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Cyprus College
cycollege.ac.cy
The college was founded in 1961 with the purpose to provide a well rounded education of high calibre where students can acquire the necessary academic knowledge.
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Wroclaw University
international.uni.wroc.pl
Founded in 1702 by Leopold I Habsburg. Since the beginning of 20th century the university has produced 9 Nobel Prize winners.
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Volyn University
vdu.edu.ua
The history dates back to 1940. At present, the university includes 4 institutes, 14 faculties and 73 departments.
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Berkeley College
berkeleycollege.edu
Through the power of internet, Berkeley college online brings the classroom to you anywhere in the world with the same high level of support as On-Campus classes.
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AIS
ais.ac.nz
New Zealand's largest international degree provider. The programmes are focused on the global marketplace.
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WORLD UNIVERSITY DIRECTORY
Medical Education Human Reproduction Update - current issues
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">BACKGROUND</div>The ovarian response to gonadotropin stimulation varies widely among women, and could impact the probability of live birth as well as treatment risks. Many studies have evaluated the impact of different gonadotropin starting doses, mainly based on predictive variables like ovarian reserve tests (ORT) including anti-Müllerian hormone (AMH), antral follicle count (AFC), and basal follicle-stimulating hormone (bFSH). A Cochrane systematic review revealed that individualizing the gonadotropin starting dose does not affect efficacy in terms of ongoing pregnancy/live birth rates, but may reduce treatment risks such as the development of ovarian hyperstimulation syndrome (OHSS). An individual patient data meta-analysis (IPD-MA) offers a unique opportunity to develop and validate a universal prediction model to help choose the optimal gonadotropin starting dose to minimize treatment risks without affecting efficacy.<div class="boxTitle">OBJECTIVE AND RATIONALE</div>The objective of this IPD-MA is to develop and validate a gonadotropin dose-selection model to guide the choice of a gonadotropin starting dose in IVF/ICSI, with the purpose of minimizing treatment risks without compromising live birth rates.<div class="boxTitle">SEARCH METHODS</div>Electronic databases including MEDLINE, EMBASE, and CRSO were searched to identify eligible studies. The last search was performed on 13 July 2022. Randomized controlled trials (RCTs) were included if they compared different doses of gonadotropins in women undergoing IVF/ICSI, presented at least one type of ORT, and reported on live birth or ongoing pregnancy. Authors of eligible studies were contacted to share their individual participant data (IPD). IPD and information within publications were used to determine the risk of bias. Generalized linear mixed multilevel models were applied for predictor selection and model development.<div class="boxTitle">OUTCOMES</div>A total of 14 RCTs with data of 3455 participants were included. After extensive modeling, women aged 39 years and over were excluded, which resulted in the definitive inclusion of 2907 women. The optimal prediction model for live birth included six predictors: age, gonadotropin starting dose, body mass index, AFC, IVF/ICSI, and AMH. This model had an area under the curve (AUC) of 0.557 (95% confidence interval (CI) from 0.536 to 0.577). The clinically feasible live birth model included age, starting dose, and AMH and had an AUC of 0.554 (95% CI from 0.530 to 0.578). Two models were selected as the optimal model for combined treatment risk, as their performance was equal. One included age, starting dose, AMH, and bFSH; the other also included gonadotropin-releasing hormone (GnRH) analog. The AUCs for both models were 0.769 (95% CI from 0.729 to 0.809). The clinically feasible model for combined treatment risk included age, starting dose, AMH, and GnRH analog, and had an AUC of 0.748 (95% CI from 0.709 to 0.787).<div class="boxTitle">WIDER IMPLICATIONS</div>The aim of this study was to create a model including patient characteristics whereby gonadotropin starting dose was predictive of both live birth and treatment risks. The model performed poorly on predicting live birth by modifying the FSH starting dose. On the contrary, predicting treatment risks in terms of OHSS occurrence and management by modifying the gonadotropin starting dose was adequate. This dose-selection model, consisting of easily obtainable patient characteristics, aids in the choice of the optimal gonadotropin starting dose for each individual patient to lower treatment risks and potentially reduce treatment costs.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">BACKGROUND</div>Successful implantation is a critical step for embryo survival. The major losses in natural and assisted human reproduction appeared to occur during the peri-implantation period. Because of ethical constraints, the fascinating maternal–fetal crosstalk during human implantation is difficult to study and thus, the possibility for clinical intervention is still limited.<div class="boxTitle">OBJECTIVE AND RATIONALE</div>This review highlights some features of human implantation as a unique, ineffective and difficult-to-model process and summarizes the pros and cons of the most used <span style="font-style:italic;">in vivo, ex vivo</span> and <span style="font-style:italic;">in vitro</span> models. We point out the variety of cell line-derived models and how these data are corroborated by well-defined primary cells of the same nature. Important aspects related to the handling, standardization, validation, and modus operandi of the advanced 3D <span style="font-style:italic;">in vitro</span> models are widely discussed. Special attention is paid to blastocyst-like models recapitulating the hybrid phenotype and HLA profile of extravillous trophoblasts, which are a unique yet poorly understood population with a major role in the successful implantation and immune mother-embryo recognition. Despite raising new ethical dilemmas, extended embryo cultures and synthetic embryo models are also in the scope of our review.<div class="boxTitle">SEARCH METHODS</div>We searched the electronic database PubMed from inception until March 2024 by using a multi-stage search strategy of MeSH terms and keywords. In addition, we conducted a forward and backward reference search of authors mentioned in selected articles.<div class="boxTitle">OUTCOMES</div>Primates and rodents are valuable <span style="font-style:italic;">in vivo</span> models for human implantation research. However, the deep interstitial, glandular, and endovascular invasion accompanied by a range of human-specific factors responsible for the survival of the fetus determines the uniqueness of the human implantation and limits the cross-species extrapolation of the data. The <span style="font-style:italic;">ex vivo</span> models are short-term cultures, not relevant to the period of implantation, and difficult to standardize. Moreover, the access to tissues from elective terminations of pregnancy raises ethical and legal concerns. Easy-to-culture cancer cell lines have many limitations such as being prone to spontaneous transformation and lacking decent tissue characteristics. The replacement of the original human explants, primary cells or cancer cell lines with cultures of immortalized cell lines with preserved stem cell characteristics appears to be superior for <span style="font-style:italic;">in vitro</span> modeling of human implantation and early placentation. Remarkable advances in our understanding of the peri-implantation stages have also been made by advanced three dimensional (3D) models i.e. spheroids, organoids, and assembloids, as placental and endometrial surrogates. Much work remains to be done for the optimization and standardization of these integrated and complex models. The inclusion of immune components in these models would be an asset to delineate mechanisms of immune tolerance. Stem cell-based embryo-like models and surplus IVF embryos for research bring intriguing possibilities and are thought to be the trend for the next decade for <span style="font-style:italic;">in vitro</span> modeling of human implantation and early embryogenesis. Along with this research, new ethical dilemmas such as the moral status of the human embryo and the potential exploitation of women consenting to donate their spare embryos have emerged. The careful appraisal and development of national legal and ethical frameworks are crucial for better regulation of studies using human embryos and embryoids to reach the potential benefits for human reproduction.<div class="boxTitle">WIDER IMPLICATIONS</div>We believe that our data provide a systematization of the available information on the modeling of human implantation and early placentation and will facilitate further research in this field. A strict classification of the advanced 3D models with their pros, cons, applicability, and availability would help improve the research quality to provide reliable outputs.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">BACKGROUND</div>Varicocele is an abnormal dilation and torsion of the pampiniform venous plexus in the scrotum due to venous reflux, primarily affecting the left side. It affects 15% of men and is a prevalent contributor to male infertility. Varicocele is a complex disorder influenced by genetic, epigenetic, and environmental factors. Epigenetic modifications, which regulate genome activity independently of DNA or RNA sequences, may contribute to the development and severity of varicocele. These include DNA methylation, histone modifications, and RNA modifications like N6-methyladenosine (m<sup>6</sup>A). Irregularities in DNA and m<sup>6</sup>A-RNA methylation during spermatogenesis can cause gene expression abnormalities, DNA damage, and decreased fertility in varicocele patients.<div class="boxTitle">OBJECTIVE AND RATIONALE</div>The review aims to comprehensively understand the underlying mechanisms of varicocele, a condition that can significantly impact male fertility. By exploring the role of methylation modifications, specifically DNA and m<sup>6</sup>A-RNA methylation, the review aims to synthesize evidence from basic, preclinical, and clinical research to expand the existing knowledge on this subject. The ultimate goal is to identify potential avenues for developing targeted treatments that can effectively improve varicocele and ultimately increase sperm quality in affected individuals.<div class="boxTitle">SEARCH METHODS</div>A thorough investigation of the scientific literature was conducted through searches in PubMed, Google Scholar, and Science Direct databases until May 2024. All studies investigating the relationship between DNA and m<sup>6</sup>A-RNA methylation and male infertility, particularly varicocele were reviewed, and the most pertinent reports were included. Keywords such as varicocele, epigenetics, DNA methylation, m<sup>6</sup>A-RNA methylation, hypermethylation, hypomethylation, spermatozoa, semen parameters, spermatogenesis, and male infertility were used during the literature search, either individually or in combination.<div class="boxTitle">OUTCOMES</div>The sperm has a specialized morphology essential for successful fertilization, and its epigenome is unique, potentially playing a key role in embryogenesis. Sperm DNA and RNA methylation, major epigenetic marks, regulate the expression of testicular genes crucial for normal spermatogenesis. This review explores the role of DNA and m<sup>6</sup>A-RNA methylation, in responding to oxidative stress and how various nutrients influence their function in varicocele condition. Evidence suggests a potential link between varicocele and aberrant DNA/m<sup>6</sup>A-RNA methylation patterns, especially hypomethylation, but the body of evidence is still limited. Further studies are needed to understand how abnormal expression of DNA/m<sup>6</sup>A-RNA methylation regulators affects testicular gene expression. Thus, analyzing sperm DNA 5mC/5hmC levels and m<sup>6</sup>A-RNA methylation regulators may reveal spermatogenesis defects and predict reproductive outcomes.<div class="boxTitle">WIDER IMPLICATIONS</div>Nutri-epigenomics is an emerging field that could enhance the knowledge and management of diseases with unpredictable risks and consequences, even among individuals with similar lifestyles, by elucidating the influence of nutrition on DNA/m<sup>6</sup>A-RNA methylation through one-carbon metabolism. However, the importance of one-carbon metabolism to varicocele is not well-recognized. Health status and diet influence one-carbon metabolism and its associated DNA/m<sup>6</sup>A-RNA methylation modification. Future research should identify optimal methylation patterns that promote health and investigate modulating one-carbon metabolism to achieve this. Furthermore, additional studies are necessary to develop personalized dietary strategies through clinical and longitudinal research. However, a research gap exists on dietary interventions utilizing epigenetics as a therapeutic method for treating varicocele.<div class="boxTitle">REGISTRATION NUMBER</div>Not applicable.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">BACKGROUND</div>To prevent the transfer of embryos affected by monogenic conditions and/or chromosomal defects, preimplantation genetic testing (PGT) requires trophectoderm biopsy and cryopreservation. In 2–6% of biopsies, the diagnosis may be inconclusive due to DNA amplification failure or low-quality results. In these cases, a round of re-warming, re-biopsy, and re-cryopreservation is required to obtain a genetic diagnosis. In other cases, when the IVF centre starts providing PGT and/or when the patients develop an indication because of multiple failures, miscarriages or the birth of an affected child after IVF, cryopreserved untested embryos may be warmed, biopsied, and then re-vitrified. However, it is still unclear whether multiple manipulations may reduce reproductive outcomes after PGT.<div class="boxTitle">OBJECTIVE AND RATIONALE</div>This study aimed at conducting a systematic review to investigate the available evidence on the safety of double biopsy and/or double cryopreservation–warming and provide recommendations in this regard. We performed meta-analyses of the differences in the reproductive outcomes (live birth per embryo transfer [LBR per ET], clinical pregnancy rate per ET [CPR per ET], and miscarriage rate per clinical pregnancy [MR per CP]) in double cryopreservation and single biopsy (CBC) or double biopsy and double cryopreservation (BCBC) flows vs the control single biopsy and single cryopreservation (BC) flow. Cryo-survival rates before ET and gestational and perinatal outcomes were also reported.<div class="boxTitle">SEARCH METHODS</div>PRISMA guidelines were followed to gather all available information from the literature (PubMed, Scopus, and Embase). We used Medical Subject Headings (MeSH) terms and a list of specific keywords relevant for the study question. We searched for original studies in humans, published in peer-reviewed journals in English up to April 2024. Four independent authors assessed the articles for inclusion. One included paper was retrieved from another source.<div class="boxTitle">OUTCOMES</div>A total of 4219 records were identified, and 10 studies were included in the meta-analysis. Certainty of evidence level ranged from low to moderate. Both the CBC and BCBC groups showed reduced reproductive outcomes compared to the control (BC). Specifically, live birth rates per embryo transfer were lower in the CBC group (OR: 0.56, 95% CI: 0.38–0.81, <span style="font-style:italic;">I</span><sup>2</sup> = 58%; six studies) and the BCBC group (OR: 0.51, 95% CI: 0.34–0.77, <span style="font-style:italic;">I</span><sup>2</sup> = 24%; six studies). CPR per ET were also lower in the CBC group (OR: 0.68, 95% CI: 0.51–0.92, <span style="font-style:italic;">I</span><sup>2</sup> = 57%; seven studies) and the BCBC group (OR: 0.60, 95% CI: 0.46–0.78, <span style="font-style:italic;">I</span><sup>2</sup> = 0%; seven studies). Additionally, MR per CPs were higher in both the CBC group (OR: 1.68, 95% CI: 1.02–2.77, <span style="font-style:italic;">I</span><sup>2</sup> = 50%; seven studies) and the BCBC group (OR: 2.08, 95% CI: 1.13–3.83, <span style="font-style:italic;">I</span><sup>2</sup> = 28%; seven studies). Cryo-survival as well as gestational and perinatal outcomes were within the expected norms in the studies reporting them.<div class="boxTitle">WIDER IMPLICATIONS</div>Improved genetic technologies, standardization of laboratory protocols, operators’ proficiency with biopsy and cryopreservation, and continuous monitoring of the performance are essential to minimize inconclusive diagnoses and the putative impact of additional embryo manipulations. Although poorer reproductive outcomes might result from double biopsy and/or double cryopreservations, these practices may still be worthwhile to avoid transferring affected/aneuploid blastocysts. Therefore, the risks must be weighed against the potential benefits for each specific couple.<div class="boxTitle">REGISTRATION NUMBER</div>PROSPERO (ID: CRD42024503678)</span>
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