = day 7
• >168 h = day 8

The embryos were cultured using time-lapse incubators and checked every 12 hours to see if the embryos were eligible for biopsy (around an expansion of “4”, ie. a 4BB or 4AB). Note that in my summary of this article I am combining the 12 hour data to present it as a single 24-hour day, which I think makes more sense for the people reading this, however in the original paper it is presented in 12 hour periods from 120 h to 168 h.

Most blastocysts were biopsied before day 7 (85.4%), and as you can see below, embryos that took longer to develop to a “4” were more likely to be aneuploid.

In this study, embryos were not discarded due to low quality, and they actually did an analysis on the quality of day 7 embryos. They found that day 7 blastocysts were more likely to be poor quality (defined as a CC, CB or BC) compared to excellent quality (AA).

They also found that euploids that took longer to develop were more likely to miscarry and had a lower live birth rate.

Women who had blastocysts after 7 days tended to be older (40.3 years vs 38.7 years) and had fewer mature oocytes after retrieval (7.9 vs 9.5). This suggests that women with a worse prognosis (older and with retrieved less mature oocytes) are more likely to benefit from day 7 culture.

The authors also compiled their data to compare how clinical outcomes would change in their 681 patients with or without culture to day 7. Without culturing to day 7 there would be a:

• 10.6% reduction in patients with blastocysts.
• 7.3% reduction in patients with euploids
• 4.4% reduction in patients with a live birth
• 13.7% reduction in patients with extra euploids (who didn’t get pregnant after transfer)
• 5.2% reduction in patients with extra euploids (who had a live birth)

An interesting observation in this study was that embryos that developed to blast on day 7 didn’t take longer to expand once expansion started. Once expansion started, it took about the same amount of time as day 5 or 6 embryos to reach a size that was eligible for biopsy (about a day). The difference was that day 7 embryos needed an extra day to start this process.

Unfortunately these authors didn’t follow up with patients to determine obstetric and perinatal outcomes. However Huang et al. (2020) found no difference in gestational age, birth weights, complications, and other outcomes among nearly 100 births from day 7 embryos compared to day 5 or 6.

Although day 7 euploids have a reduced live birth rate compared to day 5 or 6 euploids, this study shows that these embryos represent a viable option for transfer, particularly for those of advanced age or without many embryos to work with.

Reference

Cimadomo D, Soscia D, Casciani V, Innocenti F, Trio S, Chiappetta V, Albricci L, Maggiulli R, Erlich I, Ben-Meir A, Har-Vardi I, Vaiarelli A, Ubaldi FM, Rienzi L. How slow is too slow? A comprehensive portrait of Day 7 blastocysts and their clinical value standardized through artificial intelligence. Hum Reprod. 2022 May 30;37(6):1134-1147. doi: 10.1093/humrep/deac080. PMID: 35459944.

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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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