Immune Treatments After Failed IVF: What the Evidence Supports

Key Takeaways

Immune cells help an embryo implant. A failed transfer does not prove that the body rejected it. Routine NK-cell panels and add-ons such as intralipids, IVIG, PBMC or steroids still lack reliable proof that they raise live birth in everyday care. The clearer next step is usually a careful look at the embryos, uterus, transfer and hormones—before adding another drug.

Key evidence: ASRM committee opinion on recurrent implantation failure (2026) · ESHRE good practice recommendations on recurrent implantation failure (2023) · Prednisone versus placebo randomized trial (JAMA, 2023)

After more than one unsuccessful embryo transfer, many people ask: “Could my immune system be rejecting the embryo?” The question is understandable. It also offers a tidy explanation for a painful event that often has no single cause.

The biology is less tidy. Immune cells help with normal implantation; their presence does not mean the embryo is under attack. A commercially labelled “abnormal” result is not proof of why a transfer failed, and it does not identify a treatment that will improve live birth.

On this page

• Does the immune system reject an embryo?
• What do immune tests actually show?
• Do intralipids, IVIG, steroids or PBMC improve live birth?
• Why do some studies look positive?
• What should be reviewed before another transfer?
• When does a specialist immune assessment make sense?
• Clinical note
• Questions to ask before accepting an add-on
• Frequently Asked Questions for Dr. Aksoy
• More questions about immune add-ons

Does the Immune System Reject an Embryo?

Short answer: Normal implantation needs carefully coordinated immune activity. That is not the same as rejecting a transplanted organ.

Uterine natural killer (NK) cells are a normal part of the endometrium and change across the menstrual cycle. Their name often causes alarm, yet blood NK cells and uterine NK cells are not interchangeable. The HFEA’s patient evidence review explains that blood NK measurements do not give useful information about pregnancy outcomes, and that uterine NK-cell testing remains a research question.

One or two unsuccessful transfers are not evidence of an immune disorder. ASRM’s 2026 committee opinion defines recurrent implantation failure by the cumulative chance expected from the number and quality of blastocysts transferred. No single count fits every patient. The two guidelines also use different thresholds: ASRM defines RIF at a 95% cumulative chance, while ESHRE uses a 60% cumulative predicted chance of implantation to decide when further investigation should start. Age, embryo ploidy (chromosome number), embryo quality and prior transfer history all change that calculation.

Recurrent implantation failure is different from recurrent pregnancy loss. In implantation failure, the pregnancy test stays negative after transfer. In pregnancy loss, implantation has occurred and the pregnancy is then lost. The two can overlap, but they do not justify the same tests or treatments.

What Do Immune Tests Actually Show?

Most commercially offered panels measure a laboratory marker or an association that has not been validated as a cause of failed implantation.

Tests may include peripheral-blood NK-cell number or activity, uterine NK cells, Th1/Th2 cytokine ratios, broader cytokine panels or HLA compatibility. A laboratory can produce a number. The harder questions are whether that number reliably predicts live birth, and whether changing it improves the outcome.

The ESHRE good practice recommendations do not recommend routine peripheral or uterine NK-cell testing, uterine T-cell assessment, blood cytokine testing or HLA-C compatibility testing in recurrent implantation failure. Reference ranges are uncertain, methods are poorly standardised, blood and endometrial biology differ, and no proven treatment pathway follows from the result.

An “abnormal” result can feel more certain than it is. A value outside one laboratory’s range may not have caused the failed transfer. Before paying for a panel, ask what decision the result would change—and whether that change has been shown to improve live birth.

Do Intralipids, IVIG, Steroids or PBMC Improve Live Birth?

Short answer: Some small studies and pooled reviews report better pregnancy outcomes. Current major guidance does not treat that evidence as reliable enough for routine use. NICE’s 2026 fertility guideline (NG257) advises against using immunological agents—including intralipids, IVIG and steroids—as part of fertility treatment.

The outcome that matters is live birth; a shifting blood marker or an early positive test is only a step toward it. Before accepting an add-on, ask whether it has improved that outcome in patients like you, and at what safety cost.

Why Do Some Studies Look Positive?

A promising pooled result can sit alongside a cautious guideline when the underlying trials are small, overlapping or clinically different. “A meta-analysis was positive” (a study that pools several trials) is not the end of the discussion. What matters is which patients were included, how failure was defined, what else was given, and whether the studies measured live birth as well as implantation or clinical pregnancy.

What Should Be Reviewed Before Another Transfer?

Short answer: Start with a structured look at the embryos, uterus, transfer and hormone plan, before assuming an immune cause.

A useful review may include:

• the number, stage and quality of embryos transferred, plus age at egg retrieval;
• whether embryo ploidy information exists and what it would change;
• laboratory development, freezing and thawing history;
• the uterine cavity and tubes, and whether repeat imaging is justified;
• endometrial thickness, progesterone exposure and transfer timing;
• whether the transfer was technically difficult;
• endometriosis, adenomyosis or chronic endometritis when the history makes them plausible;
• the original infertility diagnosis, including relevant sperm factors.

This is not a list every patient must complete. ASRM notes that if a careful review finds no clear correctable cause, more testing is not automatically useful. Another embryo transfer can still be reasonable: ASRM notes that many patients ultimately achieve pregnancy.

PGT-A (genetic screening of embryos for chromosome number) is often offered at this stage, so it helps to be precise. ESHRE (2023) says PGT-A can be considered, because removing embryos with whole-chromosome aneuploidy is suggested to help. ASRM 2026 says it may be discussed in shared decision-making when earlier embryos were untested, but finds no evidence that PGT-A itself raises live birth in recurrent implantation failure. Hysteroscopy helps when the cavity needs a closer look; it is not a default next step after every failed transfer.

For a broader step-by-step review, see what to assess after a failed IVF cycle. Questions about other add-ons are covered in our evidence summaries on EmbryoGlue and ERA testing.

When Does a Specialist Immune Assessment Make Sense?

A specialist immune assessment follows a known or suspected immune disease. A failed transfer or a high NK result does not trigger it.

If the signs listed in the Clinical Note below are present, the relevant specialist should be involved. That is different from giving immunosuppression “empirically” to an otherwise healthy IVF patient.

Patients with a genuine immune condition should not start, stop or change medically indicated steroids, biologic drugs or IVIG without consulting the clinician managing that condition. Coordinate those decisions with reproductive medicine. Without that diagnosis, the same medicines should not be added simply to cover an unproven theory. The Clinical Note below lists the signs that prompt a rheumatology or immunology referral.

Clinical Note

The misconception I hear most often is this: “My NK cells came back high, so my immune system must be attacking the embryo and needs to be suppressed.”

Blood NK cells and uterine NK cells are not the same thing. Uterine NK cells have a normal job in implantation. An “elevated NK” result alone does not reliably tell us who will benefit from intralipid, IVIG or steroids. That is why I do not recommend those treatments solely after a failed transfer, a miscarriage, or a high NK number. ESHRE also does not recommend routine NK testing, intralipid or IVIG for this indication.

And these are not “harmless just-in-case” extras. Steroids can raise blood sugar and infection risk. IVIG can cause allergic reactions, clotting problems or kidney injury.

When do I ask for rheumatology or immunology help? When there is a known autoimmune disease, a previous blood clot, recurrent pregnancy loss with antiphospholipid antibodies, or systemic clues such as joint swelling, prolonged morning stiffness, mouth ulcers, photosensitivity, Raynaud phenomenon, an unexplained rash, low platelets or kidney findings. After two or more pregnancy losses, looking specifically for antiphospholipid syndrome can make sense.

The aim is not to blunt the immune system in the dark. If a real disease is present, treat that disease—with the right specialist, and with evidence.

— Dr. Senai Aksoy

Questions to Ask Before Accepting an Add-on

Ask for the diagnosis, the live-birth evidence that applies to you, and the safety or cost that comes with uncertainty.

• What specific diagnosis is this treatment meant to treat?
• Is the proposed test validated for implantation outcomes, and how would its result change care?
• What is the absolute live-birth benefit in patients like me, beyond the implantation or pregnancy rate?
• Is the treatment recommended by ASRM or ESHRE, or is it being offered as experimental care?
• What are the infusion, infection, allergy, clotting, kidney or pregnancy-related risks?
• Would the same budget and time be better used for another evidence-based transfer or a targeted reassessment?

These treatments are not risk-free simply because they are called add-ons. The Clinical Note above summarises the main steroid and IVIG risks; intralipid can also trigger allergic or infusion reactions. The HFEA review treats the weak evidence for intralipid separately from the safety concerns that give steroids and IVIG a red rating.

Frequently Asked Questions for Dr. Aksoy

After failed embryo transfers, do you recommend intralipid—and when would you consider or refuse it?

I do not recommend intralipid routinely after failed embryo transfers. Intralipid is a fat emulsion given into a vein. It began to be used on the idea that the immune system was blocking implantation, but we do not have reliable enough evidence that it raises the live-birth rate. Some small studies have reported positive results, yet that is not enough to make the treatment standard practice. And we are not talking about a harmless drip: allergic reactions and infusion-related complications can occur.

In a patient who has had several failed transfers, I first reassess embryo quality, the woman’s age, the uterine cavity, how the endometrium was prepared, and how progesterone was used. Even in unexplained repeated failures, I do not present intralipid as a proven treatment. I would only consider such a practice within an ethics-approved clinical trial. To offer patients a new treatment, we need to show that it leads to more healthy babies—not merely that it might work in theory.

When a patient says “my uterus is rejecting the embryo,” how do you reply? Does one failed transfer show that?

I often hear this from patients: “Doctor, my uterus will not accept the embryo.” I first explain that this is not an accurate description. The uterus does not see the embryo as a foreign organ and reject it automatically. The immune system actually plays an important role in implantation and in the development of pregnancy. A single failed transfer certainly does not show that there is a problem in the uterus, or that the immune system attacked the embryo. Even an embryo that looks very good can fail to develop for chromosomal or other biological reasons. And even embryos with a normal chromosome make-up are not guaranteed to implant at every transfer.

When there have been several failures, of course we look more carefully: embryo quality, the uterine cavity, the endometrium, and the transfer protocol. But I say this to the patient in particular: do not blame yourself or your uterus. Failure to implant does not mean your body did not want the embryo. What matters is not putting a name on the failure at all costs, but checking whether there is a cause we can change.

If there is no autoimmune diagnosis, do you add IVIG to IVF treatment?

In women without a diagnosed autoimmune disease, I do not recommend IVIG to improve IVF success. IVIG is a serious treatment prepared from antibodies from thousands of donors, used for certain immune-system diseases. It was thought that in repeated implantation failure it might raise the chance of pregnancy by regulating the immune system, but research to date has not shown a reliable benefit for live birth. It is also expensive and not free of risk. Besides headache, fever and allergic reactions, kidney failure, blood clots or serious reactions can develop rarely.

I know that some centres recommend IVIG after NK-cell tests or various immunological analyses. Most of those tests have not been shown to explain implantation failure reliably, or to identify who will benefit from IVIG. If there is a genuine immune disease that requires IVIG, that is a separate matter and should be assessed with the relevant specialist. But I do not think it is right to try to suppress or change the immune system simply because embryo transfers have failed. We have to protect both the patient’s health and her financial resources.

More questions about immune add-ons

Should I take prednisone “just in case” before transfer?

Routine use is not supported. In the largest cited randomised trial, prednisone did not improve live birth and was associated with concerning secondary safety signals.

Can I still become pregnant if no cause is found?

Yes. An unexplained unsuccessful transfer does not mean future transfers cannot work. ASRM specifically notes that after a careful review, further transfer may be reasonable rather than escalating to extensive unvalidated testing.

Sources

• Practice Committee of the American Society for Reproductive Medicine. Recurrent implantation failure: a committee opinion. Fertility and Sterility. 2026;126(2):277–293. doi:10.1016/j.fertnstert.2026.03.026.
• ESHRE Working Group on Recurrent Implantation Failure. ESHRE good practice recommendations on recurrent implantation failure. Human Reproduction Open. 2023. doi:10.1093/hropen/hoad023.
• National Institute for Health and Care Excellence. Fertility problems: assessment and treatment (NG257) — immunological treatments. 2026. Accessed 6 November 2026.
• Human Fertilisation and Embryology Authority. Immunological tests and treatments for fertility. Current patient evidence review. Accessed 6 November 2026.
• Sun Y, Cui L, Lu Y, et al. Prednisone vs placebo and live birth in patients with recurrent implantation failure undergoing in vitro fertilization. JAMA. 2023;329(17):1460–1468. doi:10.1001/jama.2023.5302.
• Almohammadi A, Choucair F, Khan KS, et al. Interventions for recurrent embryo implantation failure: an umbrella review. International Journal of Gynecology & Obstetrics. 2025;169(2):539–556. doi:10.1002/ijgo.16066.
• Incognito GG, Pittana E, Cimadomo D, et al. Immunological interventions in recurrent implantation failure: a systematic review and SWOT analysis. Minerva Obstetrics and Gynecology. 2026;78(2):130–141. doi:10.23736/S2724-606X.25.05657-X.

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.

Verified profiles: PubMed · ORCID · LinkedIn

Read full profile → Instagram YouTube

The content has been created by Dr. Senai Aksoy and medically approved.