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How HLA-F Genetics Can Influence Time to Pregnancy

Infertility is commonly defined as difficulty conceiving after a year of regular, unprotected intercourse. Many factors affect fertility, including age, health, environment, and genetics. One gene that plays a role in early pregnancy is HLA-F. This gene helps the maternal immune system tolerate the developing embryo. Variations at a specific location in HLA-F, called rs2523393, are associated with differences in how quickly some people conceive. Understanding your genotype can help you tailor lifestyle, dietary, and supplement strategies to support a healthy immune environment for conception.

Why HLA-F Matters

HLA-F is involved in early immune signaling between the mother and the embryo. Because the embryo carries DNA from both parents, the maternal immune system must adapt and accept the embryo rather than treat it as foreign. Variations at rs2523393 appear to influence how efficiently that immune adaptation happens, which can affect implantation and time to pregnancy. Genotypes at this location are typically categorized as GG, AG, or AA and are linked to different average times to conceive.

Two effect alleles (GG)

Genetic meaning

  • You carry two copies of the effect allele G at rs2523393.
  • This genotype is associated with a slower average time to pregnancy compared to other genotypes.

How this may affect fertility

  • The maternal immune system may take longer to adapt and accept the embryo, which can reduce implantation efficiency and lengthen time to conception.
  • The effect is one of many factors that influence fertility and may be more noticeable with other risk factors such as advanced age or autoimmune conditions.

Practical steps to support conception

  • Adopt an anti-inflammatory diet rich in leafy greens, colorful vegetables, whole grains, legumes, nuts, seeds, and oily fish for omega-3 fats.
  • Optimize vitamin D levels. Test serum 25(OH)D and work with a provider to reach an adequate range if low.
  • Take a prenatal vitamin that includes folate, iron, iodine, vitamin D, and B12.
  • Reduce exposure to environmental toxins by avoiding smoking, limiting processed foods, choosing low-toxin personal care products, and reducing plastic food storage and heating in plastic.
  • Prioritize quality sleep and stress management through consistent sleep schedules, relaxation practices, and mind body techniques such as gentle yoga or meditation.
  • Allow two to four months for lifestyle and supplement changes to show measurable benefits for fertility.
One effect allele (AG)

Genetic meaning

  • You carry one copy of the effect allele G and one copy of the non-effect allele A at rs2523393.
  • This genotype is associated with a moderately slower average time to pregnancy compared to AA but typically faster than GG.

How this may affect fertility

  • Your maternal immune system may require a bit more time to adapt to the embryo compared to the AA genotype, which can slightly delay implantation and conception.
  • The impact can be more pronounced when combined with other factors such as age, limited ovarian reserve, or autoimmune tendencies.

Practical steps to support conception

  • Follow an anti-inflammatory eating plan that emphasizes whole foods, high antioxidant intake, and omega-3 rich foods such as salmon, sardines, walnuts, and flaxseed.
  • Ensure adequate intake of key micronutrients. A prenatal vitamin with folate, iron, iodine, vitamin D, and B12 is recommended.
  • Check vitamin D status and correct insufficiency under the guidance of your healthcare provider.
  • Limit alcohol and avoid smoking. Reduce exposure to endocrine disrupting chemicals where possible by choosing fragrance free and phthalate free products.
  • Support stress resilience through daily routines that include light exercise, adequate rest, and relaxation techniques.
  • Expect lifestyle changes to require two to four months to influence reproductive outcomes.
Zero effect alleles (AA)

Genetic meaning

  • You carry two copies of the non-effect allele A at rs2523393.
  • This genotype is associated with the shortest average time to conception among the three genotypes.

How this may affect fertility

  • Your maternal immune system is genetically predisposed to adapt more efficiently to the developing embryo during early pregnancy, which can support implantation.
  • Genetics is only one contributor to fertility. Lifestyle, age, and medical conditions also play major roles.

Practical steps to support conception

  • Maintain an anti-inflammatory diet and continue to include omega-3 foods, a wide variety of fruits and vegetables, whole grains, and healthy protein sources.
  • Continue prenatal supplementation with folate and other essential nutrients before conception and through early pregnancy.
  • Keep vitamin D in an optimal range and follow recommended screening if you have risk factors for deficiency.
  • Practice toxin reduction, sleep hygiene, moderate exercise, and stress management to keep immune function balanced.
  • Even with a favorable genotype, allow a few months for positive lifestyle changes to improve the fertility environment.

Dietary and Supplement Recommendations

  • Anti-inflammatory diet: Emphasize leafy greens, colorful vegetables, whole grains, legumes, nuts, seeds, and olive oil. Minimize processed foods, excess sugar, and trans fats.
  • Omega-3 fats: Aim to include oily fish twice weekly or consider a medical grade omega-3 supplement if fish intake is low. Omega-3s support healthy immune signaling and inflammation balance.
  • Prenatal vitamin: Take a prenatal formulation that contains at minimum folic acid or methylfolate, iron, iodine, B12, and vitamin D. Start before conception and continue through early pregnancy.
  • Vitamin D: Test serum 25(OH)D and replace under medical guidance if low. Many people require supplementation to reach optimal levels for immune health.
  • Antioxidants: Foods high in vitamins A, C, and E and polyphenols support cellular health. Include berries, citrus, leafy greens, nuts, and seeds.

Lifestyle and Environmental Tips

  • Sleep: Aim for consistent, restorative sleep by keeping regular bedtimes and avoiding screens before bed.
  • Stress management: Use techniques such as breathing exercises, meditation, gentle movement, or counseling to reduce chronic stress that can affect immune and reproductive function.
  • Toxin reduction: Avoid tobacco, limit alcohol, reduce exposure to household pesticides, and choose low-toxin personal care and cleaning products.
  • Exercise: Engage in regular moderate activity such as brisk walking, swimming, or yoga. Avoid extreme endurance exercise which can interfere with menstrual cycles.
  • Timing: Many changes to diet, micronutrients, and lifestyle take two to four months to show benefits for reproductive health. Plan ahead when possible.

When to Talk to Your Healthcare Provider

  • If you have been trying to conceive for a year without success, or six months if you are over age 35, consult a reproductive healthcare provider.
  • If you have known autoimmune disease, irregular cycles, significant menstrual or gynecologic symptoms, or other medical concerns, discuss them with your provider.
  • Work with your provider to test vitamin D and other nutrients as needed, and to review any supplements for safety and interactions.

PlexusDx provides education about genetic predispositions and how they may relate to health. This information is educational only. PlexusDx does not provide medical advice. Always consult your healthcare provider before making changes to your diet, supplements, or lifestyle, and before starting any fertility treatments or medications.