Immune-Related Pregnancy Loss: A Deeper Dive into Reproductive Immunology

UPDATED ON 28 MAY 2025

If you’ve already read my earlier blog where I explained the basics of reproductive immunology and how the immune system interacts with pregnancy?, then this article will help you take that understanding to the next level.

Today, I want to walk you through a topic that’s both complex and extremely relevant for women experiencing recurrent miscarriages or implantation failure — immune-related pregnancy loss.

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What Makes Pregnancy an Immune Challenge?

Pregnancy is, in fact, a natural immune miracle. Your body allows something that’s partly foreign (half of the DNA comes from your partner) to grow inside you — and thrive. Medically, we call this state immuno-modulation. It’s the reason why your body doesn’t reject the embryo like it would reject a foreign organ transplant.

This immuno-tolerant state is largely regulated by a series of immune responses that start right at implantation. That’s why understanding implantation science is critical when we talk about immune-related pregnancy loss.

Implantation: More Than Just Timing

When an embryo reaches the uterus, it usually arrives during the secretory phase of your menstrual cycle. At this stage:

• The corpus luteum (a temporary hormone-producing structure in the ovary) releases progesterone,

• Along with relaxins, activins, vascular endothelial growth factor (VEGF),

• And a range of chemokines and cytokines.

These aren’t just medical terms — they are crucial messengers that prepare your uterine lining for implantation.

What’s fascinating is that the embryo displays a special protein called HLA-C antigen, which acts like a signal.

Your uterine Natural Killer (uNK) cells recognize this and help with spiral artery remodeling, making space for the placenta to develop.

When the Immune System Misfires?

Sometimes, the immune system doesn’t respond as it should:

• The number of helpful uNK cells in the uterus may drop

• While peripheral (circulating) NK cells, which are more aggressive, may rise

This imbalance can prevent even a chromosomally normal embryo (euploid) from implanting or cause an early pregnancy loss.

What Causes This Immune Imbalance?

Several pelvic conditions may disrupt the immune response:

• Endometriosis
• Uterine fibroids
• Adenomyosis
• Chronic pelvic infections (PID, Ureaplasma, etc.)

Even minor infections can create an environment where the immune system becomes hypervigilant, and instead of helping implantation, it starts resisting it.

Can We Test for This?

Yes, but here’s my experienced take as a reproductive immunology expert:

There are tests available, like Endometrial Immune Profiling, that dig into immune cell behavior in the endometrium. However:

• Their reliability varies by the day of your cycle

• Results can be hard to interpret in clinical practice

• Hormonal influences (estrogen and progesterone) play a huge role, which isn’t always reflected in lab values

So, at ImmuRepro (our reproductive immunology vertical at Shree IVF Clinic), I recommend being selective.

What Do We Recommend Instead?

We usually advise patients to test only for chronic endometritis unless clearly indicated otherwise.

Here’s why:

• Many expensive immune panels lack clinical benefit
• Over-testing often leads to confusion and unnecessary treatment

In most cases, it’s collaborative diagnosis — working with pathologists and microbiologists — that helps us understand what went wrong.

Who Should Consider Immune Testing?

We typically recommend immunological evaluation in the following cases:

• History of 2 or more unexplained pregnancy losses

• Repeated IVF failures with good-quality embryos

• Diagnosed or suspected autoimmune diseases

But let me be honest — out of every 100 women we assess, only about 30% need immunological support. The rest simply need the right diagnosis and care plan.

 Final Thoughts: The Science is Still Evolving

Even today, the exact mechanisms of embryo implantation and immune interaction are still under active research. But what we do know — and practice — is that a healthy pelvic environment, timely diagnosis, and scientific decision-making make a real difference.

So if you’ve had an unexplained pregnancy loss or failed IVF cycle, don’t lose hope. It might just be your immune system asking for balance — and we’re here to help you find it.

Want to learn more or get evaluated? Reach out to our team at ImmuRepro, part of Shree IVF Clinic. We’re committed to ethical, science-driven fertility care

AUTHOR

CONDITION

Repeated Miscarriages

Failed IVF Cycles

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