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MTHFR and Pregnancy: What Your Genotype Means for Folate, Fertility, and Pregnancy Health

Pregnancy is a time when your body’s nutritional needs and biochemical pathways are especially important. One gene often discussed in this context is MTHFR, which produces an enzyme that converts dietary folate into its active form, methylfolate. Methylfolate is essential for DNA synthesis, proper hormone regulation, and fetal development. Variations in the MTHFR gene can reduce enzyme function, which may affect folate metabolism and influence reproductive outcomes.

How MTHFR Affects Pregnancy

  • Folate activation: The MTHFR enzyme converts folate from food or supplements into methylfolate, the form your body uses for key processes including DNA and neurotransmitter synthesis.
  • Methylation support: Methylfolate feeds the body’s methylation cycle, which helps regulate hormones, gene expression, and detoxification pathways important in pregnancy.
  • Reproductive outcomes: Reduced MTHFR activity has been associated with lower folate availability, which can affect egg quality, implantation, and early fetal development. Inadequate methylfolate during early pregnancy is linked with higher risk of neural tube defects and other complications.

General Recommendations for Pregnancy-Ready Folate Support

  • Prioritize food sources of natural folate: dark leafy greens, legumes, asparagus, avocado, and citrus fruits.
  • Choose supplements containing methylfolate rather than synthetic folic acid when indicated, especially if you have reduced MTHFR function.
  • Include active forms of B vitamins: methylcobalamin (B12) and riboflavin (B2) help MTHFR function and overall methylation support.
  • Maintain a balanced diet with adequate protein, healthy fats, and micronutrients to support ovulation, implantation, and a healthy pregnancy environment.
  • Avoid environmental toxins where possible: tobacco, excessive alcohol, and occupational exposures can increase oxidative stress and interfere with fertility.
  • Seek early prenatal care: discuss folate status and supplementation with your healthcare provider before conception and in early pregnancy.
Two effect alleles (AA) — Significant reduction in MTHFR function

If your genotype at rs1801133 is AA, you carry two copies of the effect allele. This genotype is associated with a substantial reduction in MTHFR enzyme activity, commonly around 70 to 80 percent. Reduced ability to convert folate into methylfolate can lead to lower circulating methylfolate levels and may affect folate-dependent processes important in reproduction.

  • Potential risks: increased risk for infertility, recurrent miscarriage, IVF implantation failure, pregnancy complications such as pre-eclampsia, and elevated risk for neural tube defects in the fetus if methylfolate is insufficient.
  • Dietary strategies: emphasize folate-rich whole foods — dark leafy greens (spinach, kale), legumes (lentils, beans), beets, Brussels sprouts, and citrus. These foods provide natural folate and other cofactors important for absorption and use.
  • Supplement guidance: consider a prenatal supplement that contains methylfolate (L-methylfolate) rather than synthetic folic acid. Work with your healthcare provider to determine an appropriate dose, especially during preconception and the first trimester.
  • Supportive nutrients: include active vitamin B12 (methylcobalamin) and riboflavin (B2) to support MTHFR enzyme activity and overall methylation pathways.
  • Monitoring: discuss serum folate, red blood cell folate, and B12 testing with your provider to ensure adequate levels prior to and during early pregnancy.
  • Lifestyle: minimize smoking, limit alcohol, manage stress, and aim for a healthy weight to support fertility and pregnancy outcomes.
One effect allele (AG) — Moderate reduction in MTHFR function

If your genotype at rs1801133 is AG, you carry one copy of the effect allele. This variant typically reduces MTHFR enzyme activity by about 30 to 40 percent. This partial reduction can affect conversion of folate into methylfolate, particularly if dietary folate or related B vitamins are low.

  • Potential risks: mildly elevated risk of pregnancy complications such as recurrent miscarriage or IVF implantation difficulties if folate status is inadequate. Risk for neural tube defects can increase when folate intake is not sufficient.
  • Dietary strategies: prioritize folate-containing foods like leafy greens, legumes, asparagus, and fortified whole foods when needed. Whole-food sources deliver folate alongside vitamins and minerals that support absorption and metabolism.
  • Supplement guidance: a prenatal supplement containing methylfolate is often recommended to ensure reliable availability of active folate, especially during preconception and early pregnancy.
  • Supportive nutrients: include methylcobalamin (B12) and riboflavin (B2) to help optimize MTHFR activity and methylation.
  • Monitoring and care: consider discussing blood testing for folate and B12 with your provider and ensure prenatal care begins early.
  • Lifestyle: healthy diet, regular moderate exercise, and avoidance of environmental toxins help improve reproductive outcomes.
Zero effect alleles (GG) — Typical MTHFR function

If your genotype at rs1801133 is GG, you carry two copies of the non-effect allele and generally have normal MTHFR enzyme activity. Your body is typically efficient at converting dietary folate into methylfolate, supporting DNA synthesis, hormone regulation, and healthy fetal development.

  • Potential risks: with normal MTHFR activity, you do not have an increased genetic risk for folate-related pregnancy complications specifically from this variant.
  • Dietary strategies: continue to eat folate-rich foods — leafy greens, legumes, and other whole foods — to support pregnancy and overall health.
  • Supplement guidance: either standard prenatal folic acid or methylfolate supplements are appropriate; both are generally effective for those with normal MTHFR function. Follow prenatal dosing recommendations and your provider’s guidance.
  • Supportive nutrients: maintain adequate B12 and riboflavin intake to support overall methylation and energy metabolism.
  • Routine care: engage in regular prenatal care, maintain a balanced lifestyle, and address any individual health concerns with your provider.

Practical Steps Before and During Pregnancy

  • Preconception planning: start folate-rich eating and appropriate supplementation at least one to three months before trying to conceive.
  • Supplement selection: if you have reduced MTHFR function, choose a supplement providing methylfolate; otherwise standard prenatal folic acid is acceptable. Confirm dosing with your healthcare provider.
  • Test and monitor: consider testing red blood cell folate and B12 if you have a history of pregnancy loss, difficulty conceiving, or if you know you have a reduced-function MTHFR genotype.
  • Coordinate care: share your genetic information with your healthcare provider or a genetics-informed clinician to tailor prenatal care and supplementation.

Important Disclaimer

PlexusDx does not provide medical advice. This article is educational and describes genetic predispositions and general strategies to support reproductive health. Always consult your healthcare provider before starting or changing supplements, medications, or treatments, and for personalized recommendations based on your health history and current condition.