Despite the great advances in assisted reproductive techniques over the past 20 years, and the attention devoted to the research to the embryo implantation failure, the success of fertility treatments is sometimes limited by issues related to embryo implantation.

The process of studying embryo implantation is complicated. Many of the experts researching in this area focus on various problems, partly because of the differences between individual patients and also because of ethical, moral and legal restrictions that limit direct research of embryos interacting with the endometrium.

The truth is that there are different tests that help guide experts to prevent and to study the reasons for implantation failure. In this article, we will focus on two of these tests: the endometrial receptivity test and the immunological test.

Why do embryo implantation failures occur?

This is one of the questions asked by many of the patients who have not been able to get pregnant even after undergoing several fertility treatments.

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

The Spanish Society of Fertility (SEF) defines embryo implantation failure as the result of an unsuccessful pregnancy after the transfer of good quality embryos during an in vitro fertilisation (IVF) cycle in at least three attempts.

Factors involved in a successful embryo implantation

There are three main factors that influence the success of embryo implantation in assisted reproduction: endometrial receptivity, embryo quality and the efficiency of the transfer technique. If the transfer is performed in a healthy endometrium with a quality embryo, the embryo is highly likely to implant successfully.

The implantation window and its importance in achieving pregnancy

In a natural cycle, the sperm fertilises the egg in the fallopian tubes. As the new embryo develops, it travels to the uterus. In other words, for embryo implantation to take place, there must be a proper dialogue between the embryo and the uterus. More specifically, the initial embryonic contact takes place in the endometrium.

In the context of assisted reproduction, embryo transfer must take place at the optimal time of the cycle within the implantation window. This window refers to the period of time in which the endometrium presents optimal conditions to receive the embryo.

This period of time usually falls between days 20-24 of the menstrual cycle for most women and typically lasts 4 days.

Endometrial receptivity test as a deciding factor

The ER Map or Endometrial Receptivity Map assesses the expression of 48 genes involved in the development of endometrial receptivity and allows the classification of the state of the endometrium into four categories:

– Receptive: The endometrium is at the optimal point within the cycle for embryo implantation to take place.

– Pre-receptive: The endometrium has not yet reached this point, i.e. this cycle has an early implantation window.

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

– Non-receptive: At this point in the cycle the endometrium is not at a point close to the window of implantation.

This way, alterations of the implantation window, present in 20-25% of women with implantation failure, can be detected and a personalised transfer can be performed, increasing the probability of pregnancy.

Unlike other endometrial assessment tests, the ER Map test includes the assessment of immune response genes directly related to the implantation process.

How is this test performed?

It is carried out through an endometrial biopsy with a Cornier pipette that is introduced through the vagina into the uterine cavity. A sample of the endometrial tissue is then taken and a genetic analysis of the endometrial tissue is performed.

Depending on the results of the receptivity test, the timing of the transfer can be individualised. Currently, it is estimated that 20% of repeated implantation failures are due to a displaced window of implantation.

The immunological test

Once embryonic and/or endometrial factors have been ruled out, it is recommended to complete the endometrial receptivity analysis with this test in order to obtain an accurate diagnosis. The immunological test or Im MAP helps our experts identify the causes of implantation failures as well as repeated miscarriages.

The first step is to perform an endometrial biopsy during the luteal phase and a blood test to monitor the immunotherapy. The samples obtained will be analysed by flow cytometry, which is a biophysical technique used to detect immune markers and perform cell counts.

If immunological tests reveal an abnormal level of immune cells, the use of individualised immunotherapy is recommended to improve the chances of a pregnancy.

For whom are these tests recommended?

According to Dr Oliver Pack, fertility specialist at IVF-Life Alicante, “We are talking about two different types of tests. The ER Map is not recommended for all patients unless they have had multiple implantation failures, but it is true that endometrial receptivity is one of the determining factors for successful implantation”.

“Regarding the IM Map, there are many factors at play and many studies on its efficacy are currently being conducted. We know that immunological factors can affect embryo implantation, and that is why we recommend this test when other factors have already been ruled out and an immunological imbalance is suspected. With this test we analyse whether there are natural killer cells, T helper cells, regulatory T cells or elevated b lymphocytes present which may have an effect on fertility”.

Is there scientific evidence to justify the performance of this test?

Since its introduction, the endometrial receptivity test has faced several limitations regarding its use in routine medical practice.

The results obtained in various studies allow us to conclude with a high degree of certainty that the test should not be performed on all patients regardless. However, it is necessary for those patients who have suffered repeated embryo implantation failures after several in vitro fertilisation treatments or those with 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%.

By studying the immunological process surrounding embryo implantation, we have learned that successful gestation requires a dialogue between maternal and foetal cells. Recent studies have shown that alterations in this balance lead to complications during pregnancy.

Other advanced techniques to improve the implantation rate

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

• PGS – Preimplantation Genetic Screening: Analyses carried out on the embryo in order to detect and prevent the transmission of serious genetic or chromosomal diseases, prior to its transfer to the mother’s uterus. With this, we can improve the quality of the embryo, one of the key factors for successful implantation.
• Hysteroscopy: This test is performed, especially in cases where a uterine condition is suspected or in cases of difficulties in achieving pregnancy through fertility treatment. This technique allows direct visualisation of the endometrial cavity to study its morphology and function.

Communication and trust are key in reproductive treatments.

Generally, patients who are seeking this type of treatment have already suffered repeated implantation failures or miscarriages during their attempts to become pregnant, and the reality is that there are several reasons why embryo implantation failures occur.

That is why at IVF-Life we know that the most important thing for our patients is the communication with our specialists throughout the treatment. They will be the ones who will advise you on which diagnostic tests are suitable for you to reach our common goal: a successful treatment and pregnancy.

It is normal that you will search for information on the internet, we all do it, but remember that the individual characteristics of each person or couple imply that every case is different.

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.