Title: Preliminary study, characterising the region-specific abnormalities in the endometrium of women with recurrent implantation failure.
Funder: The Academy of Medical Sciences

Abstract: My research proposal aims to characterise the region-specific abnormalities in the endometrium of women with recurrent implantation failure (RIF). Thus, providing insights into possible treatments for this poorly understood, highly prevalent and distressing condition. RIF affects approximately 10% of women undergoing IVF and the broad definition incorporates the number of previous IVF embryo transfer (ET) failures as a diagnostic criterion, with three failed IVF-ET attempts to be the most widely accepted threshold. RIF is a devastating condition for patients, and the treatment constitutes one of the most difficult challenges for clinicians in the field of IVF. Although common, no good treatment exists for RIF, where good quality embryos fail to attach to the endometrium, potentially highlighting a defect in the luminal epithelium. Many tests are proposed to assess endometrial receptivity, yet they all analyse broken-down endometrium as a single entity. The GeoMx Digital Spatial Profiler will allow parallel-analysis of the whole transcriptome, and proteins of different regions of intact endometrium, collected in the window of implantation from 8 women with RIF and 8 fertile controls. The luminal epithelium (essential for embryo attachment) and the functionalis glands and stroma (both fundamental for early pregnancy establishment) will be interrogated in isolation. This preliminary study will be the first to determine the RIF-specific aberrations in distinct endometrial regions, providing the basis for a larger clinical study further exploring the possibility of establishing key proteins that could enhance embryo attachment to formulate new treatments for women with RIF.

Lay abstract: My research proposal aims to provide insights into possible treatments for the poorly understood, frequently seen, distressing condition, recurrent implantation failure (RIF). RIF affects approximately 1 in 10 women undergoing IVF and failure to achieve a pregnancy after transfer of at least three good-quality embryos is the most widely accepted definition. RIF is a devastating condition for patients, and the treatment constitutes one of the most difficult challenges for clinicians in the field of IVF, due to lack of good treatment options. Since good quality embryos repeatedly fail to attach to the lining of the womb (endometrium) in RIF, a defect specific to the uppermost surface of the endometrium is proposed to be a cause. All previously proposed tests to assess the ability of the endometrium to accept an embryo, break down the tissue prior to analysis, and they are unable to characterise the abnormalities in the different areas of the endometrium in women with RIF. Using intact samples of the endometrium, I will analyse and identify the area-specific abnormalities in the endometrium of 8 women with RIF compared with 8 women who have previously had a baby. Endometrium will be collected at the time where the endometrium is receptive to an embryo in the women`s menstrual cycle. This preliminary study will determine the RIF-specific changes in distinct regions of the endometrium for the first time, providing the basis for future studies to formulate treatments to enhance embryo attachment for women with RIF.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH