Emily never imagined that the "culprit" behind her three failed IVF attempts and two miscarriages was hidden within her folate genes.

For five years after being diagnosed with endometriosis, she tried medication and laparoscopic surgery, but she could never overcome the hurdle of pregnancy.

It wasn’t until her doctor recommended a folate metabolism gene test that the unfamiliar "c.677C>T homozygous mutation" on the report revealed the answer—this genetic variation was disrupting her folate metabolism and worsening her condition.

Recent studies have found that endometriosis patients like Emily are more than twice as likely to carry the MTHFR 677 genetic variation compared to the general infertile population.

The Overlooked Genetic Code — The Hidden Link Between MTHFR Mutation and Endometriosis

Endometriosis, often called the "invisible killer of women of reproductive age," affects approximately 10% of women worldwide.

It not only causes dysmenorrhea and pelvic pain but also silently undermines fertility.

A recent clinical study published in the Journal of Women's Health clearly reveals a strong association between MTHFR gene variation and fertility challenges in endometriosis patients.

Researchers analyzed 1,588 infertile women, including 158 with stage II or higher endometriosis confirmed by laparoscopy.

They found that among endometriosis patients who had experienced two or more failed IVF cycles or recurrent miscarriages, 21.5% had the MTHFR c.677C>T homozygous mutation—more than double the rate in the general infertile population (10.2%), with statistical significance (p<0.01).

Even more notably, the proportion of patients with the wild-type MTHFR gene (which allows normal folate metabolism) dropped from 17.2% in the general infertile population to just 8.2% (p<0.001).

This data strongly suggests that genetic folate metabolism disorders may be a hidden factor exacerbating fertility issues in endometriosis patients.

How Folate Metabolism Gene Mutations Build a "Fertility Wall"

The MTHFR gene plays a central role in folate metabolism. It converts folate into its bioactive form, 6S-5-methyltetrahydrofolate (5-MTHF), which is essential for remethylating homocysteine into methionine.

When the c.677C>T homozygous mutation occurs, MTHFR enzyme activity drops by 70%, severely impairing the production of 5-MTHF.

This triggers a cascade of effects:

·        Folate metabolism disorder: Synthetic folic acid cannot be efficiently converted into its active form, leading to accumulation of Unmetabolized Folic Acid in the body. This interferes with folate receptors and transporters, disrupts gene regulation, and poses long-term health risks.

·        Increased oxidative stress: Abnormal homocysteine metabolism causes its accumulation in the blood, inducing oxidative stress—a key factor in the pathogenesis of endometriosis that further damages the reproductive microenvironment.

·        Elevated fertility risks: Impaired methylation affects DNA synthesis and repair, increasing the risk of implantation failure and pregnancy loss, especially in endometriosis patients.

Unfortunately, many traditional treatments focus only on the lesions themselves, overlooking the "invisible barrier" of MTHFR gene variation.

Precision Breakthrough: From Genetic Testing to Successful Pregnancy

Still anxious about repeated IVF failures or early miscarriages?

Don’t worry—active folate has already helped many endometriosis patients with MTHFR mutations overcome fertility challenges.

Step 1: Genetic Screening
Women who meet the following criteria are advised to undergo MTHFR gene testing early:

·        Two or more failed IVF cycles;

·        Two or more early miscarriages
(These are also the typical characteristics of the study population.)

Step 2: Use the Right Folate to Bypass Metabolic Barriers
Directly supplement with bioactive folate—6S-5-methyltetrahydrofolate—which requires no metabolism and is readily absorbed. Naturalization folate, such as Magnafolate, is especially suitable for women preparing for pregnancy due to its practically non-toxic profile.

Clinical data shows that among 54 endometriosis patients who completed delivery after receiving treatment with 6S-5-methyltetrahydrofolate, 26 successfully gave birth—a success rate of 48.1%, with no additional pregnancy complications.

Just like Emily, who finally conceived after six months of targeted supplementation with active folate. What once seemed like an insurmountable fertility challenge was resolved through precise intervention.

Science Tip
Folate supplementation during pregnancy is not "the more, the better." The recommended daily intake is 600–800 μg. If you carry the MTHFR mutation, avoid blindly taking high doses of synthetic folic acid. Instead, consult your doctor and take bioactive folate that bypasses folate metabolism genes and is directly absorbable.

(Note: The case in this article is adapted from real research scenarios. Please follow medical advice for diagnosis and treatment.)

Reference:
Clément P, Alvarez S, Jacquesson-Fournols L, et al. T677T Methylenetetrahydrofolate Reductase Single Nucleotide Polymorphisms Increased Prevalence in a Subgroup of Infertile Patients with Endometriosis. J Womens Health (Larchmt), 2022, 31(10): 1501-1506. DOI: 10.1089/jwh.2022.0019.