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Embryo implantation failure: Immunological test and endometrial receptivity test

embryo implantation failure

Even today, the success of fertility treatments is not always guaranteed due to problems associated with embryo implantation failure. In the past 20 years, there has been great progress in the field of assisted reproductive techniques and much attention has been paid to the study of endometrial physiology, but the process of studying embryo implantation remains complicated.

Specialists working on this issue point to various causes, partly due to differences between individual patients, but also to moral, ethical and legal restrictions that limit direct research into the interaction of embryos with the endometrium.

The reality, however, is that there are several tests that help specialists prevent these implantation disorders and investigate the reasons for their occurrence. In today’s article, we will take a closer look at two of these tests: the endometrial receptivity test and the immunological test.

Embryo implantation failures – Why do they occur?

Many patients who have not been able to become pregnant even after several fertility treatments ask themselves this very question.

In order for pregnancy to be successful after IVF treatment, the embryo must implant in the mother’s uterus.

According to the Spanish Society of Fertility (SEF), embryo implantation failure occurs when the patient does not get pregnant after the transfer of good quality embryos during an in vitro fertilisation (IVF) cycle in at least three attempts.

These factors are important for the success of embryo implantation

To achieve successful embryo implantation with assisted reproduction, there are three important factors: the quality of the embryo, the receptivity of the endometrium and the efficiency of the transfer technique. The probability of successful embryo implantation is very high if the transfer is performed in a healthy endometrium with a good quality embryo.

The importance of the implantation window regarding pregnancy.

During natural fertilisation, the sperm meets the egg in the fallopian tube. As soon as the new embryo develops, it travels to the uterus. In other words, in order for the embryo to implant, proper communication between the embryo and the uterus must take place. The first embryonic contact is right here, in the endometrium.

During a fertility treatment, we have to determine the perfect moment within the implantation window of a cycle in order to be able to carry out the embryo transfer successfully. The term implantation window refers to the period of time in which the endometrium has ideal conditions to accommodate the embryo.

For most women, this implantation window falls between the 20th and 24th day of the menstrual cycle and usually lasts for 4 days.

Deciding factor: Endometrial receptivity test

The ER Map or Endometrial Receptivity Map assesses the expression of 48 genes involved in the development of endometrial receptivity. Furthermore, it classifies the condition of the endometrium into four categories:

Receptive: Optimal time of the cycle. The endometrium is ready for embryo implantation.

Pre-receptive: Ideal moment has not yet been reached. The cycle has an early implantation window.

Post-receptive: The endometrium has already reached the optimal time for implantation of the embryo, therefore the implantation window is delayed.

Non-receptive: The endometrium is not in a condition close to the implantation window.

In 20-25% of women, the reason for not being able to conceive is related to implantation failure caused by a displaced implantation window. Through this test, it is possible to determine the implantation window and increase the probability of pregnancy through a personalised transfer.

Unlike other tests that assess the endometrium, the ER Map test includes an assessment of the genes involved in the immune response that are directly related to the implantation process.

How is the ER Map performed?

The ER Map test is performed following an endometrial biopsy, where a cannula is inserted through the vagina into the uterus. A sample of the endometrial tissue is then taken and a genetic analysis is performed.

Depending on the result, the time at which the embryo transfer is carried out can be individualised. It is currently estimated that 20% of cases of repeated embryo implantation failure are caused by a delayed implantation window.

embryo implantation failure

Immunological test

It is recommended that this test be performed as an addition to the endometrial receptivity test after embryonic and/or endometrial factors have been excluded. This way, an accurate diagnosis can be obtained. The immunological test or Im MAP  gives our specialists the possibility to determine the causes of embryo implantation failure as well as repeated miscarriages.

For this test, a blood test to check for immunotherapy and an endometrial biopsy is performed during the luteal phase. Using flow cytometry, a biophysical technique that can detect immune markers and perform cell counts, the obtained samples are then analysed.

If an abnormal level of immune cells is detected, it is recommended to start individualised immunotherapy to improve the chance of pregnancy. 

When is it recommended?

According to fertility expert at IVF-Spain, Dr Oliver Pack: “We are talking about two different types of tests. The ER Map is not recommended for all patients, but usually only when patients have already had several implantation failures. However, it is true that endometrial receptivity is one of the decisive factors for successful implantation”.

“In IM Map many factors play a role. Several studies are currently being conducted on its effectiveness. At our clinic, we recommend this test because we know that immunological factors can influence embryo implantation. If other factors have already been ruled out and an imbalance at the immunological level is suspected, we recommend performing IM Map. This test analyses whether natural killer cells, T helper cells and regulatory T cells or increased B lymphocytes, that can influence implantation, are present”.

Is the performance of these tests supported by scientific evidence?

Since its introduction, the endometrial receptivity test has been subject to several limitations in its use in medical practice.

Results from various studies indicate that this test should not be performed on just any patient, but it does play an important role for patients who have suffered repeated embryo implantation failures after several in vitro fertilisation treatments  or who suffer from associated conditions such as endometriosis or adenomyosis

It has been observed that pregnancy rates following an endometrial receptivity test such as ER Map increased by 40%.

Remove term: embryo implantation failure embryo implantation failure

Based on studies of the immunological process that accompanies the implantation of the embryo, we know that an exchange between the cells of the mother and the foetus is necessary for a successful pregnancy. Other studies have also shown that complications can arise during pregnancy due to an imbalance in this communication.

Optimising the implantation rate: Other advanced techniques

As we have mentioned above, there are different tests that help to ensure the correct communication between the embryo and the uterus.

  • Hysteroscopy: This test is particularly recommended in cases of a suspected uterine condition or when pregnancy is difficult to achieve through fertility treatment. This technique allows the direct visualisation of the uterus, which enables its morphology and function to be examined.
  • PGS – Preimplantation Genetic Screening: Examination of the embryo, for early detection of severe genetic or chromosomal diseases in order to prevent the transfer of the embryo into the uterus. Thereby, improving the quality of the embryos which is one of the most important factors for the success during implantation.

Key factors in infertility treatment: communication and trust

Fact is that there are various reasons why embryo implantation may be unsuccessful. Generally, patients who opt for these type of tests, which we have described in this article today, have already suffered repeated implantation failures or miscarriages along their fertility journey.

That is why, at IVF-Spain Madrid, we know that the most important thing for our patients is communication with our experts during their treatment. Because our medical professionals are the ones that advise you on the best diagnostic tests for your circumstances and work with you towards our common goal: a successful treatment and the birth of a healthy baby.

In today’s age, it is normal to search for information on the internet, we all do it. But don’t forget that the individual circumstances of each person or couple mean that no two cases are the same.

If you have any doubts about which tests and which treatment is the most suitable for you, make an appointment with our fertility specialists. They will be available to help you obtain a complete diagnosis, one of the essential factors for the success of any fertility treatment.

About the author


At ProcreaTec, we understand the road toward a healthy pregnancy is not always easy. Through this blog, we want to reach out to all who are struggling on the path of infertility to find support. If you have any questions or would like to tell us about your situation, you can comment on the posts or send us an e-mail.
If you would like to learn more about our clinic, we invite you to visit our website
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