Conventional microscopy versus digital image analysis for histopathologic evaluation of immune cells in the endometrium

Hallager, Trine; Saxtorph, Malene Hviid; Eriksen, Jens Ole; Hviid, Thomas Vauvert F.; Macklon, Nicholas S.; Larsen, Lise Grupe

doi:10.1016/j.jri.2021.103294

Cited by 5 publications

(3 citation statements)

References 27 publications

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“…To our knowledge, our study was the first to target endometrial CD138+ plasma cells in a whole view of slides using a cloud-based CNN platform with high precision and specificity. As supported by previous publications, the implementation of the CNN platform enhances analysis capabilities by reducing intra-and inter-observer variations, minimizing hands-on time, and improving the speed and reproducibility of analysis 15,17,25 . Indeed, we analyzed 182 WSIs within an hour, surpassing what could be achieved by a pathologist alone.…”

Section: Discussionmentioning

confidence: 67%

“…RIF, often defined as three or more failed in vitro fertilization (IVF) attempts with good-quality embryos transferred, significantly impacts IVF success rates 22 . Factors from the maternal side, including age, body mass index (BMI), and immunological factors 22 , as well as unprepared endometrium for embryo implantation (e.g., shifted window of implantation, impaired decidualization in stroma) 23,24 , have an impact on the implantation rate and reproductive outcomes 22,25 . Moreover, CE is prevalent in RIF patients, affecting up to 14% of this population 9 .…”

Section: Introductionmentioning

confidence: 99%

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AI-algorithm training and validation for endometrial CD138+ cells in infertility-associated conditions; polycystic ovary syndrome (PCOS) and recurrent implantation failure (RIF)

Lee,

Arffman,

Komsi

et al. 2023

Preprint

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Immunohistochemical analysis of CD138+ plasma cells has been applied for detecting endometrial inflammation, especially chronic endometritis (CE). In this study, we developed for the first time an artificial intelligence (AI) algorithm, AITAH, to identify CD138+ plasma cells within endometrial tissue, focusing on two infertility-related conditions: polycystic ovary syndrome (PCOS) and recurrent implantation failure (RIF). We obtained 193 endometrial tissues from healthy controls (n=73), women with PCOS (n=91), and RIF patients (n=29) and compared CD138+ cell percentages across cycle phases, ovulation status, and endometrial receptivity. We trained AITAH with CD138 stained tissue images, and experienced pathologists validated the training and performance of AITAH. AITAH, with high accuracy in detecting CD138+ cells (88.57%), revealed higher CD138+ cell percentages in the proliferative phase than in the secretory phase or in the anovulatory PCOS endometrium, irrespective of PCOS diagnosis. Interestingly, CD138+ percentages differed according to PCOS phenotype in the proliferative phase (p=0.01). Different receptivity statuses had no impact on the cell percentages in RIF samples. In summary, the AI-enabled analysis is a rapid and accurate tool to examine endometrial tissues, potentially aiding clinical decision-making. Here, the AI analysis demonstrated cycle-phase differences in CD138+ aggregations pattern, but no major alterations in PCOS or RIF samples.

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Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

AI-algorithm training and validation for endometrial CD138+ cells in infertility-associated conditions; polycystic ovary syndrome (PCOS) and recurrent implantation failure (RIF)

Lee,

Arffman,

Komsi

et al. 2023

Preprint

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show abstract

“…We examined the association between these biomarkers and clinical pregnancy outcomes after treatment. Digital image analysis has recently been introduced for cell density estimation of the endometrium as an easier, faster, and standardized assessment of pathology specimens [17,29,30]. Therefore, we additionally compared immunohistochemical panel assessment with light microscopy (LM) and digital pathology (DP) performed by expert pathologists in order to assess and validate the objective criteria without major diagnostic errors and to eliminate any differences between the assessments.…”

Section: Introductionmentioning

confidence: 99%

Endometrial Staining of CD56 (Uterine Natural Killer), BCL-6, and CD138 (Plasma Cells) Improve Diagnosis and Clinical Pregnancy Outcomes in Unexplained Infertility and Recurrent IVF Failures: Standardization of Diagnosis with Digital Pathology

et al. 2023

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In women with unexplained infertility (UI) and recurrent in vitro fertilization (IVF) failures, the etiology is often unclear. Endometrial immune perturbations and the use of immune markers associated with these dysregulations are of great interest in the diagnosis and treatment of UI. However, reliable biomarkers and standardized quantification methods are lacking. Here, to address endometrial immune dysregulation in UI patients with recurrent IVF failures, we performed endometrial tissue sampling and immunostaining of CD56 (uNK), CD138, and BCL-6. Of these cases, 57.9% had positive CD56 in the endometrial stroma, while 46.1% had positive BCL-6 in the glandular epithelium, and 14.5% of the cases were found to be positive for CD138. Combined staining rates were 60.5%, 68.4%, and 71.05% for (CD56 or BCL-6), (CD56 or CD138), and (CD56, BCL-6, or CD138), respectively. There was a significant correlation between CD56 and BCL-6 positivity, while CD138 positivity was an independent parameter. After the recommended targeted therapy, pregnancy rates were found to increase from 58.5% to 61.6% and 73.8% in CD56-positive, (CD56- or BCL-6-positive), and (CD56-, BCL-6-, or CD138-positive) cases, respectively. Notably, a retrospective evaluation of digital pathology and light microscopy results showed a significant correlation. This study suggests that the examination of CD56, BCL-6, and CD138 in the same endometrial sample may be an effective method in determining the etiology of UI and reaching an early diagnosis and treatment options. Moreover, digital pathology can be used in the evaluation of CD56 and BCL-6 to provide objective, rapid, and reliable results.

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The role of immunologic tests for subfertility in the clinical environment

Kwak‐Kim

Alsubki

Luu

et al. 2022

Fertility and Sterility

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Conventional microscopy versus digital image analysis for histopathologic evaluation of immune cells in the endometrium

Cited by 5 publications

References 27 publications

AI-algorithm training and validation for endometrial CD138+ cells in infertility-associated conditions; polycystic ovary syndrome (PCOS) and recurrent implantation failure (RIF)

AI-algorithm training and validation for endometrial CD138+ cells in infertility-associated conditions; polycystic ovary syndrome (PCOS) and recurrent implantation failure (RIF)

Endometrial Staining of CD56 (Uterine Natural Killer), BCL-6, and CD138 (Plasma Cells) Improve Diagnosis and Clinical Pregnancy Outcomes in Unexplained Infertility and Recurrent IVF Failures: Standardization of Diagnosis with Digital Pathology

The role of immunologic tests for subfertility in the clinical environment

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