Mit zunehmendem Bewusstsein für die Notwendigkeit einer strengeren Indikationsstellung, um eine Übertherapie und deren negative Folgen zu vermeiden, gewinnt auch das Thema der Therapiezieländerung an Bedeutung. Um Therapiezieländerungen lege artis durchführen zu können, sollten Ärzt:innen die grundlegenden ethischen und rechtlichen Basics ebenso verinnerlicht haben und praktisch anwenden können wie die Regeln einer fürsorglichen, aber unmissverständlichen Kommunikation.
Objective The objective of this revised official guideline, published by the German Society for Gynecology and Obstetrics (DGGG) and coordinated in the joint guidelines program of the DGGG, the Austrian Society for Gynecology and Obstetrics (OEGGG), and the Swiss Society for Gynecology and Obstetrics (SGGG), is to provide evidence-based and consensus-based recommendations for the diagnosis, treatment, care, and support of girls and women with confirmed or suspected endometriosis. Methods This S2k guideline was developed through a structured consensus process involving representative members of various professions (37 professional associations, organizations, and self-help groups) and includes 25 statements and 73 recommendations which are based on a systematic literature review (2019 - 2023) and expert consensus. Recommendations For the first time, the revised guideline has placed a greater focus on individualized, symptom-oriented diagnosis and treatment that combines hormonal, surgical, and multimodal approaches. A significant innovation is the use of transvaginal ultrasound as the central diagnostic procedure for detecting endometriosis. Therapeutically, primary hormone treatment is now recommended as the first choice approach, with surgical interventions and multimodal approaches supplemented on an individual and symptom-oriented basis.
Reliable evaluation of blastocyst quality is critical for the success of in vitro fertilization (IVF) treatments. Current embryo grading practices primarily rely on visual assessment of morphological features, which introduces subjectivity, inter-embryologist variability, and challenges in standardizing quality assurance. In this study, we propose a multitask embedding-based approach for the automated analysis and prediction of key blastocyst components, including the trophectoderm (TE), inner cell mass (ICM), and blastocyst expansion (EXP). The method leverages biological and physical characteristics extracted from images of day-5 human embryos. A pretrained ResNet-18 architecture, enhanced with an embedding layer, is employed to learn discriminative representations from a limited dataset and to automatically identify TE and ICM regions along with their corresponding grades, structures that are visually similar and inherently difficult to distinguish. Experimental results demonstrate the promise of the multitask embedding approach and potential for robust and consistent blastocyst quality assessment.
Mitochondrial function can be affected by mutations in mitochondrial DNA (mtDNA). However, detecting de novo mutations in mtDNA has been challenging due to its high copy number, particularly in germline cells, and the low accuracy of conventional next-generation sequencing technologies. Using highly accurate duplex sequencing, we study the frequency of de novo insertion and deletion (indel) mtDNA mutations across multiple age groups in somatic and germline tissues of three mammalian species-mouse, macaque, and human. We demonstrate that, similar to de novo nucleotide substitutions, indels accumulate rapidly with age in somatic tissues with high energetic demand (brain and skeletal muscle) or high proliferation (liver). However, in oocytes, indels accumulate slower with age than nucleotide substitutions (or do not accumulate at all). The increases in indel frequency with age are driven mostly by deletions. Short tandem repeats are highly enriched for indels, implicating DNA replication slippage as a major driver of indel formation in mtDNA. For some species and tissues, indels are depleted at protein-coding sequences; however, indels that are multiples of 3 bp are not overrepresented. Ours is the most detailed study of de novo small indels in mtDNA to date. It provides parameters for models of mtDNA evolution, informs molecular mechanisms for a multitude of human genetic diseases, and illuminates the accumulation of indel mutations with age. Such accumulation may have functional consequences, as it affects reproduction later in life and drives the decline of mitochondrial function during aging.
