Can HLA compatibility cause infertility in every couple who shares similar genes?

No. Many couples with shared HLA alleles conceive without issues. But in a small subset of couples, especially with recurrent IVF failure or miscarriage, it may play a role.

Is HLA testing part of routine fertility evaluations?

Not usually. It’s typically recommended only after repeated pregnancy loss or failed IVF cycles.

Can lifestyle changes fix HLA compatibility issues?

No. These are genetic and immune-based factors. However, a healthy lifestyle can support overall fertility and immune resilience.

HLA Compatibility & Pregnancy: Can Genetic Similarity Impact Fertility?

Pregnancy is a delicate dance between your immune system and your baby’s developing cells. Your body must recognise the embryo as both “self” and “other”, familiar enough not to attack, but foreign enough to trigger the immune tolerance that supports implantation and growth. When that immune balance fails, conception can become difficult, and miscarriages may follow. One possible reason? HLA compatibility between you and your partner.

What Is HLA Compatibility?

Human Leukocyte Antigens (HLA) are molecules found on the surface of your cells that help your immune system distinguish between your own tissues and foreign invaders.

Each person inherits a set of HLA genes from their mother and father. These combinations are unique unless both partners happen to share too many similarities. When that happens, it may trigger a miscommunication in the immune system during conception.

In the context of pregnancy, HLA compatibility is not always a good thing. While you might assume that being genetically “similar” to your partner is beneficial, research suggests the opposite in some cases: too much similarity in certain HLA genes, particularly HLA class I and class II types, may prevent the embryo from being properly recognised, impairing maternal immune tolerance.

Why HLA Compatibility Matters in Fertility

When the immune system sees the embryo as “too similar,” it may not activate the immune modulation process that normally protects the pregnancy. This can affect fertility in several ways:

Impaired implantation: Without the proper immune signals, the embryo may fail to attach securely to the uterine lining.
Recurrent miscarriage: Shared HLA alleles between partners may lead to immune rejection or failure to develop maternal-fetal tolerance.
Reduced success in IVF: Even with high-quality embryos, implantation may not occur if the immune environment isn’t adequately supportive.
Unexplained infertility: For couples with normal hormonal profiles, sperm and egg quality, HLA compatibility may be an invisible factor.

This phenomenon is sometimes called “alloimmune infertility,” referring to the mother’s immune response, or lack thereof, to a genetically similar embryo.

Factors That Can Increase the Risk

HLA-related fertility issues aren’t common, but they may be more likely in:

Couples with multiple failed IVF or IUI attempts: Especially when embryo quality is confirmed to be good.
Recurrent pregnancy loss (2 or more unexplained miscarriages): Especially early first-trimester losses.
Consanguineous marriages: Partners who are related may share more HLA genes than unrelated couples.
Certain autoimmune conditions: People with autoimmune disorders may have more sensitive immune responses that get disrupted by HLA similarities.

Some researchers also point to natural killer (NK) cells and the role of HLA-G (a non-classical HLA molecule expressed by embryos) in immune tolerance.

How Is HLA Compatibility Tested?

HLA testing is not part of standard fertility screening, but it may be recommended in select cases. Testing involves:

HLA Typing: A blood test used to determine both partners’ HLA profiles, especially HLA-A, HLA-B, HLA-C (Class I), and HLA-DR, DQ (Class II).
HLA Matching Index: Evaluates the number of shared HLA alleles between the couple.
KIR-HLA Testing: Examines the interaction between the maternal uterine NK cell receptors (KIR) and fetal HLA-C. Some combinations (e.g., maternal KIR AA with fetal HLA-C2) are associated with higher miscarriage risk.

These tests are typically available through reproductive immunology or advanced fertility clinics.

Can HLA Compatibility Be Treated or Managed?

There is no way to change your genetic HLA profile, but certain approaches may help manage its effects:

Intravenous Immunoglobulin (IVIG): A therapy used in some cases to modulate the immune system during IVF or early pregnancy.
Lymphocyte Immunisation Therapy (LIT): Still controversial, this involves injecting white blood cells from the partner to stimulate the maternal immune response.
Prednisolone and heparin: Low-dose immunosuppressants used empirically to reduce rejection risk in some immune-related fertility cases.
Embryo selection and frozen transfers: May be timed with immunomodulatory support for higher implantation success.

These treatments are considered experimental in many contexts. Always consult a reproductive immunologist before starting any immune-based therapy.

Emotional and Practical Support for Couples Facing HLA Compatibility Issues

Fertility struggles linked to immune factors like HLA compatibility can feel deeply frustrating because the science is still evolving. Testing may not be offered widely, and treatment options are not always conclusive. If this is part of your journey:

Seek a second opinion: Look for fertility clinics with expertise in reproductive immunology.
Ask about testing: If your clinic doesn’t mention HLA or KIR testing, it’s okay to bring it up yourself.
Join support groups: Many couples facing immune-related infertility find comfort in hearing others’ stories.
Consider counselling: The emotional toll of repeated loss or “unexplained” infertility is valid and deserves support.

HLA compatibility is a complex but real factor in some cases of recurrent miscarriage or failed implantation. While it’s not widely tested or understood, acknowledging the role of immune genetics in fertility offers new pathways for diagnosis and hope. If you suspect this might be affecting your journey, specialised testing and support are available. You're not imagining things, and you’re not alone.

FAQs on HLA Compatibility and Pregnancy: Can Genetic Similarity Affect Conception or Miscarriage Risk?

Can HLA compatibility cause infertility in every couple who shares similar genes?
No. Many couples with shared HLA alleles conceive without issues. But in a small subset of couples, especially with recurrent IVF failure or miscarriage, it may play a role.
Is HLA testing part of routine fertility evaluations?
Not usually. It’s typically recommended only after repeated pregnancy loss or failed IVF cycles.
Can lifestyle changes fix HLA compatibility issues?
No. These are genetic and immune-based factors. However, a healthy lifestyle can support overall fertility and immune resilience.