Endometrial receptivity. Importance in reproductive success
For years, efforts to improve the results in assisted reproduction techniques have focused on improving the stimulation protocols in order to obtain the greatest number of oocytes, that these are of the best quality, and embryos with the greatest implantation capacity, with a normal genetic endowment (euploid). However, a good quality embryo is required, but we must not forget that the endometrium is a very important factor in implantation.
After ovulation, the endometrium undergoes structural and biochemical changes until it reaches the state of receptive endometrium, which is known as the window of implantation. This process is governed by a hormone, progesterone, which increases after ovulation and induces the transformation of the endometrium to become receptive.
What is endometrial receptivity?
Endometrial receptivity is the ability of the endometrium, the inner lining of the uterus, to receive and allow implantation of an embryo. This process is essential for a successful pregnancy, as only a healthy embryo can successfully implant in a receptive endometrium.
How do I know if my endometrium is receptive?
There are several techniques to assess endometrial receptivity, including the following:
Ultrasound
During the first phase of the cycle prior to ovulation, the endometrium thickens thanks to oestrogen stimulation and takes on a typical trilaminar appearance with an ideal thickness of 7-12m. After ovulation, it becomes secretory thanks to progesterone and is ready to receive the embryo. The ideal thickness at the time of transfer is considered to be 7-12mm, if less than 6mm, gestation rates are lower (1). These measurements are made with a 2D transvaginal ultrasound. Sometimes, for a better assessment of the volume and morphology of the cavity, a 3D ultrasound is performed, which allows us to assess both the volume of the cavity and the presence of pathology (polyps, myomas, septa…) in a more exhaustive way.
Endometrial biopsy
This allows us to visualise the cervical canal and the endometrial cavity, evaluate the characteristics of the endometrium, rule out pathology such as the presence of chronic endometritis (2), which is a cause of miscarriage and implantation failure, analyse and treat pathology of the cavity detected by ultrasound, and assess an adequate correspondence of the appearance of the endometrium with the phase of the cycle.
Analysis
We now know that measuring progesterone levels on the day prior to transfer (3) will allow women with inadequate levels to be supplemented with this hormone, favouring better gestation rates. Recently, Humaidan’s group (4) has also pointed out that adequate levels of oestradiol on the day before transfer are also related to better success rates.
Study of the microbiota
Until a few years ago, it was thought that the uterus was a sterile cavity, but today we know that this is not the case. The microbiota is the set of microorganisms that live in our body. The genital tract is dominated by lactobacilli. These lactobacilli produce inflammatory factors, antimicrobial substances and lactic acid, which allow us to maintain a suitable flora that facilitates implantation. An altered microbiota with a lower lactobacillus content is associated with a higher incidence of miscarriage and lower implantation rates (5). The presence of pathogens in particular Gardnerella, and streptococcus results in the production of inflammatory factors that interfere with embryo implantation.
Since most of these bacteria, due to their low concentration, cannot be cultured under standard conditions, we resort to gene detection techniques for their study.
Study of the immune cell population at the endometrial level
Endometrial immune cells play a crucial role in the implantation and achievement of pregnancy. At the endometrial level, an appropriate balance must develop that allows the embryo, genetically different from the mother, not to be rejected and to implant.
The precise mechanisms that allow this immunological tolerance are complex and are still being studied today. A number of immune cells have been identified, including uterine Natural Killer (uNK) cells, macrophages, T cells, dendritic cells and B cells, present at the maternal-fetal interface with varying functions and concentrations throughout the various stages of gestation. We have techniques that allow us to study this population of immune cells.
Endometrial gene profile study, receptivity test
This consists of analysing a series of genes related to endometrial receptivity, determining whether or not the endometrium is receptive at the time the sample is taken. This will make it possible to coordinate the embryo transfer at the moment of greatest endometrial receptivity. Tissue is taken in the consultation room, either in a natural cycle or with hormonal treatment.
By means of this test, displacements of the implantation window, present in 20-25% of women with implantation failure, can be detected, making a personalised transfer possible and increasing the probability of pregnancy. In these cases, both the endometrial thickness and the quality of the embryos to be transferred are adequate, but implantation does not occur because the embryo transfer has not been performed at the most optimal time.
The personalised and comprehensive study of the endometrium, ensuring the best receptivity conditions, is essential for the success of the treatment. At Clinica Fertia we take care of developing the best protocols to achieve the embryo with the best implantation capacity, but we do not forget the uterine factor, which is crucial to make your dream come true and make you a mother.
Written by:
Dr. Elena Puente
Medical director of Clinica Fertia
Bibliography
- Garcia Velasco JA, Acevedo B, Alvarez C, Alvarez m, Bellver J, Fontes J. Strategies to manage refractory endometrium. State of the art in 2016. Reprod Biomed On line. 2016;32:474-489
- Johnston-MacAnanny EB, Hartnett J, EngmannLL ,Nulsen JC, Sanders MM, Benadiva CA. Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization. Fertil Steril.2010;93:437-441.
- L.abarta, E., Mariani, G., Holtmann, N., Celada, P., Remohi, J., Bosch, E. Low serum progesterone on the day of embryo transfer is associated with a diminished ongoing pregnancy rate in oocyte donation cycles after artificial endometrial preparation: a prospective study. Human reproduction (Oxford, England) 2017; 32: 2437–2442.
- Alsberg B, Jensen MB, Elbaek HO; Laursen R.Midluteal serum estradiol levels are associated with live birth rates in hormone replacement therapy frozen embryo transfer cycle: a cohort study.Fertil Steril. 2024.
- Moreno I, Simon C. Relevance of assessing the uterine microbiota in infertility. Fertil Steril.2017;108:32-39.
