It’s probably safe to say that if you’re undergoing In Vitro Fertilization (IVF), you know all about embryo development and what it could mean for your chances of pregnancy.
Whether you’re type A or are more of a ‘roll with the punches’ type of gal, whether you’re into science or art, whether you are super detail-oriented or would instead look at the bigger picture, once you’ve undergone a round of IVF and are awaiting the results of the progression of your embryos, you’re pretty invested and knowledgeable on what your results mean.
Still, embryo development is quite technical, and a lot depends on the details – so we’ve put together a quick cheat sheet for you below. We cover everything embryos, from stages of development to the importance of the blastocyst stage to blastocyst rates and more.
Stick around, will you?
Stages of embryo development
Following egg retrieval, which happens on day 0, your eggs will be paired with either donor sperm or your partner’s sperm, and embryologists in the IVF laboratory will wait for fertilization to occur. Each egg represents one cell, and each sperm represents another cell.
Nearly a day after a single sperm is injected into a single egg through a process called Intracytoplasmic Sperm Injection (ICSI), embryologists check for fertilization of that egg. If it has occurred, this is considered day 1. At this point, your egg is no longer an egg, it’s an embryo, and two cells can be seen inside a circular shell.
On day 2, the embryo will have divided into 2-4 cells, so you’ll see about four round cells inside the circular embryo. Most cells that show normal fertilization on day 1 will continue to grow to day 2.
On day 3, the division continues, and you see 6-8 cells inside the embryo. This is called the cleavage stage.
On day 4, the division continues yet again, with more than 8-10 cells visible, although less clearly defined than before, as they begin to fuse together.
On day 5 or 6, the embryo should have at least 70 cells and maybe upwards of 200! This is the all-important blastocyst stage. The inner cell mass (the inside of the embryo that becomes the fetus) and the trophectoderm (the outside layer of the embryo that becomes the placenta) will be distinguishable.
At this point, it is time to either transfer the embryo or have it tested for chromosomal abnormalities and single gene disorders before having it frozen for future transfer when the uterus is ready to receive it.
Why is the blastocyst stage important?
You may have heard that some clinics (although fewer and fewer) will transfer day 3 embryos, two days before the blastocyst stage, so why are we talking about the blastocyst stage?
The blastocyst stage is important because reaching it (not all embryos will develop to the blastocyst stage) is an important milestone for the embryo – a major metabolic hurdle occurs between day 4 and days 5 or 6, or the 8-10 cell stage and the 200-cell stage. Passing this hurdle and reaching the blastocyst stage means the embryo has a much higher chance of implanting inside the woman’s uterus, leading to pregnancy and live birth. Here’s why:
- A blastocyst is more developed than a day 3 embryo, meaning it has already overcome a big developmental obstacle
- A blastocyst contains both an inner cell mass and a trophectoderm, meaning it has cellular material that will likely go on to make the two most vital parts of an ongoing pregnancy – the placenta and the fetus
- Transferring a blastocyst instead of a day 3 embryo mirrors nature – in the womb, an embryo implants inside the endometrium around day 5 of development
- A blastocyst has enough cells to be biopsied and tested for chromosomal abnormalities and single-gene disorders through pre-implantation genetic testing for Aneuploidy (PGT-A) and pre-implantation genetic testing for Monogenic Disorders (PGT-M), respectively. Performing these tests on a day 3 embryo does not yield accurate results, as the embryo has not yet reached the stage of development necessary to produce testable cells.
- What’s more, research conducted at RMA showed that performing a biopsy on day 3 led to lower implantation (pregnancy) rates than performing a biopsy on day 5 or 6.
For these and other reasons, blastocyst embryos are transferred over day 3 embryos in most clinics around the world dedicated to evidence-based practice and the highest standards of care. We have been strictly transferring day 5 or 6 embryos at RMA for many years.
It’s also important to keep in mind that clinics that transfer day 5 embryos aren’t just following the best clinical science – it means they also have excellent embryology laboratories and embryologists who can grow embryos to this stage of development, as it’s not easy and takes years of scientific, laboratory and professional precision and expertise.
Why are PGT-A and PGT-M important?
As mentioned above, both these tests are highly accurate (depending on the embryologist taking the biopsy and the laboratory doing the testing, of course!) in predicting whether an embryo is either genetically normal or euploid and whether the embryo has any single-gene disorders.
Let’s start with PGT-A, which identifies genetically normal and abnormal embryos. Most people have 46 chromosomes in their bodies, the correct number of chromosomes. An embryo containing 46 chromosomes is considered normal or euploid, and an embryo containing fewer or more than 46 chromosomes is considered abnormal or aneuploid.
Most reputable fertility doctors will only transfer normal embryos, as research (much of it done at RMA) shows that abnormal embryos usually do not implant inside the uterus, do not lead to pregnancy, result in miscarriage or, in rare cases, lead to an affected baby, such as one with Down syndrome.
And since abnormal embryos occur both in nature and in the world of IVF for women of all ages (although they are much more common as a woman ages), many women undergoing IVF will opt to have their blastocyst stage embryos tested before transfer to ensure the highest chance of pregnancy and healthy live birth. Again, this is done through PGT-A.
RMA research has shown that PGT-A biopsy and testing are not only not harmful to the baby, but that transferring one tested, normal embryo results in the same pregnancy rates as transferring two untested embryos, but with less risk to patients due to the very low chance of twins with single embryos (twins pose serious risks to mother and babies, including premature delivery.)
Now let’s move on to PGT-M testing. This test is also done through a biopsy taken on day 5 or 6. It tests the embryo for genetic conditions such as cystic fibrosis, Fragile X syndrome, Tay-Sachs, and sickle cell anemia, among others.
While mostly every person alive is a carrier of some genetic disease (often an obscure one), passing this disease to your child is only heightened if your partner is a carrier of the same genetic disorder.
In this case, couples will undergo genetic testing before natural conception or IVF to see if they are carriers of the same disease. If this is the case, couples pursuing IVF can have their embryos tested with PGT-M to see which embryos are unaffected by the condition and then transfer that embryo, providing it is also chromosomally normal (tested through PGT-A). The good news is that one embryo biopsy should be enough for both tests!
And remember, these tests can only be performed on blastocyst stage embryos.
Are day 7 blastocysts better than day 5 or 6 blastocysts?
In some cases, an embryo will only reach the blastocyst stage on day 7. You might be thinking that since we prefer embryos to reach a higher stage of development before the transfer, a day 7 blastocyst might be better, or have higher reproductive potential, than a day 5 or 6 blastocyst.
The opposite is the case. Research performed at RMA shed further light on the fact that day 7 blastocysts have lower rates of euploidy (lower ‘normalcy’ rates) than day 5 or 6 blastocysts. And since about 20 percent of patients will have embryos that reach the blastocyst stage only on day 7 instead of 5 or 6, this is important to know.
The key takeaway here is that reaching the blastocyst stage is crucial to reproductive success and that the rate of development to reach that stage is crucial, too – embryos that develop too slowly have lower success rates. However, they are saved for future use because some still become people!
How many fertilized eggs will make it to the blastocyst stage?
Now we’re getting into the nitty-gritty! We’re glad you asked because these statistics are available. Still, they are highly dependent on two important factors: a woman’s age and the embryology laboratory in which those embryos are grown.
As mentioned earlier, the higher quality of the laboratory, filled with experienced embryologists, the higher the chance of an embryo reaching the blastocyst stage due to the perfect orchestration of factors needed to grow embryos outside the human body (this includes the liquid or culture, the embryos are grown in, the levels of oxygen in that culture, the temperature, and loads more).
But no matter how great a lab, not every egg and sperm combination reaches the blastocyst stage, representing a type of natural selection in human reproduction.
As a general rule of thumb, at RMA New Jersey, which has one of the best embryology labs in the country (as evidenced by the clinic’s high success rates), about 80 percent of eggs will fertilize (day 1 success), and of those, about 30-50 percent will make it to the blastocyst stage (day 5 or 6).
Exactly what percent of fertilized eggs you can expect to reach the blastocyst stage depends most often on the female partner’s age and the particular IVF cycle she has just done.
For example, blastulation rates can vary significantly from cycle to cycle. While some of these variations can be attributed to a change in clinical protocol, most often, it is because of the makeup of the batch of eggs the female body recruits each month in preparation for ovulation, or in the case of IVF, for egg retrieval is different every month. Because every woman has normal and abnormal eggs, each batch will vary.
But in general, the younger a woman, the more of her fertilized eggs will reach blastulation, and the older the woman, the fewer. It’s also important to note that almost all women, no matter the age, will have fertilized eggs that do not blastulate, and this is normal.
So which blastocyst embryos are the best? What’s an embryo grading chart?
Suppose you’re really curious, and you put your embryologist hat on. In that case, you can understand which blastocyst embryos are considered ideal for implantation based on how far an embryo has developed and how it appears under the microscope. But it’s really important to understand the context of embryo grading- it is subjective, and not all embryos with the ‘highest grade’ will result in a live birth. At times, the ‘lower graded’ embryos are actually the ones that develop into people.
While there may be some clinic-to-clinic variability, here’s the gist:
Embryos will be given a grade with three figures – first a number and then two letters. For example, 6CA or 3BC.
The first figure, the number, represents the expansion of the blastocyst, and grades range from 1-to 6, with 6 being the most advanced. Next is the appearance of the inner cell mass, and grades range from A to D, with A being the most favorable. Finally comes the appearance of the trophectoderm, with grades again ranging from A to D, with A being the best score. The goal of grading is to assist with embryo selection when the embryos can no longer be compared to one another, such as when they have already been frozen. It’s just a guide, not a bible, and sometimes just a few hours will result in cellular changes that change the way an embryo appears.
At the end of the day, the fertility world is full of technical information that may be hard to grasp, but understanding the basics (as complicated as they may seem at first) of your treatment can help make it easier. Remember that your whole team includes medical professionals and embryologists who do this every day, and it’s likely to help you more to trust their judgment than to pursue your embryology degree.
And also remember – ‘blast’ is best!