Understanding Immune-Related Pregnancy Loss

Losing a pregnancy is one of the most painful experiences a woman and her family can face. When pregnancy loss happens more than once, it becomes even more difficult to understand and accept. Many couples who experience repeated miscarriages wonder why this keeps happening to them. One important cause that doctors have found is related to the immune system.

In this article, we will explain what immune-related pregnancy loss means, why it happens, and what treatment options are available. We want to help you understand this condition in simple words so you can make informed decisions about your health.

What is Recurrent Pregnancy Loss?

Recurrent pregnancy loss means losing two or more pregnancies before the baby can survive outside the womb. This affects about 2 to 3 out of every 100 couples trying to have a baby. While one miscarriage can happen due to random reasons, repeated losses often have a specific cause that needs to be found and treated.

Many factors can cause recurrent pregnancy loss, including genetic problems, structural issues in the womb, hormonal imbalances, and immune system disorders. Among these causes, immune-related problems are responsible for approximately 20% of cases, making them an important area to understand.

How Does the Immune System Affect Pregnancy?

Your immune system is your body's defense against infections and diseases. It protects you by fighting bacteria, viruses, and other harmful things. However, during pregnancy, the immune system needs to do something very special and unusual.

The baby growing inside the mother carries genetic material from both parents. This means the baby is partly "foreign" to the mother's body. Normally, the immune system would attack anything foreign. But during a healthy pregnancy, the immune system learns to accept and protect the baby instead of rejecting it.

This acceptance happens through a delicate balance of immune cells and chemical messengers in the body. When this balance gets disturbed, the immune system may mistakenly see the pregnancy as a threat and attack it, leading to pregnancy loss.

Types of Immune-Related Pregnancy Loss

There are two main types of immune problems that can cause pregnancy loss:

1. Autoimmune Causes

In autoimmune conditions, the body's immune system creates antibodies that attack its own tissues. These antibodies can also harm the pregnancy. The most common autoimmune cause of pregnancy loss is Antiphospholipid Syndrome.

Antiphospholipid Syndrome (APS)

This condition occurs when the body produces antibodies called antiphospholipid antibodies. These antibodies can cause blood clots to form in the small blood vessels of the placenta. The placenta is the organ that provides oxygen and nutrients to the growing baby. When blood clots block the placenta's blood vessels, the baby cannot get enough nutrition and oxygen, which can lead to miscarriage or stillbirth.

Research shows that women with antiphospholipid antibodies face higher risks not just of early miscarriage, but also of late pregnancy complications like preeclampsia, poor fetal growth, and premature birth.

Other autoimmune conditions that can affect pregnancy include:

• Systemic Lupus Erythematosus (SLE)
• Hashimoto's thyroiditis (thyroid antibodies)
• Undifferentiated Connective Tissue Disease

2. Alloimmune Causes

Alloimmune problems happen when the mother's immune system reacts too strongly to the father's genetic material in the baby. This involves several types of immune cells and chemical signals.

Natural Killer (NK) Cells

Natural killer cells are white blood cells that are part of the immune system. In the womb, these cells play an important role during pregnancy. They help the embryo implant and help the placenta develop properly. However, when there are too many NK cells or when they become too active, they can harm the pregnancy instead of helping it.

Studies have found that some women with recurrent pregnancy loss have higher numbers of NK cells in their blood and in the lining of their womb compared to women who have successful pregnancies. These cells can release inflammatory substances that interfere with implantation and early pregnancy development.

T Cells and Regulatory Balance

The immune system has different types of T cells that work like an orchestra, each playing a specific role. For a healthy pregnancy, the body needs more "helper" T cells (called Th2 cells) that support pregnancy, and fewer "inflammatory" T cells (called Th1 and Th17 cells) that can harm it.

When this balance shifts toward more inflammatory cells, it creates an environment that is hostile to pregnancy. Research indicates that women with recurrent pregnancy loss often show increased levels of inflammatory T cells and decreased levels of regulatory T cells that would normally protect the pregnancy.

Signs and Symptoms

Many women with immune-related pregnancy loss do not have any symptoms before pregnancy. The main sign is repeated miscarriages. However, some warning signs might include:

• History of blood clots in legs or lungs
• Unexplained rashes on the skin
• Joint pain or swelling
• Previous diagnosis of autoimmune diseases
• Family history of autoimmune conditions
• Thyroid problems

It is important to talk to your doctor if you have had two or more pregnancy losses, especially if you have any of the above symptoms.

Diagnosis and Testing

If you have experienced recurrent pregnancy loss, your doctor will want to find out the cause. Diagnosis usually involves several steps:

Blood Tests

Your doctor will check for:

• Antiphospholipid antibodies (Lupus anticoagulant and anticardiolipin antibodies)
• Thyroid function tests and thyroid antibodies
• Other autoimmune markers

These tests need to be done carefully and sometimes repeated to confirm the diagnosis. For antiphospholipid syndrome, the antibodies need to be present on two separate occasions at least 12 weeks apart.

Immune Cell Testing

Some specialized centers may test:

• Natural killer cell levels in the blood
• The activity level of NK cells
• T cell populations and their balance

However, it is important to know that testing for NK cells is controversial. The number of NK cells in the blood may not always reflect what is happening in the womb, and these numbers can change based on stress, hormones, and other factors.

Genetic and Structural Tests

Your doctor will also check for other causes of pregnancy loss such as:

• Chromosome problems in both parents
• Structural problems in the uterus
• Hormonal imbalances

Treatment Options

The good news is that many cases of immune-related pregnancy loss can be treated successfully. Treatment depends on the specific cause found.

Treatment for Antiphospholipid Syndrome

The standard treatment for women with antiphospholipid syndrome includes:

Low-Dose Aspirin and Heparin

This combination is the most proven treatment. Low-dose aspirin (usually 75-150mg daily) helps prevent blood clots and improves blood flow to the placenta. Heparin (given as daily injections) is an anticoagulant that further prevents clot formation.

Clinical studies show that this treatment can reduce pregnancy loss from about 75% to around 25%, meaning 3 out of 4 women who receive treatment can have a successful pregnancy.

Treatment typically starts before pregnancy or as soon as pregnancy is confirmed and continues throughout pregnancy and for several weeks after delivery. Your doctor will monitor you closely throughout this time.

Additional Treatments

In some cases where standard treatment is not enough, doctors may add:

• Hydroxychloroquine: This medication, typically used for lupus, has shown promise in improving pregnancy outcomes for women with antiphospholipid syndrome
• Low-dose corticosteroids: These may help in specific situations
• Intravenous immunoglobulin: This is reserved for difficult cases that do not respond to standard treatment

Treatment for Elevated NK Cells

The treatment for high NK cells is more controversial because the research is not as clear. However, some treatment options include:

Corticosteroids

Low-dose prednisone or prednisolone may help reduce NK cell activity and numbers in the uterus. Some studies suggest this can improve pregnancy success rates, though results vary.

Intravenous Immunoglobulin (IVIG)

This treatment involves infusions of antibodies collected from donated blood. Some studies show it may help women with high NK cells, but evidence is mixed, and it is expensive.

Intralipid Therapy

This is a fat emulsion given through an IV that may help regulate immune function. However, like IVIG, the evidence for its effectiveness is not conclusive.

Treatment for Thyroid Antibodies

When women have thyroid antibodies (particularly thyroid peroxidase antibodies) along with recurrent pregnancy loss, the treatment approach depends on thyroid function.

If Thyroid Function is Normal

Recent large studies have shown that levothyroxine treatment in women with normal thyroid function does not significantly improve pregnancy outcomes, even when thyroid antibodies are present. Therefore, treatment is not routinely recommended for women with thyroid antibodies alone.

If Thyroid Function is Abnormal

Women with high TSH levels (above 2.5-4.0 mIU/L) should receive levothyroxine treatment, as thyroid hormone deficiency can cause pregnancy loss. The dose is adjusted to keep TSH in the optimal range throughout pregnancy.

Supportive Treatments

Regardless of the specific immune problem, supportive care is important:

Progesterone Support

Progesterone hormones help maintain early pregnancy. Your doctor may prescribe progesterone supplements in early pregnancy.

Lifestyle Modifications

• Maintain a healthy weight
• Follow a balanced, nutritious diet
• Reduce stress through yoga, meditation, or counseling
• Get regular moderate exercise
• Avoid smoking and alcohol
• Get adequate sleep

Emotional Support

Recurrent pregnancy loss takes an emotional toll. Counseling, support groups, and psychological care are important parts of treatment.

Success Rates and What to Expect

With proper diagnosis and treatment, many women with immune-related pregnancy loss can achieve successful pregnancies. Success rates vary depending on the specific condition:

• Women with antiphospholipid syndrome treated with aspirin and heparin have about 70-75% chance of having a live baby
• Women with high NK cells who receive treatment may see improved outcomes, though success rates vary more widely
• Early and consistent treatment generally leads to better results

It is important to work closely with a specialist who has experience in treating immune-related pregnancy loss. At specialized centers like Thakral Hospital, a team approach involving obstetricians, immunologists, and other specialists ensures comprehensive care.

When to Seek Medical Help

You should consult a doctor if:

• You have had two or more miscarriages
• You have a family history of recurrent pregnancy loss or autoimmune diseases
• You have been diagnosed with an autoimmune condition and are planning a pregnancy
• You have symptoms of blood-clotting disorders
• You have unexplained fertility problems

Early evaluation can help identify problems and start treatment before another pregnancy loss occurs.

Prevention and Future Pregnancies

After successful treatment and a healthy pregnancy, maintaining follow-up care is important:

• Continue monitoring if you have an autoimmune condition
• Discuss family planning and the need for treatment in future pregnancies with your doctor
• Maintain a healthy lifestyle
• Manage stress and emotional well-being

Some women may need treatment in every pregnancy, while others may only need it in some pregnancies. Your doctor will guide you based on your specific situation.

Research and Hope for the Future

Medical research continues to improve our understanding of immune-related pregnancy loss. Scientists are studying:

• New biomarkers to better predict who is at risk
• More targeted treatments with fewer side effects
• Better ways to test immune function in the womb
• Understanding of how stress and lifestyle affect immune function

As research progresses, treatment options are becoming more precise and effective.

Conclusion

Immune-related pregnancy loss is a complex but treatable condition. Understanding that your immune system plays a role in pregnancy health is the first step toward getting appropriate care. While the journey through recurrent pregnancy loss is emotionally and physically challenging, modern medicine offers real hope.

If you have experienced repeated pregnancy losses, do not lose hope. Seek evaluation from experienced specialists who can diagnose immune problems and provide appropriate treatment. With the right care, many couples go on to have healthy babies.

At Thakral Hospital, we understand the pain of pregnancy loss and are committed to providing compassionate, evidence-based care to help you achieve your dream of having a healthy baby. Our team of specialists works together to diagnose and treat all causes of recurrent pregnancy loss, including immune-related factors.

Remember, you are not alone in this journey, and help is available. Reach out to healthcare providers who can support you through diagnosis, treatment, and hopefully, a successful pregnancy.

---

Blog References

1. National Center for Biotechnology Information (NCBI). "Immunology and Pregnancy Losses: HLA, Autoantibodies and Cellular Immunity." Available at: https://www.ncbi.nlm.nih.gov/books/NBK6615/

2. MDPI Journal. "Alloimmune Causes of Recurrent Pregnancy Loss: Cellular Mechanisms and Overview of Therapeutic Approaches." Available at:
   https://www.mdpi.com/1648-9144/60/11/1896

3. National Institutes of Health (NIH). "Immunological basis for recurrent fetal loss and pregnancy complications." Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC6566855/

4. Chinese Medical Journal. "Systemic autoimmune diseases and recurrent pregnancy loss: research progress in diagnosis and treatment." Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC8439985/

5. American Society of Hematology - Blood Journal. "How I diagnose and treat antiphospholipid syndrome in pregnancy." Available at: https://ashpublications.org/blood/article/143/9/757/506724/

6. National Institutes of Health. "Antiphospholipid Syndrome during pregnancy: the state of the art." Available at:
   https://pmc.ncbi.nlm.nih.gov/articles/PMC3279165/

7. BMC Pregnancy and Childbirth. "Antiphospholipid syndrome in pregnancy: a comprehensive literature review." Available at:
   https://link.springer.com/article/10.1186/s12884-025-07471-w

8. Tommy's Charity UK. "What are natural killer (NK) cells?" Available at:
   https://www.tommys.org/baby-loss-support/miscarriage-information-and-support/natural-killer-cells

9. Frontiers in Immunology. "Role of Decidual Natural Killer Cells in Human Pregnancy and Related Pregnancy Complications." Available at: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.728291/full

10. National Institutes of Health. "Treatment of recurrent pregnancy loss by Levothyroxine in women with high Anti-TPO antibody." Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC4165956/

---

Disclaimer: This article is for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.