Immunity and Fertility: Can Your Body Reject Pregnancy?

If you are seeking fertility guidance, you are not alone. Infertility affects millions, and the use of assisted reproductive technology (ART) has steadily increased since the 1980s. In 2018 alone, over 200,000 ART procedures were performed, resulting in more than 80,000 infants—about 2% of all U.S. births that year. Yet, access to effective fertility treatments remains uneven, with high out-of-pocket costs and insurance disparities creating barriers for many individuals and couples.

Your concerns about the risks and complexities of fertility treatments are valid. While ART and other fertility options have helped many build families, they can also increase the chances of multiple births, which carry higher health risks for both parents and babies. Efforts to improve safety such as single-embryo transfer are making a difference, but outcomes and policies still vary widely across clinics and states. Understanding these realities can empower you to make informed, compassionate choices on your fertility journey.

What does it really mean when people say “your body rejected the pregnancy”?

When people say “your body rejected the pregnancy,” they are usually referring to an early pregnancy loss, often called a miscarriage. This phrase can sound harsh, but it is important to know that most early losses are not caused by anything you did or did not do. The most common reason is a problem with the embryo’s chromosomes—genetic changes that prevent the pregnancy from developing normally. In fact, chromosomal abnormalities account for more than two-thirds of early pregnancy losses between 6 and 10 weeks.

Other factors can also play a role, such as certain medical conditions (like diabetes or thyroid disorders), chronic inflammation of the uterus, obesity, older age, or harmful exposures (such as some infections, medications, or environmental toxins). Sometimes, the lining of the uterus actively prevents unhealthy embryos from implanting, which is a natural way your body tries to protect you and future pregnancies. While the term “rejection” suggests an active process, most early losses are due to factors beyond your control and are not a sign of your body failing you. Timing matters too—if the embryo arrives outside the Implantation Window, even a perfect immune system can’t help.

How does a healthy immune system normally protect the embryo instead of attacking it?

During pregnancy, your immune system must strike a delicate balance: it needs to protect you from infections while also tolerating the embryo, which carries genetic material from both you and your partner. This tolerance is achieved through a complex network of signals and specialized cells at the maternal-fetal interface. One of the most important players is HLA-G, a molecule produced by placental cells called trophoblasts. HLA-G interacts with your immune cells such as T cells, natural killer (NK) cells, macrophages, and dendritic cells, to calm their activity and prevent them from attacking the embryo.

Regulatory T cells (Tregs) are another key component. These cells, promoted by the cytokine TGF-β1, suppress inflammation and help maintain a peaceful environment for the developing fetus. The balance between different types of T helper cells (like Th1 and Th2) also shifts during pregnancy: early on, a controlled inflammatory response helps with implantation, but soon after, anti-inflammatory signals dominate to protect the fetus. Placenta-derived exosomes; tiny vesicles released into your bloodstream, carry proteins and genetic material that further guide your immune system to support pregnancy. The crosstalk between placental cells and your immune cells, along with these molecular signals, creates a unique, tolerant environment that allows your body to nurture the embryo without compromising your own health.

When does immune dysfunction disrupt fertility or trigger miscarriage?

Immune dysfunction can disrupt fertility or trigger miscarriage when your body’s immune system fails to maintain the delicate balance needed for pregnancy. Normally, immune cells like regulatory T cells (Tregs) and uterine natural killer (NK) cells help your body accept and support the embryo. When this balance is lost, your immune system may become overactive or misdirected, leading to reproductive problems.

Key ways immune dysfunction can affect fertility and pregnancy include:

• Low regulatory T cells (Tregs): Lower levels or poor function of Tregs are strongly linked to recurrent miscarriage. Tregs help prevent your immune system from attacking the embryo.
• Increased or overactive uterine NK cells: High numbers or heightened activity of uterine NK cells are associated with both recurrent miscarriage and implantation failure. These cells can become too aggressive, harming the developing placenta.
• Imbalance in T helper cells: Too many pro-inflammatory T helper 17 (Th17) cells or not enough anti-inflammatory T helper 2 (Th2) cells can create a hostile environment for the embryo.
• Chronic endometritis: Ongoing inflammation in the uterine lining can lead to excessive immune cell infiltration, reducing the uterus’s ability to support a pregnancy. Healthy Uterine Lining.

According to a 2022 systematic review in Human Reproduction Update, “Women with recurrent miscarriage have significantly higher levels of uterine natural killer cells compared to controls, suggesting an underlying disturbance of the immune environment that may culminate in implantation or placentation failure”.

If you have experienced repeated pregnancy loss or trouble conceiving, immune testing and targeted therapies may help identify and address these issues. About 5% of couples face recurrent pregnancy loss, and up to half of these cases may involve immune dysfunction.

Who should consider immunological testing, and what does the work-up look like?

You should consider immunological testing if you have experienced recurrent pregnancy loss (two or more miscarriages), repeated implantation failure during in vitro fertilization (IVF), unexplained infertility, or a history of autoimmune disorders. Testing may also be appropriate if you have risk factors such as endometriosis, chronic inflammation, or a family history of immune-related reproductive issues. The American College of Obstetricians and Gynecologists (ACOG) and other expert bodies recommend targeted immune testing in these scenarios, rather than for all infertility cases.

A typical immunological work-up may include:

• Antiphospholipid antibody (APA) testing: Screens for antibodies linked to blood clotting and miscarriage risk.
• Antithyroid antibody (ATA) testing: Assesses for thyroid autoimmunity, which can affect fertility and pregnancy outcomes.
• Antinuclear antibody (ANA) testing: Detects general autoimmune activity that may disrupt implantation or early pregnancy.
• Antisperm antibody (ASA) testing: Evaluates for immune responses against sperm, relevant for both partners.
• Uterine natural killer (NK) cell assessment: Investigates abnormal immune cell activity in the uterus, though this remains controversial and is not standardized.
• Endometrial evaluation: May include biopsy or molecular markers to assess inflammation or readiness for implantation.

As Dr. Mary Kathryn Abel, MD, reproductive endocrinologist, notes: “There are significant limitations to immunological testing in this setting. Larger, prospective studies are needed prior to mass adoption of many immunologic tests”. According to a 2023 PubMed review, more than half of women with unexplained infertility had at least one abnormal immune marker, but the clinical significance and best treatment approaches are still being defined. Always discuss the risks, benefits, and limitations of testing with your fertility specialist to ensure a personalized, evidence-based approach.

Remember, only about 30 % of evaluated patients ultimately need immune-targeted therapy. Key Hormones—remains essential, as endocrine issues often mimic immune problems.

Which medical treatments can calm an over-active reproductive immune response?

Several medical treatments can help calm an over-active reproductive immune response, but these should be tailored to your specific diagnosis and immune profile. Here are the main options:

• Corticosteroids (e.g., prednisolone): These drugs suppress inflammation and immune activity. They may benefit some people with clear immune pathology, such as autoimmune disorders or high uterine natural killer (NK) cell activity. However, routine use is not recommended for everyone, as unnecessary suppression can harm implantation and fetal development.
• Intravenous immunoglobulin (IVIg): IVIg is used in cases of recurrent pregnancy loss or repeated implantation failure with abnormal immune markers (like high NK cell activity or Th1/Th2 imbalance). It works by modulating immune cell function and reducing harmful immune responses. Some guidelines recommend IVIg for select patients, but evidence is still evolving and protocols vary.
• Intralipid infusions: These are fat emulsions given intravenously. They may help reduce NK cell activity and inflammation in the uterus, especially in people with repeated IVF failure and documented immune over-activation.
• Targeted therapies: For specific immune conditions (such as antiphospholipid syndrome), treatments may include low-dose aspirin, heparin, or other immunomodulatory drugs.
• Emerging therapies: Research is ongoing into new agents, such as anti-inflammatory compounds (e.g., MIT-001), which have shown promise in animal studies for reducing ovarian inflammation and improving fertility.

“Better diagnostics and more preclinical studies are essential to define patient groups, build evidence for efficacy and fine-tune treatments so as not to inhibit essential actions of immune cells. Unless overt immune pathology is evident, utilization of corticosteroids is not warranted and may be harmful” — Sarah Robertson, PhD, Professor of Reproductive Immunology.

A 2022 review in the American Journal of Reproductive Immunology found that starting IVIg before conception and using strict criteria for patient selection improved outcomes in women with unexplained recurrent pregnancy loss or implantation failure. Always consult your fertility specialist to discuss the risks, benefits, and evidence for these treatments in your situation.

Can lifestyle and nutrition balance immunity for better conception chances?

Yes, your lifestyle and nutrition can help balance your immune system and improve your chances of conception. Research shows that a diet rich in antioxidants, healthy fats (like omega-3s), plant-based proteins, fiber, vitamins, and minerals such as the Mediterranean diet, supports reproductive health by reducing inflammation and oxidative stress, both of which can disrupt fertility. Avoiding trans fats, refined carbohydrates, and added sugars is important, as these can negatively affect hormone balance and immune function.

Key steps you can take:

• Eat more fruits, vegetables, whole grains, nuts, and seeds.
• Choose healthy fats (olive oil, fatty fish) and limit red and processed meats.
• Maintain a healthy weight, as both obesity and being underweight can disrupt immune and hormone balance.
• Manage stress, as chronic stress can impair immune regulation and fertility.
• Stay physically active, but avoid excessive or strenuous exercise.

A recent U.S. study found that women with higher antioxidant-rich diet and lifestyle scores had a 6.4% lower risk of infertility, highlighting the power of healthy habits. Dr. Simon Alesi, MD, notes, “Adherence to anti-inflammatory diets such as the Mediterranean diet improves fertility, assisted reproductive technology success, and sperm quality in men”.

Supplement with folic acid, and check your vitamin D and iodine levels, as deficiencies are common and can impact fertility. These changes are safe, low-risk, and can be a valuable part of your fertility journey.

Need better egg energy? Explore Strong Egg Mitochondria: Simple Ways to Boost Cell Power for synergistic tips.

Does the male partner’s immune health influence conception too?

Yes, your immune health as a male partner can influence conception. The immune system in your testes protects developing sperm but must remain balanced. When this balance is disrupted, fertility can suffer.

Key points to consider:

• Chronic inflammation in your reproductive tract can damage sperm, lower sperm count, and reduce sperm quality. This can result from infections, autoimmune conditions, obesity, or exposure to toxins.
• Immune cells in your testes like macrophages and T cells; help maintain a healthy environment for sperm development. If these cells become overactive, they may attack sperm or disrupt hormone production.
• Anti-sperm antibodies (ASAs) can form if your immune system mistakenly targets your own sperm. Up to 18% of men with unexplained infertility have ASAs, which can impair sperm movement and fertilization.
• Conditions like varicocele (enlarged veins in the scrotum) are linked to increased inflammation and immune dysfunction, further harming fertility.
• Environmental factors, such as radiation or certain medications, can trigger immune changes that affect sperm quality and even future generations.

If you are facing fertility challenges, consider a medical evaluation that includes immune and inflammatory markers. Addressing infections, managing chronic health conditions, and adopting a healthy lifestyle can help restore immune balance and improve your chances of conception.

Obesity and high-fat diets raise systemic inflammation, warping sperm shape—see Sperm Morphology Basics. Partners can:

How can couples and clinicians build a personalized, evidence-based roadmap?

To build a personalized, evidence-based fertility roadmap, you and your clinician should work together step by step. Start with a thorough evaluation of both partners, including medical history, lifestyle, and targeted diagnostic tests. Use current guidelines from organizations like the American Society for Reproductive Medicine (ASRM) and the World Health Organization (WHO) to guide testing and treatment choices.

Key steps include:

• Identify and address modifiable lifestyle factors (nutrition, weight, stress, smoking, alcohol).
• Use evidence-based treatments first, such as ovarian stimulation with oral medications and intrauterine insemination (IUI) for unexplained infertility, before moving to in vitro fertilization (IVF) if needed.
• For male partners, follow WHO guidance for semen analysis and consider further evaluation if abnormalities are found.
• Consider new tools, like artificial intelligence-powered fertility assessments, to help personalize your plan and predict outcomes based on your unique data.
• Discuss all options, including fertility preservation if you face medical treatments that may affect fertility.
• Regularly review your progress and adjust your plan based on real-world outcomes and new evidence.

Personalized fertility care means using the best available evidence, your unique health profile, and your values to guide every decision. This approach empowers you to make informed choices and increases your chances of success.

IVF “immune add-ons”: fact or hype?

IVF “immune add-ons”—such as corticosteroids, intravenous immunoglobulin (IVIg), intralipids, and other immunotherapies—are widely marketed to improve implantation and pregnancy rates, especially for those with recurrent implantation failure (RIF) or recurrent pregnancy loss (RPL). For people with clear immune-related issues, some studies show that immunomodulatory treatments can increase pregnancy and live birth rates compared to historical controls, particularly when combined with anticoagulation therapies. Recent meta-analyses suggest IVIg may benefit select patients with RIF, improving clinical pregnancy and live birth rates, especially when immune abnormalities are present.

However, large systematic reviews and expert guidelines caution that most immune add-ons lack robust evidence from high-quality randomized controlled trials, and their safety and effectiveness remain unproven for the general IVF population. Many of these treatments are expensive and may divert resources from evidence-based care. Experts recommend reserving immune add-ons for carefully selected cases with documented immune dysfunction, and only after discussing potential risks, costs, and uncertainties. In summary, immune add-ons may offer hope for a small subset of patients, but for most, they remain more hype than fact until stronger evidence emerges.

Expert mantra: “If there’s no clear biomarker guiding the treatment, think twice.” Non-immune issues like a Short Luteal Phase can mimic rejection and may respond better to progesterone support than to costly add-ons.

Your Top Questions, Answered

Can stress alone cause immune rejection of an embryo?
Stress can disrupt the immune tolerance needed for pregnancy. Severe or chronic stress may impair regulatory T cells and other immune mechanisms, increasing inflammation and the risk of embryo rejection or miscarriage. However, stress alone rarely causes immune rejection without other risk factors; it acts as a trigger in those already vulnerable.

How soon after an immune-related miscarriage can we try again?
There is no universal waiting period. Most experts recommend waiting until you have physically and emotionally recovered, and any underlying immune issues are addressed. For many, this means waiting for at least one normal menstrual cycle, but your clinician may advise differently based on your health and test results.

Do vaccines hurt implantation?
Current evidence does not show that vaccines, including those for COVID-19, harm embryo implantation. Vaccines do not trigger the type of immune response that leads to embryo rejection or miscarriage. They are considered safe for people trying to conceive.

Is there a blood test for “embryo-toxic” antibodies?
No standard blood test exists for so-called “embryo-toxic” antibodies. Some clinics may offer tests for certain immune markers, but these are not universally validated or recommended for routine use. Research is ongoing to better define and detect immune factors linked to pregnancy loss.

Could my body still reject pregnancy if I fix a thin lining?
Yes, correcting a thin uterine lining improves implantation chances, but immune factors can still cause rejection. Successful pregnancy depends on both a receptive lining and a balanced immune response. If immune dysfunction persists, miscarriage or implantation failure can still occur.

Final Thoughts: Turning Immune Insight into Pregnancy Hope

Turning immune insight into pregnancy hope means recognizing that your immune system is not just a barrier, but a partner in conception and healthy pregnancy. Success depends on a delicate balance: your immune system must tolerate the embryo while still protecting you from infections. Specialized immune cells like regulatory T cells, B regulatory cells, natural killer cells, and myeloid-derived suppressor cells; work together to create a nurturing environment for the embryo and placenta. Hormones such as estrogen and progesterone help guide these immune responses, ensuring your body welcomes the pregnancy.

Disruptions in this balance, whether from inflammation, infection, or immune miscommunication, can lead to challenges like miscarriage, preeclampsia, or implantation failure. Understanding these immune mechanisms allows you and your clinician to identify and address issues early, personalize your care, and make evidence-based choices. Advances in reproductive immunology offer new hope, from targeted therapies to better diagnostics, but the foundation remains a holistic, compassionate approach that considers your unique biology and life circumstances. With knowledge and partnership, immune insight can truly become a source of hope on your path to parenthood.

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