Relationship between endometrium and embryo implantation

  With the development of assisted reproductive technology, embryo implantation directly affects the success rate of assisted reproductive technology in the treatment of infertility. Successful embryo implantation requires three conditions: (1) a synchronized developing embryo; (2) the establishment of endometrial tolerance; and (3) maternal-embryo interaction.  As the name suggests, endometrial receptivity is the acceptance of the embryo by the endometrium, and the successful establishment of endometrial receptivity in this process is essential to ensure successful embryo implantation. Embryo implantation can be divided into 3 processes: directional positioning, adhesive attachment, and invasion, through which the embryo penetrates through the epithelial cells of the uterine cavity, and these processes are regulated by a complex of various molecules and molecular receptors, so when is endometrial receptivity established? Is the timing of implantation arbitrary? As early as the 1990s, researchers have confirmed that the endometrial lining accepts embryos at a relatively fixed time, and that the “implantation window” for embryos is 6-10 days after ovulation, when the uterine environment is most suitable for embryo implantation and endometrial receptivity is successfully established.  With the use of assisted reproductive technology, the use of ovulation-promoting drugs directly affects the physiological regulation of the endometrium by endogenous hormones, resulting in changes in the morphology of the endometrium, the expression of receptors and related factors, which affects the endometrial tolerance of the embryo during implantation and reduces the pregnancy rate. Therefore, the assessment of endometrial tolerance is an important part of improving pregnancy outcomes, and there are four main indicators that can assess endometrial tolerance: (1) endometrial thickness: endometrial thickness during the menstrual cycle can partially reflect endometrial tolerance. Some authors believe that no pregnancy occurs when the endometrial thickness is less than 5 mm, but this study is also controversial, as we have encountered cases of successful pregnancy after transfer of high-quality blastocysts in patients with an endometrial thickness of 5 mm, so some authors believe that there is no correlation between endometrial thickness and pregnancy rate. However, in order to ensure pregnancy rates, our center’s experience is that patients with an endometrial thickness of 8 mm or more, with good endometrial morphology and no abnormal echogenicity, can be transferred. For some patients with poor endometrial growth, we will adjust this transplantation criterion according to the actual situation of the patient.  (2) Types of endometrium: At present, the morphology of endometrium is mainly divided into three types: type A is trilinear endometrium with strong echogenicity in the outer and middle layers and hypoechogenicity in the inner layer with obvious midline echogenicity in the uterine cavity; type B is weakly trilinear with inconspicuous midline echogenicity in the uterine cavity; type C is uniformly strong echogenicity with no midline echogenicity in the uterine cavity. The three forms of endometrium are not good or bad, but just different imaging manifestations of endometrium in different menstrual stages. However, if there are areas of strong echogenicity or uneven echogenicity on the endometrium, we would highly suspect the presence of polyps on the endometrium and should first confirm the diagnosis by hysteroscopy and wait for the exclusion of polyps or removal of polyps before embryo transfer.  (3) Uterine arterial and subendometrial flow parameters: The most commonly used indicators are the pulsatility index (PI) and resistance index (RI). It is currently believed that high PI and RI are effective predictors of pregnancy outcome due to increased resistance to uterine flow and decreased uterine blood flow, which affects endometrial tolerance.  (4) Important bioactive molecules: The timing of peak expression of integrins, leukemia inhibitory factors, tissue inhibitors of matrix metalloproteinases, calcitonin and many other bioactive molecules is highly consistent with the opening of the endometrial implantation window, and numerous studies have confirmed that the expression of these bioactive molecules is directly related to embryo implantation, but the exact mechanism remains unclear and needs to be confirmed by more studies.  The relationship between the endometrium and embryo implantation remains unclear and what we know is only the tip of the iceberg. More research is needed to unravel this mystery and ultimately improve pregnancy outcomes with assisted reproduction techniques.