It’s hard to describe the mental and emotional stress incurred by patients undergoing fertility treatment. It’s a long, anxiety-laden process made all the more stressful by the knowledge that there is a high chance it won’t work out.
The treatment journey begins with patients self-administering at-home hormone injections. They must take the right dose at the right time to cause egg release. If the hormones work, the eggs are collected in a clinical setting, and the patient is sent home.
For many patients, what happens next is a mystery, but understanding what goes on in the lab is crucial to understanding why IVF cycles are still more likely to fail than succeed and why success rates vary across clinics. Below are six facts that patients should know before they undergo the IVF process.
1. Embryologists must take more than 30 steps to turn an egg into an embryo.
Every one of these steps is risk prone.
Eggs are very small (0.1 mm), and embryos are highly sensitive to their environment, so each time an embryologist has to manipulate an egg or embryo–whether it’s extracting it from an incubator, transferring it or moving it within a petri dish–they induce risk. Most steps are time sensitive, and every step is temperature and pH sensitive.
Much of the preparation for fertility treatment varies depending on whether a patient needs traditional IVF or intracytoplasmic sperm injection (ICSI). In traditional IVF, embryologists deposit sperm into the same petri dish as the eggs and allow the sperm to select an egg for fertilisation. In ICSI, embryologists inject sperm into the eggs. Nowadays, most patients undergo ICSI if any of the fertility tests hint at an abnormality.
2. Fertility treatments cause unnatural stress for eggs, sperm, and embryos
Embryologists begin to work on the eggs as soon as they arrive in the lab, removing their nurse cells– cells which would usually stay on until after fertilisation– so that they can better see the egg to monitor fertilisation and, for ICSI, increase injection precision.
Embryologists also clean up semen samples, separating out the best sperm. In traditional IVF, embryologists then place a dollop of sperm into a petri dish and wait, hoping that the sperm will find the eggs.
For ICSI, each selected sperm needs its membrane broken, a rupture which would naturally occur in the body when the sperm enters the egg. Embryologists immerse the sperm in a polyvinyl alcohol solution to slow them down; then, they use a pipette to carefully slash the membrane– which breaks naturally during in-body fertilisation– before picking up the sperm for injection with another pipette.
The injection process puts a lot of pressure on the egg: the cytoplasm nearly separates into two pieces as the egg briefly transforms into a dumbbell-like shape. Then, the quick release of the sperm and accompanying withdrawal of the pipette causes the egg to bounce back into its normal shape.
For both ICSI and traditional IVF, the eggs will then remain in the same solution for hours as embryologists wait overnight to discover whether fertilisation occurred. The problem with these treatments is that they don’t actually mimic the human body very well. When cells grow naturally in the human body, they’re in a dynamic environment where small and subtle changes occur constantly. In IVF, embryologists attempt to culture cells and grow embryos within an almost entirely static environment.
2. Fertility treatments cause unnatural stress for eggs, sperm, and embryos
Embryologists begin to work on the eggs as soon as they arrive in the lab, removing their nurse cells– cells which would usually stay on until after fertilisation– so that they can better see the egg to monitor fertilisation and, for ICSI, increase injection precision.
Embryologists also clean up semen samples, separating out the best sperm. In traditional IVF, embryologists then place a dollop of sperm into a petri dish and wait, hoping that the sperm will find the eggs.
For ICSI, each selected sperm needs its membrane broken, a rupture which would naturally occur in the body when the sperm enters the egg. Embryologists immerse the sperm in a polyvinyl alcohol solution to slow them down; then, they use a pipette to carefully slash the membrane– which breaks naturally during in-body fertilisation– before picking up the sperm for injection with another pipette.
The injection process puts a lot of pressure on the egg: the cytoplasm nearly separates into two pieces as the egg briefly transforms into a dumbbell-like shape. Then, the quick release of the sperm and accompanying withdrawal of the pipette causes the egg to bounce back into its normal shape.
For both ICSI and traditional IVF, the eggs will then remain in the same solution for hours as embryologists wait overnight to discover whether fertilisation occurred. The problem with these treatments is that they don’t actually mimic the human body very well. When cells grow naturally in the human body, they’re in a dynamic environment where small and subtle changes occur constantly. In IVF, embryologists attempt to culture cells and grow embryos within an almost entirely static environment.
3. The process for monitoring embryo development varies greatly from lab to lab
When embryologists return to the lab the next morning, they remove the eggs from an incubator and look for signs of fertilisation. They then pipette the fertilised eggs into a new solution, put them back into an incubator, and use time lapse equipment to monitor embryo development.
However, there’s a tremendous amount of variation between IVF clinics when it comes to embryo development and transfer procedures.
Different clinics follow different schools of thought about the best practices for embryo development, but there’s no set standard for the process. Some labs follow a one-step system in which they will monitor the eggs but will not interfere or transfer them until Day 5. Some labs will transfer as early as Day 3, and others will evaluate on Day 3, making the decision then whether to leave them until Day 5.
Embryologists have universal grading scales for evaluating embryo quality for implantation. However, most embryologists rate the embryos using a microscope and without the help of technologies such as computer vision, so there’s still some subjectivity involved. This subjectivity means that even individuals who undergo treatment at the same clinic may have different experiences regarding the evaluation of their embryo quality.
4. Only about 25 percent of eggs retrieved will become an embryo
The number of eggs retrieved depends on a variety of factors, especially age. Clinicians aim to retrieve about eight to ten mature eggs because it balances the risk of failure during the IVF process with the risk of hyperstimulation during the patient’s hormone treatment.
If mistiming occurs during hormone treatment, patients may not release the eggs. However, overstimulation by the hormone treatment leads to an increase in the quantity of eggs released but substantially decreases their quality.
Because fertilisation rates are about 75 percent, collecting eight eggs results in six fertilised ones. During the embryo development cycle, another four to five eggs will usually fail to develop into embryos of the quality needed for transfer. From the eight original eggs, one to two viable embryos will likely develop.
5. The risks don’t end once embryos develop
If a patient is fortunate enough to have two quality embryos, embryologists must decide which one to transfer and which one to save for later use. The rule of thumb is to transfer the best one first and cryopreserve the other.
Cryopreservation requires the use of toxic cryoprotectants. The procedure is intensely time dependent. Embryologists must race against the clock to preserve the embryo by exposing it to three cryoprotectants without subjecting it to high toxicity levels. Labs rely on stopwatches and egg timers because every second of exposure matters.
When cryopreservation is done well, the embryo remains viable for later use without deteriorating in quality. If it’s done poorly, the embryo is no longer viable.
Meanwhile, the transfer embryo goes back to the clinician for implantation, which requires another tricky technique where embryologists load it into a catheter. A clinician then implants the embryo into the uterus. Here comes one of the biggest risks.
If a clinician has problems with the insertion into the uterine cavity, then the embryo could remain in the catheter and outside of an incubator, exposing it to the external environment for a prolonged amount of time. Another risk is that the clinician could also replace the embryo in an unfavourable section of the uterine cavity. As a result, a clinician’s error during implantation can negate an embryologist’s successful lab work.
6. It’s incredible that IVF success rates are as good as they are
After 40 years of clinical practice and research, an IVF cycle is still more likely to fail than succeed. Despite this, more than 8 million babies have been born via IVF and ICSI during that time frame. Considering the amount of risk at each stage of the procedure and the lack of standardisation, automation, and technological progress in IVF labs, that number is an incredible achievement.
This achievement has been made possible because embryologists are extremely well trained and passionate about their work. They know exactly what they’re doing, and they do it as quickly and carefully as they can. In addition, lab directors are stringent about quality assurance when it comes to lab conditions such as temperature, pH levels, cleaning agents, and more.
Nonetheless, standardisation and automation of the IVF process is practically non-existent. It’s in the hands of humans, and, unfortunately, even the best of us can have an off day.
As the global demand for fertility treatment continues to rise, IVF labs need to adopt new technologies to automate parts of the process, remove the risk of human error, increase standardisation, and relieve embryologists of unnecessary stress in an already pressurised job. Without technological advancement in IVF labs, the number of patients seeking treatment will soon outstrip the number of highly trained embryologists capable of turning eggs into embryos. That means that aspiring parents will have to wait even longer– and face even greater risks– before their dream of parenthood can become a reality.