Human reproduction open最新文献

筛选
英文 中文
Effects of ovarian stimulation on embryo euploidy: an analysis of 12 874 oocytes and 3106 blastocysts in cycles with preimplantation genetic testing for monogenic disorders. 卵巢刺激对胚胎非整倍体的影响:对 12 874 个卵母细胞和 3106 个囊胚进行的分析,这些卵母细胞和囊胚都进行了单基因遗传病植入前基因检测。
IF 8.3
Human reproduction open Pub Date : 2024-10-03 eCollection Date: 2024-01-01 DOI: 10.1093/hropen/hoae054
Congcong Ma, Xiaoyu Long, Liying Yan, Xiaohui Zhu, Lixue Chen, Rong Li, Ying Wang, Jie Qiao
{"title":"Effects of ovarian stimulation on embryo euploidy: an analysis of 12 874 oocytes and 3106 blastocysts in cycles with preimplantation genetic testing for monogenic disorders.","authors":"Congcong Ma, Xiaoyu Long, Liying Yan, Xiaohui Zhu, Lixue Chen, Rong Li, Ying Wang, Jie Qiao","doi":"10.1093/hropen/hoae054","DOIUrl":"https://doi.org/10.1093/hropen/hoae054","url":null,"abstract":"<p><strong>Study question: </strong>Does ovarian stimulation and the ovarian response affect embryo euploidy?</p><p><strong>Summary answer: </strong>Ovarian stimulation and the ovarian response in women undergoing preimplantation genetic testing for monogenic disorders (PGT-M) cycles did not affect the rates of blastocyst euploidy.</p><p><strong>What is known already: </strong>Whether or not ovarian stimulation in IVF-embryo transfer has potential effects on embryo euploidy is controversial among studies for several reasons: (i) heterogeneity of the study populations, (ii) biopsies being performed at different stages of embryo development and (iii) evolution of the platforms utilized for ploidy assessment. Patients who undergo PGT-M cycles typically have no additional risks of aneuploidy, providing an ideal study population for exploring this issue.</p><p><strong>Study design size duration: </strong>A retrospective cohort study including embryos undergoing PGT-M was conducted at a single academically affiliated fertility clinic between June 2014 and July 2021.</p><p><strong>Participants/materials setting methods: </strong>A total of 617 women with 867 PGT-M cycles involving 12 874 retrieved oocytes and 3106 trophectoderm biopsies of blastocysts were included. The primary outcome of the study was median euploidy rate, which was calculated by dividing the number of euploid blastocysts by the total number of biopsied blastocysts for each cycle. Secondary outcomes included the median normal fertilization rate (two-pronuclear (2PN) embryos/metaphase II oocytes) and median blastulation rate (blastocyst numbers/2PN embryos).</p><p><strong>Main results and the role of chance: </strong>Comparable euploidy rates and fertilization rates were observed across all age groups, regardless of variations in ovarian stimulation protocols, gonadotropin dosages (both the starting and total dosages), stimulation durations, the inclusion of human menopausal gonadotrophin supplementation, or the number of oocytes retrieved (all <i>P</i> > 0.05). Blastulation rates declined with increasing starting doses of gonadotropins in women aged 31-34 years old (<i>P</i> = 0.005) but increased with increasing gonadotrophin starting doses in women aged 35-37 years old (<i>P</i> = 0.017). In women aged 31-34, 35-37, and 38-40 years old, blastulation rates were significantly reduced with increases in the number of oocytes retrieved (<i>P</i> = 0.001, <0.001, and 0.012, respectively).</p><p><strong>Limitations reasons for caution: </strong>Limitations include the study's retrospective nature and the relatively small number of patients of advanced age, especially patients older than 40 years old, leading to quite low statistical power. Second, as we considered euploidy rates as outcome measures, we did not analyze the effects of ovarian stimulation on uniform aneuploidy and mosaicism, respectively. Finally, we did not consider the effects of paternal characteristics on embryo euploidy s","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae054"},"PeriodicalIF":8.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486110","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
Speaking up for the safety of the children following frozen embryo transfer. 为冷冻胚胎移植后的儿童安全大声疾呼。
IF 8.3
Human reproduction open Pub Date : 2024-09-30 eCollection Date: 2024-01-01 DOI: 10.1093/hropen/hoae058
Anja Pinborg, Christophe Blockeel, Giovanni Coticchio, Juan Garcia-Velasco, Pietro Santulli, Alison Campbell
{"title":"Speaking up for the safety of the children following frozen embryo transfer.","authors":"Anja Pinborg, Christophe Blockeel, Giovanni Coticchio, Juan Garcia-Velasco, Pietro Santulli, Alison Campbell","doi":"10.1093/hropen/hoae058","DOIUrl":"https://doi.org/10.1093/hropen/hoae058","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae058"},"PeriodicalIF":8.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486112","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
High rate of detected variants in male PLCZ1 and ACTL7A genes causing failed fertilization after ICSI. 雄性 PLCZ1 和 ACTL7A 基因变异的高检出率导致卵胞浆内单精子显微注射受精失败。
IF 8.3
Human reproduction open Pub Date : 2024-09-28 eCollection Date: 2024-01-01 DOI: 10.1093/hropen/hoae057
Arantxa Cardona Barberán, Ramesh Reddy Guggilla, Cora Colenbier, Emma Van der Velden, Andrei Rybouchkin, Dominic Stoop, Luc Leybaert, Paul Coucke, Sofie Symoens, Annekatrien Boel, Frauke Vanden Meerschaut, Björn Heindryckx
{"title":"High rate of detected variants in male <i>PLCZ1</i> and <i>ACTL7A</i> genes causing failed fertilization after ICSI.","authors":"Arantxa Cardona Barberán, Ramesh Reddy Guggilla, Cora Colenbier, Emma Van der Velden, Andrei Rybouchkin, Dominic Stoop, Luc Leybaert, Paul Coucke, Sofie Symoens, Annekatrien Boel, Frauke Vanden Meerschaut, Björn Heindryckx","doi":"10.1093/hropen/hoae057","DOIUrl":"https://doi.org/10.1093/hropen/hoae057","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;What is the frequency of &lt;i&gt;PLCZ1&lt;/i&gt;, &lt;i&gt;ACTL7A&lt;/i&gt;, and &lt;i&gt;ACTL9&lt;/i&gt; variants in male patients showing fertilization failure after ICSI, and how effective is assisted oocyte activation (AOA) for them?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Male patients with fertilization failure after ICSI manifest variants in &lt;i&gt;PLCZ1&lt;/i&gt; (29.09%), &lt;i&gt;ACTL7A&lt;/i&gt; (14.81%), and &lt;i&gt;ACTL9&lt;/i&gt; (3.70%), which can be efficiently overcome by AOA treatment with ionomycin.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Genetic variants in &lt;i&gt;PLCZ1&lt;/i&gt;, and more recently, in &lt;i&gt;ACTL7A&lt;/i&gt;, and &lt;i&gt;ACTL9&lt;/i&gt; male genes, have been associated with total fertilization failure or low fertilization after ICSI. A larger patient cohort is required to understand the frequency at which these variants occur, and to assess their effect on the calcium ion (Ca&lt;sup&gt;2+&lt;/sup&gt;) release during oocyte activation. AOA, using ionomycin, can restore fertilization and pregnancy rates in patients with &lt;i&gt;PLCZ1&lt;/i&gt; variants, but it remains unknown how efficient this is for patients with &lt;i&gt;ACTL7A&lt;/i&gt; and &lt;i&gt;ACTL9&lt;/i&gt; variants.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This prospective study involved two patient cohorts. In the first setting, group 1 (N = 28, 2006-2020) underwent only &lt;i&gt;PLCZ1&lt;/i&gt; genetic screening, while group 2 (N = 27, 2020-2023) underwent &lt;i&gt;PLCZ1, ACTL7A&lt;/i&gt;, and &lt;i&gt;ACTL9&lt;/i&gt; genetic screening. Patients were only recruited when they had a mean fertilization rate of ≤33.33% in at least one ICSI cycle with at least four MII oocytes. Patients underwent a mouse oocyte activation test (MOAT) and at least one ICSI-AOA cycle using calcium chloride (CaCl&lt;sub&gt;2&lt;/sub&gt;) injection and double ionomycin exposure at our centre. All patients donated a saliva sample for genetic screening and a sperm sample for further diagnostic tests, including Ca&lt;sup&gt;2+&lt;/sup&gt; imaging.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Genetic screening was performed via targeted next-generation sequencing. Identified variants were classified by applying the revised ACMG guidelines into a Bayesian framework and were confirmed by bidirectional Sanger sequencing. If variants of uncertain significance or likely pathogenic or pathogenic variants were found, patients underwent additional determination of the sperm Ca&lt;sup&gt;2+&lt;/sup&gt;-releasing pattern in mouse (MOCA) and in IVM human (HOCA) oocytes. Additionally, ACTL7A immunofluorescence and acrosome ultrastructure analyses by transmission electron microscopy (TEM) were performed for patients with &lt;i&gt;ACTL7A&lt;/i&gt; and/or &lt;i&gt;ACTL9&lt;/i&gt; variants.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Overall, the frequency rate of &lt;i&gt;PLCZ1&lt;/i&gt; variants was 29.09%. Moreover, 14.81% of patients carried &lt;i&gt;ACTL7A&lt;/i&gt; variants and 3.70% carried &lt;i&gt;ACTL9&lt;/i&gt; variants. Seven different &lt;i&gt;PLCZ1&lt;/i&gt; variants were identified (p.Ile74Thr, p.Gln94*, p.Arg141His, p.His233Leu, p.Lys322*, p.Ile379Thr, and p.Ser500Leu), five o","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae057"},"PeriodicalIF":8.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11479693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486111","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
Aligning genotyping and copy number data in single trophectoderm biopsies for aneuploidy prediction: uncovering incomplete concordance. 对单个滋养层活检中的基因分型和拷贝数数据进行比对,以预测非整倍体:发现不完全一致。
IF 8.3
Human reproduction open Pub Date : 2024-09-18 eCollection Date: 2024-01-01 DOI: 10.1093/hropen/hoae056
Lisa De Witte, Machteld Baetens, Kelly Tilleman, Frauke Vanden Meerschaut, Sandra Janssens, Ariane Van Tongerloo, Virginie Szymczak, Dominic Stoop, Annelies Dheedene, Sofie Symoens, Björn Menten
{"title":"Aligning genotyping and copy number data in single trophectoderm biopsies for aneuploidy prediction: uncovering incomplete concordance.","authors":"Lisa De Witte, Machteld Baetens, Kelly Tilleman, Frauke Vanden Meerschaut, Sandra Janssens, Ariane Van Tongerloo, Virginie Szymczak, Dominic Stoop, Annelies Dheedene, Sofie Symoens, Björn Menten","doi":"10.1093/hropen/hoae056","DOIUrl":"10.1093/hropen/hoae056","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;To what extent can genotype analysis aid in the classification of (mosaic) aneuploid embryos diagnosed through copy number analysis of a trophectoderm (TE) biopsy?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;In a small portion of embryos, genotype analysis revealed signatures of meiotic or uniform aneuploidy in those diagnosed with intermediate copy number changes, and signatures of presumed mitotic or putative mosaic aneuploidy in those diagnosed with full copy number changes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Comprehensive chromosome screening (CCS) for preimplantation genetic testing has provided valuable insights into the prevalence of (mosaic) chromosomal aneuploidy at the blastocyst stage. However, diagnosis of (mosaic) aneuploidy often relies solely on (intermediate) copy number analysis of a single TE biopsy. Integrating genotype information allows for independent assessment of the origin and degree of aneuploidy. Yet, studies aligning both datasets to predict (putative mosaic) aneuploidy in embryos remain scarce.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;A single TE biopsy was collected from 1560 embryos derived from 221 couples tested for a monogenic disorder (n = 218) or microdeletion-/microduplication syndrome (n = 3). TE samples were subjected to both copy number and genotyping analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Copy number and SNP genotyping analysis were conducted using GENType. Unbalanced chromosomal anomalies ≥10 Mb (or ≥20 Mb for copy number calls &lt;50%) were classified by degree, based on low-range intermediate (LR, 30-50%), high-range intermediate (HR, 50-70%) or full (&gt;70%) copy number changes. These categories were further subjected to genotyping analysis to ascertain the origin (and/or degree) of aneuploidy. For chromosomal gains, the meiotic division of origin (meiotic I/II versus non-meiotic or presumed mitotic) was established by studying the haplotypes. The level of monosomy (uniform versus putative mosaic) in the biopsy could be ascertained from the B-allele frequencies. For segmental aneuploidies, genotyping was restricted to deletions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Of 1479 analysed embryos, 24% (n = 356) exhibited a whole-chromosome aneuploidy, with 19% (n = 280) showing full copy number changes suggestive of uniform aneuploidy. Among 258 embryos further investigated by genotyping, 95% of trisomies with full copy number changes were identified to be of meiotic origin. For monosomies, a complete loss of heterozygosity (LOH) in the biopsy was observed in 97% of cases, yielding a 96% concordance rate at the embryo level (n = 248/258). Interestingly, 4% of embryos (n = 10/258) showed SNP signatures of non-meiotic gain or putative mosaic loss instead. Meanwhile, 5% of embryos (n = 76/1479) solely displayed HR (2.5%; n = 37) or LR (2.6%; n = 39) intermediate copy number changes, with an additional 2% showi","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae056"},"PeriodicalIF":8.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402646","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
Will a government subsidy increase couples' further fertility intentions? A real-world study from a large-scale online survey in Eastern China. 政府补贴会增加夫妇的进一步生育意愿吗?一项来自华东地区大规模在线调查的真实世界研究。
IF 8.3
Human reproduction open Pub Date : 2024-09-17 eCollection Date: 2024-01-01 DOI: 10.1093/hropen/hoae055
Wen-Hong Dong, Xia Wang, Fan Yuan, Lei Wang, Tian-Miao Gu, Bing-Quan Zhu, Jie Shao
{"title":"Will a government subsidy increase couples' further fertility intentions? A real-world study from a large-scale online survey in Eastern China.","authors":"Wen-Hong Dong, Xia Wang, Fan Yuan, Lei Wang, Tian-Miao Gu, Bing-Quan Zhu, Jie Shao","doi":"10.1093/hropen/hoae055","DOIUrl":"https://doi.org/10.1093/hropen/hoae055","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;How many couples with at least one child under 3 years would like to have another one or more child(ren) in Eastern China and will an in-cash subsidy be conducive to couple's fertility intentions?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;In sum, only 15.1% of respondents had further fertility intentions (FFI) before learning about the subsidy, and the planned in-cash subsidy policy increased respondents' overall FFI by 8.5%.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Fertility has been declining globally and has reached a new low in China. The reasons why the Chinese three-child policy was under-realized, and how couples will react to a planned monthly ¥1000 (€141.2) subsidy policy, are not fully understood.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;During January and February 2022, a cross-sectional online survey aiming to understand families' expenses of raising a child under 3 years old, and couples' FFI, was conducted. During the survey period, 272 510 respondents scanned the QR code. This study reports the findings pertaining to questions on respondents' sociodemographic characteristics, household factors, FFI, and changes in intention from negative to positive after learning about the planned in-cash subsidy. After exclusion, 144 893 eligible responses were included.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Respondents' FFI, the effect of a planned ¥1000/month*36 months' in-cash subsidy (€5083.2 in total) on people with a negative FFI before the subsidy, and potential reasons for persistent negative FFI after learning about the subsidy were collected through an anonymous online survey. Stepwise binary logistic regression models were used to select associated factors. The potential fertility rate change and government costs were estimated. A stratified analysis by current child number and sensitivity analysis were also conducted.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;In sum, 15.7% (22 804/144 893) of respondents were male, 15.1% of respondents reported a positive FFI, and 10.0% (12 288/123 051) without an FFI at first changed their intention after learning about the planned in-cash subsidy policy. For those who still said 'no FFI', 46.5%, 20.6%, and 14.7% chose pressure on housing status, expenses on children's education, and lack of time or energy for caring for another child as their first reasons. FFI was strongest in participants receiving the most financial support from their parents, i.e. grandparents (OR = 1.73, 95% CI = 1.63-1.84 for the &gt;¥100 000/year group), and weakest in those already having two children (OR = 0.23, 95% CI = 0.22-0.24). For those with no FFI before learning about the subsidy policy, respondents with the highest house loan/rent (&gt;¥120 000/year, OR = 1.27, 95% CI = 1.18-1.36) were more likely to change their FFI from 'No' to 'Yes', and those with the highest household income (&gt;¥300 000/year, OR = 0.65, 95% CI = 0.60-0.71) were","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae055"},"PeriodicalIF":8.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482355","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
Genetic architecture of congenital hypogonadotropic hypogonadism: insights from analysis of a Portuguese cohort. 先天性性腺功能减退症的遗传结构:葡萄牙队列分析的启示。
IF 8.3
Human reproduction open Pub Date : 2024-09-11 eCollection Date: 2024-01-01 DOI: 10.1093/hropen/hoae053
Josianne Nunes Carriço, Catarina Inês Gonçalves, Asma Al-Naama, Najeeb Syed, José Maria Aragüés, Margarida Bastos, Fernando Fonseca, Teresa Borges, Bernardo Dias Pereira, Duarte Pignatelli, Davide Carvalho, Filipe Cunha, Ana Saavedra, Elisabete Rodrigues, Joana Saraiva, Luisa Ruas, Nuno Vicente, João Martin Martins, Adriana De Sousa Lages, Maria João Oliveira, Cíntia Castro-Correia, Miguel Melo, Raquel Gomes Martins, Joana Couto, Carolina Moreno, Diana Martins, Patrícia Oliveira, Teresa Martins, Sofia Almeida Martins, Olinda Marques, Carla Meireles, António Garrão, Cláudia Nogueira, Carla Baptista, Susana Gama-de-Sousa, Cláudia Amaral, Mariana Martinho, Catarina Limbert, Luisa Barros, Inês Henriques Vieira, Teresa Sabino, Luís R Saraiva, Manuel Carlos Lemos
{"title":"Genetic architecture of congenital hypogonadotropic hypogonadism: insights from analysis of a Portuguese cohort.","authors":"Josianne Nunes Carriço, Catarina Inês Gonçalves, Asma Al-Naama, Najeeb Syed, José Maria Aragüés, Margarida Bastos, Fernando Fonseca, Teresa Borges, Bernardo Dias Pereira, Duarte Pignatelli, Davide Carvalho, Filipe Cunha, Ana Saavedra, Elisabete Rodrigues, Joana Saraiva, Luisa Ruas, Nuno Vicente, João Martin Martins, Adriana De Sousa Lages, Maria João Oliveira, Cíntia Castro-Correia, Miguel Melo, Raquel Gomes Martins, Joana Couto, Carolina Moreno, Diana Martins, Patrícia Oliveira, Teresa Martins, Sofia Almeida Martins, Olinda Marques, Carla Meireles, António Garrão, Cláudia Nogueira, Carla Baptista, Susana Gama-de-Sousa, Cláudia Amaral, Mariana Martinho, Catarina Limbert, Luisa Barros, Inês Henriques Vieira, Teresa Sabino, Luís R Saraiva, Manuel Carlos Lemos","doi":"10.1093/hropen/hoae053","DOIUrl":"10.1093/hropen/hoae053","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;What is the contribution of genetic defects in Portuguese patients with congenital hypogonadotropic hypogonadism (CHH)?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Approximately one-third of patients with CHH were found to have a genetic cause for their disorder, with causal pathogenic and likely pathogenic germline variants distributed among 10 different genes; cases of oligogenic inheritance were also included.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;CHH is a rare and genetically heterogeneous disorder characterized by deficient production, secretion, or action of GnRH, LH, and FSH, resulting in delayed or absent puberty, and infertility.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;Genetic screening was performed on a cohort of 81 Portuguese patients with CHH (36 with Kallmann syndrome and 45 with normosmic hypogonadotropic hypogonadism) and 263 unaffected controls.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;The genetic analysis was performed by whole-exome sequencing followed by the analysis of a virtual panel of 169 CHH-associated genes. The main outcome measures were non-synonymous rare sequence variants (population allele frequency &lt;0.01) classified as pathogenic, likely pathogenic, and variants of uncertain significance (VUS).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;A genetic cause was identified in 29.6% of patients. Causal pathogenic and likely pathogenic variants were distributed among 10 of the analysed genes. The most frequently implicated genes were &lt;i&gt;GNRHR&lt;/i&gt;, &lt;i&gt;FGFR1&lt;/i&gt;, &lt;i&gt;ANOS1&lt;/i&gt;, and &lt;i&gt;CHD7&lt;/i&gt;. Oligogenicity for pathogenic and likely pathogenic variants was observed in 6.2% of patients. VUS and oligogenicity for VUS variants were observed in 85.2% and 54.3% of patients, respectively, but were not significantly different from that observed in controls.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Large scale data: &lt;/strong&gt;N/A.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;The identification of a large number of VUS presents challenges in interpretation and these may require reclassification as more evidence becomes available. Non-coding and copy number variants were not studied. Functional studies of the variants were not undertaken.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong&gt;This study highlights the genetic heterogeneity of CHH and identified several novel variants that expand the mutational spectrum of the disorder. A significant proportion of patients remained without a genetic diagnosis, suggesting the involvement of additional genetic, epigenetic, or environmental factors. The high frequency of VUS underscores the importance of cautious variant interpretation. These findings contribute to the understanding of the genetic architecture of CHH and emphasize the need for further studies to elucidate the underlying mechanisms and identify additional causes of CHH.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study funding/competing interests: &lt;/strong&gt;This research was fun","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae053"},"PeriodicalIF":8.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302595","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
Birth rate decline in the later phase of the COVID-19 pandemic: the role of policy interventions, vaccination programmes, and economic uncertainty. COVID-19 大流行后期出生率下降:政策干预、疫苗接种计划和经济不确定性的作用。
IF 8.3
Human reproduction open Pub Date : 2024-09-10 eCollection Date: 2024-01-01 DOI: 10.1093/hropen/hoae052
Maria Winkler-Dworak, Kryštof Zeman, Tomáš Sobotka
{"title":"Birth rate decline in the later phase of the COVID-19 pandemic: the role of policy interventions, vaccination programmes, and economic uncertainty.","authors":"Maria Winkler-Dworak, Kryštof Zeman, Tomáš Sobotka","doi":"10.1093/hropen/hoae052","DOIUrl":"https://doi.org/10.1093/hropen/hoae052","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;What are the factors influencing the decline in the birth rates observed in higher-income countries in the later phase of the COVID-19 pandemic?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Our results suggest that economic uncertainty, non-pharmaceutical policy interventions, and the first wave of the population-wide vaccination campaign were associated with the decline in birth rates during 2022.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;During the COVID-19 pandemic, birth rates in most higher-income countries first briefly declined and then shortly recovered, showing no common trends afterwards until early 2022, when they unexpectedly dropped.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This study uses population-wide data on monthly total fertility rates (TFRs) adjusted for seasonality and calendar effects provided in the Human Fertility Database (HFD). Births taking place between November 2020 and October 2022 correspond to conceptions occurring between February 2020 and January 2022, i.e. after the onset of the pandemic but prior to the Russian invasion of Ukraine. The data cover 26 countries, including 21 countries in Europe, the USA, Canada, Israel, Japan, and the Republic of Korea.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;First, we provided a descriptive analysis of the monthly changes in the TFR. Second, we employed linear fixed effects regression models to estimate the association of explanatory factors with the observed seasonally adjusted TFRs. Our analysis considered three broader sets of explanatory factors: economic uncertainty, policy interventions restricting mobility and social activities outside the home, and the progression of vaccination programmes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;We found that birth trends during the COVID-19 pandemic were associated with economic uncertainty, as measured by increased inflation (&lt;i&gt;P&lt;/i&gt; &lt; 0.001), whereas unemployment did not show any link to births during the pandemic (&lt;i&gt;P&lt;/i&gt; = 0.677). The stringency of pandemic policy interventions was linked to a postponement of births, but only in countries with lower institutional trust and only in the early phase of the pandemic (&lt;i&gt;P&lt;/i&gt; = 0.003). In countries with higher trust, stricter containment measures were positively associated with birth rates, both for conceptions in the first year of the pandemic (&lt;i&gt;P&lt;/i&gt; = 0.019) and, albeit only weakly significant, for conceptions later in the pandemic (&lt;i&gt;P&lt;/i&gt; = 0.057). Furthermore, we found a negative association between the share of the population having received the first dose of the COVID-19 vaccination and TFRs (&lt;i&gt;P&lt;/i&gt; &lt; 0.001), whereas the share of the population having completed the primary vaccination course (usually consisting of two doses) was linked to a recovery of birth rates (&lt;i&gt;P&lt;/i&gt; &lt; 0.001).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Large scale data: &lt;/strong&gt;N/A.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae052"},"PeriodicalIF":8.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333819","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
Correlation of anogenital distance from childhood to age 9 years-a prospective population-based birth cohort-the Odense Child Cohort. 童年至 9 岁期间肛门距离的相关性--基于人口的前瞻性出生队列--欧登塞儿童队列。
IF 8.3
Human reproduction open Pub Date : 2024-09-09 eCollection Date: 2024-01-01 DOI: 10.1093/hropen/hoae050
Sarah Munk Andreasen, Lise Gehrt, Casper P Hagen, Anders Juul, Gylli Mola, Margit Bistrup Fischer, Marianne Skovsager Andersen, David Møbjerg Kristensen, Tina Kold Jensen
{"title":"Correlation of anogenital distance from childhood to age 9 years-a prospective population-based birth cohort-the Odense Child Cohort.","authors":"Sarah Munk Andreasen, Lise Gehrt, Casper P Hagen, Anders Juul, Gylli Mola, Margit Bistrup Fischer, Marianne Skovsager Andersen, David Møbjerg Kristensen, Tina Kold Jensen","doi":"10.1093/hropen/hoae050","DOIUrl":"10.1093/hropen/hoae050","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Does anogenital distance (AGD) - distance from the anus to the genitals - correlate from infancy (3 months) to the age of 9 years in boys and girls?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;In boys, AGD correlated from infancy to 9 years of age, whereas in girls, correlations were weaker, especially between infancy and later childhood.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;AGD is considered a marker for prenatal androgen action. In males, reduced AGD is associated with testicular cancer, infertility, and lower sperm count. In females, AGD is associated with endometriosis and polycystic ovary syndrome.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;In the Odense Child Cohort, a prospective population-based birth cohort, pregnant women were enrolled in early pregnancy. AGD and BMI were measured repeatedly in children at ages 3 and 18 months, as well as at 3, 5, 7, and 9 years.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;AGD was measured from the anus to the scrotum (AGDas) and to the penis (AGDap) in 1022 boys, and to the posterior fourchette and the clitoris in 887 girls repeatedly between the age of 3 months to 9 years. In total, 7706 assessments were made. AGD was adjusted for body weight, and &lt;i&gt;SD scores&lt;/i&gt; (the difference between individual AGD and the mean of AGD in the population divided by SD of AGD) were calculated for each child. Pearson correlation coefficient (&lt;i&gt;r&lt;/i&gt;) of each measurement was performed to investigate whether individual AGD was stable during childhood. Short predictive values at 3 months (20th percentile) to 9 years were investigated using the AUC produced by the receiver operating characteristic curve.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;In boys, AGD/body size-index &lt;i&gt;SD score&lt;/i&gt; correlated significantly between infancy and 9 years, strongest for AGDas (&lt;i&gt;r&lt;/i&gt; = 0.540 &lt;i&gt;P&lt;/i&gt; &gt; 0.001). In girls, weaker significant correlation coefficients were found between AGD at infancy and 9 years; higher correlation coefficients were found between AGD from 3 to 9 years (&lt;i&gt;P&lt;/i&gt; &gt; 0.001). Short AGDas in infancy predicted short AGDas in boys aged 9 years (AUC: 0.767, sensitivity 0.71, specificity 0.71). The predictive values of short infant AGDap, penile width (in boys), and AGD (in girls) concerning short outcomes at 9 years were low.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;The AGD measurements are less precisely measurable in girls compared to boys, especially in infancy, resulting in less reproducible measurements. Additionally, because AGD is shorter in girls, the same absolute measurement error is relatively more significant, potentially contributing to greater variability and lower reproducibility in girls. This may contribute to the weaker correlations in girls compared to boys.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong&gt;In boys, AGDas, relative to body size, correlated from infancy to 9 years, sugge","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae050"},"PeriodicalIF":8.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302594","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
Association of ambient air pollutant mixtures with IVF/ICSI-ET clinical pregnancy rates during critical exposure periods. 环境空气污染物混合物与关键暴露期试管婴儿/ICSI-ET 临床妊娠率的关系。
IF 8.3
Human reproduction open Pub Date : 2024-09-06 eCollection Date: 2024-01-01 DOI: 10.1093/hropen/hoae051
Rui-Ling Liu, Tong Wang, Ying-Ling Yao, Xing-Yu Lv, Yu-Ling Hu, Xin-Zhen Chen, Xiao-Jun Tang, Zhao-Hui Zhong, Li-Juan Fu, Xin Luo, Li-Hong Geng, Shao-Min Yu, Yu-Bin Ding
{"title":"Association of ambient air pollutant mixtures with IVF/ICSI-ET clinical pregnancy rates during critical exposure periods.","authors":"Rui-Ling Liu, Tong Wang, Ying-Ling Yao, Xing-Yu Lv, Yu-Ling Hu, Xin-Zhen Chen, Xiao-Jun Tang, Zhao-Hui Zhong, Li-Juan Fu, Xin Luo, Li-Hong Geng, Shao-Min Yu, Yu-Bin Ding","doi":"10.1093/hropen/hoae051","DOIUrl":"https://doi.org/10.1093/hropen/hoae051","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Does exposure to a mixture of ambient air pollutants during specific exposure periods influence clinical pregnancy rates in women undergoing IVF/ICSI-embryo transfer (ET) cycles?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;The specific exposure period from ET to the serum hCG test was identified as a critical exposure window as exposure to sulfur dioxide (SO&lt;sub&gt;2&lt;/sub&gt;) or a combination of air pollutants was associated with a decreased likelihood of clinical pregnancy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Exposure to a single pollutant may impact pregnancy outcomes in women undergoing ART. However, in daily life, individuals often encounter mixed pollution, and limited research exists on the effects of mixed air pollutants and the specific exposure periods.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This retrospective cohort study involved infertile patients who underwent their initial IVF/ICSI-ET cycle at an assisted reproduction center between January 2020 and January 2023. Exclusions were applied for patients meeting specific criteria, such as no fresh ET, incomplete clinical and address information, residency outside the 17 cities in the Sichuan Basin, age over 45 years, use of donor semen, thin endometrium (&lt;8 mm) and infertility factors unrelated to tubal or ovulation issues. In total, 5208 individuals were included in the study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Daily average levels of six air pollutants (fine particulate matter (PM&lt;sub&gt;2.5&lt;/sub&gt;), inhalable particulate matter (PM&lt;sub&gt;10&lt;/sub&gt;), SO&lt;sub&gt;2&lt;/sub&gt;, nitrogen dioxide (NO&lt;sub&gt;2&lt;/sub&gt;), carbon monoxide (CO), and ozone (O&lt;sub&gt;3&lt;/sub&gt;)) were acquired from air quality monitoring stations. The cumulative average levels of various pollutants were determined using the inverse distance weighting (IDW) method across four distinct exposure periods (Period 1: 90 days before oocyte retrieval; Period 2: oocyte retrieval to ET; Period 3: ET to serum hCG test; Period 4: 90 days before oocyte retrieval to serum hCG test). Single-pollutant logistic regression, two-pollutant logistic regression, Quantile g-computation (QG-C) regression, and Bayesian kernel machine regression (BKMR) were employed to evaluate the influence of pollutants on clinical pregnancy rates. Stratified analyses were executed to discern potentially vulnerable populations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;The clinical pregnancy rate for participants during the study period was 54.53%. Single-pollutant logistic models indicated that for PM&lt;sub&gt;2.5&lt;/sub&gt; during specific exposure Period 1 (adjusted odds ratio [aOR] = 0.83, 95% CI: 0.70-0.99) and specific exposure Period 4 (aOR = 0.83, 95% CI: 0.69-0.98), and SO&lt;sub&gt;2&lt;/sub&gt; in specific exposure Period 3 (aOR = 0.92, 95% CI: 0.86-0.99), each interquartile range (IQR) increment exhibited an association with a decreased probability of clinical pregnancy. Consistent results were obs","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae051"},"PeriodicalIF":8.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302593","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
Prior exposure to alkylating agents negatively impacts testicular organoid formation in cells obtained from childhood cancer patients. 儿童癌症患者的细胞事先接触烷化剂会对睾丸类器官的形成产生负面影响。
IF 8.3
Human reproduction open Pub Date : 2024-08-13 eCollection Date: 2024-01-01 DOI: 10.1093/hropen/hoae049
Yanhua Cui, Femke Harteveld, Hajar Ali Mohammed Ba Omar, Yifan Yang, Ragnar Bjarnason, Patrik Romerius, Mikael Sundin, Ulrika Norén Nyström, Cecilia Langenskiöld, Hartmut Vogt, Lars Henningsohn, Per Frisk, Kaisa Vepsäläinen, Cecilia Petersen, Rod T Mitchell, Jingtao Guo, João Pedro Alves-Lopes, Kirsi Jahnukainen, Jan-Bernd Stukenborg
{"title":"Prior exposure to alkylating agents negatively impacts testicular organoid formation in cells obtained from childhood cancer patients.","authors":"Yanhua Cui, Femke Harteveld, Hajar Ali Mohammed Ba Omar, Yifan Yang, Ragnar Bjarnason, Patrik Romerius, Mikael Sundin, Ulrika Norén Nyström, Cecilia Langenskiöld, Hartmut Vogt, Lars Henningsohn, Per Frisk, Kaisa Vepsäläinen, Cecilia Petersen, Rod T Mitchell, Jingtao Guo, João Pedro Alves-Lopes, Kirsi Jahnukainen, Jan-Bernd Stukenborg","doi":"10.1093/hropen/hoae049","DOIUrl":"10.1093/hropen/hoae049","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Can human pre- and peri-pubertal testicular cells obtained from childhood cancer patients, previously treated with chemotherapy, form testicular organoids (TOs)?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Organoid formation from testicular tissue collected from childhood cancer patients positively correlates with SRY-Box transcription factor 9 (SOX9) expression in Sertoli cells, which in turn negatively correlates with previous exposure to alkylating chemotherapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Pre- and peri-pubertal boys exposed to highly gonadotoxic therapies can only safeguard their fertility potential through testicular tissue cryopreservation. Today, there is no established clinical tool to restore fertility using these testicular samples. Organoids hold promise in providing fundamental early insights in creating such platforms. However, the generation of TOs that closely resemble the innate testis, to enable a thorough monitoring of the necessary steps for germ cell differentiation and somatic functionalities, remains a challenge.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;We used a Matrigel-based three-layer gradient culture system to generate human TOs and to reveal whether chemotherapy exposure affects TO formation capacity and the functionality of pre- and peri-pubertal testicular somatic cells. Testicular cells of 11 boys (aged 7.7 ± 4.1 (mean ± SD) years) were assessed for TO formation in relation to previous chemotherapy exposure and SOX9 expression in histological sections of paraffin-embedded testicular tissue samples collected on the day of biopsy and compared with testicular tissue samples obtained from 28 consecutive patients (aged 6.9 ± 3.8 (mean ± SD) years). All 39 patients were part of the fertility preservation project NORDFERTIL; an additional 10 samples (from boys aged 5.5 ± 3.5 (mean ± SD) years, without an underlying pathology) in an internal biobank collection were used as controls.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;We obtained 49 testicular tissue samples from boys aged 0.8-13.4 years. Fresh samples (n = 11) were dissociated into single-cell suspensions and applied to a three-layer gradient culture system for organoid formation. Histological sections of another 28 samples obtained as part of the fertility preservation project NORDFERTIL, and 10 samples from a sample collection of a pathology biobank were used to evaluate the effects of prior exposure to alkylating agents on testicular samples. Testicular organoid formation was defined based on morphological features, such as compartmentalized structures showing cord formation, and protein expression of testicular cell-specific markers for germ and somatic cells was evaluated via immunohistochemical staining. Hormone secretion was analysed by specific enzyme-linked immunosorbent assays for testosterone and anti-Müllerian hormone (AMH) production.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 3","pages":"hoae049"},"PeriodicalIF":8.3,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074678","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
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信