How much can I reduce my children’s chances for a chronic disease with Orchid’s embryo report?

In most cases you can see a significant reduction in risk with Orchid’s embryo report. How much reduction you get really depends on a lot of different factors.

For example, in some situations it is possible to reduce your future child’s chances for breast cancer from 39% to the typical 12% with an embryo report. In other words, your child would go from having a high chance of breast cancer to having a typical chance.

You can get reductions like this if one embryo is “high risk” and the others have a typical risk. These situations can happen but they are not that common.

High risk is defined as being at higher risk than 97% or more of the population. By definition, that is only 3% of people.

But you can still see a big effect on your child’s chances even if no embryos are at high risk. For example, reducing the chance of developing Alzheimer’s by 50% is reasonable with five embryos. As is reducing the chances for schizophrenia by a third with just three.

Over 10% of the population will develop Alzheimer’s which means reducing the risk by a third is significant. The chances would be 7% instead of 10%.

Schizophrenia is a different story as it is not common–reducing risk by one third is taking risk from very low to very, very low. But this can be significant if schizophrenia runs in your family.

Around 0.5% or 1 in 200 people in the U.S. has schizophrenia. But if you or your partner has schizophrenia, your child’s chances of developing the disease go up to 10%. Now reducing risk for schizophrenia is important for your family.

Of these scenarios, the easiest to understand is the first one. If one embryo is at high risk, prioritizing a lower risk embryo for implantation will lower your future child’s chances for developing the disease.

The other cases are not as intuitive. How can we get such big reductions when none of the embryos is at high risk?

A recent study discusses why you can get such reductions and what the key factors are in determining the size of the reduction. We will spend the rest of the guide going over that study. But before we do, we first need to talk about genetic risk scores.

Genetic risk scores quantify risk for chronic diseases

Many people know about “simple” genetic diseases like cystic fibrosis (CF). If both parents are carriers, then each child has a 1 in 4 chance of having CF. In this case carrier parents can genetically test embryos created during IVF and choose to implant those that will not develop CF.

Diseases like schizophrenia or type 2 diabetes are a bit more complicated. Your chances for developing diseases like these depend on both your genetics and your environment. And their genetics are more complicated as well. (Click here to see the list of diseases that Orchid can determine risk for.)

Instead of a single DNA difference (or variant) that causes the disease, you can have over 1 million, each of which makes you a bit more or less likely to develop the disease. Your genetic risk is all of those variants totaled up into a single genetic risk score.

Having a high genetic risk score does not mean you will get the disease. And conversely, having a low genetic risk score does not mean you will be disease-free. A genetic risk score tells you how likely you are to develop a disease, not whether you will develop the disease or not.

A genetic risk score also only tallies up the genetic part of the disease. How big a role a genetic risk score plays in a disease is represented by the liability r². The higher the liability r², the bigger the role genetics plays.

Prioritizing the lowest risk embryo can result in significant risk reduction

A theoretical study came out in 2021 that explored how much you can lower your future child’s chances for a disease if you implant the embryo with the lowest chance for developing a particular disease compared to selecting an embryo at random.

The researchers found that you could get a significant reduction even in cases where you have only 2 or 3 embryos. The three most important parameters for determining how much lower a child’s chances for developing a disease were:

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How common is the disease?

This is represented by K in their model. If K=1, then everyone has the disease, if K=0.5 then half of everyone has it and so on.

How many embryos are available to test?

This is represented by n in their model.

How big a role does the genetic risk score play in the disease risk?

This is that liability r² we talked about earlier. The higher the liability r², the bigger the role the genetic risk score plays in determining the disease. The upper bound for the liability r² for genetic risk scores is thought to be around 0.3 (at least for now).

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The researchers then plotted all three of these parameters against each other to get a feel for how much reduction you would get under different circumstances with different diseases.

In the first graph, they looked at a disease that affects 1% of the population (that is what the K=.01 means):

**Figure 1.** **The relative risk reduction across disease parameters for K=0.01**. The relative risk reduction is defined as (K−P(disease))/K, where K is the disease prevalence, and P(disease) is the probability of the implanted embryo to become affected. Black straight lines correspond to the relative risk reduction achieved when selecting the lowest risk embryo out of n=5. See Lencz et. al. for technical details.

There is a lot going on here but it is simpler than it looks.

Along the x-axis we have the number of embryos from 0-20. As you can see, in all three cases, there is a steep increase in risk reduction up to 5 embryos after which the risk reduction starts to fall off. Note you can still get significant reduction with 2, 3 or 4 embryos.

Next, let’s look at how much of the risk can be explained by the genetic risk score. Here they are showing three possibilities, a liability r² of 0.05, 0.1, and 0.3. Remember, the higher the liability r², the more of the risk the genetic risk score explains.

As expected, you get the biggest effect when the genetic risk score explains more of the genetic risk. With 5 embryos you get up to an 80% reduction in risk if the liability r²=0.3. You also get over a 50% reduction with just two embryos in this case.

Risk reduction falls to around 55% if the liability r²=0.1 and a little over 40% if the liability r²=0.05. In other words, even when the genetic risk score explains a small part of the risk, you can still get more than a 40% reduction in risk with 5 embryos and over a 20% reduction with just two.

Now let’s see what happens when we change how common the disease is:

**Figure 2.The relative risk reduction across disease parameters**. The relative risk reduction is defined as (K−P(disease))/K, where K is the disease prevalence, and P(disease) is the probability of the implanted embryo to become affected. Black straight lines correspond to the relative risk reduction achieved when selecting the lowest risk embryo out of n=5. See Lencz et. al. for technical details.

What we have here is the same data graphed if 1%, 5%, or 20% of the population has the disease. In every case there is a significant reduction in risk but the more common the disease, the lower the risk reduction. For example, if 1% of the population has the disease, then you can get an 80% reduction with 5 embryos and a liability r² of 0.3. With the same number of embryos and liability r² you get a 55% reduction in risk if 20% of the population has the disease.

The bottom line is that in this model, you can get a significant reduction in risk with 5 embryos no matter how common the disease is and how much of the genetic risk is explained by the genetic risk score.

When a smaller reduction is more significant

Looking at the data so far you might think the biggest reductions in risk are with less common diseases. And you’d be right. But it may be that the more significant results are actually with the more common diseases.

To explain, we first need a couple of definitions–relative vs absolute risk reduction. Relative risk reduction is how much risk goes down compared to one group. In this case, how much less the risk is for one embryo compared to another.

Absolute risk reduction is how much your risk for the disease actually goes down. This factors in how common the disease is in the population.

Let’s look at our examples to see why these matter. In the example where 1% of the population has a disease, you can get up to an 80% reduction in disease risk with 5 embryos. Your future child’s chances of developing the disease go from 1% to 0.2%–they are reduced by 0.8%.

Another way to think about this is that the risk of NOT getting the disease goes from 99% to 99.8%. That 80% reduction may seem less meaningful when absolute risk is used.

In the example where 20% of the population has the disease, the 55% reduction in risk means the child has a 9% chance of developing the disease. The risk is reduced by 11%. This is a much larger drop in absolute risk.

It is important to keep both relative and absolute reduction in mind when thinking about embryos.

Family history makes a disease more common for you

Someone with a family history of a disease will be at higher risk of developing a disease. For example, the typical risk for type 1 diabetes is around 0.6%. But if one of your parents has type 1 diabetes, you could have up to a 6% chance of developing it as well. And if both your parents have type 1 diabetes, your chances could go as high as 25%.

With numbers like this, numbers like an 80% reduction in risk starts to look more significant!

When thinking back on absolute risk reduction, that less common disease becomes more common for you. Your absolute risk reduction is more meaningful if a disease runs in your family.

Not just a model

The researchers then took real people’s DNA and simulated potential embryos. (This is similar to what Orchid’s couple report does.)

They looked at two diseases, Crohn’s disease and schizophrenia. They found that with five embryos, they can get around a 45% reduction in risk with both diseases.

And in fact, Orchid has found something similar using a different method.

It isn’t really possible to directly test how well genetic risk scores work with embryos. The tests have not been around long enough and the diseases we test for can take decades to develop.

So we did the next best thing. We asked how well genetic risk scores work to predict disease in siblings.

Remember, embryos are as similar to each other genetically as are siblings. Or to put it another way, you and your siblings were once embryos with the same parents.

Orchid scientists looked in the UK Biobank for sisters who would be at the high end and the low end of a typical range in genetic risk scores for breast cancer for five embryos. They then looked for pairs of these sisters where one sister developed breast cancer and the other did not. They found 170 sisters that fit the bill.

Orchid scientists found that around 3 times as many of the sisters with the higher genetic risk score developed breast cancer compared to the sisters with the lower genetic risk scores. The data is graphed below:

**Figure 3: Breast cancer cases in high risk and low risk sisters**. A total of 170 sister pairs were identified in the UK Biobank where two sisters had a typical difference in breast cancer genetic risk scores that would be reflected between the lowest and the highest risk scores among five embryos and one sister developed breast cancer. The dotted line indicates expected numbers if the genetic risk score was not predictive of breast cancer risk.

If embryos were chosen at random, you would expect around 85 of each risk group would develop breast cancer (the dashed line). Instead, 127 sisters with the higher genetic risk score developed breast cancer while only 43 sisters with the lower genetic risk score did. Around one third of the lower risk sisters developed breast cancer compared to the higher risk sisters.

Reducing risk for your future children

An embryo report from Orchid can significantly lower your future child’s chances for disease. How much reduction depends on how common the disease is, how much of the genetic risk the genetic risk score explains, and how many embryos are available for screening.