How does the immune system affect embryo implantation?
The immune system affects implantation by helping the uterine lining accept an embryo that carries genetic material from both parents. Implantation needs a finely balanced immune environment, not a suppressed one, and researchers are still mapping exactly how that balance works.
Three immune topics come up most often when good embryos do not implant:
- Antiphospholipid antibodies: autoantibodies that can cause clotting and inflammation in the small blood vessels of the developing placenta. This is the best-established immune cause of pregnancy loss.
- Natural killer (NK) cells: immune cells that are normally abundant in the uterine lining and help remodel its blood vessels. Their role in implantation failure is still debated.
- Thyroid antibodies: markers of thyroid autoimmunity that are associated with higher miscarriage risk, even when thyroid hormone levels are normal.
These three are not equal. ESHRE’s 2023 good practice recommendations on recurrent implantation failure support antiphospholipid testing in women with additional risk factors, while advising against NK cell and other immune cell testing.
What is antiphospholipid syndrome, and how does it affect pregnancy?
Antiphospholipid syndrome (APS) is an autoimmune condition in which antibodies against phospholipids raise the tendency to form blood clots, including in the vessels that supply a developing placenta. It is associated with recurrent early pregnancy loss, later pregnancy complications, and blood clots outside pregnancy.
APS often causes no symptoms before pregnancy and does not show up in a standard fertility workup. It is diagnosed with three blood tests:
- Lupus anticoagulant
- Anticardiolipin antibodies (IgG and IgM)
- Anti-beta-2 glycoprotein I antibodies (IgG and IgM)
A positive result is confirmed with a repeat test about 12 weeks later, because antibody levels can rise temporarily.
The American Society for Reproductive Medicine’s 2026 guidance recommends antiphospholipid testing for women with three or more pregnancy losses or a personal history of blood clots. When APS is confirmed, treatment during pregnancy with low-dose aspirin and heparin is standard care, which is why this test matters more than most immune panels.
Should I get my natural killer cells tested?
For most women, no. ASRM’s 2026 guidance on recurrent pregnancy loss and ESHRE’s 2023 recommendations on recurrent implantation failure both advise against NK cell testing, whether from a blood sample or a uterine biopsy.
The reasoning is practical. NK cells in the blood behave differently from NK cells in the uterine lining, studies use different methods and thresholds, and there is no agreed definition of a “high” result. Most importantly, the treatments offered for abnormal results have not been shown to improve live birth rates.
ESHRE specifically recommends against:
- Peripheral and uterine NK cell testing
- Blood cytokine testing and HLA-C compatibility testing
- Intravenous immunoglobulin (IVIG), intralipid infusions, glucocorticoids such as prednisolone, and G-CSF for implantation failure
Some clinics still offer these tests and treatments, often at significant cost. If you have already had NK testing or treatment, that is nothing to feel bad about. Many women were offered it in good faith. Today’s evidence simply points the next appointment somewhere more useful.
Do thyroid antibodies matter if my thyroid levels are normal?
Thyroid antibodies matter as information, but treating them on their own has not improved outcomes. Thyroid peroxidase (TPO) antibodies are linked with a higher risk of miscarriage, even when TSH and thyroid hormone levels are normal.
The open question was whether treating those antibodies would help. The TABLET trial, published in the New England Journal of Medicine in 2019, tested this directly. It randomly assigned 952 women with TPO antibodies, normal thyroid function, and a history of miscarriage or infertility to levothyroxine or placebo. Live birth rates were 37.4 percent with levothyroxine and 37.9 percent with placebo, essentially identical.
Based on evidence like this, ASRM’s 2026 guidance does not recommend screening for thyroid antibodies after pregnancy loss. TSH remains the recommended thyroid test, and ASRM recommends treatment when TSH is above 4 mIU/L or above the lab’s upper limit of normal.
If you already know you have thyroid antibodies, it is still worth keeping an eye on your TSH, because antibodies can signal a thyroid that may become underactive over time.
What should I ask about if good embryos are not implanting?
If good embryos are not implanting, ask first about the investigations with the most support: the uterus, progesterone, antiphospholipid antibodies when risk factors are present, and thyroid function. ESHRE’s 2023 recommendations list these among the investigations worth considering in recurrent implantation failure.
Questions to bring to your next appointment:
- “Has my uterine cavity been examined directly, with a hysteroscopy or saline ultrasound?”
- “Has chronic endometritis been ruled out?”
- “What were my progesterone levels around transfer?”
- “Given my history, should I be tested for antiphospholipid antibodies?”
- “What was my TSH, and is it where you want it before a transfer?”
ESHRE also recommends reviewing lifestyle factors such as smoking, alcohol, and weight whenever implantation failure is encountered. Those are areas where you have real influence, and they deserve attention alongside the medical workup.
From Heather
Good embryos that don't implant deserve a careful look, not every test on the menu.
Few things in fertility treatment hurt like hearing you had good embryos and then watching them not implant. The natural response is to want every test that might explain it, and there is a whole market ready to sell them.
The evidence on immune testing has moved in the last few years, and I would rather tell you that plainly than repeat something the research no longer supports. NK cell testing and the treatments built around it have not been shown to help, and they cost real money and real hope.
What has held up is less exciting and more useful: a direct look at the uterus, progesterone around transfer, antiphospholipid testing when your history calls for it, thyroid function, and the lifestyle factors within your reach.
That is how I use Fertility Block Mapping here. Not as a longer list of tests, but as a way to sort your history so the next appointment asks the questions most likely to change something.
