Role of HLA Sharing in Repeated IVF Failure

BySamradni Pradhan
Updated: 7 Jul 2025, 8:49 am

HLA sharing is a possible, often overlooked reason for multiple failed IVF attempts despite healthy embryos and a receptive uterus. This blog will explain how gene similarity between individuals can confuse your immune system into rejecting embryo implantation. This increases the need to seek out more specific treatment alternatives for your reproductive journey.

Pregatips.com
If you’ve gone through IVF with hope in your heart and trust in the process, you may have heard reassuring words, perhaps the embryo looked promising, and your uterus seemed ready. Even though the outcome was disappointing, you might have found comfort in the idea that sometimes, these things just take time. But as the journey continues without clear answers, it’s completely natural to feel uncertain, emotionally drained, and unsure of where to turn next.

In this article:


One possible, yet often unrecognised, reason for this is HLA sharing with your partner. This is about your immune system and how it will respond to the embryo. If both individuals are too genetically similar in compatible ways, your immune system may not provide the embryo with the necessary support to grow. If you understand this, it may permit you to consider new options in your fertility journey.


What Is HLA and Why Does It Matter in IVF?

HLA is short for Human Leukocyte Antigen. These are specialised genes in your body that help your immune system distinguish between your own cells and foreign ones.

During pregnancy, the embryo contains both your partner's and your genes. The embryo is considered "foreign" by your immune system. Typically, your body accepts and supports the pregnancy. If you and your partner share similar HLA genes, it is possible that the immune system will not respond appropriately. The embryo will not receive the necessary signals and support for it to grow.

Here’s why HLA matters in IVF:

  • HLA genes help your immune system recognise what's “self” and what's “foreign.”
  • In pregnancy, a little “foreign” signal helps trigger immune protection for the embryo.
  • If you and your partner have similar HLA genes, that signal may be too weak.
  • Without that signal, your body may not support the embryo properly.
  • This can affect the success of implantation, even with healthy embryos.
Understanding this can help you explore whether immune-related issues are behind repeated IVF failures.


Understanding HLA Sharing in Pregnancy

During a healthy pregnancy, your body creates unique antibodies that protect the baby and help it grow. This is conceivable because the embryo is partly alien to your body.

However, suppose you and your partner share very similar HLA genes. In that case, there may not be enough difference for your body to recognise the embryo as 'foreign' enough to develop the proper immune response to create a healthy pregnancy.

This can affect how well your uterus supports the embryo, even if:

  • The embryo is of high quality
  • Your uterus is healthy.
  • Hormone levels are normal.
  • Other basic fertility factors look fine.
When this immune support is missing, implantation may fail repeatedly without a clear medical explanation.


How HLA Sharing Affects IVF Success

Here’s what might happen when there is too much similarity in HLA genes:

  • Your immune system doesn’t create a protective response.
  • Your uterine lining may not be capable of adequately supporting implantation.
  • Natural killer (NK) cells might become too active.
  • The embryo might be seen as unfit to grow and develop further.
You might not have any signs that this is happening. Sometimes, the embryo implants for a short time and then stops growing. That’s why this issue often goes unnoticed until you’ve had multiple failed IVF attempts.


When Should You Consider HLA Sharing Tests?

If you’ve had two or more failed IVF cycles using good-quality embryos and your uterus looks healthy, it might be time to test for HLA sharing. These tests are often considered when:

  • You have unexplained infertility.
  • You’ve had multiple IVF cycles with no success.
  • You’ve experienced miscarriages after IVF.
  • Doctors suspect immune system issues.
Remember, HLA sharing is only one part of the bigger picture. But checking for it might uncover a reason when everything else seems normal.


What Types of HLA Sharing Can Affect IVF?

When assessing your possibilities for immune-related IVF issues, doctors focus on two main categories of HLA genes; this group of genes helps your immune system determine an appropriate response to the embryo. The closer these genes are between you and your partner, the more likely your body may not offer the correct support for the implantation. Doctors usually focus on:

  • Class I genes – like HLA-A, HLA-B, and HLA-C
  • Class II genes – like HLA-DR and HLA-DQ
A healthy pregnancy requires a balanced approach. The embryo should be different enough from you to stimulate appropriate immune support, although if it is too similar, your body could ignore it. If it is too similar, it can cause failed implantation, everything is healthy, including your embryo, so it is not a uterine problem.


How Do Doctors Test for HLA Sharing?

If your fertility doctor thinks immune issues might be affecting implantation, they may suggest tests like:

  • High-resolution HLA typing for both partners: to check for genetic similarity.
  • Immune testing: to look at NK cell activity and other immune signals (like cytokines).
These are blood tests. The results help decide if special treatments can improve your chances in the next IVF cycle.


What Can Be Done If HLA Sharing Is a Problem?

If HLA sharing is a problem, there is also a positive aspect, highlighting the availability of potential treatment options. If doctors find that HLA sharing may be causing IVF failure, they might suggest:

  • IVIG (Intravenous Immunoglobulin) therapy helps balance the immune response.
  • Intralipids infusion: reduces NK cell activity.
  • Steroids control overactive immune reactions.
  • Donor sperm or egg: used rarely, but can reduce genetic similarity if needed.
Your treatment plan depends on your test results and history. Many couples with this issue go on to have healthy pregnancies with the right support.


Why Isn’t This Test Routine in IVF?

You might wonder why this isn’t checked during your first IVF cycle. Here’s why:

  • Not all IVF failures are due to immune issues.
  • HLA testing is advanced and costs more.
  • It needs experts in reproductive immunology to understand the results.
  • Most clinics begin by addressing more common issues, such as hormonal or anatomical problems.
If IVF continues to fail without answers, HLA testing may provide a clearer path forward.

You are not in this alone, and with the right support, you will still be able to achieve your dream of starting a family with the next step that feels right for you, which, with any luck, will be working with a reproductive immunologist for further testing.

Knowing about HLA sharing allows you another avenue to examine your fertility challenges. It won't affect every couple, but it is certainly important for any couple faced with undiagnosed IVF failure. Taking steps to consult with specialists for advanced testing can provide you with more options to move forward with confidence.

FAQs On Role of HLA Sharing in Repeated IVF Failure

  1. Is HLA sharing prevalent in IVF collapse cases??
    Not often, but it does happen in some couples experiencing recurrent unexplained IVF failure. Eliminating other possible reasons is crucial.
  2. Can HLA sharing affect natural pregnancy, too?
    Yes, it can. Some couples with some degree of HLA similarity may have issues with repeated miscarriage or difficulty conceiving naturally as well.
  3. Is there a cure for HLA-sharing-related fertility issues?
    There is no cure, but therapeutics are available to help alleviate symptoms. Therapies like IVIG, steroids, or donor gametes can increase a couple's chance of achieving a successful pregnancy.
Disclaimer: Medically approved by Dr Mannan Gupta, Chairman & HOD- Obstetrics & Gynaecology, Elantis Healthcare New Delhi