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Repeated IVF Failure and the Immune System: What Is Actually Known?

Dr. Senai Aksoy · · Updated · 6 min read
Medically reviewed on 28 September 2026 - Dr. Senai Aksoy
A fertility specialist and an adult patient reviewing an immune-system diagram

Key Takeaways

A failed embryo transfer does not by itself diagnose an immune disorder. After repeated failure, review the medical history and previous IVF cycles before considering further tests. Routine NK-cell testing and immune add-on treatments are not supported by current recommendations. A diagnosed or suspected autoimmune or clotting condition may need a separate, targeted assessment.

Key evidence: ESHRE — Good practice recommendations on recurrent implantation failure ASRM — Role of immunotherapy in IVF guideline ASRM — Recurrent implantation failure committee opinion (2026)

Intralipids and IVF: what immune add-ons can and cannot do — Dr. Senai Aksoy

Intralipids and IVF: what immune add-ons can and cannot do — Dr. Senai Aksoy

This video supports the immune-testing and add-on-treatment sections; it does not cover every autoimmune condition discussed in the article.

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After an unsuccessful embryo transfer, an immune explanation can seem to offer a reason for what happened and a treatment to try next. The difficulty is knowing whether the proposed test can identify a cause, and whether treating its result would help. A failed transfer alone does not establish an immune disorder or justify a broad immune panel (ESHRE guidance on recurrent implantation failure).

When several transfers have failed, the starting point is a review of the treatment so far. A history of autoimmune disease or blood clots may lead to a more specific investigation. These are different reasons for testing, with different implications for care.

More Common Causes Still Come First

Before thinking about immune treatment, I first look for a correctable problem with the embryo, the uterine cavity, the fallopian tubes, the timing of progesterone or the transfer itself. Previous cycle records make that possible: they show how the embryos developed, what was found in the uterus and how the transfers went. The ASRM 2026 committee opinion also recommends reviewing the medical history alongside these records. The assessment usually covers:

Not every finding leads to a treatment. Age and embryo ploidy, or whether an embryo has a normal chromosome count, also help put the outcome in context and inform expectations for another attempt. Reviewing the whole history helps establish which questions remain open before adding more tests.

Why the Immune System Is Discussed

Immune cells are a normal part of the uterine lining. Their role in implantation has led researchers to investigate whether changes in immune activity could contribute to failure. The ESHRE recommendations discuss this biology and the difficulties of applying it in clinical care.

A plausible explanation still needs a reliable way to test it. For many of the immune tests offered after IVF, that link between the biology, the test result and a useful treatment has not been established.

The Problem With Many Immune Tests

Natural killer (NK) cells illustrate the problem. Despite their name, their presence in the uterine lining is normal. NK cells in the blood differ from those in the uterus, so a blood count cannot directly tell us what is happening where an embryo implants. Even a uterine measurement has limits: the number of cells does not explain how they are functioning.

Laboratories also differ in how they measure NK cells and which ranges they use. An abnormal result can therefore leave a patient with another uncertain finding, rather than an explanation for the failed transfer. ESHRE does not recommend blood or uterine NK-cell testing, or blood cytokine testing, for recurrent implantation failure.

Before agreeing to a test, ask the clinician to explain what each possible result would change. Repeating an unvalidated test does not resolve the uncertainty about what it means.

When an Immune Workup May Be Considered

Testing for a suspected medical condition serves a different purpose from looking for an immune explanation for IVF failure. Symptoms, a previous blood clot or other findings in the history or examination may give a clinician a specific reason to investigate an autoimmune or clotting disorder. Someone with an established diagnosis may instead need a review with the relevant specialist before fertility treatment.

Recurrent pregnancy loss also needs its own assessment. It should not be treated as interchangeable with failure to implant, or used as a reason to proceed straight to a commercial immune panel.

For recurrent implantation failure alone, the ASRM 2026 opinion finds insufficient evidence for routine antiphospholipid-antibody testing. The reason for ordering a test should be clear from the medical history, along with how the result could change care.

What About Immune Treatments?

Steroids, intravenous immunoglobulin (IVIG), intralipids and anticoagulants are sometimes discussed together as immune add-ons. They have different actions and indications, and cannot be substituted for one another. A prescription for a diagnosed condition does not establish that the same drug improves implantation in patients without that condition.

For IVF patients without another medical reason for treatment, the ASRM immunotherapy guideline advises against routine corticosteroids and finds insufficient evidence for intralipids or IVIG. The 2026 opinion on recurrent implantation failure also finds insufficient evidence for routine anticoagulation. Anticoagulants may be prescribed for a separately confirmed condition such as antiphospholipid syndrome; that does not support adding the other treatments to an IVF cycle.

Some research reports more encouraging results. A 2025 umbrella review of treatments for recurrent implantation failure found possible benefits for several interventions, including intralipids. It brought together existing systematic reviews, most of which were rated low or critically low in methodological quality. Some included the same trials, and definitions of implantation failure varied.

Those weaknesses matter when deciding whether to offer treatment routinely. The review identifies possibilities for further investigation, but does not establish a reliable benefit for routine care. These treatments can also cause harm, so adding one as a precaution after a failed transfer is not a neutral choice.

Can IVF Trigger Autoimmune Disease?

For a patient who already has multiple sclerosis (MS) or lupus, planning fertility treatment raises another question: could treatment affect the existing disease? The studies discussed below concern that situation. They cannot tell us whether IVF causes a new autoimmune disease in a previously healthy person.

Studies of MS have reached different conclusions about relapses after fertility treatment. A 2023 review by Sparaco and colleagues considers a GnRH-antagonist stimulation protocol a reasonable choice, without establishing that it prevents relapse. This is how I weigh that choice alongside disease activity and medication planning:

Dr Aksoy’s clinical perspective

“An MS diagnosis alone does not determine the IVF protocol. I first review the timing of the last relapse, any new or active MRI lesions, the disease course and the pregnancy medication plan with the neurologist. If the disease is active or there has been a recent relapse, we agree on treatment timing together. I do not want a patient to stop her MS medication on her own simply because IVF is starting.

“Depending on the expected ovarian response, I may choose an antagonist protocol. When the risk of ovarian hyperstimulation syndrome (OHSS) is high, this can allow a GnRH-agonist trigger to prepare the eggs for collection, with embryo freezing if needed, in a suitable patient.

“I would not describe this as preventing hormonal fluctuations to reduce MS relapses. Antagonist protocols have not been shown to prevent MS attacks better than other protocols. My priority is a safe stimulation plan coordinated with management of the neurological disease and its medication.”

The ASRM guideline on preventing ovarian hyperstimulation syndrome supports the measures described here for reducing OHSS risk. That evidence concerns the safety of ovarian stimulation; it does not demonstrate protection against MS relapse.

Lupus requires similar attention to the circumstances in which results were obtained. In a French prospective study of women with lupus, pregnancy outcomes and disease flares did not differ significantly between pregnancies achieved with fertility treatment and spontaneous pregnancies. Most women in the treatment group had inactive disease at the outset. The findings therefore do not establish safety for women with active or severe lupus.

The study followed pregnancies that had already been achieved, so it also cannot give the chance of a live birth for each IVF cycle started. If you have an autoimmune, neurological or rheumatological condition, your specialist and fertility team need to consider disease activity, recent relapses and the medication plan before treatment, alongside the fertility assessment.

Conclusion

After repeated failure, I start with the previous cycles and the medical history. If an immune test or treatment is proposed, ask which finding makes it relevant to you. An uncertain result should not be presented as a confirmed cause.

Request a Case Review

You may request a confidential case review to discuss the findings from previous cycles and whether further investigation is relevant.

Frequently Asked Questions for Dr. Aksoy

Does IVF weaken the immune system?

No. The ovarian stimulation drugs used in IVF and the progesterone support given after transfer are not treatments that weaken the immune system in general. Hormone levels change, but that does not mean your body’s defences are down. Cortisone, which is sometimes suggested as an add-on, is different: it can suppress the immune response, and I do not recommend giving it routinely to everyone.

Should immune testing be done after a single failed transfer?

A negative first transfer is very hard to take, but on its own it does not mean your immune system rejected the embryo. Even an embryo that looks good may not implant for chromosomal or other biological reasons; we do not expect every suitable transfer to lead to a pregnancy. I first review how the embryo developed, the uterus and the conditions of the transfer. I do not order immune tests on the strength of a single result.

This approach is consistent with the ESHRE recommendations on recurrent implantation failure, which call for each patient’s situation to be assessed individually.

What does a high NK cell count in the blood mean?

It is understandable to feel anxious when a report says “NK high”. But this test measures cells in the blood. NK cells in the uterine lining have different characteristics, and they also have normal roles in early pregnancy. A high value in the blood therefore does not show that the embryo is being attacked in the uterus. Nor is there an accepted threshold that reliably predicts the chance of pregnancy or tells us which treatment is needed. I do not start treatment on the basis of this result.

ESHRE does not recommend measuring NK cells in either the blood or the uterine lining for recurrent implantation failure.

Should intralipids or cortisone be added “just in case”?

I understand wanting to do everything you can before the next attempt. But intralipid is an intravenous infusion, and cortisone is a medicine with effects of its own; I do not add either on the grounds that it “can’t hurt”. Intralipid has not been reliably shown to increase live births. In a large trial in women with repeated failed transfers, prednisone did not increase live births, and there were warning signs for some adverse pregnancy outcomes.

I first look for a correctable problem with the embryo, the uterine cavity, the fallopian tubes, the timing of progesterone or the transfer itself. If there is a diagnosed condition that needs treatment, I manage it together with the relevant specialist.

Sources

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Dr. Senai Aksoy

Dr. Senai Aksoy studied and trained in France before returning to Turkey, where he was a member of the ICSI team at Sevgi Hospital, Ankara — the country's first ICSI centre (1994-95) — and a co-author on the first Turkish ICSI publications produced in collaboration with the Brussels Van Steirteghem group (Human Reproduction, 1996; PMID 8671323). He helped build the IVF programme at the American Hospital Istanbul and has been running his own fertility practice since 1998.

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