Available online 7 October 2023, 104162

Author links open overlay panel, Abstract

A cyclical evolvement of the endometrium into a transient state of receptivity is crucial for acceptance of the semi-allogeneic foetus, conducive to pregnancy. Despite documentation of aberrances in this process within patients experiencing repeated embryo implantation failures and miscarriages, the endometrium is often overlooked in IVF clinics as the cause for failure. Focus instead is usually given to embryo-derived factors, such as aneuploidy. Nevertheless, failure of approximately 30% of euploid embryos to implant demonstrates that other factors such as the endometrium require clinical exploration. Here, we review both traditional and novel methods used to assess endometrial receptivity such as identifying the WOI, endometrial immune profiling and transcriptomics panel testing. Where reported, we will also discuss their clinical application, as well as novel potential biomarkers within the pre-clinical research stages which show promise in their ability to assess endometrial receptivity.

Section snippetsIntroduction/background

There are two essential prerequisites for successful embryo implantation; arrival of a viable embryo in the uterine cavity and an endometrium in a state of receptivity. Cyclically, a responsive endometrium will begin thickening in an oestrogen-dependent manner, known as its proliferative phase. Driven by rising progesterone levels from the corpus luteum (CL), the endometrium metamorphoses into a receptive tissue. This secretory phase is characterised by a wealth of immunological and cellular

Defining the window of implantation (WOI)

Remarkable changes occur to the endometrium following CL formation. Secreted directly from the developing CL, rising levels of progesterone govern the crucial changes required to initiate endometrial decidualisation, driving epithelial and stromal differentiation. It further plays a key immunomodulatory role (Szekeres-Bartho et al., 1989). In the secretory phase, progesterone receptor (PR)-expressing immune cell populations increase via progesterone-regulated recruitment and activation (

Immunological markers of receptivity

Decidualisation of the endometrium is characterised by an influx of a distinct immune cell milieu that functions to exert immunomodulatory effects towards the implanting blastocyst. Implantation itself is a highly invasive process where, once cell receptor-ligand-facilitated tethering of the embryo to the endometrium has occurred, trophoblastic cells permeate deep into the decidua. To prevent mounting of an immune response which would result in foetal rejection, specific immune cell populations

Potential novel biomarkers of endometrial receptivity

Some biomarkers of endometrial receptivity are novel and at the pre-clinical stage, or just starting to permeate the clinical domain. Within those, we will discuss the vaginal and endometrial microbiome, miRNAs and extracellular vesicles (EVs), and glycobiology.

Conclusions

To conclude, cyclic evolvement of the endometrium into a receptive tissue is a complex mechanism governed by a multitude of intricate signalling pathways, immunomodulation and mass changes in gene expression within epithelial and stromal cells. Thus, the endometrium requires an assessment which encompasses its transient, complex nature. Whether directly or indirectly, at the crux of most methods of assessment are immune cells and their respective modulators, cytokines and signalling pathways,

Uncited references

(Blois et al., 2007, Patel et al., 2022, Schindler, 2009)

Declaration of Competing Interest

The authors declare that they have no known competing financial interests that could have appeared to influence the work reported in this paper.

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