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Ovarian tissue cryopreservation has been gradually applied. It is essential to elucidate the differences between cryopreserved and fresh ovarian tissue and to refine cryopreservation protocols for improved outcomes. To explore the transcriptomic differences between fresh ovarian tissue and tissue cryopreserved with an elevated thawing rate. Ovarian tissue samples were collected and cryopreserved (frozen and thawed) following RNA sequencing and histological evaluation. Three groups were formed: fresh tissue (Group 1), frozen tissue after quick thawing at 100 °C (Group 2), and frozen tissue after slow thawing at 37 °C (Group 3). KEGG analysis showed that in comparison with Group 1, DEGs in Group 2 were mainly enriched in the cortisol synthesis and ovarian steroidogenesis pathways, and DEGs in the cells of Group 3 were mainly enriched in the ovarian steroidogenesis pathway. GO analysis showed that compared to cells of Group 2, DEGs in Group 3 were primarily enriched in the SRP-dependent co-translational protein targeting pathway and co-translational protein targeting to the membrane. The results were formulated with a minimal difference in the histological evaluation of cells after quick and slow thawed tissue. Cryopreservation of ovarian tissue by the described method does not decrease follicle production but downregulates the ovarian steroidogenesis pathway, reducing estrogen and progesterone secretion. The quick thawing of ovarian tissue increases the proliferation and apoptosis pathways of cells. [ABSTRACT FROM AUTHOR]

Background: Earlier studies have established that culturing human ovarian tissue in a 3D system with a small amount of soluble Matrigel (a basement membrane protein) for 7 days in vitro increased gene fusion and alternative splicing events, cellular functions, and potentially impacted gene expression. However, this method was not suitable for in vitro culture of human testicular tissue. Objective: To test a new method for long-time in vitro culture of testicular fragments, thawed with two different regimes, with evaluation of transcriptomic differences by RNA sequencing. Methods: Testicular tissue samples were collected, cryopreserved (frozen and thawed), and evaluated immediately after thawing and following one week of in vitro culture. Before in vitro culture, tissue fragments were encapsulated in fibrin. Four experimental groups were formed. Group 1: tissue quickly thawed (in boiling water at 100 °C) and immediately evaluated. Group 2: tissue quickly thawed (in boiling water at 100 °C) and evaluated after one week of in vitro culture. Group 3: tissue slowly thawed (by a physiological temperature 37 °C) and immediately evaluated. Group 4: tissue slowly thawed (by a physiological temperature 37 °C) and evaluated after one week of in vitro culture. Results: There are the fewest differentially expressed genes in the comparison between Group 2 and Group 4. In this comparison, significantly up-regulated genes included C4B_2, LOC107987373, and GJA4, while significantly down-regulated genes included SULT1A4, FBLN2, and CCN2. Differential genes in cells of Group 2 were mainly enriched in KEGG: regulation of actin cytoskeleton, lysosome, proteoglycans in cancer, TGF-beta signaling pathway, focal adhesion, and endocytosis. These Group 2- genes were mainly enriched in GO: spermatogenesis, cilium movement, collagen fibril organization, cell differentiation, meiotic cell cycle, and flagellated spermatozoa motility. Conclusions: Encapsulation of testicular tissue in fibrin and long-time in vitro culture with constant stirring in a large volume of culture medium can reduce the impact of thawing methods on cryopreserved testicular tissue. [ABSTRACT FROM AUTHOR]

Background/Aim: The aim of the present retrospective study was to examine the efficiency and safety of the induction of labor with Misoprostol, administered either vaginally or orally. Patients and Methods: This retrospective cohort study included pregnant women with a gestational age of ≥36 +0 weeks and a singleton pregnancy who underwent induction of labor with Misoprostol as vaginal insert or as tablet (oral) between January 2014 and January 2019 at the Department of Obstetrics and Gynecology of the University Hospital of Cologne. The objective of this study was to analyze the time until delivery and the maternal and neonatal outcomes. Results: A total of 1,511 patients were included in this retrospective analysis, of whom 1,035 patients (68.5%) underwent induction of labor with a misoprostol vaginal insert (MVI) and 476 (31.5%) with tablets (oral misoprostol: OM). MVI significantly shortened the time from application to delivery (p<0.001) in comparison to OM, reduced the need for epidural anesthesia (EA) (p=0.018) without an increase in caesarean sections (CS) (p=1), ventouse deliveries (VD) (p=0.715), maternal birth injuries or a reduced neonatal outcome (APGAR-Score, umbilical cord pH). Conclusion: MVI is superior to OM in terms of efficiency (primary outcome: time from application to delivery) and is equally safe (primary outcome: CS rate). Our study, along with existing literature, highlights the need for further research, particularly regarding neonatal outcomes. Additionally, it underscores the importance of careful consideration when inducing labor and ensuring informed consent. [ABSTRACT FROM AUTHOR]

Introduction: Malignant ascites indicates ovarian cancer progression and predicts poor clinical outcome. Various ascites components induce an immunosuppressive crosstalk between tumor and immune cells, which is poorly understood. In our previous study, imbalanced electrolytes, particularly high sodium content in malignant ascites, have been identified as a main immunosuppressive mechanism that impaired NK and T-cell activity. Methods: In the present study, we explored the role of high concentrations of ascites proteins and immunoglobulins on antitumoral NK effector functions. To this end, a coculture system consisting of healthy donor NK cells and ovarian cancer cells was used. The anti-EGFR antibody Cetuximab was added to induce antibody-dependent cellular cytotoxicity (ADCC). NK activity was assessed in the presence of different patient ascites samples and immunoglobulins that were isolated from ascites. Results: Overall high protein concentration in ascites impaired NK cell degranulation, conjugation to tumor cells, and intracellular calcium signaling. Immunoglobulins isolated from ascites samples competitively interfered with NK ADCC and inhibited the conjugation to target cells. Furthermore, downregulation of regulatory surface markers CD16 and DNAM-1 on NK cells was prevented by ascites-derived immunoglobulins during NK cell activation. Conclusion: Our data show that high protein concentrations in biological fluids are able to suppress antitumoral activity of NK cells independent from the mechanism mediated by imbalanced electrolytes. The competitive interference between immunoglobulins of ascites and specific therapeutic antibodies could diminish the efficacy of antibody-based therapies and should be considered in antibody-based immunotherapies. [ABSTRACT FROM AUTHOR]

Background/Aim: At the beginning of the 21st century, obstetric medicine took a turn from interventional to restrictive in low-risk birth. The present study examined the changes in peripartum management over the past 20 years at the Women's University Hospital Cologne. The attitudes of the becoming mother and physicians towards anesthesia, episiotomy, and vaginal-operative deliveries were compared and the factors influencing the duration of birth over the past 20 years were examined. Patients and Methods: In this retrospective study, the low-risk singleton birth of 955 in 2000/2001 and 944 births in 2018 at the Women's University Hospital Cologne were analyzed. Results: The age of women who tended to give birth has significantly increased at present compared to 20 years ago. In 2018, labor was induced significantly more often than in 2000/2001. The rate of vaginal operative deliveries has fluctuated between 15% and 20% in the last 20 years. Forceps are no longer used. The use of episiotomy has taken a fundamental turn in the last 20 years. Prophylactic episiotomy is not performed anymore, most vaginal operative deliveries take place without the episiotomy. The birth duration has been significantly shortened at present compared to 20 years ago. Conclusion: Pregnancy and childbirth over the last years are not considered as a disease, but as a natural course, and the trend of minimizing interventions in low-risk delivery has a positive effect on childbirth. [ABSTRACT FROM AUTHOR]

Background/Aim: Due to still controversial discussion regarding appropriate termination of low-risk singleton pregnancies beyond term, this retrospective study aimed to evaluate maternal and perinatal outcomes depending on gestational age and obstetric management. Patients and Methods: This is a retrospective cohort analysis including 3.242 low-risk singleton deliveries at the Department of Obstetrics of the University Hospital of Cologne between 2017 and 2022. According to current national guidelines, the cohort was subdivided into three gestational groups, group 1: 40+0- 40+6 weeks, group 2: 40+7-40+10 weeks and group 3>40+10 weeks. Results: In our cohort, advanced gestational age was associated with higher rates of secondary caesarean sections, lower rates of spontaneous vaginal deliveries, higher rates of meconium-stained amniotic fluid and depressed neonates with APGAR < 7 after 5 min. Analyzing obstetric management, induction of labor significantly increased the rate of secondary sections and reduced the rate of spontaneous deliveries, while the percentage of assistant vaginal deliveries was independent from obstetric management and gestational age. Induction of labor also significantly enhanced the need for tocolytic subpartu and epidural anesthesia and caused higher rates of abnormalities in cardiotocography (CTG), which also resulted in more frequent fetal scalp blood testing; however, the rate of fetal acidosis was independent of both obstetric management and gestational age. Conclusion: Our study supports expectant management of low-risk pregnancies beyond term, as induction of labor increased the rate of secondary sections and did not improve perinatal outcome. [ABSTRACT FROM AUTHOR]

Cryopreservation of human testicular tissue, as a key element of anticancer therapy, includes the following stages: saturation with cryoprotectants, freezing, thawing, and removal of cryoprotectants. According to the point of view existing in "classical" cryobiology, the thawing mode is the most important consideration in the entire process of cryopreservation of any type of cells, including cells of testicular tissue. The existing postulate in cryobiology states that any frozen types of cells must be thawed as quickly as possible. The technologically maximum possible thawing temperature is 100 °C, which is used in our technology for the cryopreservation of testicular tissue. However, there are other points of view on the rate of cell thawing, according to how thawing should be carried out at physiological temperatures. In fact, there are morphological and functional differences between immature (from prepubertal patients) and mature testicular tissue. Accordingly, the question of the influence of thawing temperature on both types of tissues is relevant. The purpose of this study is to explore the transcriptomic differences of cryopreserved mature and immature testicular tissue subjected to different thawing methods by RNA sequencing. Collected and frozen testicular tissue samples were divided into four groups: quickly (in boiling water at 100 °C) thawed cryopreserved mature testicular tissue (group 1), slowly (by a physiological temperature of 37 °C) thawed mature testicular tissue (group 2), quickly thawed immature testicular tissue (group 3), and slowly thawed immature testicular tissue (group 4). Transcriptomic differences were assessed using differentially expressed genes (DEG), the Kyoto Encyclopedia of Genes and Genomes (KEGG), gene ontology (GO), and protein–protein interaction (PPI) analyses. No fundamental differences in the quality of cells of mature and immature testicular tissue after cryopreservation were found. Generally, thawing of mature and immature testicular tissue was more effective at 100 °C. The greatest difference in the intensity of gene expression was observed in ribosomes of cells thawed at 100 °C in comparison with cells thawed at 37 °C. In conclusion, an elevated speed of thawing is beneficial for frozen testicular tissue. [ABSTRACT FROM AUTHOR]

Background/Aim: Due to better career opportunities for women and a shift in sex roles, as well as improved reproductive medicine, the age of women who conceive children is rising. A variety of maternal risks and complications that may occur during pregnancy or childbirth in women with advanced maternal age has been examined and reported controversial results. The present study focused on controversial and debatable conclusions regarding the impact of advanced maternal age on maternal and neonatal outcomes. Patients and Methods: Data from 8,523 patients, who gave singleton birth at the Women's University Hospital Cologne between 2014 and 2018, were subdivided into two groups: those with maternal age =40 years and those <40, and analyzed. Results: A significantly higher rate of Csection, more preterm births, more low birth weight, and higher incidence of retained placenta were observed in women older than or equal to 40. There were no significant differences regarding postpartum hemorrhage and fetal position. Younger patients tend to have more birth injuries and use more epidural administration. The evaluation of neonatal outcomes using fetal base-excess, birth pH, and Apgar score showed no significant clinical differences. Conclusion: More antenatal complications could be identified in patients with advanced maternal age. Nonetheless, the neonatal outcomes were comparable and no severe complications in women with advanced maternal age were observed. These findings are due to a well standardized management system for women with risk pregnancies. This encourages better monitoring and care of pregnant women with risk factors. [ABSTRACT FROM AUTHOR]

Calcium phosphate nanoparticles (CaP-NPs) are biodegradable carriers that can be functionalized with biologically active molecules. As such, they are potential candidates for delivery of therapeutic molecules in cancer therapies. In this context, it is important to explore whether CaP-NPs impair the natural or therapy-induced immune cell activity against cancer cells. Therefore, in this study, we have investigated the effects of different CaP-NPs on the anti-tumor activity of natural killer (NK) cells using different ovarian cancer (OC) cell line models. We explored these interactions in coculture systems consisting of NK cells, OC cells, CaP-NPs, and therapeutic Cetuximab antibodies (anti-EGFR, ADCC-inducing antibody). Our experiments revealed that aggregated CaP-NPs can serve as artificial targets, which activate NK cell degranulation and impair ADCC directed against tumor targets. However, when CaP-NPs were properly dissolved by sonication, they did not cause substantial activation. CaP-NPs with SiO2-SH-shell induced some activation of NK cells that was not observed with polyethyleneimine-coated CaP-NPs. Addition of CaP-NPs to NK killing assays did not impair conjugation of NK with OC and subsequent tumor cytolytic NK degranulation. Therapeutic antibody coupled to functionalized CaP-NPs maintained substantial levels of antibody-dependent cellular cytotoxic activity. Our study provides a cell biological basis for the application of functionalized CaP-NPs in immunologic anti-cancer therapies. [ABSTRACT FROM AUTHOR]

The adverse prognosis of most patients with ovarian cancer is related to recurrent disease caused by resistance to chemotherapeutic and targeted therapeutics. Besides their direct activity against tumor cells, monoclonal antibodies and tyrosine kinase inhibitors (TKIs) also influence the antitumoral activity of immune cells, which has important implications for the design of immunotherapies. In this preclinical study, we treated different ovarian cancer cell lines with anti-epidermal growth factor receptor (EGFR) TKIs and co-incubated them with natural killer (NK) cells. We studied treatment-related structural and functional changes on tumor and immune cells in the presence of the anti-EGFR antibody cetuximab and investigated NK-mediated antitumoral activity. We show that long-term exposure of ovarian cancer cells to TKIs leads to reduced responsiveness of intrinsically sensitive cancer cells over time. Inversely, neither long-term treatment with TKIs nor cetuximab could overcome the intrinsic resistance of certain ovarian cancer cells to anti-EGFR agents. Remarkably, tumor cells pretreated with anti-EGFR TKIs showed increased sensitivity towards NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). In contrast, the cytokine secretion of NK cells was reduced by TKI sensitization. Our data suggest that sensitization of tumor cells by anti-EGFR TKIs differentially modulates interactions with NK cells. These data have important implications for the design of chemo-immuno combination therapies in this tumor entity. [ABSTRACT FROM AUTHOR]

The quality of pathological assessment is crucial for the safety of patients with cervical cancer if pelvic lymph node dissection is to be replaced by sentinel lymph node (SLN) biopsy. Central pathology review of SLN pathological ultrastaging was conducted in the prospective SENTIX/European Network of Gynaecological Oncological Trial (ENGOT)-CX2 study. All specimens from at least two patients per site were submitted for the central review. For cases with major or critical deviations, the sites were requested to submit all samples from all additional patients for second-round assessment. From the group of 300 patients, samples from 83 cases from 37 sites were reviewed in the first round. Minor, major, critical, and no deviations were identified in 28%, 19%, 14%, and 39% of cases, respectively. Samples from 26 patients were submitted for the second-round review, with only two major deviations found. In conclusion, a high rate of major or critical deviations was identified in the first round of the central pathology review (28% of samples). This reflects a substantial heterogeneity in current practice, despite trial protocol requirements. The importance of the central review conducted prospectively at the early phase of the trial is demonstrated by a substantial improvement of SLN ultrastaging quality in the second-round review., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.