MiFert Immunology

The Immune Balance of Implantation

Successful pregnancy requires a delicate immunological paradox - the maternal immune system must:

• Tolerate the semi-allogeneic embryo (50% foreign paternal DNA)
• Maintain immune defenses against infections
• Support placental development through controlled inflammation
• Prevent excessive inflammation that would reject the embryo
• When endometrial immune balance is disrupted, the result is:
• Recurrent implantation failure
• Recurrent pregnancy loss
• Poor embryo development post-implantation

MiFert Immunology evaluates the endometrial immune environment, identifying imbalances that impair reproductive success.

What is MiFert Immunology?

MiFert Immunology performs comprehensive analysis of immune cells and inflammatory markers in the endometrial tissue, measuring:

• Natural Killer (NK) Cell Populations: Both total numbers and activation status
• Pro-inflammatory Cytokines: Markers of excessive inflammation (TNF-α, IL-1β, IL-6, IFN-γ)
• Regulatory Immune Cells: T-regulatory cells (Tregs) that promote tolerance
• Immune Balance Ratios: Pro-inflammatory vs. anti-inflammatory profiles

This analysis reveals whether the endometrial immune environment is hostile or welcoming to embryo implantation.

Clinical Applications

Primary Indications:

Recurrent Implantation Failure (RIF)

• Especially after multiple failed cycles with good embryos
• Immune dysfunction found in 20-30% of RIF patients

Recurrent Pregnancy Loss (RPL)

• 2+ miscarriages, especially early losses (before 10 weeks)
• May indicate immune rejection of embryo

Autoimmune Conditions

• Systemic lupus erythematosus (SLE)
• Antiphospholipid syndrome (APS)
• Hashimoto's thyroiditis
• Rheumatoid arthritis
• Other autoimmune disorders affecting reproductive outcomes

Elevated Peripheral NK Cells

• Blood tests showing high NK cell counts or activity
• May correlate with endometrial immune dysfunction

Poor Endometrial Response

• Thin endometrium despite hormonal support
• Chronic inflammation may impair endometrial development

Previous Immunomodulatory Therapy Failure

• Empirical treatment (steroids, intralipids) without testing
• Immunology testing guides targeted therapy

MiFert Immunology Analysis

Technology: Flow Cytometry & Immunohistochemistry

Analysis Methods:

• Flow cytometry of endometrial cells for NK cell quantification and phenotyping
• Immunohistochemistry staining for CD56+ cells (uNK marker)
• ELISA or multiplex assays for cytokine quantification
• Protein expression analysis of inflammatory markers

What the Test Measures:

• Total uNK Cell Count: CD56+ cells per high-power field (HPF)
• Activated NK Cells: CD56+/CD16+ (more cytotoxic subset)
• NK Cell Activation Markers: NKp46, NKG2D expression
• Pro-inflammatory Cytokines: TNF-α, IL-1β, IL-6, IFN-γ levels
• Anti-inflammatory Markers: IL-10, TGF-β levels
• Th1/Th2 Balance: Ratio of pro-inflammatory vs. pregnancy-supportive immune response
• T-Regulatory Cells: Foxp3+ Treg quantification

Immunology Classification & Interpretation

Normal Immune Profile:

• Moderate uNK cell levels (5-15% of stromal cells)
• Low pro-inflammatory cytokines
• Adequate regulatory T cells
• Balanced Th1/Th2 ratio
• Recommendation: No immune intervention needed

Elevated NK Cell Profile:

• High uNK cells (>15% of stromal cells)
• Increased NK cell activation markers
• Recommendation: NK suppression therapy (corticosteroids, intralipids, IVIG)

Pro-Inflammatory Profile:

• Elevated TNF-α, IL-1β, IL-6, IFN-γ
• Low IL-10, TGF-β
• High Th1/Th2 ratio
• Recommendation: Anti-inflammatory therapy (corticosteroids, omega-3, aspirin)

Immunodeficient Profile:

• Low uNK cells (<5%)
• Reduced immune activation
• Recommendation: Immune stimulation may be needed (rare)

Mixed/Complex Profile:

• Multiple immune dysfunction patterns
• Recommendation: Combination immunomodulation therapy

Sample Collection

Red Tube (Separate from Receptivity/Microbiome):

• Protein preservation buffer for immunology analysis
• From the same endometrial biopsy
• Requires adequate tissue sample for immune cell analysis
• Turnaround Time: ~15 days