Úvod a cíl studie: Uterinní NK (uNK) buňky jsou specializovanou subpopulací NK (natural killer) lymfocytů nacházejících se v endometriu. Hrají klíčovou roli v regulaci imunitní odpovědi a v procesu implantace embrya. Cílem této studie je retrospektivní analýza výsledků léčby metodou in vitro fertilizace (IVF) v souboru žen, které podstoupily imunofenotypizaci uNK buněk a na základě výsledků tohoto vyšetření byly, nebo nebyly léčeny imunomodulační terapií. Metody: Studie zahrnovala 122 pacientek, které podstoupily imunofenotypizaci uNK buněk v období od dubna do prosince 2023. Imunofenotypizace byla provedena metodou průtokové cytometrie. Pacientky byly roztříděny do čtyř skupin dle fenotypu uNK buněk: normální nálezy, nízké absolutní a relativní počty uNK (LOW-IMMUNE profil), nízké počty uNK v kombinaci s nežádoucím posunem směrem k cytotoxickému uNKdim imunofenotypu (MIXED-IMMUNE profil) a normální počty uNK, ale nežádoucí posun v poměru cytotoxických a regulačních uNK s cytotoxickým fenotypem (OVER-IMMUNE profil). Byly hodnoceny výsledky embryotransferu a výskyt potratů do ukončeného 12. týdne těhotenství v jednotlivých skupinách. Výsledky: Nejvyšší míra dosažení klinické gravidity byla nalezena v léčené skupině OVER- -IMMUNE (70 %), následované skupinou MIXED-IMMUNE (60 %). Skupina LOW-IMMUNE se od neléčené NORMAL skupiny signifikantně nelišila (p = 0,205). Nedostatečná imunitní aktivace (LOW-IMMUNE profil) byla signifikantně nejčastěji sdružena s prvotrimestrální těhotenskou ztrátou (p < 0,0001). Závěr: Tato studie přináší nové poznatky o potenciálu imunofenotypizace uNK buněk a následné imunomodulační terapie v léčbě poruch plodnosti. Ačkoli výsledky naznačují možné klinické přínosy, je zapotřebí dalšího výzkumu k potvrzení těchto zjištění a k objasnění mechanizmů, které vedou ke zlepšení výsledků léčby technikami asistované reprodukce.

Introduction and objective: Uterine NK (uNK) cells, a specialized subpopulation of natural killer (NK) lymphocytes located in the endometrium, play a crucial role in regulating the immune response and in the process of embryo implantation. This study aims to retrospectively analyze the outcomes of in vitro fertilization (IVF) treatment in a cohort of women who underwent uNK cell immunophenotyping with subsequent immunomodulatory therapy applied based on the results. Methods: The study included 122 patients who underwent uNK cell immunophenotyping between April and December 2023. Immunophenotyping was performed using flow cytometry. Patients were categorized into four groups according to their uNK cell phenotypes: normal findings, low absolute and relative numbers of uNK cells (LOW-IMMUNE profile), low numbers of uNK cells combined with the shift towards the cytotoxic uNKc dim immunophenotype (MIXED-IMMUNE profile), and normal numbers of uNK cells, but an undesirable shift in the ratio of cytotoxic to regulatory uNK cells towards the cytotoxic uNK dim phenotype (OVER-IMMUNE profile). Embryo transfer outcomes and the occurrence of miscarriages up to the 12th week of pregnancy were evaluated in each group. Results: The highest clinical pregnancy rate was observed in the treated OVER-IMMUNE group (70%), fol lowed by the MIXED-IMMUNE group (60%). The LOW-IMMUNE group did not differ significantly from the untreated NORMAL group (P = 0.205). Insufficient immune activation (LOW-IMMUNE profile) was significantly associated with first-trimester pregnancy loss (P < 0.0001). Conclusion: This study provides new insights into the potential benefits of uNK cell immunophenotyping and subsequent immunomodulatory therapy in treating fertility disorders. While the results indicate possible clinical advantages, further research is necessary to confirm these findings and elucidate the mechanisms leading to improved outcomes in assisted reproductive techniques.

• Klíčová slova
• uterinní NK buňky, imunofenotypizace lymfocytů, opakované selhání implantace,
• MeSH
• buňky NK MeSH
• endometrium cytologie   MeSH
• fertilizace in vitro * MeSH
• habituální potrat MeSH
• imunofenotypizace MeSH
• imunomodulace MeSH
• lidé MeSH
• průtoková cytometrie metody   MeSH
• retrospektivní studie MeSH
• ženská infertilita * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH

Circulating endometrial cells (CECs) have emerged as a new biomarker of advanced disease in women with endometriosis. The identification of several subtypes of CECs (e.g., stem cell-like, epithelial, glandular, stromal) has opened the way for characterization of endometriosis-associated CECs. This study focused on the isolation and characterization of CECs and disseminated endometrial cells (DECs) in patients with spontaneous pneumothorax (SP). The primary objective was to differentiate between cancer and non-cancer cells in patients with no previous cancer diagnosis. The MetaCell® size-based separation protocol was used to enrich CECs/DECs. Evaluation of the captured cells by 3D microscopy was performed using a NANOLIVETM microscope using a holographic approach. Based on gene expression analysis (GEA), we can conclude that mitochondria are much more active in primary tumors compared to endometriosis tissue (e.g. MT-ND1, MT-ATP6 genes). The culture of DECs is made of stromal, stem and immune cells. In vitro culture of DECs is characterized by an increase in the epithelial marker KRT18. Similarly, NFE2L2, a proerythroid factor, is also elevated. Further, a significant decrease in the amount of stem and immune cells was observed in the cell culture of DECs. The data presented here show how morphologically plastic the changes in the mitochondrial network can be and how cells can reflect them at the level of gene expression. The markers identified could help in the accompanying diagnostic process of the spontaneous pneumothorax in women of reproductive age.

• MeSH
• dospělí MeSH
• endometrióza * patologie   diagnóza   genetika   MeSH
• endometrium patologie   metabolismus   MeSH
• lidé MeSH
• mitochondrie * metabolismus   patologie   MeSH
• pneumotorax * patologie   diagnóza   MeSH
• stanovení celkové genové exprese metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Cíl: Endometriální polypy (EP) představují patologii, která je v klinické praxi běžná. Ačkoli jejich přesná etiologie není úplně známá, existují důkazy o tom, že jsou citlivé vůči hormonální stimulaci. Naším cílem bylo prozkoumat vztah mezi kisspeptinem (KP) a EP pomocí srovnání míry genetické exprese (tkáň–krev) a imunohistochemické (IHC) exprese KP v lézích EP u pacientek s normálním endometriálním nálezem. Materiál a metody: Byla provedena retrospektivní případová studie u 50 pacientek s EP (n = 25) a normálním endometriálním nálezem (n = 25) z biopsie a/nebo materiálu z excize. Krev a vzorky z biopsie od všech pacientek byly uchovávány při –80 °C. Exprese genů KP byla stanovena v parafinových blocích a vzorcích periferní žilní krve získaných z bioptických vzorků a analýza skóre IHC-H byla provedena na parafinových blocích. EP a příslušné kontroly byly srovnány z hlediska KP. Výsledky: Po IHC bylo KP-H skóre v kontrolní skupině vyšší než ve skupině s EP a tento rozdíl byl statisticky významný; H skóre: kontroly: 5 (++; 1–15); polypy: 1 (+; 0–12) (p < 0,05). Ačkoli byla exprese KP jak v tkáni, tak v krvi vyšší v kontrolní skupině oproti skupině s EP, tento rozdíl nebyl statisticky významný (p > 0,05). V krvi ani tkáni nebyla zjištěna významná korelace mezi IHC-H skóre a expresí KP. Podle analýzy ROC cut-off hodnoty exprese KP v tkáni a krvi a plocha pod křivkou (AUC), která predikuje pravděpodobnost vzniku EP, nebyly významné (KP v tkáni: 1,04; AUC: 0,570; p = 0,388; senzitivita 56 %, specificita 60 % / KP v krvi: 1,06; AUC: 0,569; p = 0,401; senzitivita 80 %, specificita 40 %). Závěry: Snížená míra exprese KP v lézích EP může predikovat diagnózu EP a v budoucnu může mít KP při benigních gynekologických patologiích, jako jsou polypy, terapeutický potenciál.

Objective: Endometrial polyp (EP) is a type of pathology that is quite common in clinical practice. Although its exact etiology is not fully known, there is evidence to support that it is sensitive to hormonal stimuli. We aimed to investigate the relationship between kisspeptin (KP) and EP by comparing the genetic (tissue-blood) and immunohistochemical (IHC) expression of KP in EP lesions in patients with normal endometrial findings. Materials and methods: A prospective case-control study of 50 patients with EP (N = 25) and normal endometrial findings (N = 25) on biopsy and/or excision material was performed. Blood and biopsy samples obtained from all patients were stored at –80 °C. KP gene expression levels were determined from paraffin blocks, and peripheral venous blood samples obtained from biopsy specimens and IHC-H-score analysis were performed from paraffin blocks. EP and matched controls were compared for KP. Results: After IHC, the KP H-score of the control group was higher than the EP group, and this difference was statistically significant; H-score: control: 5 (++; 1–15); polyp: 1 (+; 0–12) (P < 0.05). Although KP expression in both tissue and blood was higher in the control group than in the EP group, this difference was not statistically significant (P > 0.05). No significant correlation was found between IHC H-score and KP expression levels in tissue and blood. According to the ROC analysis, the tissue and blood KP expression cut-off value and area under the curve (AUC) predicting the likelihood of developing EP were not significant (tissue KP: 1.04, AUC: 0.570, P = 0.388, sensitivity 56%, specificity 60%, Blood KP: 1.06, AUC: 0.569, P = 0.401, sensitivity 80%, specificity 40%). Conclusions: Decreased KP expression level in EP lesions may predict the diagnosis of EP, and in the future, KP may have therapeutic potential for benign gynecological pathologies such as polyps.

• MeSH
• endometrium * metabolismus   patologie   MeSH
• imunohistochemie metody   MeSH
• kisspeptiny genetika   metabolismus   MeSH
• lidé MeSH
• nemoci dělohy genetika   krev   metabolismus   patologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí metody   MeSH
• polypy genetika   metabolismus   patologie   MeSH
• prospektivní studie MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH

During pregnancy, two fetomaternal interfaces, the placenta-decidua basalis and the fetal membrane-decidua parietals, allow for fetal growth and maturation and fetal-maternal crosstalk, and protect the fetus from infectious and inflammatory signaling that could lead to adverse pregnancy outcomes. While the placenta has been studied extensively, the fetal membranes have been understudied, even though they play critical roles in pregnancy maintenance and the initiation of term or preterm parturition. Fetal membrane dysfunction has been associated with spontaneous preterm birth (PTB, < 37 weeks gestation) and preterm prelabor rupture of the membranes (PPROM), which is a disease of the fetal membranes. However, it is unknown how the individual layers of the fetal membrane decidual interface (the amnion epithelium [AEC], the amnion mesenchyme [AMC], the chorion [CTC], and the decidua [DEC]) contribute to these pregnancy outcomes. In this study, we used a single-cell transcriptomics approach to unravel the transcriptomics network at spatial levels to discern the contributions of each layer of the fetal membranes and the adjoining maternal decidua during the following conditions: scheduled caesarian section (term not in labor [TNIL]; n = 4), vaginal term in labor (TIL; n = 3), preterm labor with and without rupture of membranes (PPROM; n = 3; and PTB; n = 3). The data included 18,815 genes from 13 patients (including TIL, PTB, PPROM, and TNIL) expressed across the four layers. After quality control, there were 11,921 genes and 44 samples. The data were processed by two pipelines: one by hierarchical clustering the combined cases and the other to evaluate heterogeneity within the cases. Our visual analytical approach revealed spatially recognized differentially expressed genes that aligned with four gene clusters. Cluster 1 genes were present predominantly in DECs and Cluster 3 centered around CTC genes in all labor phenotypes. Cluster 2 genes were predominantly found in AECs in PPROM and PTB, while Cluster 4 contained AMC and CTC genes identified in term labor cases. We identified the top 10 differentially expressed genes and their connected pathways (kinase activation, NF-κB, inflammation, cytoskeletal remodeling, and hormone regulation) per cluster in each tissue layer. An in-depth understanding of the involvement of each system and cell layer may help provide targeted and tailored interventions to reduce the risk of PTB.

• MeSH
• amnion metabolismus   cytologie   MeSH
• chorion metabolismus   MeSH
• decidua * metabolismus   MeSH
• dospělí MeSH
• extraembryonální obaly * metabolismus   MeSH
• lidé MeSH
• porod v termínu genetika   MeSH
• předčasný odtok plodové vody genetika   metabolismus   MeSH
• předčasný porod * genetika   MeSH
• stanovení celkové genové exprese MeSH
• těhotenství MeSH
• transkriptom * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Cíl: Vliv autoplazmy obohacené o krevní destičky na tloušťku endometria a citlivost receptorů na estrogen a progesteron. Materiál a metody: Do této prospektivní studie bylo zařazeno 200 pacientek. Účastnice studie byly rozděleny do dvou skupin. První, kontrolní skupina dostávala hormonální substituční terapii (HRT – hormone replacement therapy). Druhá, studijní skupina dostávala intrauterinní infuzi autoplazmy obohacené o krevní destičky (PRP – platelet-rich autoplasma). Devatenáctý den menstruačního cyklu bylo provedeno ultrazvukové vyšetření s cílem zhodnotit tloušťku endometria a dále imunohistochemická analýza k stanovení citlivosti receptorů pro estrogen a progesteron. Výsledky: Během studie jsme zjistili, že po podání autoplazmy obohacené o krevní destičky se zvýšila tloušťka endometria o 0,85 mm; průměrná tloušťka endometria ve skupině na terapii PRP byla 8,25 mm (8,25–8,61 mm) a ve skupině pacientek, které dostávaly pouze HRT, byla 7,40 mm (7,34–7,65 mm). Citlivost receptorů pro estrogen se v experimentální skupině zvýšila o 3,5, přičemž v této skupině dosáhla hodnoty 75,00 (71,43–74,22) a v kontrolní skupině 71,50 (67,05–70,85). Citlivost receptorů pro progesteron se zvýšila o 9,0, hodnota v této skupině byla 95,0 (91,4–93,8) a v kontrolní skupině 86,0 (83,47–86,27). Závěr: Díky působení destičkových faktorů má terapie PRP pozitivní vliv na endometrium, kdy zvyšuje jeho tloušťku a zlepšuje receptivitu. Je tedy možné vyvodit závěr, že tato metoda zřejmě nalezne velké praktické uplatnění při zlepšování výsledků programů asistované reprodukce.

Aim: The effect of platelet-rich autoplasma on endometrial thickness and receptor sensitivity to estrogen and progesterone. Materials and methods: This prospective clinical study included 200 patients. The participants in the study were divided into two groups. The first control group received hormone replacement therapy (HRT). The second study group received an intrauterine infusion of platelet-rich autoplasma (PRP group). On the 19th day of the menstrual cycle, an ultrasound examination was performed to assess endometrial thickness, as well as an immunohistochemical analysis to determine receptor sensitivity to estrogen and progesterone. Results: In the course of the study, we found that the use of platelet-rich autoplasma increased the thickness of the endometrium by 0.85 mm; the average thickness of the endometrium in the group who received PRP therapy was 8.25 (8.25–8.61) mm; and in the group of patients who only received HRT, it was 7.40 (7.34–7.65) mm. The sensitivity of receptors to estrogen in the experimental group increased by 3.5, in the experimental group it was 75.00 (71.43–74.22), and in the control group it was 71.50 (67.05–70.85). The sensitivity of receptors to progesterone also increased by 9.0, in the experimental group it was 95.0 (91.4–93.8), and in the control group it was 86.0 (83.47–86.27). Conclusion: Due to the action of platelet factors, PRP therapy has a positive effect on the endometrium, increasing its thickness and improving its receptivity. Therefore, it can be concluded that this method can find great practical application to improve the outcomes of assisted reproductive technology programs.

• Klíčová slova
• autoplazma,
• MeSH
• dospělí MeSH
• endometrium * anatomie a histologie   krevní zásobení   patologie   MeSH
• hormonální substituční terapie metody   MeSH
• imunohistochemie MeSH
• lidé MeSH
• parenterální infuze * metody   MeSH
• prospektivní studie MeSH
• statistika jako téma MeSH
• steroidní receptory MeSH
• trombocyty MeSH
• ultrasonografie MeSH
• velikost orgánu MeSH
• ženská infertilita etiologie   terapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• klinická studie MeSH

Nitroděložní systém s levonorgestrelem má vynikající antikoncepční účinnost za současného snížení menstruační krevní ztráty. V perimenopauze jej lze s výhodou využít k léčbě hyperplazie endometria. Jako gestagenní složka hormonální substituční terapie vykazuje výbornou kontrolu proliferace endometria. V kombinaci s transdermální aplikací estrogenu má výhodu nulového zvýšení rizika tromboembolické nemoci.

Levonorgestrel releasing intrauterine system have excellent contraceptive efficacy with simultaneous lowering of menstruation’s blood loss. It could be used for therapy of endometrial hyperplasia in perimenopause. In position of gestagen part of the hormone replacement therapy it has high control of endometrial proliferation. It is conjoined with the zero increasing of risk of thromboembolic disease in combination with transdermal oestrogen’s application.

• MeSH
• aplikace kožní MeSH
• endometrium účinky léků   MeSH
• hormonální substituční terapie * metody   MeSH
• hyperplazie endometria prevence a kontrola   MeSH
• levonorgestrel aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• lidé MeSH
• menopauza * účinky léků   MeSH
• nitroděložní tělíska hormonální MeSH
• tromboembolie chemicky indukované   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH

The majority of endometrial and cervical cancers present with abnormal vaginal bleeding but only a small proportion of women suffering from vaginal bleeding actually have such a cancer. A simple, operator-independent and accurate test to correctly identify women presenting with abnormal bleeding as a consequence of endometrial or cervical cancer is urgently required. We have recently developed and validated the WID-qEC test, which assesses DNA methylation of ZSCAN12 and GYPC via real-time PCR, to triage women with symptoms suggestive of endometrial cancer using ThinPrep-based liquid cytology samples. Here, we investigated whether the WID-qEC test can additionally identify women with cervical cancer. Moreover, we evaluate the test's applicability in a SurePath-based hospital-cohort by comparing its ability to detect endometrial and cervical cancer to cytology. In a set of 23 cervical cancer cases and 28 matched controls the receiver operating characteristic (ROC) area under the curve (AUC) is 0.99 (95% confidence interval [CI]: 0.97-1.00) with a sensitivity and specificity of 100% and 92.9%, respectively. Amongst the hospital-cohort (n = 330), the ROC AUC is 0.99 (95% CI: 0.98-1) with a sensitivity and specificity of 100% and 82.5% for the WID-qEC test, respectively, and 33.3% and 96.9% for cytology (considering PAP IV/V as positive). Our data suggest that the WID-qEC test detects both endometrial and cervical cancer with high accuracy.

• MeSH
• cytodiagnostika MeSH
• děložní krvácení diagnóza   patologie   MeSH
• dysplazie děložního hrdla * diagnóza   MeSH
• endometrium patologie   MeSH
• infekce papilomavirem * diagnóza   MeSH
• lidé MeSH
• nádory děložního čípku * diagnóza   genetika   patologie   MeSH
• senzitivita a specificita MeSH
• studie proveditelnosti MeSH
• vaginální stěr MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• endometrióza chirurgie   diagnóza   farmakoterapie   MeSH
• endometrium chirurgie   patologie   MeSH
• kongresy jako téma MeSH
• Publikační typ
• zprávy MeSH

• MeSH
• endometrium patologie   MeSH
• kongresy jako téma MeSH
• nádory endometria chirurgie   diagnóza   terapie   MeSH
• staging nádorů trendy   MeSH
• Publikační typ
• zprávy MeSH

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.

• MeSH
• buňky NK MeSH
• endometrium MeSH
• lidé MeSH
• placenta * MeSH
• studium lékařství * MeSH
• těhotenství MeSH
• uterus MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH