Immune testing and treatment after recurrent loss — what holds up?

If you've had losses that nobody can explain, you will eventually find the world of reproductive immunology: natural killer cells, intralipids, IVIG, steroids, blood thinners. Some of it is well-founded. Most of it is not yet, and the difference is worth knowing before you spend thousands of dollars.

What is recommended

• Strong evidence Antiphospholipid antibody testing, and aspirin plus heparin if it's positive. This is the one immune-related cause of recurrent loss with a treatment behind it. What counts as a positive result →
• Strong evidence Thyroid function, and a look at the uterus. The standard evaluation →

Moderate evidence Inherited clotting disorders

Factor V Leiden, the prothrombin gene variant, MTHFR: these are inherited, and they are not the same as antiphospholipid syndrome. The ALIFE2 trial randomized 326 women with recurrent loss and a confirmed inherited thrombophilia to heparin injections or standard care. Live births were 71.6% with heparin and 70.9% without.

The authors' conclusion was blunt: don't use heparin routinely in this group, and don't routinely screen for inherited thrombophilia after recurrent loss. If you've been offered injections on the basis of one of these results, this trial is the thing to ask about.

Limited or mixed NK cells, IVIG, steroids, intralipids

Natural killer cells in the blood are not the same as the ones in the uterine lining, and no test has been validated to tell you whether yours are causing losses. ESHRE lists NK cell testing and HLA testing among the investigations not routinely recommended, and lists intralipids, IVIG and steroids among treatments with insufficient proof.

A placebo-controlled trial published in 2025 gave IVIG plus prednisolone to women with unexplained recurrent loss after fertility treatment. Overall pregnancy rates did not improve. Among the smaller group who did conceive, more pregnancies continued — interesting, and the kind of signal that justifies a bigger trial rather than a bill.

These treatments are not harmless. Steroids affect blood sugar and blood pressure, IVIG is a blood product given by infusion, and the costs run into thousands.

Emerging evidence Chronic endometritis

This one is more interesting than the rest. It's a low-grade inflammation of the uterine lining, found on biopsy by staining for particular immune cells, and it's reported in a meaningful share of women with recurrent loss or repeated failed transfers. Studies that treat it with antibiotics report better outcomes afterwards — but those studies aren't randomized, and labs don't agree on where the diagnostic line sits.

Worth discussing, particularly after failed transfers. Worth knowing it isn't settled.

If you're seeing a specialist who offers these

Plenty of thoughtful doctors treat empirically in this space, because the alternative is telling someone with five losses that there's nothing left to try. That's a real position, held by real specialists, and it isn't quackery. It is also not the same as proven.

What makes the conversation productive:

• "What specifically did you find in my results that makes you recommend this?"
• "What would you expect it to change for me, in numbers?"
• "What are your own outcomes in patients like me, and compared with what?"
• "What's the total cost, and what happens if I don't do it?"

A doctor who can answer those four questions clearly is worth listening to, whatever they recommend. One who can't is worth a second opinion.

What to hold onto

Most recurrent loss, even after a full evaluation, ends in a live birth without any of this. Among women with unexplained recurrent loss, the chance of a successful next pregnancy remains substantial. That's not a reason to stop asking questions — it is a reason not to be rushed into expensive treatments by fear.