Immunological Testing (IMF) in IVF: Indications and Clinical Utility
Immunological testing (IMF) during IVF is not routinely recommended for all patients due to insufficient evidence supporting its clinical utility, and should be reserved only for specific cases of recurrent implantation failure after multiple failed high-quality embryo transfers.
What is Immunological Testing (IMF) in IVF?
Immunological testing in the context of IVF refers to various tests that evaluate potential immune-related causes of implantation failure or pregnancy loss, including:
- Antiphospholipid antibody testing (including lupus anticoagulant and anticardiolipin antibodies) 1, 2
- Antinuclear antibody (ANA) testing 2
- Natural killer (NK) cell testing (both peripheral blood and uterine) 3, 4
- Embryotoxic assays and leukocyte antibody testing 1
Who May Need Immunological Testing During IVF?
Immunological testing is primarily considered for:
- Patients with recurrent implantation failure (RIF), defined as failure to achieve pregnancy after three or more embryo transfer cycles with high-quality blastocysts 3, 4
- Patients with unexplained recurrent pregnancy loss 1, 2
Who Does NOT Need Immunological Testing During IVF?
Immunological testing is NOT routinely recommended for:
- First-time IVF patients 1, 4
- Patients with identified causes of infertility (such as male factor, ovulatory disorders, tubal factor) 1
- Patients who have had successful IVF outcomes previously 2
Current Practice Patterns and Evidence
The use of immunological testing in IVF remains controversial due to limited high-quality evidence:
- A survey of fertility specialists in Australia and New Zealand found that 40% ordered uterine NK cell testing and 13.3% ordered peripheral blood NK cell testing, primarily for recurrent implantation failure 4
- Among specialists who did not offer these tests, 87% cited insufficient evidence as the main reason 4
- Studies have shown varying rates of autoimmune antibodies in IVF failure patients, with one study finding 32.1% of patients who failed to conceive following IVF-ET tested positive for one or more autoimmune antibodies 2
Potential Treatments Following Positive Immunological Testing
For patients with positive immunological test results, various treatments have been proposed:
- Corticosteroids (such as prednisone) 2, 3, 4
- Anticoagulants and antiplatelets (such as aspirin or heparin) 2, 4
- Intravenous immunoglobulin (IVIg) 5, 3, 4
- Intralipid infusions 3, 4
- Tacrolimus (for patients with high Th1/Th2 ratio) 3
Limitations and Considerations
Important caveats regarding immunological testing in IVF include:
- Lack of standardized testing protocols and reference ranges 3, 4
- Heterogeneity in immune dysfunction among women with RIF, suggesting a "one-size-fits-all" approach is inappropriate 3
- Limited evidence from well-designed randomized controlled trials supporting immunological treatments 5, 4
- Potential risks and costs associated with immunomodulatory treatments 5, 4
Recommendations Based on Current Evidence
Based on the available evidence:
- Immunological testing should not be routinely offered to all IVF patients 1, 4
- Testing may be considered in cases of recurrent implantation failure after excluding other causes 3, 4
- Treatment decisions should be individualized based on specific test results rather than empirical approaches 3
- Patients should be counseled about the limited evidence supporting immunological testing and treatments in IVF 5, 4
Future Directions
To improve the clinical utility of immunological testing in IVF:
- Standardized tests for evaluation of immune status in patients are needed 3
- Sufficiently powered randomized controlled trials for personalized therapies should be conducted 5, 3
- Until stronger evidence emerges, the use of immunological add-on interventions should be limited to specific cases of recurrent implantation failure 3