P–361 Endometrium optical coherence tomography (OCT) and histomorphometry in implantation window and their relationships with reproductive failure and implantation outcome
Authors: Zhang R , Law T S M , Liang B , Hung S W , Lin S , Li T C , Wang C C 
Published: August 2021

Abstract

Study question
How do endometrium OCT image characteristics during peri-implantation window correlate with histomorphometry and associate with implantation outcomes in women with reproductive failure?

Summary answer
Endometrium OCT intensity correlated with stromal cell density and gland size. Endometrium with recurrent implantation failure had low OCT intensity but reversed in successful implantation.

What is known already
OCT is a non-invasive imaging technique using low energy near-infrared light to capture micrometer-scale resolution images from optical scattering media. An image produced by OCT resembles tissue architecture observed in histology, so OCT imaging has been regarded as “optical biopsy”. Our previous findings demonstrated OCT is better than ultrasound to identify endometrial pathology. We also showed association of OCT signal with microvessel density in peri-implantation endometrium. However, other histomorphometry were not evaluated. It is still unclear whether endometrium OCT image characteristics are different in reproductive failure and can predict implantation outcomes.

Study design, size, duration
This was a prospective study conducted at teaching hospital of The Chinese University of Hong Kong from Jan 2018 to Dec 2019. 46 infertile women with or without recurrent miscarriage (RM) and implantation failure (RIF) were recruited in this study. Endometrium OCT imaging and subsequent biopsy were performed on the seventh day after luteal hormone surge (LH + 7) in natural cycle prior to the consecutive natural conception or embryo transfer (ET) cycle.

Participants/materials, setting, methods
At least 5 systematic random endometrium OCT images from uterine fundus, body and lower segment of each subject were included for intensity analysis by two independent observers. OCT intensity of each image was classified as low, moderate, high based on optical range and then average OCT intensity in each uterine region was calculated for group comparison. Endometrium glandular epithelial, stromal, endothelial, uNK cells were defined by standard H&E and specific immunostaining for histomorphometry and correlation.

Main results and the role of chance
OCT intensity significantly correlated with endometrial cell and gland parameters regardless classifications of reproductive failure and implantation outcome. Higher OCT intensity indicated higher stromal cell density, gland to stromal (G/S) ratio and average gland area, but fewer microvessel and uNK cells. None of the endometrium histomorphometry were significantly different among different reproductive failure types and implantation outcomes, suggesting it may not be sensitive enough to detect the abnormal histological features. However, OCT intensity was significantly lower in the uterine fundus and body of RIF group than in that of infertile and RM groups. There was no significant difference of OCT intensity in the lower part of the endometrium among three groups. It indicates that OCT intensity is a sensitive marker to differentiate endometrium with RIF from the endometrium with other conditions and also endometrium with RIF is characterized with less stromal cells and smaller glands. Compared with infertile group with unsuccessful implantation, OCT intensity was higher in all three parts of the uterus from the infertile group with successful implantation, but the results were not statistically different. The results further implied that endometrial cells and gland size may potentially contribute to the endometrium receptivity for implantation.

Limitations, reasons for caution
Current endometrium OCT imaging depth is within 3mm, change beyond this thickness is inaccessible but still the most important layer for implantation. This is a pilot and small study with lack of normal fertile control. Endometrium OCT imaging in the same natural conception or ET cycle will be more accurate.
Wider implications of the findings: OCT imaging could be used as a potential noninvasive modality to evaluate peri-implantation window endometrium. It enables real-time and in-situ visualization of endometrium structure and pathology with no additional biopsy risk and examination delay. Larger clinical trials are needed to confirm its clinical applications and utilities.

Trial registration number
CREC 2016.160