An IVF cycle should result in the retrieval of mature eggs. The eggs will be allowed to settle for a few hours, and then, that afternoon, fertilized with sperm.
Choosing the best embryo
The next day -day 1- each healthy embryo will still be a single cell, now at the two-Pro-Nucleii (2PN) stage. It is a black-or-white assessment, with little room for interpretation: either you have 2PN embryos, or you don’t. Most couples can expect 80-90% of the mature eggs to turn into 2PN embryos.
Embryos are rarely transferred at this point, because you really can’t tell which embryos of the group will be the most likely to continue to grow properly.
By day 2, the embryo should be 3-4 cells.
By day 3, the lab staff can finally grade the quality of the embryos by looking at them under a microscope. It is not a perfect science, but, it is our standard of care for the moment. The grading is done in two ways:
- We count cells. The ideal embryo has 8, 7, or 6 cells. More than this, and embryos may be growing too fast, using up the energy stored by the egg, and therefore more likely to burn out before they get the chance to implant. Slower than this, and the concern is that the embryos won’t continue to divide at all.
- As cells divide, they leave fragments behind…and too many fragments suggest that cells may not be dividing properly. We grade fragmentation on a 5 point scale, and ideally your embryos will be grade 1 or 2.
A perfect grading system would allow us to spot the ideal embryo every time. We’re working on that*, but in the meantime, to make up for our uncertainty, we usually encourage the transfer of more than one embryo.
For greater specificity in embryo selection , some doctors will encourage you to grow embryos along to day 5.
By day 5, listed in increasing order for pregnancy, we hope to see:
- morula
- cavitating morula
- blastocyst
- hatching blastocyst
A blastocyst will be about twice as likely to result in pregnancy as a morula.
Sometimes we will allow an embryo to grow to day 6 to become a blastocyst, but we won’t go further than that.
The pregnancy rate per blastocyst transferred is certainly higher than per day 3 embryo transferred, because the extra two days has allowed greater selection to occur. But in some ways, it isn’t a fair comparison. Perhaps pregnancy rates would have been just as good transferring 3 embryos on day 3 cf. 2 embryos on day 5.
In fact, doctors and laboratory staff will cite many factors when comparing day 3 to day 5, including patient age (some say >40y should always be day 3), optimization for freezing (historically better on day 3, but perhaps vitrification changes this equation), embryo health, the implantation window, uterine contractility…the debate goes on. Good people can disagree.
My advice would be to accept the day that your particular lab favours. In this way, you will be maximizing your chances as your work to the strengths of your particular group.
* Note that there are newer systems for embryo grading, include proteomics, metabolomics, and other variations in preimplantation genetic screening (PGS). I am happy to write to these topics, but they generally will not be offered in most laboratories in Canada or elsewhere.