What is an early blastocyst? (And does it matter?)

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Published on: January 3, 2020

Written by Dr. Jennifer Barfield

This year at the annual AETA/CETA meeting in Colorado Springs approximately 100 people signed up for a pre-conference symposium on Advanced ET. One of the three sessions was embryo grading where the audience was asked to stage and grade a variety of embryos from both pictures and videos. This is an exercise that we have done at this meeting in the past and it was interesting to revisit some of the same questions. As in the past, I polled the participants in this session to gauge what level of expertise was in the audience. The breakdown according to years of experience was 0-5 (25%), 6-10 (19%), 11-15 (12%), 16-20 (12%), and 21+ (32%).

For many of the questions the results showed a general consensus, but there was one question for which the distribution was not what I expected. The slide below is the question as it was presented to the audience. The embryo photo is from the IETS Bovine In Vivo Ova Tutorial (see p. 85, IETS members can access the document here https://www.iets.org/pubs_educational.asp).

Across all 3 sessions the answers were A 7%, B 54%, C 34%, D 1%, and E 4% with more disagreement in the first and third session than in the second. See Figure 2. In all sessions more people classified this embryo as an early blastocyst but the number of people who classified this a full blastocyst surprised me. I went back to look at the IETS guide and it stated that as the blastocoele of this embryo is approaching 50% of the embryo that this may be considered a stage 6 embryo.

As someone who often teaches students about classifying and grading embryos, the idea that I may have been instructing people incorrectly troubled me. At Colorado State University, I teach that an early blastocyst is one in which there is a blastocoele cavity present that has not yet filled the perivitelline space of the embryo, even if the blastocoele cavity is larger than 50% of the embryo. A full blastocyst is characterized by a blastocoele cavity that touches the zona pellucida on all sides, except for where it touches the inner cell mass, thus there is no PV space. I wondered if perhaps my interpretation of an early blastocyst is the result of a drift in teaching from an earlier time when these definitions were more strictly and/or widely followed. So I broke down the answers for this question according to years of experience thinking that perhaps practitioners who were learning how to classify embryos when the guidelines were developed would adhere to them more strictly, i.e. more often calling an embryo like this a full blastocyst. That wasn’t the case.

Of the respondents who had over 20 years of experience, 69% classified this embryo as an early blastocyst (24/35) while 52% of the youngest cohort classified this embryo as early (14/27). The only group in which more people called this a blastocyst than an early blastocyst was the 11-15 years group, although there were few respondents overall in this group (8/13 called this a blastocyst). So, I was wrong about the oldest yet wisest of us following the IETS staging guidelines more strictly.

That led me to ask the question, does it even matter if we are all calling this embryo an early blastocyst or a blastocyst? If you are collecting and transferring day 7 in vivo-produced embryos, probably not. The pregnancy rates from transferring grade 1 early blastocysts and grade 1 blastocysts are not significantly different (Hasler, 2001). This slight difference in stage would not change the synchrony of the recipient you choose. It would likely not change how you would cryopreserve this embryo as most in vivo embryos are slow frozen rather than vitrified. From a research standpoint we often make distinctions in stage depending on the question being asked, so it’s possible that inconsistencies in classifying embryos in the field could yield some erroneous conclusions, although I’ll admit I cannot give you any examples of this as I have not scoured the literature for papers where there were significant differences in outcome between early blastocysts and blastocysts for any tested hypothesis.

Outside of simply desiring consistency, the only time when the decision to call it an early blastocyst verses a blastocyst may be important is when grading in vitro-produced embryos. Grading embryos is not only based on the physical appearance of the embryo but also on its stage of development. The slide below was also discussed during the embryo grading sessions in the context of how to incorporate stage into overall embryo grade. In vitro-produced embryos are approximately 1 day more advanced in development than in vivo-produced embryos because of what we consider day 0 in these 2 systems (in vivo day 0 = standing heat, in vitro day 0 = initiation of co-incubation of sperm and oocytes). All morulae would be a day behind in development in an IVP system and given a grade 2 no matter how perfect but early blastocysts sit on the fence. Grading may be an instance where the > or < 50% blastocoele volume distinction matters with embryos with <50% of the volume being the blastocoele cavity being grade 2 and those with >50% volume being blastocoele grade 1. Still, I would be surprised if this fine distinction and difference in grade would translate into a significant difference in pregnancy rates, which is what matters. If anyone has data that may provide insight, please share it! 

So does it matter if we are all calling this small subset of embryos early blastocysts or blastocysts? Probably not, at least not for in-vivo produced embryos. Is it interesting? I think so, particularly from an educational and research perspective. Is it something that we as a community of reproductive practitioners and embryologists should talk more about as we consider developing a separate grading system for in vitro-produced embryos? I’d say yes.

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