If you’re trying to get pregnant, you’ve probably already heard about the most common fertility tests—the ones that measure hormone levels and overall reproductive functioning. But there are other lab tests that can be useful in tracking down the cause of your subfertility. Here are five of them:
MTHFR Genetic Testing
So, what is the MTHFR mutation?
First, let’s start with the basics: MTHFR stands for methylenetetrahydrofolate reductase, and it’s an enzyme that plays a crucial role in the body’s metabolism. It helps convert folate, a B-vitamin, into its active form (methylfolate), which is necessary for making DNA and the production of red blood cells.
Now, here’s where things get a little more complicated: sometimes, there are changes in the gene that codes for MTHFR, which are called MTHFR mutations. These mutations can affect fertility in both men and women. In women, MTHFR mutations have been linked to an increased risk of miscarriage and complications during pregnancy. This is, in part, due to the body’s inability to properly utilize folic acid, which is important for fetal development. In men, MTHFR mutations may lead to low sperm count and motility. MTHFR mutations may also affect the production of testosterone, which is necessary for sperm production.
But before you start panicking, it’s important to know that not everyone with an MTHFR mutation will experience fertility issues. MTHFR mutations are actually quite common, with about 30-40% of the population carrying at least one mutation, and individuals of Hispanic descent tend to have a higher risk of carrying a mutation. However, the impact of MTHFR mutations on fertility can vary greatly depending on the specific mutation and whether or not an individual carries multiple mutations.
So, how do you know if you carry the mutation that impacts fertility?
The two genetic “locations” in the MTHFR gene that people most commonly have mutations in are known as A1298C and C677T. The highest risk mutation that is related to a lot of the mentioned fertility and pregnancy complications is the C677T mutation. You may be wondering, what does C677T even mean?? Genes are made up of DNA, which is made up of building blocks denoted as the letters A, C, T, and G. So, the number 677 in the C677T mutation means someone has a mutation at the 677th position of the DNA sequence. The C and T in the C677T mutation means that usually in the 677th position there is a “C”, but the mutation changed it to a “T”. These mutations are inherited by our parents, so you will receive one copy from mom and one from dad for the C677T gene location. So that means you can have either a CC, CT, or TT combination of the C677T MTHFR gene. If you have the CT or TT variant your ability to process folate is 35-90% less efficient. When the body is not able to process folate properly, an amino acid called homocysteine increases. The high homocysteine levels are what cause the fertility and pregnancy complications associated with this mutation.
How do you know if you have this mutation?
I order the MTHFR genetic test for any couples struggling with fertility. When I order this test for my patients, I order a saliva swab or blood draw that can test for the MTHFR mutation. Your doctor can also order this test depending on the clinic location they practice at. In my practice, I check for both the C677T and A1298C mutations. Although the A1298C mutation is lower risk I personally like to be comprehensive in my testing. I will sometimes also test for homocysteine to see if there is any homocysteine elevation as a result of the mutation.
What do you do if you carry an MTHFR mutation?
If you carry the C677T mutation, don’t fret! The solution is actually quite simple. Since carriers of this mutation cannot convert folic acid into the active form of folate in the body as efficiently, you simply need to supplement with the active form of folate directly, methylfolate, or sometimes called 5-methyltetrahydrofolate (5-MTHF). That allows your body to bypass that conversion step in the MTHFR pathway, and you avoid the health risks associated with the mutation. This means that you need to check in your prenatal vitamin whether they have folic acid (non-bioactive form) or methylfolate (bioactive form) listed. Here is an example of what to look for in the supplement nutrition facts:
Folate … 1,333mcg DFE (800 mcg L-5-MTHF)
As long as it lists methylfolate, 5-MTHF, or 5-methyltetrahydrofolate then that’s the right form! Many studies recommend a dose of 800 mcg of methylfolate (the bioactive folate) for MTHFR carriers. It’s not necessary to go beyond 1000 mcg and would run the risk of overdosing.
Vitamin D is actually a vitamin and a hormone! It helps the body absorb calcium and phosphorus, two minerals that are essential to healthy sperm and eggs. Studies have shown that vitamin D has a positive effect on fertility in both men and women. In men, vitamin D may help to improve sperm quality and quantity, while in women, it may improve ovarian function and egg quality. It’s important to make sure your vitamin D levels are in the optimal range, especially if you’re trying to conceive.
The optimal range for vitamin D is between 50-80 ng/mL of 25-hydroxy (25-OH) vitamin D. Good sources of vitamin D include sunlight, fatty fish like salmon, and fortified foods like milk or milk alternatives. However, if you are not in the optimal range supplementing with additional vitamin D may be a good option for you. Supplementing with 2000 IUs per day of vitamin D is generally considered safe; however, it’s important to consult with your doctor or dietitian about your specific needs first before starting any supplement in pregnancy.
Ferritin is a protein that stores iron, and it’s especially important in pregnancy. When ferritin levels are low, the body doesn’t have enough stored iron to make healthy red blood cells. This can lead to anemia and affect fertility by reducing the amount of oxygen that reaches the reproductive organs. In women, low ferritin levels have been linked to irregular periods and difficulty getting pregnant. In men, low ferritin can lead to poor sperm quality.
Optimal levels of ferritin are between 50-100 mcg/L. To maintain healthy ferritin levels, it’s important to eat a diet rich in iron, such as leafy green vegetables, lean meat, and nuts. I also like to use the iron fish and cast-iron skillets combined with lemon juice to boost iron absorption while cooking. If you need to use an iron supplement, I prefer gentle iron supplements like iron bisglycinate that are less likely to cause constipation or nausea. If you are vegan or vegetarian then supplementing with iron is necessary. However, it is important to note that too much iron is not a good thing either. So, as always, if you need to supplement make sure to consult with your doctor or dietitian.
How does my thyroid impact my fertility?
Thyroid hormone is essential for fertility. In addition to regulating metabolism, it also helps regulate ovulation. If you are not ovulating, one potential cause may be low thyroid hormone. There are two primary thyroid hormones in the body, T4 (thyroxine) and T3 (triiodothyronine). If your levels of free T4 or free T3 are low or not optimal, this could be causing fertility issues. I specifically wrote out “free” T3 and “free” T4 because the “free” forms of these hormones are the ones that the body can actually use, the non-free form is bound up by proteins and not as accessible for the body to use. For that reason in my practice I make sure to test for the free forms of T3/T4. The body needs enough thyroid hormones to produce healthy eggs that can result in pregnancy. In some cases, a woman’s thyroid gland produces too much thyroid hormones or too little thyroid hormones, and this can affect fertility.
What are the right tests for my thyroid?
Most doctors will test one thyroid marker, usually TSH, when there are actually 6 markers that give you a comprehensive picture of your thyroid health! A thorough panel includes thyroid stimulating hormone (TSH), free T4, free T3, anti-TPO antibodies, anti-Tg antibodies, and reverse T3. I like to compare your thyroid to the AC unit and thermostat of your house (i.e., your body). In this example, TSH is like the thermostat that signals to the AC unit (your thyroid) to pump out thyroid hormones for your body, like “heating the house”. Just because the thermostat, TSH, is working it does not guarantee that the AC unit is working optimally. As for the reverse T3 and antibody tests, think of those like kinks to the system that can start to wear down your thyroid over time long before the thyroid itself gives out. For this reason, to get a very comprehensive picture of thyroid health, I recommend all these markers for any woman struggling with subfertility. If you’re asking for these tests from your doctor, an endocrinologist would be the best specialist to seek out for this thorough testing.
I got tested, now what?
If your thyroid hormones are out of range, your doctor will go over the medication options best for you. The American Thyroid Association recommends that TSH levels stay below 2.5mU/L for miscarriage prevention. Women with higher TSH levels had higher chances of miscarriage. In the least you want to ensure that your TSH levels are below 2.5mU/L, alongside normal free T3 & free T4 levels But, let’s say you got tested and your TSH, free T3, and free T4 came back normal while the antibody markers came back abnormal. I see this often in my practice, where for example, someone’s thyroid hormones will be in normal range but their antibodies will be elevated. In those scenarios, there is no “medication” that can necessarily help, but there are so many nutrients and herbs that can!
It is also very valuable information because having a baseline of your thyroid labs before pregnancy can tell you if you are at a higher risk of developing thyroid issues during pregnancy or postpartum. We know that women with elevated thyroid antibodies before pregnancy may be at higher risk for thyroid impairments during and after pregnancy, such as hypothyroidism and postpartum thyroiditis. That’s why having this information before pregnancy empowers you to ask for routine testing and follow-up throughout your pregnancy and postpartum period.
IMPORTANT NOTE: If your TSH or free T3/T4 hormones are out of normal range and you are trying to conceive I do recommend you take the medication prescribed by your doctor instead of relying on herbal alternatives. Thyroid medication is very safe, it’s actually the same as your own body’s thyroid hormone, it’s just supplementing you with what your body isn’t making.
Celiac Genetics and Antibodies
What is celiac disease and how does it affect fertility?
Celiac disease is an autoimmune disorder that affects the small intestine and is triggered by eating gluten. Gluten is a protein found in wheat, barley, and rye. When someone with celiac disease eats gluten, their immune system attacks the small intestine, causing damage to the villi (tiny hair-like projections in the intestine that absorb nutrients). This can lead to many nutritional deficiencies and a range of health problems, including fertility issues. In women, untreated celiac disease can cause irregular periods, difficulty getting pregnant, recurrent miscarriages, and birth defects. In men, it can lead to low sperm count and poor sperm quality.
So why do you need to test for both the celiac genes and antibodies?
To answer this question, we need to first establish how celiac disease manifests. Every autoimmune disease, including celiac, is inherited genetically. But that does not mean that you will develop the disease. That is because many autoimmune related genes like celiac are usually “dormant” or “turned off” upon birth. The genes can get “turned on” at any moment of someone’s life. This on/off switch phenomenon is part of a process called epigenetics. With celiac disease, once the gene has turned on it does not turn off unfortunately. So that means if someone carries the celiac disease gene at any moment of their life they can develop celiac disease, that can be at 2 years old, 70 years old, or never. So, if you have the gene how do you know if the gene has “turned on”?
Testing for the celiac disease antibodies tells you whether you currently have active celiac disease and need to go on a 100% gluten-free diet. If you get tested for the gene and you carry the high-risk gene for celiac disease, then you have one of two choices: 1) You can go gluten-free preventatively in case the gene ever turns on or 2) You can ask your doctor to get screened for the antibodies annually to make sure you detect if the gene ever turns on. If you get tested for the antibodies but not the gene it tells you if you have celiac at the moment, but if it’s negative that doesn’t help you rule out the potential that you may develop celiac disease later. If you don’t carry the gene at all, then it’s impossible to develop celiac disease. Of note, it’s important to keep in mind that if you want to get tested for the antibodies you must not be eating gluten free. Yes, I said that right, you must NOT be eating gluten free. That’s because if you are not eating gluten then there won’t be any antibodies against gluten to detect!
If I have active celiac disease, won’t I have symptoms?
No, not necessarily. There are people who have celiac disease with little to no symptoms. It’s also important to note that the symptom could be your subfertility or recurrent miscarriages for example. Celiac disease symptoms can present in many forms. For this reason, I always screen for both the celiac antibodies and genes.
I have celiac disease, what do I do?
If you have diagnosed celiac disease, it is crucial to be 100% gluten-free, no exceptions. The reason the guidelines are so strict for celiac is because the consequences of eating gluten with celiac are quite severe. Not following a gluten-free diet with celiac disease can significantly increase your risk of multiple cancers and many other conditions.
So, there you have it! I hope this post helps you understand how important it is to get a holistic view of your subfertility causes. Having these labs checked helps you be better informed about your subfertility and choose the best treatment for you.