For years, efforts to improve outcomes in assisted reproduction techniques have focused on improving stimulation protocols in order to obtain the greatest possible number of oocytes, of the best possible quality, and embryos with the greatest implantation capacity, with a normal genetic makeup (euploid). However, while a good-quality embryo is necessary, 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 receptive endometrium state, which is what we know as the implantation window. This process is governed by a hormone, progesterone, which increases after ovulation and induces the transformation of the endometrium so that it becomes receptive.
What is endometrial receptivity?
Endometrial receptivity is the ability of the endometrium, the inner lining of the uterus, to receive and allow the implantation of an embryo. This process is essential for pregnancy success, since only a healthy embryo will be able to implant correctly in a receptive endometrium.
How can I know if my endometrium is receptive?
There are various techniques for assessing endometrial receptivity, including:
Ultrasound
During the first phase of the cycle prior to ovulation, the endometrium thickens thanks to the stimulus of estrogens and acquires a typical trilaminar appearance with an ideal thickness of between 7-12 mm. After ovulation, it becomes secretory thanks to progesterone and is now ready to receive the embryo. The ideal thickness at the time of transfer is considered to be 7-12 mm; if it is less than 6 mm, pregnancy rates are lower (1). These measurements are taken using 2D transvaginal ultrasound. In some cases, for a better assessment of the volume and morphology of the cavity, a 3D ultrasound is performed, which allows us to more thoroughly assess both the volume of the cavity and the presence of pathology (polyps, fibroids, septa…).
Endometrial biopsy
This allows us to visualize the cervical canal and endometrial cavity, assess 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, analyze and treat cavity pathology detected via ultrasound, as well as assess an appropriate match between the appearance of the endometrium and the phase of the cycle.
Blood tests
Today we know that measuring progesterone levels the day before transfer (3) makes it possible to supplement this hormone in women with inadequate levels, favoring better pregnancy rates. Humaidan’s group (4) has recently also reported that adequate estradiol levels the day before transfer are also linked to better success rates.
Studying the microbiota
Until a few years ago, the uterus was thought to be a sterile cavity; today we know this is not the case. We refer to the set of microorganisms that live in our body as the microbiota. At the level of the genital tract, it is dominated by lactobacilli. These lactobacilli produce inflammatory factors, antimicrobial substances, and lactic acid, which help maintain an adequate flora that facilitates implantation. An altered microbiota, with lower lactobacilli content, is associated with a higher incidence of miscarriage and lower implantation rates (5). The presence of pathogens, particularly Gardnerella and streptococcus, leads to 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 rely on genetic detection techniques to study them.
Studying the population of immune cells at the endometrial level
Immune cells at the level of the endometrium play a crucial role in implantation and achieving pregnancy. At the endometrial level, an adequate balance must develop that allows the embryo, genetically distinct from the mother, to avoid being rejected and to implant.
The precise mechanisms that allow this immune tolerance are complex and remain under study today. A number of immune cells have been identified, including: uterine Natural Killer cells (uNK), macrophages, T cells, dendritic cells, and B cells, present at the maternal-fetal interface with variable functions and concentrations throughout the different stages of pregnancy. We have techniques available that allow us to study this population of immune cells.
Endometrial genetic profile study, receptivity test
This involves analyzing a series of genes related to endometrial receptivity, determining whether the endometrium is or is not receptive at the time the sample is taken. This allows the embryo transfer to be coordinated with the moment of greatest endometrial receptivity. The tissue sample is taken during a consultation, either in a natural cycle or with hormonal treatment.
This test can detect shifts in the implantation window, present in 20-25% of women with implantation failure, allowing for a personalized transfer 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 was not performed at the most optimal time.
A personalized, comprehensive study of the endometrium, ensuring the best possible receptivity conditions, is essential for treatment success. At Clínica Fertia, we work to develop the best protocols to obtain the embryo with the greatest implantation capacity, but we never lose sight of the uterine factor, which is crucial to making your dream come true and helping you become a mother.
Contact us for your first free fertility consultation.
References
- 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 Online. 2016;32:474-489.
- Johnston-MacAnanny EB, Hartnett J, Engmann LL, 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.
- Labarta 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. Hum Reprod. 2017;32:2437-2442.
- Alsbjerg B, Jensen MB, Elbaek HO, Laursen R. Midluteal serum estradiol levels are associated with live birth rates in hormone replacement therapy frozen embryo transfer cycles: a cohort study. Fertil Steril. 2024.
- Moreno I, Simon C. Relevance of assessing the uterine microbiota in infertility. Fertil Steril. 2017;108:32-39.
