Immune testing for infertility looks for signs that the immune system may be affecting implantation or early pregnancy. It is usually offered after several failed IVF transfers or repeated miscarriage. The tests include natural killer (NK) cell tests, cytokine ratios and antibody screens.
The evidence for most of these tests is weak. The UK regulator, the HFEA, states that blood NK cell tests offer no useful information about pregnancy outcomes. It rates several immune treatments red or grey.
This article explains what immune testing involves, what recurrent implantation failure means and which causes doctors usually check first. It also sets out what the HFEA and the European Society of Human Reproduction and Embryology (ESHRE) say about each test and treatment.
If you have had unsuccessful cycles, you can book a free fertility advisory call to review your history. IVF Matters also offers immune tests with clinical review after counselling.
What Is Immune Testing for Infertility?
Immune testing for infertility is a group of blood or womb lining tests that look at immune cells, immune signalling proteins and antibodies. The aim is to find an immune cause for failed implantation or miscarriage.
The HFEA classes these tests as treatment add-ons. An add-on is an optional extra offered on top of routine treatment, often at extra cost. The HFEA states that evidence for many add-ons is limited or missing, and that clinics should give you evidence of effectiveness for anything they offer. See the HFEA guide to treatment add-ons.
How the Immune System and Fertility Are Linked
The immune system and fertility interact because an embryo carries genetic material from both parents. The womb lining must allow the embryo to attach without attacking it. Immune cells, including uterine NK cells, are present in the lining and take part in this process.
What is not proven is that measuring these cells predicts success or that changing them improves it. Immune cells in blood may not reflect what happens inside the womb.
Some immune conditions are well established. Autoimmune diseases such as antiphospholipid syndrome can affect pregnancy and are diagnosed with standard blood tests. These are different from the research tests described below.
What Is Recurrent Implantation Failure?
Recurrent implantation failure (RIF) is when embryos considered viable repeatedly fail to produce a pregnancy. There is no single agreed number of failed transfers.
ESHRE published good practice recommendations on RIF in 2023. It defines RIF as transfer of viable embryos failing to give a positive pregnancy test often enough in a specific patient to justify further investigation or treatment. It recommends a threshold of a 60% cumulative predicted chance of implantation to identify RIF.
ESHRE also challenges the idea of RIF as a disease that can be diagnosed and treated. Its working group lists many tests and treatments as not recommended while better research is awaited. See the ESHRE RIF recommendations.
IVF Implantation Failure: What Doctors Check First
IVF implantation failure has several causes, and most are not immune related. Doctors usually review these first:
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Embryo factors. Many embryos have the wrong number of chromosomes. This becomes more common with age. See our guide to PGT A testing.
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Womb cavity. Polyps, fibroids, scarring or fluid in the tubes can interfere with implantation. A saline scan or HYCOSY looks at the cavity.
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Chromosomes in either partner. A karyotype test checks for structural changes.
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Thyroid and metabolic health. A thyroid profile checks thyroid hormones and antibodies.
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Sperm quality. A semen analysis and, where needed, DNA fragmentation testing.
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Transfer technique and lab conditions. Including culture methods and the embryo glue medium used at transfer.
IVF Matters offers an implantation profile that covers chromosome analysis, thyroid tests, antinuclear antibody, blood sugar and liver function.
Immune Testing After Failed IVF: Which Tests Are Offered?
Immune testing after failed IVF can include the tests below. The table shows what each measures and what the HFEA says.
| Test | What It Measures | Position |
|---|---|---|
| Blood NK cell tests | Number and activity of NK cells in blood | HFEA: no useful information about pregnancy outcomes |
| Uterine NK cell biopsy | NK cells in the womb lining | HFEA: should only be offered in a research setting |
| TH1/TH2 cytokine ratio | Balance of immune signalling proteins | No HFEA rating listed |
| Antiphospholipid antibodies | Antibodies linked to clotting and pregnancy loss | Established autoimmune diagnosis, tested on clinical grounds |
| Autoimmune screen | Antibodies such as antinuclear antibody | Used to find autoimmune disease |
The HFEA position comes from its page on immunological tests and treatments for fertility, published on 16 October 2023.
Immunological Testing in IVF: What Is the Evidence?
Immunological testing in IVF has not been shown to improve live birth rates. The HFEA states that for most patients a routine cycle of proven treatment works without add-ons.
Treatments given after immune testing carry their own risks. The HFEA ratings are:
| Treatment | HFEA Rating | Main Concern |
|---|---|---|
| Intralipids | Grey (cannot rate) | No moderate or high quality studies show they improve the chance of a baby |
| Steroids | Red | Potential safety concerns, including infection risk |
| Intravenous immunoglobulins (IVIG) | Red | A blood product given by weekly infusion, with risks including blood clots and kidney failure |
| TNF alpha inhibitors | No rating | No evidence to support use |
Who Might Consider Immune Testing?
Immune testing is considered most often by patients with repeated unexplained failures or recurrent miscarriage after other causes have been checked. Even then, it should follow a specialist discussion.
Reasonable situations to discuss include:
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A known or suspected autoimmune condition
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A history of clotting problems or pregnancy loss
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Several failed transfers of good quality embryos with normal investigations
The IVF Matters immune test page states that the tests remain controversial and should be done only after discussion with a specialist.
Immune Tests at IVF Matters
The IVF Matters immune test package is £499. You choose either an NK assay or a TH1/TH2 cytokine ratio. Prices may change, so confirm on the immune tests page.
How it works:
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You book a blood draw at the London clinic. The page states walk in appointments run on Mondays and Tuesdays.
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The sample is analysed and results arrive in up to 14 working days through your secure patient portal.
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Dr Irfana Koita reviews the results and discusses them on a complimentary call.
The HFEA view on blood NK cell tests is stated above. We recommend discussing this before ordering. You can arrange a private fertility consultation first.
Questions to Ask Your Clinic
Use this checklist before agreeing to immune tests or treatment:
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What is the HFEA rating for this test or treatment?
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Which non immune causes have we already ruled out?
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How would a result change my treatment plan?
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What are the risks of the treatment that follows?
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Is this offered as part of research, and is it free if so?
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Can I have an itemised cost plan?
Frequently Asked Questions
How long do immune test results take?
At IVF Matters, results arrive in up to 14 working days. Other providers may differ.
Can I take part in research on immune testing?
Yes, where trials are available. The HFEA states that patients should not be charged extra to take part in research, including clinical trials.
Should I stop immune medicines I already take?
No. The HFEA advises that patients who take these drugs for an immunological disease should continue them under their immunologist's supervision.
Are intralipid infusions safe for everyone?
No. The HFEA states they are not suitable for people with allergies to eggs, soya beans or peanut oil. Infusions carry a risk of infection, and reactions range from rashes to anaphylaxis.
Does a failed cycle mean I have an immune problem?
No. One failed cycle is common and usually has no immune cause. Embryo chromosomes and the womb cavity are checked first.
Conclusion
Immune testing for infertility remains controversial. The HFEA does not support blood NK cell tests, rates steroids and IVIG red and cannot rate intralipids. ESHRE advises individual assessment of repeated implantation failure and lists many tests and treatments as not recommended.
Review embryo quality, the womb cavity, chromosomes and thyroid health first. If you still want immune tests, ask for the evidence and the cost in writing. Book a free fertility advisory call to plan your next step.
Resources
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HFEA: Treatment add-ons
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HFEA: Pre implantation genetic testing for aneuploidy (PGT A)
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ESHRE: Recurrent implantation failure good practice recommendations
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Human Reproduction Open, 2023: ESHRE good practice recommendations on recurrent implantation failure
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