Fertility and nutrition: biomarkers that matter when trying to conceive

Folate, methylation, and the MTHFR gene

Folate is essential for DNA synthesis, cell division, and the methylation reactions that regulate gene expression during embryo development. The MTHFR gene encodes an enzyme that converts dietary folate into its active form, methyltetrahydrofolate (methyl-THF), which the body uses in the remethylation of homocysteine to methionine. Variants in the MTHFR gene, particularly C677T and A1298C, reduce the efficiency of this conversion by 30 to 70% depending on whether one or two copies of the variant are inherited. These variants are extremely common: approximately 10 to 25% of people in northern European populations carry two copies of the C677T variant. When folate metabolism is impaired by MTHFR variants, homocysteine can accumulate, and the availability of methyl groups for DNA methylation during cell division is reduced. This matters because the period immediately before and after conception is the most methylation-intensive of any developmental stage. Testing homocysteine levels alongside MTHFR status is more actionable than genetic testing alone, because homocysteine reflects how effectively folate metabolism is actually functioning in your specific biology, accounting for both genetics and dietary folate intake.

Thyroid function and fertility

Thyroid dysfunction is one of the most common and most underdiagnosed causes of subfertility and early pregnancy loss. Thyroid hormones regulate ovulation, luteal phase function, and the endometrial environment required for implantation. An underactive thyroid, including subclinical hypothyroidism (elevated TSH with normal T4 and no obvious symptoms), is associated with a significantly higher rate of irregular cycles, anovulation, and miscarriage. Research shows that the presence of thyroid peroxidase antibodies (Anti-TPO), even in women with normal TSH, is associated with miscarriage rates up to 43%, compared with 2 to 6% in the general population. Many reproductive specialists now recommend TSH below 2.5 mIU/L as the target in the preconception period, rather than the standard laboratory upper limit of 4.5, which is set for the general population rather than for conception. Testing TSH, Free T4, Free T3, and Anti-TPO together gives a complete thyroid picture.

Iron, ferritin, and blood formation

Iron and ferritin are essential not just for energy and cognition but specifically for reproductive function. Low ferritin is associated with irregular ovulation, reduced egg quality, and impaired early embryo development. The mechanism involves both reduced oxygen delivery to the developing follicle and impaired mitochondrial function in egg cells. In pregnancy, iron demands increase substantially to support the growth of the placenta and fetal blood volume. Beginning the preconception period with confirmed adequate ferritin levels, rather than simply assuming adequacy, means you enter pregnancy with a reserve rather than a deficit. Ferritin below 50 ng/mL is considered suboptimal for reproductive health by many fertility nutritionists, even though the standard lower reference limit is typically set at 12 to 15 ng/mL.

Vitamin D and reproductive outcomes

Vitamin D receptors are present in ovarian tissue, the endometrium, and the developing follicle. The evidence linking vitamin D status to fertility outcomes includes associations with ovarian reserve, IVF success rates, and implantation success. In women with PCOS, low vitamin D is associated with more severe insulin resistance and poorer reproductive outcomes. For men, vitamin D is associated with sperm motility and testosterone production. UK-based couples trying to conceive are at high risk of vitamin D insufficiency given the latitude and limited sunlight exposure for most of the year, making testing and correcting vitamin D a high-priority step in preconception planning.

Vitamin B12 and homocysteine in conception

Vitamin B12 is a cofactor in the same methylation pathway as folate. Deficiency impairs DNA synthesis, cell division, and the methylation of homocysteine. Elevated homocysteine is associated with impaired implantation, higher miscarriage risk, and neural tube defects. Women who are vegetarian, vegan, or who have been taking oral contraceptives for several years are at particular risk of B12 insufficiency. Testing B12 and homocysteine together is more informative than testing B12 alone, because B12 in the serum may appear adequate while functional deficiency exists at the cellular level where methylation occurs.

Blood glucose, HbA1c, and reproductive hormones

Insulin resistance and elevated blood glucose have direct effects on reproductive hormones. In women, insulin resistance drives excess androgen production by the ovaries, disrupting the hormonal balance that governs ovulation. PCOS, which affects approximately 10% of women of reproductive age, is characterised by insulin resistance, elevated androgens, and disrupted ovulation. Even in women without PCOS, blood glucose instability affects the hypothalamic-pituitary-ovarian axis that regulates the menstrual cycle. For men, insulin resistance is associated with lower testosterone and reduced sperm quality. HbA1c provides a three-month average blood glucose picture and is considerably more informative than a single fasting glucose reading.

Standard NHS fertility investigations typically begin only after twelve months of trying to conceive, and focus on hormonal assessment of ovarian reserve and basic sperm analysis. The nutritional and metabolic picture that is often the most modifiable element of fertility is rarely examined.

A comprehensive preconception biomarker panel should include:

TSH, Free T4, Free T3, and Anti-TPO antibodies give a complete thyroid picture. Standard testing often measures only TSH, missing subclinical hypothyroidism and autoimmune activity that significantly affect reproductive outcomes.

Folate and homocysteine together reveal how effectively the methylation pathway is functioning. Elevated homocysteine in the context of low-normal folate is a clear signal to optimise methylation support before conception.

Vitamin B12 is essential for DNA synthesis and cell division in the early embryo. Testing B12 status alongside homocysteine is more informative than B12 alone.

Ferritin reflects iron stores available to support ovulation, egg quality, and the increased demands of early pregnancy.

Vitamin D supports ovarian function, endometrial receptivity, and implantation. UK-based women should test and correct vitamin D as a standard preconception step.

HbA1c reveals whether blood glucose patterns are affecting the hormonal environment for fertility. Particularly relevant for women with PCOS, irregular cycles, or a family history of type 2 diabetes.

MTHFR genetic testing reveals which variants are present in the MTHFR gene, informing which form of folate supplementation is most appropriate (folic acid vs. methylfolate) and whether homocysteine requires active management.

Home biomarker testing is most useful before starting to actively try to conceive, or at any point during the trying to conceive (TTC) period where unexplained sub-fertility is present. It provides a modifiable biological picture that standard fertility investigations do not capture.

Folate and methylation support

Adequate folate intake in the preconception period is well validated to reduce the risk of neural tube defects and supports the methylation reactions essential for early embryo development. The standard recommendation is 400 micrograms of folic acid per day for at least one month before conception. For women with MTHFR variants, particularly those who are homozygous for C677T or A1298C, methylfolate (the active form of folate) is more directly usable than synthetic folic acid, which requires MTHFR enzyme activity to convert it. Testing both MTHFR status and homocysteine levels allows you to select the right form and dose of folate for your specific genetics, rather than relying on population-average supplementation guidelines.

Iron and nutrient-dense eating

Building iron stores before conception is considerably easier than correcting iron deficiency during pregnancy, when demands increase and nausea may limit dietary intake. Food sources with the best iron bioavailability include red meat, liver, shellfish, and dark leafy greens eaten alongside vitamin C to enhance non-haem iron absorption. Ferritin should be tested and, where possible, raised to at least 50 ng/mL before conception. This creates a reserve that supports the demands of early pregnancy without the fatigue and impaired immune function that accompany iron deficiency.

Vitamin D optimisation through testing

A standard vitamin D supplement (400 to 1000 IU daily) is insufficient to correct deficiency in most UK adults during winter months. Testing 25-OH vitamin D and targeting levels above 75 nmol/L before conception is a more reliable approach than universal supplementation without a baseline. Vitamin D correction typically takes three to four months, making preconception testing timeline-relevant for anyone actively planning a pregnancy.

Blood glucose stability and insulin sensitivity

The dietary strategies that support insulin sensitivity and stable blood glucose are highly relevant in the preconception period. These include prioritising whole foods, distributing carbohydrate across meals rather than concentrated intake, pairing carbohydrate-containing foods with protein and fibre to blunt glucose peaks, and reducing processed food intake. For women with PCOS or insulin resistance, even modest improvements in HbA1c are associated with meaningful improvements in ovulatory function and cycle regularity. Tracking HbA1c over three to six months gives an objective measure of whether dietary changes are producing the expected metabolic improvement.