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Purpose The aim of this guideline is to standardize the diagnosis and therapy of recurrent miscarriage (RM) using evidence from the recent literature. This is done by using consistent definitions, objective evaluations and standardized treatment protocols. Methods When this guideline was compiled, special consideration was given to previous recommendations in prior versions of this guideline and the recommendations of the European Society of Human Reproduction and Embryology, the Royal College of Obstetricians and Gynecologists, the American College of Obstetricians and Gynecologists and the American Society for Reproductive Medicine, and a detailed individual search of the literature about the different topics was carried out. Recommendations Recommendations about the diagnostic and therapeutic procedures offered to couples with RM were developed based on the international literature. Special attention was paid to known risk factors such as chromosomal, anatomical, endocrinological, physiological coagulation, psychological, infectious and immune disorders. Recommendations were also developed for those cases where investigations are unable to find any abnormality (idiopathic RM)., Competing Interests: Conflict of Interest/Interessenkonflikt The authorsʼ conflicts of interest are listed in the long version of the guideline./Die Interessenkonflikte der Autoren sind in der Langfassung der Leitlinie aufgelistet., (Thieme. All rights reserved.)

The human leukocyte antigen (HLA) genes are cell-surface proteins, essential for immune cell interaction. HLA-G is known for their high immunosuppressive effect and its potential as predictive marker in breast cancer. However, nothing is known about the HLA-J and its immunosuppressive, prognostic and predictive features, as it is assumed to be a "pseudogene" by in silico sequence interpretation. HLA-J, ESR1, ERBB2, KRT5 and KRT20 mRNA expression were analysed in 29 fresh frozen breast cancer biopsies and their corresponding resectates obtained from patients treated with neoadjuvant chemotherapy (NACT). mRNA was analysed with gene specific TaqMan-based Primer/Probe sets and normalized to Calmodulin 2. All breast cancer samples did express HLA-J and frequently increased HLA-J mRNA levels after NACT. HLA-J mRNA was significantly associated with overexpression of the ESR1 mRNA status (Spearman ρ 0,5679; p = 0.0090) and KRT5 mRNA (Spearman ρ 0,6121; p = 0.0041) in breast cancer core biopsies and dominated in luminal B subtype. Kaplan Meier analysis revealed that an increase of HLA-J mRNA expression after NACT had worse progression free survival (p = 0,0096), indicating a counterreaction of tumor tissues presumably to prevent elimination by enhanced immune infiltration induced by NACT. This counterreaction is associated with worse prognosis. To our knowledge this is the first study identifying HLA-J as a new predictive marker in breast cancer being involved in immune evasion mechanisms., Competing Interests: Conflict of Interest Some of the results represented in this work are part of the patent WO 2019/207039 A1. Würfel FM and Wirtz RM are employees of STRATIFYER Molecular Pathology GmbH. Winterhalter C and Würfel W are founders and hold company shares of the Intellexon GmbH. The other authors declare no conflicts of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

The granted European patent EP 2 561 890 describes a procedure for an immunological treatment of cancer. It is based on the principles of the HLA-supported communication of implantation and pregnancy. These principles ensure that the embryo is not rejected by the mother. In pregnancy, the placenta, more specifically the trophoblast, creates an "interface" between the embryo/fetus and the maternal immune system. Trophoblasts do not express the "original" HLA identification of the embryo/fetus (HLA-A to -DQ), but instead show the non-classical HLA groups E, F, and G. During interaction with specific receptors of NK cells (e.g., killer-immunoglobulin-like receptors (KIR)) and lymphocytes (lymphocyte-immunoglobulin-like receptors (LIL-R)), the non-classical HLA groups inhibit these immunocompetent cells outside pregnancy. However, tumors are known to be able to express these non-classical HLA groups and thus make use of an immuno-communication as in pregnancies. If this occurs, the prognosis usually worsens. This patent describes, in a first step, the profiling of the non-classical HLA groups in primary tumor tissue as well as metastases and recurrent tumors. The second step comprises tailored antibody therapies, which is the subject of this patent. In this review, we analyze the underlying mechanisms and describe the currently known differences between HLA-supported communication of implantation and that of tumors.

Purpose: Official guideline of the German Society of Gynecology and Obstetrics (DGGG), the Austrian Society of Gynecology and Obstetrics (ÖGGG) and the Swiss Society of Gynecology and Obstetrics (SGGG). The aim of this guideline was to standardize the diagnosis and treatment of couples with recurrent miscarriage (RM). Recommendations were based on the current literature and the views of the involved committee members., Methods: Based on the current literature, the committee members developed the statements and recommendations of this guideline in a formalized process which included DELPHI rounds and a formal consensus meeting., Recommendations: Recommendations for the diagnosis and treatment of patients with RM were compiled based on the international literature. Specific established risk factors such as chromosomal, anatomical, endocrine, hemostatic, psychological, infectious and immunological disorders were taken into consideration.

Cochlear Implants (CIs) are medical implantable devices that can restore the sense of hearing in people with profound hearing loss. Clinical trials assessing speech intelligibility in CI users have found large intersubject variability. One possibility to explain the variability is the individual differences in the interface created between electrodes of the CI and the auditory nerve. In order to understand the variability, models of the voltage distribution of the electrically stimulated cochlea may be useful. With this purpose in mind, we developed a parametric model that can be adapted to each CI user based on landmarks from individual cone beam computed tomography (CBCT) scans of the cochlea before and after implantation. The conductivity values of each cochlea compartment as well as the weighting factors of different grounding modes have also been parameterized. Simulations were performed modeling the cochlea and electrode positions of 12 CI users. Three models were compared with different levels of detail: a homogeneous model (HM), a non-patient-specific model (NPSM), and a patient-specific model (PSM). The model simulations were compared with voltage distribution measurements obtained from the backward telemetry of the 12 CI users. Results show that the PSM produces the lowest error when predicting individual voltage distributions. Given a patient-specific geometry and electrode positions, we show an example on how to optimize the parameters of the model and how to couple it to an auditory nerve model. The model here presented may help to understand speech performance variability and support the development of new sound coding strategies for CIs.

Objective: To systematically review the reporting of MII (MII) oocyte development after xenotransplantation of human ovarian tissue., Design: Systematic review in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)., Setting: Not applicable., Patient(s): Not applicable., Intervention(s): Formation of MII oocytes after xenotransplantation of human ovarian tissue., Main Outcome Measure(s): Any outcome reported in Pubmed., Result(s): Six publications were identified that report on formation of MII oocytes after xenotransplantation of human ovarian tissue., Conclusion(s): Xenografting of human ovarian tissue has proved to be a useful model for examining ovarian function and follicle development in vivo. With human follicles that have matured through xenografting, the possibility of cancer transmission and relapse can also be eliminated, because cancer cells are not able to penetrate the zona pellucida. The reported studies have demonstrated that xenografted ovarian tissue from a range of species, including humans, can produce antral follicles that contain mature (MII) oocytes, and it has been shown that mice oocytes have the potential to give rise to live young. Although some ethical questions remain unresolved, xenotransplantation may be a promising method for restoring fertility. This review furthermore describes the value of xenotransplantation as a tool in reproductive biology and discusses the ethical and potential safety issues regarding ovarian tissue xenotransplantation as a means of recovering fertility., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Granulocyte colony-stimulating factor (G-CSF) belongs to the family of colony-stimulating factors (CSF). As the name suggests, it was initially identified as being able to target and influence granulopoiesis, but was soon shown to be a ubiquitous growth factor, with synthesis and receptors, such as the related granulocyte macrophage colony-stimulating factor (GM-CSF), which is found in a wide variety of tissue types, including the organs and cell populations involved in reproduction. It must now be assumed that both G-CSF and GM-CSF control, or play a role in controlling, key processes in oocyte and sperm maturation, endometrial receptivity, implantation, and embryo and fetal development, possibly extending to birth. The following article offers an overview of the current findings with regard to animal experimental studies, initial clinical applications in reproductive medicine, and potential risks., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)