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Understanding LHCGR and Fertility: What Your Genotype Means

Infertility is commonly defined as the inability to conceive after 12 months of trying. Genetics can be one of many contributors. Variations in the LHCGR gene, which encodes the receptor for luteinizing hormone (LH) and human chorionic gonadotropin (hCG), influence ovulation and early pregnancy support. Changes at the rs2293275 location in LHCGR can affect hormone signaling and are linked to differing risks for polycystic ovary syndrome (PCOS), a frequent cause of irregular cycles and ovulation problems.

How LHCGR affects reproductive health

  • LH and hCG bind to the LHCGR receptor on ovarian cells to trigger ovulation and support the corpus luteum in early pregnancy.
  • Variants that alter receptor function can change how ovarian cells respond to these hormones, potentially affecting the timing and quality of ovulation.
  • PCOS is a condition characterized by irregular cycles, elevated androgens, and often insulin resistance. Certain LHCGR variants are associated with higher PCOS risk and the downstream effects that can reduce fertility.

General lifestyle and nutritional strategies to support fertility

Regardless of genotype, lifestyle approaches that support hormone balance, ovulatory regularity, and metabolic health can help reproductive outcomes. Use these as educational suggestions and discuss changes with your healthcare provider.

  • Diet: Emphasize vegetables, fiber, lean proteins, whole grains, legumes, nuts, seeds, and healthy fats like olive oil and avocado. Favor low-glycemic carbohydrates to help stabilize blood sugar.
  • Weight and metabolic health: Maintaining a healthy weight can improve ovulation and fertility. Even modest weight loss (if overweight) can restore ovulation in some people with PCOS.
  • Physical activity: Aim for regular moderate exercise such as brisk walking, cycling, or strength training, which improves insulin sensitivity and supports hormonal balance.
  • Sleep and stress: Prioritize 7 to 9 hours of quality sleep and use stress-reduction techniques such as mindfulness, yoga, or breathing exercises to support hormone regulation.
  • Limit endocrine disruptors: Reduce exposure to certain plastics, nonstick cookware when overheated, and personal care products with phthalates or parabens where possible.

Supplements and nutrients to consider

Supplements may be helpful when used appropriately, but they should be discussed with your healthcare provider before starting. Typical nutrients considered for reproductive and metabolic support include:

  • Myoinositol (commonly used in PCOS) to support insulin sensitivity and ovarian function
  • Vitamin D if deficient, as low levels are common and can affect reproductive outcomes
  • Omega-3 fatty acids for inflammation support and overall reproductive health
  • Folate (5-MTHF preferred if you have known MTHFR variants) for preconception care
  • Magnesium and B vitamins to support metabolic health and stress response

Tests to discuss with your clinician

Routine testing that can clarify reproductive and metabolic status includes:

  • Serum progesterone in the luteal phase to confirm ovulation
  • Day 2 to 4 FSH and LH to evaluate ovarian reserve and pituitary signaling
  • Anti-Mullerian hormone (AMH) to estimate ovarian reserve
  • Fasting glucose and fasting insulin or HbA1c to assess insulin sensitivity
  • Thyroid function tests (TSH, free T4) and prolactin when clinically indicated

Genetic Interpretation for rs2293275 (LHCGR)

The section below explains how different genotypes at rs2293275 in the LHCGR gene relate to PCOS risk and reproductive function. Use this information to inform conversations with your healthcare team. PlexusDx provides educational genetic information and does not offer medical advice.

Two effect alleles (TT) — substantially increased PCOS risk

What this means

  • Carrying two copies of the T allele is associated with a substantially increased risk for PCOS compared with other genotypes at this location.
  • Potential effects include disrupted LH/hCG receptor signaling, both irregular menstrual cycles and anovulation, and a higher likelihood of hormonal imbalances typical of PCOS.

Practical steps to consider

  • Work with your clinician to screen for PCOS and metabolic issues. Consider testing fasting glucose, fasting insulin, HbA1c, AMH, and reproductive hormones as indicated.
  • Adopt a lower-glycemic, nutrient-dense diet emphasizing vegetables, fiber, lean protein, and healthy fats to support stable blood sugar.
  • Incorporate regular physical activity and strategies for sleep and stress management to improve insulin sensitivity and hormonal balance.
  • Discuss supplements such as myoinositol, vitamin D, and omega-3s with your provider if appropriate.
  • If fertility is a priority, early referral to a reproductive endocrinologist may be helpful to discuss ovulation induction options and personalized management.
One effect allele (CT) — increased PCOS risk

What this means

  • Carrying one T allele is associated with an increased risk for PCOS compared with the CC genotype.
  • Possible manifestations include menstrual irregularities, ovulatory changes, and metabolic features such as insulin resistance that can affect fertility.

Practical steps to consider

  • Monitor cycle regularity and discuss baseline reproductive and metabolic testing with your healthcare provider if you have symptoms such as irregular periods, excessive hair growth, or difficulty conceiving.
  • Prioritize a balanced, low-glycemic diet and consistent exercise to support hormone function and metabolic health.
  • Address lifestyle factors: sleep, stress reduction, and limiting exposure to endocrine-disrupting chemicals.
  • Consider targeted supplements under clinician guidance, and follow-up with screening tests such as fasting glucose and AMH when planning pregnancy.
Zero effect alleles (CC) — typical genetic risk at this locus

What this means

  • Carrying two copies of the C allele is the most favorable genotype at rs2293275. It indicates you do not carry the T effect allele linked to increased PCOS risk at this site.
  • This genotype supports normal LH/hCG receptor signaling related to this variant, but it does not eliminate other genetic or non-genetic causes of infertility.

Practical steps to consider

  • Continue general reproductive health measures: balanced diet, regular exercise, sleep, and stress management.
  • If you experience fertility challenges despite a favorable genotype here, pursue a comprehensive evaluation since many factors influence fertility beyond a single genetic variant.
  • Use routine testing and clinical evaluation to identify or rule out other causes of infertility such as tubal factors, male factor infertility, endometriosis, or other hormonal issues.

Final notes and important disclaimer

This information is educational and intended to help you understand how the rs2293275 variant in LHCGR can relate to reproductive health. PlexusDx does not provide medical advice. Always consult with your healthcare provider or a reproductive specialist before making changes to diet, supplements, medications, or fertility treatment plans. Your genotype is one piece of a broader health picture that includes lifestyle, environmental exposures, medical history, and other genetic and non-genetic factors.