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Efficacy and safety of vilaprisan in women with uterine fibroids: data from the ASTEROID 3 randomized controlled trial vilaprisan在子宫肌瘤患者中的疗效和安全性:来自ASTEROID 3随机对照试验的数据。
F&S science Pub Date : 2023-11-01 DOI: 10.1016/j.xfss.2023.06.003
Ayman Al-Hendy M.D., Ph.D. , Ying F. Zhou M.D. , Thomas Faustmann M.D. , Esther Groettrup-Wolfers M.D. , Kaisa Laapas M.Sc. , Susanne Parke M.D. , Christian Seitz M.D.
{"title":"Efficacy and safety of vilaprisan in women with uterine fibroids: data from the ASTEROID 3 randomized controlled trial","authors":"Ayman Al-Hendy M.D., Ph.D. ,&nbsp;Ying F. Zhou M.D. ,&nbsp;Thomas Faustmann M.D. ,&nbsp;Esther Groettrup-Wolfers M.D. ,&nbsp;Kaisa Laapas M.Sc. ,&nbsp;Susanne Parke M.D. ,&nbsp;Christian Seitz M.D.","doi":"10.1016/j.xfss.2023.06.003","DOIUrl":"10.1016/j.xfss.2023.06.003","url":null,"abstract":"<div><h3>Objective</h3><p>Vilaprisan is a highly potent selective progesterone receptor modulator<span><span> shown to reduce heavy menstrual bleeding, induce </span>amenorrhea<span>, and diminish uterine fibroid<span> volume in phase 2 studies. The objective of ASTEROID 3 was to demonstrate the superiority of vilaprisan compared with placebo in the treatment of heavy menstrual bleeding in women with uterine fibroids.</span></span></span></p></div><div><h3>Design</h3><p>Randomized, double-blind, placebo-controlled, multicenter phase 3 study.</p></div><div><h3>Setting</h3><p>Hospitals and medical centers.</p></div><div><h3>Patient(s)</h3><p>Women with ≥1 uterine fibroid of ≥3 cm and heavy menstrual bleeding of &gt;80 mL/cycle.</p></div><div><h3>Intervention(s)</h3><p>Women were randomly assigned to 1 of 4 treatment arms, which were planned to comprise 2 treatment periods of 12 weeks, each with vilaprisan (2 mg/d) or placebo that were continuous or separated by a break of one bleed.</p></div><div><h3>Main Outcome Measure(s)</h3><p>Amenorrhea (primary end point; &lt;2 mL in the last 28 days of treatment) and heavy menstrual bleeding response (key secondary end point; &lt;80 mL/cycle and &gt;50% reduction in bleeding from baseline) were measured with the alkaline hematin method. Change in volume of the 3 largest fibroids from baseline to end of treatment was assessed by ultrasound. Safety was monitored throughout the study.</p></div><div><h3>Result(s)</h3><p>Overall, 75 women completed the first 12 weeks of treatment. Statistically significant and clinically meaningful differences were observed between the vilaprisan- and placebo-treated groups in both the full analysis and per-protocol sets. In the per-protocol set (n = 36 and n = 12 for the vilaprisan and placebo groups, respectively), amenorrhea was observed more frequently in women treated with vilaprisan than in those who received placebo (83.3% vs. 0%, <em>P</em>&lt;.0001), with a median time to onset of 3 days in the vilaprisan group. Similarly, more vilaprisan- than placebo-treated women achieved a response in heavy menstrual bleeding (91.7% vs. 25.0%, <em>P</em>&lt;.0001). Serious adverse events were reported for 22 (27.8%) of 79 women and were evenly distributed among the 4 groups receiving vilaprisan and/or placebo. None of these events led to study discontinuation or were related to the liver, and no new safety findings were identified compared with the earlier phase 2 ASTEROID studies.</p></div><div><h3>Conclusion(s)</h3><p>Vilaprisan is efficacious and well tolerated over 12 weeks in the treatment of heavy menstrual bleeding associated with uterine fibroids. Further investigations of the long-term efficacy and safety of vilaprisan are warranted.</p></div><div><h3>Clinical Trial Registration Number</h3><p>NCT03400943 (<span>ClinicalTrials.gov</span><svg><path></path></svg>).</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 4","pages":"Pages 317-326"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9940805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Epigenetic determinants of reproductive potential augment the predictive ability of the semen analysis 生殖潜力的表观遗传学决定因素增强了精液分析的预测能力。
F&S science Pub Date : 2023-11-01 DOI: 10.1016/j.xfss.2023.09.001
Ryan H. Miller M.S. , Elizabeth A. DeVilbiss Ph.D. , Kristin R. Brogaard Ph.D. , Carter R. Norton , Chad A. Pollard B.S. , Benjamin R. Emery M.S. , Kenneth I. Aston Ph.D. , James M. Hotaling M.D., M.S. , Tim G. Jenkins Ph.D.
{"title":"Epigenetic determinants of reproductive potential augment the predictive ability of the semen analysis","authors":"Ryan H. Miller M.S. ,&nbsp;Elizabeth A. DeVilbiss Ph.D. ,&nbsp;Kristin R. Brogaard Ph.D. ,&nbsp;Carter R. Norton ,&nbsp;Chad A. Pollard B.S. ,&nbsp;Benjamin R. Emery M.S. ,&nbsp;Kenneth I. Aston Ph.D. ,&nbsp;James M. Hotaling M.D., M.S. ,&nbsp;Tim G. Jenkins Ph.D.","doi":"10.1016/j.xfss.2023.09.001","DOIUrl":"10.1016/j.xfss.2023.09.001","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the power of DNA methylation variability in sperm cells in assessing male fertility potential.</p></div><div><h3>Design</h3><p>Retrospective cohort.</p></div><div><h3>Setting</h3><p>Fertility care centers.</p></div><div><h3>Patients</h3><p>Male patients seeking infertility treatment and fertile male sperm donors.</p></div><div><h3>Intervention</h3><p>None.</p></div><div><h3>Main Outcome Measures</h3><p>Sperm DNA methylation data from 43 fertile sperm donors were analyzed and compared with the data from 1344 men seeking fertility assessment or treatment. Methylation at gene promoters with the least variable methylation in fertile patients was used to create 3 categories of promoter dysregulation in the infertility treatment cohort: poor, average, and excellent sperm quality.</p></div><div><h3>Results</h3><p>After controlling for female factors, there were significant differences in intrauterine insemination pregnancy and live birth outcomes between the poor and excellent groups across a cumulative average of 2–3 cycles: 19.4% vs. 51.7% (<em>P</em>=.008) and 19.4% vs. 44.8% (<em>P</em>=.03), respectively. Live birth outcomes from in vitro fertilization, primarily with intracytoplasmic sperm injection, were not found to be significantly different among any of the 3 groups.</p></div><div><h3>Conclusion</h3><p>Methylation variability in a panel of 1233 gene promoters could augment the predictive ability of semen analysis and be a reliable biomarker for assessing intrauterine insemination outcomes. In vitro fertilization with intracytoplasmic sperm injection appears to overcome high levels of epigenetic instability in sperm.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 4","pages":"Pages 279-285"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666335X23000496/pdfft?md5=43c638c46631220e714347868ce6e311&pid=1-s2.0-S2666335X23000496-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10316832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deep learning system for classification of ploidy status using time-lapse videos 使用延时视频对倍性状态进行分类的深度学习系统
F&S science Pub Date : 2023-08-01 DOI: 10.1016/j.xfss.2023.06.002
Elena Paya M.Sc. , Cristian Pulgarín M.Sc. , Lorena Bori M.Sc. , Adrián Colomer Ph.D. , Valery Naranjo Ph.D. , Marcos Meseguer Ph.D.
{"title":"Deep learning system for classification of ploidy status using time-lapse videos","authors":"Elena Paya M.Sc. ,&nbsp;Cristian Pulgarín M.Sc. ,&nbsp;Lorena Bori M.Sc. ,&nbsp;Adrián Colomer Ph.D. ,&nbsp;Valery Naranjo Ph.D. ,&nbsp;Marcos Meseguer Ph.D.","doi":"10.1016/j.xfss.2023.06.002","DOIUrl":"10.1016/j.xfss.2023.06.002","url":null,"abstract":"<div><h3>Objective</h3><p>To develop a spatiotemporal model for de prediction of euploid and aneuploid<span> embryos using time-lapse videos from 10–115 hours after insemination (hpi).</span></p></div><div><h3>Design</h3><p>Retrospective study.</p></div><div><h3>Main Outcome Measures</h3><p>The research used an end-to-end approach to develop an automated artificial intelligence system capable of extracting features from images and classifying them, considering spatiotemporal dependencies. A convolutional neural network extracted the most relevant features from each video frame. A bidirectional long short-term memory layer received this information and analyzed the temporal dependencies, obtaining a low-dimensional feature vector that characterized each video. A multilayer perceptron classified them into 2 groups, euploid and noneuploid.</p></div><div><h3>Results</h3><p>The model performance in accuracy fell between 0.6170 and 0.7308. A multi-input model with a gate recurrent unit module performed better than others; the precision (or positive predictive value) is 0.8205 for predicting euploidy. Sensitivity, specificity, F1-Score and accuracy are 0.6957, 0.7813, 0.7042, and 0.7308, respectively.</p></div><div><h3>Conclusions</h3><p>This article proposes an artificial intelligence solution for prioritizing euploid embryo transfer. We can highlight the identification of a noninvasive method for chromosomal status diagnosis using a deep learning approach that analyzes raw data provided by time-lapse incubators. This method demonstrated potential automation of the evaluation process, allowing spatial and temporal information to encode.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 3","pages":"Pages 211-218"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10393453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
EZH2 activates Wnt/β-catenin signaling in human uterine fibroids, which is inhibited by the natural compound methyl jasmonate EZH2激活人类子宫肌瘤中的Wnt/β-catenin信号传导,该信号传导被天然化合物茉莉酸甲酯抑制。
F&S science Pub Date : 2023-08-01 DOI: 10.1016/j.xfss.2023.05.003
Mohamed Ali Ph.D. , David Stone M.D. , Archana Laknaur Ph.D. , Qiwei Yang Ph.D. , Ayman Al-Hendy M.D., Ph.D.
{"title":"EZH2 activates Wnt/β-catenin signaling in human uterine fibroids, which is inhibited by the natural compound methyl jasmonate","authors":"Mohamed Ali Ph.D. ,&nbsp;David Stone M.D. ,&nbsp;Archana Laknaur Ph.D. ,&nbsp;Qiwei Yang Ph.D. ,&nbsp;Ayman Al-Hendy M.D., Ph.D.","doi":"10.1016/j.xfss.2023.05.003","DOIUrl":"10.1016/j.xfss.2023.05.003","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the link between EZH2 and Wnt/β-catenin signaling and its role in uterine fibroids (UFs) pathogenesis and explore the potential effect of natural compound methyl jasmonate (MJ) against UFs.</p></div><div><h3>Design</h3><p>EZH2 overexpression or inhibition was achieved in human uterine leiomyoma (HuLM) cells using EZH2-expressing adenovirus or chemical EZH2 inhibitor (DZNep), respectively. The HuLM and normal uterine smooth muscle cells were treated with 0.1–3 mM of MJ, and several experiments were employed.</p></div><div><h3>Setting</h3><p>Laboratory study.</p></div><div><h3>Patients(s)</h3><p>None.</p></div><div><h3>Intervention(s)</h3><p>Methyl jasmonate.</p></div><div><h3>Main Outcome Measure(s)</h3><p>Protein expression of EZH2, β-catenin, and proliferating cell nuclear antigen (PCNA) was measured by Western blot as well as gene expression alterations of Wnt ligands (<em>Wnt5A</em>, <em>Wnt5b</em>, and <em>Wnt9A</em>), <em>WISP1</em>, <em>CTNNB1</em>, and its responsive gene <em>PITX2</em> using quantitative real-time polymerase chain reaction. The protein and ribonucleic acid (RNA) levels of several markers were measured in MJ-treated or untreated HuLM cells, including EZH2 and β-catenin, extracellular matrix markers collagen type 1 (COL1A1) and fibronectin (FN), proliferation markers cyclin D1 (CCND1) and PCNA, tumor suppressor marker p21, and apoptotic markers (BAX, cytochrome c, and cleaved caspase 3).</p></div><div><h3>Result(s)</h3><p>EZH2 overexpression significantly increased the gene expression of several Wnt ligands (<em>PITX2</em>, <em>WISP1</em>, <em>WNT5A</em>, <em>WNT5B</em>, and <em>WNT9A</em>), which increased nuclear translocation of β-catenin and PCNA and eventually HuLM cell proliferation. EZH2 inhibition blocked Wnt/β-catenin signaling activation where the aforementioned genes significantly decreased as well as PCNA, cyclin D1, and PITX2 protein expression compared with those in untreated HuLM. Methyl jasmonate showed a potent antiproliferative effect on HuLM cells in a dose- and time-dependent manner. Interestingly, the dose range (0.1–0.5 mM) showed a selective growth inhibitory effect on HuLM cells, not on normal uterine smooth muscle cells. Methyl jasmonate treatment at 0.5 mM for 24 hours significantly decreased both protein and RNA levels of EZH2, β-catenin, COL1A1, FN, CCND1, PCNA, WISP1, and PITX2 but increased the protein levels of p21, BAX, cytochrome, c and cleaved caspase 3 compared with untreated HuLM. Methyl jasmonate–treated cells exhibited down-regulation in the RNA expression of 36 genes, including <em>CTNNB1</em>, <em>CCND1</em>, <em>Wnt5A</em>, <em>Wnt5B</em>, and <em>Wnt9A</em>, and up-regulation in the expression of 34 genes, including Wnt antagonist genes <em>WIF1</em>, <em>PRICKlE1</em>, and DKK1 compared with control, confirming the quantitative real-time polymerase chain reaction results.</p></div><div><h3>Conclusion(s)</h3><p>Our studies provide a novel lin","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 3","pages":"Pages 239-256"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10151011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An integrative analysis of endometrial steroid metabolism and transcriptome in relation to endometrial receptivity in in vitro fertilization patients 体外受精患者子宫内膜类固醇代谢和转录组与子宫内膜容受性关系的综合分析
F&S science Pub Date : 2023-08-01 DOI: 10.1016/j.xfss.2023.04.003
Linda B.P.M. Stevens Brentjens M.D., M.Sc. , Darina Obukhova M.Sc. , Janneke E. den Hartog M.D., Ph.D. , Bert Delvoux M.Sc. , Johanna Koskivuori M.Sc. , Seppo Auriola Prof. , Merja R. Häkkinen Ph.D. , Bich N. Bui M.D. , Nienke E. van Hoogenhuijze M.D., Ph.D. , Shari Mackens M.D., Prof. , Femke Mol M.D., Ph.D. , Jan Peter de Bruin M.D., Ph.D. , Dagmar Besselink M.D. , Gijs Teklenburg M.D., Ph.D , Viktorija Kukushkina M.Sc. , Andres Salumets Prof. , Frank J.M. Broekmans M.D., Prof. , Ron J.T. van Golde M.D., Ph.D. , Masoud Zamani Esteki Ph.D. , Andrea Romano Ph.D.
{"title":"An integrative analysis of endometrial steroid metabolism and transcriptome in relation to endometrial receptivity in in vitro fertilization patients","authors":"Linda B.P.M. Stevens Brentjens M.D., M.Sc. ,&nbsp;Darina Obukhova M.Sc. ,&nbsp;Janneke E. den Hartog M.D., Ph.D. ,&nbsp;Bert Delvoux M.Sc. ,&nbsp;Johanna Koskivuori M.Sc. ,&nbsp;Seppo Auriola Prof. ,&nbsp;Merja R. Häkkinen Ph.D. ,&nbsp;Bich N. Bui M.D. ,&nbsp;Nienke E. van Hoogenhuijze M.D., Ph.D. ,&nbsp;Shari Mackens M.D., Prof. ,&nbsp;Femke Mol M.D., Ph.D. ,&nbsp;Jan Peter de Bruin M.D., Ph.D. ,&nbsp;Dagmar Besselink M.D. ,&nbsp;Gijs Teklenburg M.D., Ph.D ,&nbsp;Viktorija Kukushkina M.Sc. ,&nbsp;Andres Salumets Prof. ,&nbsp;Frank J.M. Broekmans M.D., Prof. ,&nbsp;Ron J.T. van Golde M.D., Ph.D. ,&nbsp;Masoud Zamani Esteki Ph.D. ,&nbsp;Andrea Romano Ph.D.","doi":"10.1016/j.xfss.2023.04.003","DOIUrl":"10.1016/j.xfss.2023.04.003","url":null,"abstract":"<div><h3>Objective</h3><p>To study the relationship between the steroid concentration in the endometrium, in serum, and the gene expression level of steroid-metabolizing enzymes in the context of endometrial receptivity in in vitro fertilization (IVF) patients.</p></div><div><h3>Design</h3><p>Case-control study of 40 IVF patients recruited in the SCRaTCH study (NTR5342), a randomized controlled trial investigating pregnancy outcome after “endometrial scratching.” Endometrial biopsies and serum were obtained from patients with a first failed IVF cycle randomized to the endometrial scratch in the midluteal phase of the natural cycle before the next fresh embryo transfer during the second IVF cycle.</p></div><div><h3>Setting</h3><p>University hopsital.</p></div><div><h3>Patients</h3><p>Twenty women with clinical pregnancy were compared with 20 women who did not conceive after fresh embryo transfer. Cases and controls were matched for primary vs. secondary infertility, embryo quality, and age.</p></div><div><h3>Intervention</h3><p>None.</p></div><div><h3>Main Outcome Measure(s)</h3><p>Steroid concentrations in endometrial tissue homogenates and serum were measured with liquid chromatography-mass spectrometry. The endometrial transcriptome was profiled by RNA-sequencing, followed by principal component analysis and differential expression analysis. False discovery rate-adjusted and log-fold change &gt;|0.5| were selected as the threshold for differentially expressed genes.</p></div><div><h3>Result(s)</h3><p>Estrogen levels were comparable in both serum (n = 16) and endometrium (n = 40). Androgens and 17-hydroxyprogesterone were higher in serum than that in endometrium. Although steroid levels did not vary between pregnant and nonpregnant groups, subgroup analysis of primary women with infertility showed a significantly lower estrone concentration and estrone:androstenedione ratio in serum of the pregnant group (n = 5) compared with the nonpregnant group (n = 2). Expression of 34 out of 46 genes encoding the enzymes controlling the local steroid metabolism was detected, and estrogen receptor β gene was differentially expressed between pregnant and nonpregnant women. When only the primary infertile group was considered, 28 genes were differentially expressed between pregnant and nonpregnant women, including <em>HSD11B2</em>, that catalyzes the conversion of cortisol into cortisone.</p></div><div><h3>Conclusion(s)</h3><p>Steroidomic and transcriptomic analyses show that steroid concentrations are regulated by the local metabolism in the endometrium. Although no differences were found in endometrial steroid concentration in the pregnant and nonpregnant IVF patients, primary women with infertility showed deviations in steroid levels and gene expression, indicating that a more homogeneous patient group is required to uncover the exact role of steroid metabolism in endometrial receptivity.</p></div><div><h3>Clinical Trial Registration Number</h3><p>The study","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 3","pages":"Pages 219-228"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10411060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Understanding the impact of varicocele on sperm capacitation 了解精索静脉曲张对精子获能的影响
F&S science Pub Date : 2023-08-01 DOI: 10.1016/j.xfss.2023.05.001
Rhayza Roberta Andretta Ph.D. , Letícia Signori de Castro Ph.D. , Renata Cristina de Carvalho M.Sc. , Jheysson Alfredo Cordeiro de Moura M.Sc. , Renato Fraietta Ph.D. , Fatima Kazue Okada Ph.D. , Ricardo Pimenta Bertolla Ph.D.
{"title":"Understanding the impact of varicocele on sperm capacitation","authors":"Rhayza Roberta Andretta Ph.D. ,&nbsp;Letícia Signori de Castro Ph.D. ,&nbsp;Renata Cristina de Carvalho M.Sc. ,&nbsp;Jheysson Alfredo Cordeiro de Moura M.Sc. ,&nbsp;Renato Fraietta Ph.D. ,&nbsp;Fatima Kazue Okada Ph.D. ,&nbsp;Ricardo Pimenta Bertolla Ph.D.","doi":"10.1016/j.xfss.2023.05.001","DOIUrl":"10.1016/j.xfss.2023.05.001","url":null,"abstract":"<div><h3>Objective</h3><p><span>To study the relationship between the seminal sample quality of men with varicocele and </span>sperm capacitation.</p></div><div><h3>Design</h3><p>Cross-sectional observational study.</p></div><div><h3>Setting</h3><p>Academic hospital.</p></div><div><h3>Patient(s)</h3><p>Seventy-six men (19 control and 57 with varicocele) were analyzed.</p></div><div><h3>Intervention(s)</h3><p>Semen samples were submitted to a discontinuous density gradient for sperm selection. Sperm capacitation was induced using a human tubal fluid medium supplemented with bovine serum albumin.</p></div><div><h3>Main Outcome Measure(s)</h3><p><span>After capacitation induction, the sperm were assessed by capacitation state, computer-assisted sperm motility, mitochondrial activity, membrane integrity, </span>acrosome reaction<span>, and intracellular oxidative stress.</span></p></div><div><h3>Result(s)</h3><p>The capacitation period increased sperm motility, showing an increase in the average path velocity and a decrease in the straightness compared with sperm before capacitation (paired analysis). After capacitation, the rate of capacitated sperm, motility, and mitochondrial activity showed differences between groups (control and varicocele). The varicocele group showed lower mitochondrial activity and capacitation than the control group. On the other hand, no significant differences were observed in the other variables evaluated.</p></div><div><h3>Conclusion(s)</h3><p>Varicocele men showed less viable sperm and mitochondrial activity than control men after capacitation sperm. The induction of capacitation altered motility by increasing path velocity and decreasing straightness in all of the studied groups, evidencing the occurrence of hyperactivation.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 3","pages":"Pages 229-238"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10036779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Endogenous retrotransposons cause catastrophic deoxyribonucleic acid damage in human trophoblasts 内源性逆转录转座子对人类滋养层细胞造成灾难性的脱氧核糖核酸损伤
F&S science Pub Date : 2023-08-01 DOI: 10.1016/j.xfss.2023.05.005
Maurizio Mauro Ph.D. , Shan Wei Ph.D. , Andrzej Breborowicz M.D. , Xin Li Ph.D. , Claudia Bognanni Ph.D. , Zachary Fuller Ph.D. , Thomas Philipp M.D. , Torrin McDonald Ph.D. , Miriam Temmeh Lattin B.A. , Zev Williams M.D., Ph.D.
{"title":"Endogenous retrotransposons cause catastrophic deoxyribonucleic acid damage in human trophoblasts","authors":"Maurizio Mauro Ph.D. ,&nbsp;Shan Wei Ph.D. ,&nbsp;Andrzej Breborowicz M.D. ,&nbsp;Xin Li Ph.D. ,&nbsp;Claudia Bognanni Ph.D. ,&nbsp;Zachary Fuller Ph.D. ,&nbsp;Thomas Philipp M.D. ,&nbsp;Torrin McDonald Ph.D. ,&nbsp;Miriam Temmeh Lattin B.A. ,&nbsp;Zev Williams M.D., Ph.D.","doi":"10.1016/j.xfss.2023.05.005","DOIUrl":"10.1016/j.xfss.2023.05.005","url":null,"abstract":"<div><h3>Objective</h3><p>To determine the mechanistic role of mobile genetic elements in causing widespread DNA damage in primary human trophoblasts.</p></div><div><h3>Design</h3><p>Experimental ex vivo study.</p></div><div><h3>Setting</h3><p>Hospital-affiliated University.</p></div><div><h3>Patient(s)</h3><p><span>Trophoblasts from a patient with unexplained recurrent pregnancy loss and patients with spontaneous and </span>elective abortions (n = 10).</p></div><div><h3>Intervention(s)</h3><p>Biochemical and genetic analysis and modification of primary human trophoblasts.</p></div><div><h3>Main Outcome Measure(s)</h3><p><span>To phenotype and systematically evaluate the underlying pathogenic mechanism for elevated DNA damage observed in trophoblasts derived from a patient with unexplained recurrent pregnancy loss, transcervical embryoscopy, G-band karyotyping, </span>RNA sequencing<span>, quantitative polymerase chain reaction, immunoblotting<span>, biochemical and siRNA assays, and whole-genome sequencing were performed.</span></span></p></div><div><h3>Result(s)</h3><p>Transcervical embryoscopy revealed a severely dysmorphic embryo that was euploid on G-band karyotyping. RNA sequencing was notable for markedly elevated LINE-1 expression, confirmed with quantitative polymerase chain reaction, and that resulted in elevated expression of LINE-1-encoded proteins, as shown by immunoblotting. Immunofluorescence<span>, biochemical and genetic approaches demonstrated that overexpression of LINE-1 caused reversible widespread genomic damage and apoptosis.</span></p></div><div><h3>Conclusion(s)</h3><p>Derepression of LINE-1 elements in early trophoblasts results in reversible but widespread DNA damage.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 3","pages":"Pages 200-210"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10038945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From the Editor-in-Chief 来自主编
F&S science Pub Date : 2023-08-01 DOI: 10.1016/j.xfss.2023.07.002
William H. Catherino M.D., Ph.D. (Editor-in-Chief, Fertility and Sterility - Science)
{"title":"From the Editor-in-Chief","authors":"William H. Catherino M.D., Ph.D. (Editor-in-Chief, Fertility and Sterility - Science)","doi":"10.1016/j.xfss.2023.07.002","DOIUrl":"10.1016/j.xfss.2023.07.002","url":null,"abstract":"","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 3","pages":"Page 184"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10018793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The effect of parental carrier of de novo mutated vs. inherited balanced reciprocal translocation on the chance of euploid embryos 新突变与遗传平衡相互易位亲本携带者对整倍体胚胎机会的影响
F&S science Pub Date : 2023-08-01 DOI: 10.1016/j.xfss.2023.05.002
Jialin Zou M.D. , Tianxiang Ni M.D., Ph.D. , Min Yang M.D. , Hongchang Li M.D., Ph.D. , Ming Gao M.D., Ph.D. , Yueting Zhu M.D., Ph.D. , Wenjie Jiang M.D., Ph.D. , Qian Zhang M.D., Ph.D. , Junhao Yan M.D., Ph.D. , Daimin Wei M.D., Ph.D. , Zi-Jiang Chen M.D., Ph.D.
{"title":"The effect of parental carrier of de novo mutated vs. inherited balanced reciprocal translocation on the chance of euploid embryos","authors":"Jialin Zou M.D. ,&nbsp;Tianxiang Ni M.D., Ph.D. ,&nbsp;Min Yang M.D. ,&nbsp;Hongchang Li M.D., Ph.D. ,&nbsp;Ming Gao M.D., Ph.D. ,&nbsp;Yueting Zhu M.D., Ph.D. ,&nbsp;Wenjie Jiang M.D., Ph.D. ,&nbsp;Qian Zhang M.D., Ph.D. ,&nbsp;Junhao Yan M.D., Ph.D. ,&nbsp;Daimin Wei M.D., Ph.D. ,&nbsp;Zi-Jiang Chen M.D., Ph.D.","doi":"10.1016/j.xfss.2023.05.002","DOIUrl":"10.1016/j.xfss.2023.05.002","url":null,"abstract":"<div><h3>Objective</h3><p>To evaluate whether the effect of de novo mutated balanced reciprocal translocation on the rate of euploid embryos varied from inherited balanced reciprocal translocation.</p></div><div><h3>Design</h3><p>A retrospective cohort study compared the percentage of euploid embryo and proportion of patients with at least 1 euploid embryo between de novo mutated balanced reciprocal translocation (i.e., the group of de novo mutated carriers) and inherited balanced reciprocal translocation (i.e., the group of inherited carriers).</p></div><div><h3>Setting</h3><p>An academic fertility center.</p></div><div><h3>Patient(s)</h3><p>A total of 413 couples with balanced reciprocal translocation (219 female carriers and 194 male carriers) who underwent their first cycle of preimplantation genetic testing for structural rearrangements were included.</p></div><div><h3>Intervention(s)</h3><p>Carriers of balanced reciprocal translocation either de novo mutated or inherited.</p></div><div><h3>Main Outcome Measure(s)</h3><p>The percentage of euploid embryo and proportion of patients with at least 1 euploid embryo.</p></div><div><h3>Result(s)</h3><p>The carriers of the de novo mutated balanced reciprocal translocation had a lower percentage of euploid embryos (19.5% vs. 25.5%), and were less likely to have at least 1 euploid embryo (47.1% vs. 60.1%) compared with the carriers of the inherited balanced reciprocal translocation. In the male-carrier subgroup, the percentage of euploid embryos (16.7% vs. 26.7%) and proportion of patients with at least 1 euploid embryo (41.9% vs. 67.5%) were lower among the de novo mutated carriers than those among the inherited carriers. However, in the female-carrier subgroup, there was no statistically significant difference in the percentage of euploid embryos (22.4% vs. 24.4%) or the proportion of patients with at least 1 euploid embryo (52.3% vs. 53.7%) between the de novo mutated carriers and inherited carriers.</p></div><div><h3>Conclusion(s)</h3><p>The de novo mutated balanced reciprocal translocation was associated with a lower percentage of euploid embryos and lower chance of obtaining at least 1 euploid embryo than the inherited balanced reciprocal translocation.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 3","pages":"Pages 193-199"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10033990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cumulus cell co-culture in media drops does not improve rescue in vitro maturation of vitrified-warmed immature oocytes 培养基滴液中的Cumulus细胞共培养不能改善玻璃化加温未成熟卵母细胞的体外成熟挽救
F&S science Pub Date : 2023-08-01 DOI: 10.1016/j.xfss.2023.05.004
Catherine E. Gordon M.D. , Catherine MH. Combelles Ph.D. , Andrea Lanes Ph.D. , Jay Patel M. Sc. , Catherine Racowsky Ph.D.
{"title":"Cumulus cell co-culture in media drops does not improve rescue in vitro maturation of vitrified-warmed immature oocytes","authors":"Catherine E. Gordon M.D. ,&nbsp;Catherine MH. Combelles Ph.D. ,&nbsp;Andrea Lanes Ph.D. ,&nbsp;Jay Patel M. Sc. ,&nbsp;Catherine Racowsky Ph.D.","doi":"10.1016/j.xfss.2023.05.004","DOIUrl":"10.1016/j.xfss.2023.05.004","url":null,"abstract":"<div><h3>Objective</h3><p>To assess whether co-culture with vitrified-warmed cumulus cells<span> (CCs) in media drops improves rescue in vitro maturation (IVM) of previously vitrified immature oocytes. Previous studies have shown improved rescue IVM of fresh immature oocytes when cocultured with CCs in a three-dimensional matrix. However, the scheduling and workload of embryologists would benefit from a simpler IVM approach, particularly in the setting of time-sensitive oncofertility oocyte cryopreservation (OC) cases. Although the yield of developmentally competent mature metaphase II (MII) oocytes is increased when rescue IVM is performed before cryopreservation, it is unknown whether maturation of previously vitrified immature oocytes is improved after coculture with CCs in a simple system not involving a three-dimensional matrix.</span></p></div><div><h3>Design</h3><p>Randomized controlled trial.</p></div><div><h3>Setting</h3><p>Academic hospital.</p></div><div><h3>Patients</h3><p>A total of 320 (160 germinal vesicles<span> [GVs] and 160 metaphase I [MI]) immature oocytes and autologous CC clumps were vitrified from patients who were undergoing planned OC or intracytoplasmic sperm injection from July 2020 until September 2021.</span></p></div><div><h3>Interventions</h3><p>On warming, the oocytes were randomized to culture in IVM media with CCs (+CC) or without CCs (-CC). Germinal vesicles and MI oocytes were cultured in 25 μL (SAGE IVM medium) for 32 hours and 20–22 hours, respectively.</p></div><div><h3>Main Outcome Measures</h3><p>Oocytes with a polar body (MII) were randomized to confocal microscopy<span> for analysis of spindle integrity and chromosomal alignment to assess nuclear maturity or to parthenogenetic activation to assess cytoplasmic maturity. Wilcoxon rank sum tests for continuous variables and the chi square or Fisher’s exact test for categorical variables assessed statistical significance. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated.</span></p></div><div><h3>Results</h3><p>Patient demographic characteristics were similar for both the GV and MI groups after randomization to +CC vs. -CC. No statistically significant differences were observed between +CC vs. -CC groups regarding the percentage of MII from either GV (42.5% [34/80] vs. 52.5% [42/80]; RR 0.81; 95% CI: 0.57–1.15]) or MI (76.3% [61/80]; vs. 72.5% [58/80]; RR 1.05; 95% CI: 0.88–1.26]) oocytes. An increased percentage of GV-matured MIIs underwent parthenogenetic activation in the +CC group (92.3% [12/13] vs. 70.8% [17/24]), but the difference was not statistically significant (RR 1.30; 95% CI: 0.97–1.75), whereas the activation rate was identical for MI-matured oocytes (74.3% [26/35] vs. 75.0% [18/24], CC+ vs. CC-; RR 0.99; 95% CI: 0.74–1.32). No significant differences were observed between +CC vs. -CC groups for cleavage of parthenotes from GV-matured oocytes (91.7% [11/12] vs. 82.4% [14/17]) or blastulation (0 for both) or for MI-matured ","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 3","pages":"Pages 185-192"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10038937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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