Uterine Natural Killer Cells in the Context of Implantation: Immunohistochemical Analysis of Endometrial Samples from Women with Habitual Abortion and Recurrent Implantation Failure

Lapides, Lenka; Klein, Martin; Belušáková, V; Csöbönyeiová, M; Varga, Ivan; Babál, P

doi:10.33549/physiolres.935012

Cited by 8 publications

(3 citation statements)

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“…The recent principal histopathological approach in the study of uNK cells in uterine bioptic samples is immunohistochemistry. Most published immunohistochemical studies evaluated the CD56-positive cells in the endometrium and decidua of patients with unexplained recurrent implantation failure and habitual abortion as absolute numbers of CD56-positive cells per square millimeter [ 55 , 56 , 57 , 58 , 59 , 60 ]. The advantage of such a histological approach is the possibility of studying the cyto-architectonics in the endometrial tissue.…”

Section: Current Histological Knowledge and Immunohistochemistry Of U...mentioning

confidence: 99%

The Neglected Uterine NK Cells/Hamperl Cells/Endometrial Stromal Granular Cell, or K Cells: A Narrative Review from History through Histology and to Medical Education

Lapides

Varga

Csöbönyeiová

et al. 2023

IJMS

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Reproductive immunology is at the forefront of research interests, aiming to better understand the mechanisms of immune regulation during gestation. The relationship between the immune system and the implanting embryo is profound because the embryo is semi-allogenic but not targeted by the maternal immune system, as expected in graft-versus-host reactions. The most prominent cell population at the maternal–fetal interface is the population of uterine natural killer (uNK) cells. Uterine NK cells are two-faced immunologically active cells, bearing comparison with Janus, the ancient Roman god of beginnings and endings. Their first face can be seen as natural killer cells, namely lymphocytes, which are critical for host defense against viruses and tumors. Even though uNK cells contain cytolytic molecules, their cytotoxic effect is not applied to classical target cells in vivo, playing a permissive rather than a defensive role. Their second face is crucial in maintaining physiological gestation—uNK cells show critical immunomodulatory functions with the potential to control embryo implantation and trophoblast invasion, regulate placental vascular remodeling, and promote embryonic/fetal growth. Therefore, we believe that their current designation “natural killer cells” (the first “cytotoxic” Janus’s face) is misleading and inappropriate, considering their principal function is supporting and maintaining pregnancy. In this narrative review, we will focus on three lesser-known areas of knowledge about uNK cells. First, from the point of view of histology, we will comprehensively map the history of the discovery of these cells, as well as the current histological possibilities of their identification within the endometrium. To be brief, the discovery of uNK cells is generally attributed to Herwig Hamperl, one of the most influential and prominent representatives of German pathology in the 20th century, and his co-worker, Gisela Hellweg. Secondly, we will discuss the interesting aspect of terminology, since uNK cells are probably one of the human cells with the highest number of synonymous names, leading to significant discrepancies in their descriptions in scientific literature. From the first description of this cell type, they were referred to as endometrial granulocytes, granular endometrial stromal cells, or large granular lymphocytes until the end of the 1980s and the beginning of the 1990s of the last century, when the first publications appeared where the name “uterine NK cells” was used. The third area of present review is medical teaching of histology and clinical embryology. We can confirm that uNK cells are, in most textbooks, overlooked and almost forgotten cells despite their enormous importance. In the present narrative review, we summarize the lesser-known historical and terminological facts about uNK cells. We can state that within the textbooks of histology and embryology, this important cell population is still “overlooked and neglected” and is not given the same importance as in fields of clinical research and clinical practice.

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Section: Current Histological Knowledge and Immunohistochemistry Of U...mentioning

confidence: 99%

The Neglected Uterine NK Cells/Hamperl Cells/Endometrial Stromal Granular Cell, or K Cells: A Narrative Review from History through Histology and to Medical Education

Lapides

Varga

Csöbönyeiová

et al. 2023

IJMS

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“…Эти параметры более чем вдвое повышаются при проведении предимпланционной генетической диагностики (ПГД) или при переносе размороженного эмбриона, что безусловно подтверждает ведущую роль эмбрионального фактора в исходах ВРТ. Однако число женщин старшего репродуктивного возраста, со снижением естественной фертильности, обратившихся в клиники ВРТ, неуклонно растет, а повторяющиеся неудачи программ ВРТ у пациенток с бесплодием при переносе эмбрионов высокого качества указывают на то, что причиной могут быть нарушения процессов имплантации эмбриона, связанные с нарушением рецептивности и функциональности эндометрия [1][2][3]. Морфологические, иммунологические и иммуногистохимические изменения в эндометрии, связанные с возрастным фактором, могут оказаться определяющими для формирования «окна имплантации», и коррекция этих изменений, возможно, улучшит исходы ВРТ для когорты пациенток старшего репродуктивного возраста.…”

Section: Introductionunclassified

Immunological and immunohistochemical features of endometrial implantation factor in healthy patients of late reproductive age

Кравцова

Колесникова

Lukoshkina

et al. 2023

Vestn. Ross. univ. družby nar., Ser. Med.

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Аbstract. Relevance. The number of women of older reproductive age is steadily increasing, and repeated failures of Assisted Reproductive Technologies programs during the transfer of high-quality embryos indicate the possibility of disruption of embryo implantation processes associated with impaired receptivity and functionality of the endometrium. Morphological, immunological and immunohistochemical changes in the endometrium associated with age factor may be decisive for the formation of the «implantation window» and correction of these changes and may improve the outcomes of Assisted Reproductive Technologies for a cohort of patients of older reproductive age. The aim of the study - to expand the pathogenetic understanding of the violation of the implantation ability of the endometrium in healthy patients of older reproductive age. Materials and Methods. A prospective sample study of 46 patients (group 1), aged 38 to 45 years with an officially registered diagnosis of infertility lasting no more than 4 years, with a successful gynecological and obstetric history, who were about to have their first IVF attempt, was conducted. The patients were examined according to Order № 803n of the Ministry of Health of the Russian Federation. Additionally, the level of peripheral blood melatonin, the determination of progesterone, estrogen, HLA-DR (MHC II), CD56 (NK cells), CD138, leukemia inhibiting factor receptors in the endometrium were studied. Concentrations of IL-6, IL-10, TGFß, and VGEF were determined in the cervical secretion, with the calculation of the pro-inflammatory index, as the ratio of IL-6/IL-10 cu and the ratio of TGFß1/VEGF. Statistical data processing was performed using the Statistica 10.0 application software package (StatSoft, Inc., USA). Results and Discussion. In the group of healthy patients of older reproductive age, there is an imbalance of steroid receptors and secretory transformation of the endometrium against the background of relative hyperestrogenism, with a decrease in the reception of own hormones in the endometrium. A decrease in melatonin signals a disorder of pineal and pituitary control over ovarian cycling. There is a decrease in the expression of leukemia inhibiting factor. Signs of inactive chronic endometritis with an autoimmune component are monitored, confirmed by a pro-inflammatory cytokine balance. The predominance of fibrosis processes over angiogenesis processes is confirmed by an increase in the ratio of TGFß1/VEGF and highly resistant blood flow in the uterine arteries. Conclusion. Standard pre-gravidar preparation cannot compensate for all factors that violate the implantation potential of the endometrium in this cohort of patients and requires the development of new complex techniques that directly affect the diversity of all factors that ensure the natural extinction of reproductive potential in order to increase the effectiveness of Assisted Reproductive Technologies programs.

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“…Endometrial sampling for tissue retrieval is often required for a variety of clinical reasons, 1,2 and the Pipelle device is commonly used in the outpatient setting because of its efficacy in detecting endometrial cancer. 2 Pipelle sampling has proved to be a reliable, minimally invasive alternative to dilatation and curettage and hysteroscopic biopsy because of its high accuracy, cost-effectiveness, and safety.…”

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confidence: 99%

Pipelle Endometrial Sampling With a Full Bladder Compared With Standard Care

Hashim,

Hong,

Woo

et al. 2024

Obstetrics &Amp; Gynecology

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OBJECTIVE: To compare insertion failure rates for Pipelle endometrial sampling with a full bladder compared with the standard process (not taking into account bladder status) without cervical manipulation. METHODS: A single-masked randomized trial was conducted in a single tertiary care center from July 2021 to January 2022. Two hundred fourteen participants aged 18 years or older who were scheduled for outpatient Pipelle endometrial sampling were randomized: 107 each to having a full bladder (by oral water intake) or standard process (without delayed sampling and bladder status not taken into account). Women with known cervical stenosis, gynecologic malignancy, uterine anomalies, leiomyoma distorting the uterine cavity, acute cervicitis, urge bladder dysfunction, intense anxiety, need for anesthesia or analgesic before the procedure, positive pregnancy test, or previous failed office endometrial sampling were excluded. The primary outcome was the insertion failure rate of endometrial sampling at first attempt. Secondary outcomes were pain during procedure, satisfaction score, analgesia use, procedure duration, and need for cervical manipulation. Factoring in a baseline insertion failure rate of 30.0%, relative risk of 0.45, α of 0.05, 80.0% power, and a dropout rate of 10.0%, we needed 107 participants in each arm. RESULTS: The insertion failure rate was significantly lower in the full bladder group compared with standard process: 25 of 107 (23.4%) compared with 45 of 107 (42.1%) (relative risk 0.56, 95% CI, 0.37–0.84; number needed to treat to benefit 6.0, 95% CI, 3.20–15.70). Pain score (median) during the procedure (interquartile range) was 4 (3–6) compared with 5 (3–8) (P=.004); patient satisfaction score was 8 (7–9) compared with 7 (4–8) (P<.001); and mean±SD procedure duration was 3.0±2.4 compared with 4.7±2.9 minutes (P<.001) for the full bladder and standard process arm, respectively. Other secondary outcomes of cervical laceration, analgesia use, and adequacy of endometrial tissue for histopathologic assessment were not significantly different between groups. CONCLUSION: Pipelle endometrial sampling with a full bladder reduces the initial insertion failure rate, procedure-related pain, and duration of sampling and increases patient satisfaction compared with the standard process. CLINICAL TRIAL REGISTRATION: ISRCTN, ISRCTN33938192.

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Uterine Natural Killer Cells in the Context of Implantation: Immunohistochemical Analysis of Endometrial Samples from Women with Habitual Abortion and Recurrent Implantation Failure

Cited by 8 publications

References 31 publications

The Neglected Uterine NK Cells/Hamperl Cells/Endometrial Stromal Granular Cell, or K Cells: A Narrative Review from History through Histology and to Medical Education

The Neglected Uterine NK Cells/Hamperl Cells/Endometrial Stromal Granular Cell, or K Cells: A Narrative Review from History through Histology and to Medical Education

Immunological and immunohistochemical features of endometrial implantation factor in healthy patients of late reproductive age

Pipelle Endometrial Sampling With a Full Bladder Compared With Standard Care

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