Researchers compared 50 women who had repeated failed IVF attempts with 50 women who got pregnant naturally to understand what goes wrong. They found that women with repeated failures had imbalanced hormone receptors in their uterus lining and lower levels of vitamin D and a fertility hormone called AMH. They also had higher inflammation markers. These findings suggest that checking hormone receptor patterns, vitamin D levels, and inflammation could help doctors identify why some women’s embryos don’t stick to the uterus, potentially opening new treatment paths.

The Quick Take

  • What they studied: Why embryos fail to implant in the uterus during IVF by comparing hormone receptor patterns and blood markers in women with repeated implantation failures versus women who conceive naturally
  • Who participated: 100 women total: 50 women with unexplained repeated IVF failures and 50 fertile women who conceived naturally, all studied in Tehran between 2021-2023
  • Key finding: Women with repeated IVF failures had abnormal patterns of hormone receptors in their uterus lining—too much of one type (ESR-α) and too little of another (ESR-β and PGR-B)—plus lower vitamin D and higher inflammation
  • What it means for you: If you’re struggling with repeated IVF failures, doctors may soon be able to test your vitamin D levels, inflammation markers, and uterus lining hormone patterns to understand why embryos aren’t implanting. This could lead to targeted treatments, though more research is needed before these tests become standard care

The Research Details

This was a case-control study, which means researchers compared two groups: women who had experienced repeated IVF failures (the problem group) and women who got pregnant naturally (the comparison group). They collected blood samples and tiny tissue samples from the uterus lining at a specific point in the menstrual cycle. They then measured hormone receptor levels in the tissue using laboratory techniques and checked blood levels of vitamin D, inflammation markers, and a fertility hormone called AMH.

The researchers used specialized lab tests to measure how much of different hormone receptors were present in the uterus tissue. Think of hormone receptors like locks on cells—if the locks are broken or in the wrong amounts, the hormones can’t work properly. They also measured inflammation in the blood and vitamin D levels, which previous research suggested might affect whether embryos can implant.

This approach matters because it looks at the actual tissue where embryos need to implant, not just blood tests. By comparing women with problems to women without problems, researchers can identify what’s different. The study also connected multiple factors—hormone receptors, vitamin D, inflammation, and fertility hormones—which helps create a more complete picture of what might be going wrong

Strengths: The study used objective laboratory measurements rather than relying on patient reports, and it examined actual uterus tissue where the problem occurs. The sample size of 100 women is reasonable for this type of study. Limitations: The study only included women in one city in Iran, so results may not apply to all populations. The study is observational, meaning it shows associations but can’t prove that these hormone imbalances directly cause implantation failure. More research is needed to confirm these findings and test whether treating these imbalances actually improves pregnancy rates

What the Results Show

Women with repeated IVF failures had significantly different hormone receptor patterns compared to fertile women. Specifically, they had higher levels of one type of estrogen receptor (called ESR-α) but lower levels of another estrogen receptor (ESR-β) and lower levels of a progesterone receptor (PGR-B). These differences were quite striking—the lab tests could distinguish between the two groups with very high accuracy (over 89% accuracy for some markers).

Women with repeated failures also had lower vitamin D levels and lower AMH (a hormone that reflects egg supply). Interestingly, they had higher inflammation markers in their blood, suggesting their bodies were in a more inflamed state. In the fertile women, there was a positive relationship between one of the progesterone receptors and vitamin D levels, suggesting these two factors work together in healthy pregnancies.

The combination of these markers—abnormal hormone receptors, low vitamin D, low AMH, and high inflammation—appeared to be a pattern that distinguished women with implantation problems from fertile women. The researchers suggest this pattern could potentially be used as a diagnostic tool to identify why some women’s embryos aren’t implanting

The study found that the progesterone receptor (PGR-B) was connected to AMH levels, suggesting that hormone receptor function may be linked to overall reproductive health. The inflammation marker (hs-CRP) was elevated in women with implantation failures, indicating that excessive inflammation in the body might interfere with the delicate process of embryo implantation. The study also noted that vitamin D appeared to play a role in regulating these processes, as it was lower in women with problems and was associated with progesterone receptor function in fertile women

Previous research has suggested that vitamin D deficiency and inflammation are associated with infertility, and this study supports those findings. The discovery that hormone receptor imbalances are involved adds a new layer of understanding. The study builds on earlier work showing that the uterus lining’s ability to receive an embryo (called receptivity) is crucial for IVF success, and it identifies specific molecular changes that might explain why receptivity fails in some women

This study shows associations but cannot prove cause-and-effect relationships. It’s possible that the hormone imbalances are a result of infertility rather than a cause. The study only included women in one location, so results may not apply to women from different ethnic backgrounds or geographic regions. The study didn’t test whether treating low vitamin D or inflammation actually improves implantation rates. Additionally, the study didn’t follow women over time to see if these markers changed or predicted future pregnancy success. More research with larger, more diverse groups of women is needed to confirm these findings

The Bottom Line

Based on this research (moderate confidence level): Women with repeated IVF failures should have their vitamin D levels checked and consider supplementation if deficient, as vitamin D appears important for uterus lining health. Testing for inflammation markers and AMH levels may help identify why implantation is failing. However, these recommendations are preliminary—doctors should not yet use these tests as the sole basis for treatment decisions. More research is needed to determine whether treating these imbalances actually improves pregnancy success rates

This research is most relevant to women experiencing repeated IVF failures without an obvious explanation. It may also interest fertility specialists looking for new diagnostic tools. Women with a single failed IVF cycle should not be overly concerned, as one failure is common. Women with other known causes of infertility (like blocked tubes or severe male factor) may have different underlying issues. General population women not pursuing IVF don’t need to act on these findings

If vitamin D deficiency is identified and treated, it may take 2-3 months to significantly raise vitamin D levels. Inflammation reduction through lifestyle changes or treatment may take 4-8 weeks to show effects. Any improvements in implantation success would only be measurable after attempting another IVF cycle, which typically takes 1-2 months to prepare for. Realistic expectations: these interventions are not guaranteed to solve implantation problems, as multiple factors are involved

Want to Apply This Research?

  • Track vitamin D supplementation daily and log blood test results (vitamin D levels, inflammation markers, AMH) every 3 months. Users can set reminders for supplement timing and record any dietary sources of vitamin D
  • Users can set a daily reminder to take vitamin D supplements if deficient, track sun exposure time (which helps vitamin D production), and log anti-inflammatory foods consumed (like fatty fish, leafy greens, berries). They can also track IVF cycle dates and correlate them with vitamin D and inflammation marker test results
  • Create a long-term tracking dashboard showing vitamin D levels, inflammation markers, and AMH over time alongside IVF cycle attempts. Users can visualize trends and share this data with their fertility specialist. Set quarterly reminders for blood work to monitor progress and adjust supplementation as needed

This research is preliminary and should not replace personalized medical advice from your fertility specialist. The findings suggest potential associations but do not prove that these factors directly cause implantation failure or that treating them will improve pregnancy rates. Do not start, stop, or change any fertility treatments or supplements based solely on this study. Vitamin D supplementation should be discussed with your doctor, as excessive vitamin D can be harmful. These diagnostic markers are not yet standard clinical practice and should only be used as part of comprehensive fertility evaluation under professional medical guidance. If you’re experiencing repeated IVF failures, work with your fertility team to identify the specific cause in your situation