Dr. Robyn Murphy ND

Dr Robyn Murphy (RM): When discussing preconception or the period before fertilisation, it’s roughly three months that the egg and sperm are maturing. We know that lifestyle and diet have an impact on that process. That’s where we do our upfront work. We see that it will impact the timing of conception, the health of embryos when we’re doing IVF and the health of the pregnancy.

In fertility, you’ll see a lot of different types of genetic tests that are offered. There are chromosomal tests where they look at the number of chromosomes. Normally, we have 23 pairs, so we should have 46. But in certain diseases, you’ll see the wrong number. And that can lead to conditions like Down syndrome. The embryo can be tested, but we can do nothing once the chromosomes have divided and made up that cell.

There’s also pre-genetic testing that’s done for different types of genetic diseases. Again, we can do nothing with that information except know whether or not it’s a healthy embryo.

But when we talk about nutrigenomic testing, we’re looking at genes that have something to do with certain cellular processes that affect nutrients. And they affect how we respond to nutrients or dietary interventions.

We see that these pathways influence different conditions that will impact fertility. Everyone has these genes, and what we identify with research helps us understand why we can give the same diet to two different people, and one person does great on it, and the other sees no change. The difference has to do with our genetics. So we’re looking for these pathways in relationship to fertility.

Dr Jennifer Fitzgerald (JF): I can think of, like, ten common questions that I get from patients all the time: What prenatal should I take? What should I be eating when I’m trying to get pregnant or when I’m pregnant? Etc. Given that there are 100s of different variations in the market for prenatal vitamins that vary in some type of folate, iron, vitamin D or their bioavailability and dosage amount, based on our individual needs, we can’t utilise the same things in the same way.

As Robyn said, we give two people the same diet, one does well, and one doesn’t. It’s the same with every type of medication, vitamin and nutrient. This comes down to genetics and how our body can absorb, transport or metabolise those specific nutrients. So that’s how I tend to use a lot of this information clinically: The prenatal we will use, the ideal diet for preconception, understanding genetic predispositions to endometriosis or PCOS or a pattern for implantation failures and pregnancy losses.

RM: I can split it into two different categories. Genes influence how our bodies produce proteins and enzymes and how we digest them, absorb them, transport them, take them up into the cell and metabolise them. You may have heard of MTHFR, a DNA synthesis and repair gene. This gene can effectively impact every single cell that is creating DNA. And that’s why we see so many connections to different chronic diseases and conditions.

Some people have a 75% reduction in enzyme efficiency, and we know that it can influence how they take folic acid or folate and turn it into the active form, methyl folate. Apart from that, it also helps us understand the ideal amount or form of the dose.

Another big one that I see in fertility is choline. This is part of that same pathway that’s involved in folate. It comes up very often for women and men. It increases the likelihood of non-alcoholic fatty liver disease in men, so it’s important to, especially if liver enzymes have been high.

Another key one I come across in a subtype of the population is histamine. Histamine intolerance and allergy symptoms have a connection with implantation failure and pregnancy loss.

The other side is getting into the genes that will impact different conditions associated with infertility. Genes within the liver are part of a glutathione pathway. We have these enzymes all over our body. They take antioxidants and bind them to toxic compounds. This damages the DNA, proteins, and fats within ourselves, and our gametes are highly sensitive to the environment.

These genes are called GSTs, and people can be missing them. We’ve found that they have a link to endometriosis and male infertility. Talking about these from a longevity standpoint, we also see an increased likelihood of cardiovascular disease.

The same processes that are impacting fertility go on to impact cardiovascular health, metabolic health or neurological health. The impact of these genes increases oxidative stress or damage to the cells and also increases susceptibility to environmental toxins.

JF: It’s interesting because sometimes I get patients just starting. We use this type of thing to guide us in what they might need and see them being successful from the beginning. But other times, we’re seeing people that have failed repeatedly. And that’s where the most profound impact can happen. For example, a male had very high DNA fragmentation in his semen analysis. A high fragmentation rate means that it’s not a very good prognosis to create an embryo with that particular sample. The treatment strategy is to put them on antioxidants for three months and retest afterwards. Nine times out of 10, that number goes down. But in this case, his wasn’t budging.

We only see this a handful of times, where we don’t see those numbers improving with treatment. And one of the really interesting things that have come out in research in the last few years is the GST gene. Individuals that have their GST nulled can’t utilise these antioxidants in the same way. And so even if we can give them all the antioxidants under the sun, it won’t help unless we give them the right ones.

Knowing that there’s something that we can do and altering the treatment protocol or accepting that there isn’t something we can do is good to know. It helps us make educated decisions and save time.

The other thing is poor egg quality can be unexpected when we see healthy women of good reproductive age. Often, there are no signs of anything abnormal. That’s where this can be very helpful as well. When our hormones are high, which they are during an IVF cycle, it can create a storm if we put extra oxidative stress on those developing eggs at the wrong time.

But when we know about that, we can be proactive and protect those follicles during that cycle. Or we can use that information to modify the cycle or medication protocol. So this type of testing not only works for nutraceuticals or vitamins and dietary stuff and helps us understand how our hormones and medications can behave.

JF: Two really interesting stories: The first was a 35-year-old female who was not undergoing fertility treatments. She was trying to conceive on her own. She easily conceived twice in a row and miscarried both times. That can be something that needs a lot of investigation. She came in for a workup before going to a fertility clinic because the waitlist was long.

We did my basic lab workup, but she had also come in with nutrigenomic testing that she had already done, which helped guide the treatment. I could analyse that report, do some lab work and make clinical decisions. So one of the things that we found is that she had hypothyroidism, and she also had an increased risk of hypothyroidism from a genetic perspective.

She also had an impaired beta carotene pathway, which is the pathway that breaks beta carotene into vitamin A. Vitamin A has a bad rep from the fertility perspective because high doses of vitamin A and pregnancy are considered to be transgenic or negative. Still, we also need vitamin A to stimulate follicular genesis and embryogenesis. It’s a critical nutrient for egg quality and embryo quality. Long story short, she had high beta-carotene and low vitamin A, which resulted from that pathway.

Most prenatal vitamins have beta carotene instead of vitamin A. Since she’s vegetarian, there are only a few dietary sources of vitamin A. So we had to give her vitamin A and a few other things to help balance her thyroid.

Based on her detoxification genes, she had an increased risk for things like inflammation and a high risk of developing endometriosis. We supported those things and brought her beta carotene levels down pretty significantly. Then she went on to try again and, this time, successfully had her baby.

The second example is of a long, chronic case. This was a 34-year-old female who had had six miscarriages. Those miscarriages were all spontaneous conceptions. They were all miscarried by eight weeks of gestation.

By that point, she had done a lot of testing and an unsuccessful IVF cycle. Later, he came in for naturopathic preconception care. She happened to have some nutrigenomic testing done. So we analysed that and found a detoxification/GST issue, and she was MTHFR homozygous, so needing folic or folate. She also required a lot of choline.

We also gave her glutathione instead of n-acetyl cysteine, which she had been taking before her previous cycle. So she was still on some CoQ10 and other things. She repeated IVF. And this time, she got four embryos that were sent for genetic testing. She got two normal embryos and was pregnant after her first transfer. That one was a good example of how it can improve egg quality on an IVF cycle.

RM: The knowledge around genetic testing is starting to become more prevalent, but it’s still new. Firstly, it’s important to find a company focusing on fertility. Genes do several different things, so it takes training for people to understand and interpret them. I suggest going to a practitioner with some knowledge or experience with nutrigenomic testing. You can use a Canadian or US company, just know their privacy agreements around where the genetic data is stored.

Often patients will take the nutrigenomic information to their medical or fertility doctor. But since they are trained in monogenetic diseases and diagnostic genetics, they may need help understanding some of the nutrigenomics sides of it.

When you’re looking for dietary supplement lifestyle modifications, going to an integrative practitioner or naturopathic doctor is best. A lot of these clinics and companies will also do 15-minute introductory calls. A good relationship with the person you’re working with is essential, as the process tends to be at least three months, if not longer.

I suggest booking a 15-minute introductory call and seeing if the practitioner has experience in testing and interpreting nutrigenomic testing and how they utilise it in their practice. These would be some good questions to start with.