Orchid offers advanced genetic testing for couples who want their child to have the best shot of a healthy life. We talked with IVF laboratory director Dr. Barry Behr, PhD, HCLD, to demystify what happens in the embryology lab and answer some common questions patients have about the embryo creation process.
- What procedures trained embryologists do
- How can I be sure these embryos are mine and that the right embryo is transferred?
- A week in the life of an embryo
Chapter 1: What procedures trained embryologists do
Embryologists are highly-trained specialists that perform procedures to create embryos. Dr. Behr tells us, embryologists are the “custodians of patient's gametes and embryos… it is a highly coveted job, to be able to have a hand in creating life or assisting in creating life.”
There are five main areas embryologists are involved in:
- Egg retrieval — from the embryologist’s perspective, this involves isolating the eggs from the follicular fluid collected from the patient’s egg retrieval procedure.
- Egg fertilization — the next step is getting the sperm and egg together to achieve fertilization and make an embryo. This can be done either by an embryologist directly injecting a sperm cell into an egg or mixing sperm with each egg in a dish for conventional fertilization.
- Growing embryos — embryos grow in special conditions that mimic the environment found in a woman’s fallopian tubes. Elements like temperature, pH, humidity, gas levels and nutrients in the growth media are meticulously controlled to provide an ideal growth environment for the embryos.
- Embryo sampling and freezing — for patients electing to do embryo genetic testing, a few cells are carefully sampled by an embryologist from each embryo. Embryos are then frozen and kept safely in the IVF lab.
- Embryo thawing and transfer — during the embryo transfer procedure, an embryologist loads a catheter (a long, thin, flexible straw) with an embryo and hands it to the physician to transfer the embryo to the patient’s uterus. Today, most embryo transfers are from previously frozen embryos that are thawed right before transfer.
These procedures require a high degree of precision by the embryologist and can significantly impact IVF treatment success for patients. According to Dr. Behr, “one thing is for certain today is that we cannot make a “bad” embryo good. But we certainly can make a “good” embryo bad by poor technology, poor treatment, lack of oversight, and not taking this huge honor that we have to manage and handle gametes seriously. So the most important thing is really the people behind the scenes, the embryologist, the facility, and ensuring that we're not taking any shortcuts.”
Dr. Behr talks through some examples of high-quality practices in the lab to ensure things go smoothly:
Embryo sampling is like a “haircut” for the embryo
“The embryo sampling should be very much like a haircut, where the embryo may look slightly different after the haircut, but it's not impaired in any way,” says Dr. Behr.
During embryo sampling, the embryologist uses a special microscope equipped with micro-manipulators. Typically, the embryo is held on one side with a holding pipette, which creates a little bit of suction to anchor the embryo in place. On the other side, another manipulator uses a pipette to grab onto three to five cells that are already hanging out of the embryo’s shell. With the embryo held still, a laser performs the “haircut” to separate and remove those three to five cells.
This is a safe way to analyze the genetic information of an embryo. “It's very important to appreciate that in embryo sampling, we're removing cells from the trophectoderm that become the placenta, not from the inner cell mass that becomes the baby. We expect the genetic information we get from the trophectoderm to reflect the same information you would get from the inner cell mass or the fetal component,” Dr. Behr tells us.
Frozen embryos are kept safe by “OCD-like” monitoring
After embryos are created, they are often kept frozen in a tank maintained at liquid nitrogen temperature for future use. Keeping patients’ frozen embryos safe is one of the most important things the IVF lab does, and a lot of resources are put into ensuring the safety of all embryos.
Dr. Behr shares with us the safety measures the top IVF lab he runs has put into place:
Monitor the temperature of the tanks
A good tank monitoring plan ensures that the conditions for embryo storage are maintained in the safe zone all the time. Dr. Behr’s and his team’s IVF lab uses real-time digital monitors — “I can tell you the temperature inside every one of my tanks right now, real-time. I can also tell you the temperature outside my tank,” says Dr. Behr.
You might think, “why does this matter?” The temperature differential between the inside and outside of the tank is important because the tanks are designed to insulate the inside from the outside. If that vacuum or insulation is breached, the outside of the tank will start to get very cold very quickly. According to Dr. Behr, “the first sign of a problem would be that the outside of my tank is starting to get cold. And that will occur way before the temperature starts getting warm inside.” If any of the tanks go above the threshold temperature for safety, an alarm system will go off and be promptly addressed.
Inspect each tank daily
In addition to remote monitoring, tanks are also physically checked daily. “We physically measure and inspect the tanks every day, seven days a week. Every day, no excuse, no exception. It's like you have your gas gauge in your car. But you're opening the door, and you're sticking a stick inside just to make sure that your gas gauge is actually not faulty,” says Dr. Behr.
Maintain backup tanks at the ready
Dr. Behr and his lab team has set up empty backup tanks maintained at liquid nitrogen temperature to quickly and safely move samples into a backup tank in the unlikely event of a tank malfunction.
A tank failure has never happened at this IVF lab. Still, it’s a procedure put into place to accommodate for the worst-case scenario — “I would say it’s virtually impossible. But again, we cannot take a chance. We want to be prepared for any kind of condition,” Dr. Behr explains.
Chapter 2: How can I be sure these embryos are mine and that the right embryo is transferred?
Two embryologists witness every step along the way
A cornerstone of an embryology lab is ensuring that every step of the process is witnessed. This means the right egg goes with the right sperm, and the right embryo is implanted in the patient. IVF labs often implement a “double ID” system.
At various checkpoints throughout the embryo creation process, two embryologists witness each step. This double ID system is done any time eggs, sperm, or embryos are moved from one dish to another, taken out of storage, or transferred into a patient. Dr. Behr’s leading IVF lab is also soon to employ a digital tracking system for frozen egg and embryo samples using an automated software platform, TMRW.
How embryos are labeled and stored
When embryos are sampled for genetic testing, each of the tubes that contain a sample of a few cells is carefully labeled to ensure the samples correspond to the right embryo. Those tubes are shipped to the genetic testing laboratory while the embryos remain safely in the IVF lab.
To store frozen embryos, embryologists label each embryo as #1, #2, #3, etc. While each of the embryos are individually frozen, all of the sibling embryos from one patient are stored together.
You can think of your embryos being stored like a box of popsicle sticks, each with a unique flavor. While each of the popsicles are individually wrapped, they are all kept in the same box. When you need to take them out from the freezer, you would take the box out and see each one clearly labeled.
The bottom line is: when embryologists return to thaw the embryos for transfer, they are confident that it’s not just the right patient’s embryo, but the right embryo based on the genetic test results.
Chapter 3: A week in the life of an embryo
Dr. Behr walks us through what embryo development looks like and how embryologists take care of the embryos as they’re growing day by day in the lab.
Day 1: fertilization check
The first "success" in the IVF lab is the presence of fertilized eggs. This measurement tells embryologists there are potentially viable eggs that have been fertilized that can now progress onto an embryo. At this point, the fertilized eggs are called a “zygote” or a “two pronuclei (2PN) oocyte.”
Day 1 or 3: morphology check and assisted hatching procedure
At this IVF lab, the approach to growing embryos is to leave the embryo undisturbed as much as possible. “It's just like baking a cake. It doesn't help the cake to check it every 15 minutes,” says Dr. Behr.
What that means is that after the initial fertilization check on day 1, the next time an embryologist would look at the embryo would be on day 5.
If the patient plans to do genetic testing on their embryos, a commonly done procedure is something called “assisted hatching.” This is when the embryologist makes a small hole in the shell that surrounds the embryo to encourage hatching. The purpose of this procedure is to make the embryo sampling easier for the embryologist to perform since some cells will be “waving at us, hanging out of the hole that we created earlier.”
Dr. Behr explains that their approach is to perform assisted hatching on day 1, at the same time fertilization check happens. Some other IVF labs prefer to do assisted hatching on day 3 while checking how the embryos are growing.
Day 5 to 7: blastocyst stage
The last stage for the embryo to reach is the blastocyst stage. This is when embryos are typically sampled for genetic testing.
One important thing to appreciate about IVF is that the process of embryo creation acts much like a funnel and that along the way, some eggs and embryos get lost naturally through the process. As Dr. Behr puts it, “it’s a process of diminishing returns, meaning as you go down the line, the numbers decrease. In a good IVF lab with high-quality embryo growing conditions, one should expect about half of your fertilized eggs to make it to usable blastocysts.”
However, predicted averages can only tell you so much. “We’re not machines; we’re biological organisms, each a little bit different,” Dr. Behr adds, “the combination of everyone's egg and sperm is a little bit different each time. So we can't prognosticate exactly what you're going to get on day 5,” or by the end of the IVF process.
How much does embryo morphology matter? “You can’t always judge a book by its cover.”
“Although we highly prefer and desire perfect or good morphology, I know of hundreds, if not thousands, of perfect babies born from "poor" morphology embryos,” Dr. Behr says. Patients often ask what their embryos’ morphology grading means and how much they should read into it.
According to Dr. Behr, “morphology is just a beauty contest at this point. In the absence of any other information, we do select the prettiest embryos for transfer. But certainly, not everyone has perfect looking embryos, and we don't always have that luxury.”
The bottom line of morphology is that it can be one factor. But it is still subjective in terms of how it correlates with successful pregnancy outcomes.
What does the future of embryo testing look like?
Over the years, Dr. Behr has seen the rapid evolution of genetic testing on embryos firsthand. “The advent of the genetic revolution allows us to optimize the outcomes for patients through better embryo selection for viability and, hopefully, soon through better embryo selection for a greater quality of life.”
Such advanced technologies would allow future parents a glimpse of not only the viability of their embryos, but also whether their future child could have a successful health profile going forward. After all, as Dr. Behr says, “these little embryos may make little human beings and onto productive citizens, wherever they may be.”
- Embryologists are highly trained caretakers of your embryos as they grow and develop.
- There are checkpoints implemented in the lab to ensure proper identification and labeling every step of the way.
- The embryology lab uses the latest and most advanced tools to perform procedures and keep frozen embryos safe.