Embryo implantation is the least well known phase of reproduction within the field of reproductive medicine. This fact is of special relevance if we also take into account that the human embryo is not very efficient when compared to other closely-related species in the evolution timeline.
We currently know that pregnancy is based upon three basic pillars: the embryo, the endometrium and the tolerance of the mother’s immune system. Not only is it essential that all three function correctly, but there needs to be optimum interaction between them. We have already covered the role of the embryo and the immune system in detail. Therefore, we will now concentrate on the endometrium and, more specifically, on studying endometrial receptivity.
We have known for some time that the end
ometrium, the tissue which covers the uterine cavity, is only receptive to the embryo for a short space of time known as the implantation window. This window usually occurs around day seven following ovulation and it is subject to in-depth research. In the 1950s, Noyes established different structural patterns across a woman’s cycle and, in the 90s, some specific changes were detected using an electron microscope. They are denominated pinopodes. However, in later studies, these structural, or morphological, parameters were proven to be unreliable.
As a result of this and as a result of significant progress in the field of molecular genetics, new potential tools have been developed over the last decade in order to try to detect if an endometrium is receptive or not. These tools are called endometrial receptivity array (ERA) tests and their aim is to detect signs or labels to locate the endometrial cells in the implantation window. These labels correspond to gene expression levels which need to be ‘active’ during this short period only. In other words, the receptivity test enables us to understand the ID of an endometrium which is suitable for receiving an embryo.
The ERA test falls within the field denominated transcriptome, a term which comes from transcription, the gene expression process.
To date, genetic profiles for different phases of a woman’s natural cycle in different pathologies such as endometriosis and in women undergoing assisted reproduction treatment have been identified. The test has also been shown to be safe (that is, it gives the same results when repeated under similar conditions) and consistent (the result is valid for a relatively long period). However, there are still two significant limitations in terms of its use in standard medicine.
The first is that a group of genes that classifies a receptive endometrium with sufficient clarity has not yet been found. The studies carried out to date have been done with small groups of patients and with very concrete populations and, whilst positive results have been obtained, global verification is necessary.
The second is that it is important to evaluate the role of the test in patients suffering from repeat embryo implantation failure in successive cases of in vitro fertilisation treatment. Preliminary data suggests that up to a quarter of these patients may have an early or late implantation window and that, by adapting the point at which embryo transfer is carried out, the possibilities of pregnancy could be increased. Increased research work in this group of women is essential.
Personalised medicine is increasingly common across all medical specialities. Without going any further, the application of ovarian stimulation protocols based on a woman’s ovarian reserve, the use of IVF (in vitro fertilisation) or ICSI (intracytoplasmic sperm injection) based on sperm parameters are clear examples of this. With this in mind, the development of an endometrial receptivity test which would allow us to choose the ideal moment to transfer the embryo is, without a doubt, very appealing.