Researchers in a 2019 study collected embryos that developed in the uterus and compared their quality to embryos that developed in the lab, finding that uterine-developed embryos performed slightly better.
Determining whether the embryo performs better in the uterus vs the lab is a tricky thing to study. For one, it’s not possible to split an embryo between the lab and the uterus. Unless we clone the embryo. But, ethically, that’s not going to happen. So the next best thing is to compare embryos that develop in the uterus to embryos that develop in the lab.
The problem is how do we determine the quality of an embryo that’s inside the uterus?
Now, before I get into it let me explain a bit about the way this paper is presented. It’s a paper by Munné et al. (2019) and this paper is less about embryo quality in the uterus vs the lab, and is more about finding a way to do PGT-A for those who are doing IUIs. I’m not focusing on this aspect (although it is interesting) – my interest, and probably yours, is to find out how embryos that develop in the uterus compare to embryos that develop in the lab.
🔗 Original studies are referenced in this post or within the linked Remembryo posts.
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So how did they do this?
It’s fairly simple. To generate the uterine-developed embryos, they perform an IUI and let the embryos develop in the uterus.
Some important background information on the study:
- This study consisted of 81 women, 70 of which were egg donors and 11 that were infertile.
- All women had a normal uterine cavity, tubal patency, a BMI <40 kg/m^2, and no history of ovarian cystectomy.
- Egg donors were paired with sperm donors, and the 11 infertility patients were paired with their partners who were in good health and had normal sperm.
- All 81 patients received ovarian stimulation and an IUI with donor or partner sperm, with some contributing more than once, for a total of 134 stimulated IUIs. 20 of these women also had IVF as a control.
About 120 h after the IUI, they had to get the embryos out of the uterus. To do this, they basically perform a reverse embryo transfer. So instead of delivering embryos from the lab to the uterus using a catheter, they use a catheter to lavage, or wash out, the embryos that have grown in the uterus. The “lavage catheter” they use to do this is a bit more intimidating than a conventional catheter, and looks more like a blaster you might find in Star Wars:
But if it gets the job done, so be it!
It has a “fluid supply port” to deliver fluid into the uterus and get the embryos into suspension, and a “collection port” where the fluid (and embryos) can be sucked back up into a container outside the uterus. And yes, this was done under sedation.
So let’s pause for a moment and ask ourselves, now that we have these embryos, how do we measure embryo quality? There’s at least a couple of ways: one way is to determine the embryo grade which depends on the embryo’s expansion, and quality of the ICM and trophectoderm, and another way is to see if the embryo is euploid. Highly graded euploid embryos are the highest quality embryos.
And that’s what they did! Embryos that were recovered from the uterus were graded and biopsied for PGT-A. On the other side of things, they also looked at how embryo’s performed when they were grown in the lab using IVF.
In the IUI group, a total of 136 embryos were collected from 81 women, 72 of which were blasts while the rest were cleavage stage embryos. These cleavage stage embryos were placed in culture and allowed to develop further, where an additional 24 became blast. So in total they had 96 blasts for the uterine-developed embryo group. Yes, this is cheating a bit because they grew some of them in the lab, but the majority of their growth was in the uterus, and it’s what they did!
In the IVF group, a total of 163 blasts were generated and available for PGT-A.
Overall, there were a similar proportion of euploid embryos: 54% from the uterine-developed group were euploid compared to 51% from the IVF lab-developed group. There were no differences in low level mosaics (<40% mosaic), high level mosaic (>40% mosaic), aneuploid, or complex aneuploid embryos.
So generally, in terms of euploidy, embryos that develop in the uterus are similar to embryos that develop in the lab.
In terms of morphology and embryo grading, of the 96 uterine-developed embryos, 74% were graded as “good” (>3BB) and 26% were graded as “poor” (<3BB). About 28% were 4AA or 5AA. In the IVF group (of 178 blasts), 43% were good quality and 57% were poor quality, which was found to be statistically significant.
So, at least in this study, there is a difference in embryo grades from uterine-developed embryos compared to IVF lab-developed embryos. Uterine-developed embryos tend to have higher morphological grades compared to IVF embryos. On the other hand, euploid rates were similar between the groups.
What this really means is hard to say. Does this mean that embryos that develop in the uterus are more likely to succeed compared to those that develop in the lab? If you’re thinking of the whole day 3 vs day 5 argument, the evidence points mostly to day 5 being the better performer.
But if we were to do an IUI, then remove the embryos and choose the best of the cohort – would those embryos have a higher chance than embryos developed in the lab? Good question! All this study tells us is that embryos that develop in the uterus may have higher morphological grades. And this might imply higher success rates, but until this kind of study is actually done, we don’t know.
Reference
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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.
Related posts:
Complete Guide to Embryo Grading and Success Rates
Embryo Arrest
Day 3 or Day 5 embryo transfer?
Study examines potential of PGT-A on poor quality embryos
Fast growing day 3 embryos and their reproductive potential
Transfer of day 7 embryos a viable option
Predicting live birth rates, multiples based on 223,377 transfers
An Italian consensus on key performance indicators for assessing IVF clinics