Human reproduction open最新文献

{"title":"Study protocol for a Developmental Epidemiological Study of Children born through Reproductive Technologies (DESCRT).","authors":"A J Adeleye, L Zablotska, P Rinaudo, D Huang, R H Lustig, M I Cedars","doi":"10.1093/hropen/hoad013","DOIUrl":"https://doi.org/10.1093/hropen/hoad013","url":null,"abstract":"<p><strong>Study questions: </strong>The primary objective of this study is to determine what parental factors or specific ART may influence the risk for adverse cardiometabolic outcomes among children so conceived and their parents. The secondary objective of this study is to prospectively examine the effects of infertility or ART on the intrauterine environment, obstetric and neonatal outcomes.</p><p><strong>What is known already: </strong>Pregnancies conceived with ART are at an increased risk of being affected by adverse obstetric and neonatal outcomes when compared to spontaneously conceived (SC) pregnancies among fertile women. Small cohort studies have suggested ART-conceived children may have a higher risk of long-term cardiometabolic disturbances as well. Currently, few studies have compared long-term cardiometabolic outcomes among ART-conceived children and non-IVF treated (NIFT) children, to children conceived spontaneously to parents with infertility (subfertile parents).</p><p><strong>Study design size duration: </strong>The Developmental Epidemiological Study of Children born through Reproductive Technologies (DESCRT) is a prospective cohort study that aims to: establish a biobank and epidemiological cohort of children born to subfertile or infertile parents who either conceived spontaneously (without assistance) or used reproductive technologies to conceive (all offspring were from couples assessed and/or treated in the same institute); prospectively examine the effects of infertility or ART on the intrauterine environment, obstetric and neonatal outcomes; and determine what parental factors or ART may influence the cardiometabolic risk of children so conceived. Pregnancies and resultant children will be compared by mode of conception, namely offspring that were conceived without medical assistance or SC or following NIFT, IVF with fresh embryo transfer or frozen embryo transfer (FET), and by fertilization method (conventional versus ICSI). DESCRT has a Child group evaluating long-term outcomes of children as well as a Pregnancy group that will compare obstetric and neonatal outcomes of children conceived since the commencement of the study. Recruitment started in May of 2017 and is ongoing. When the study began, we estimated that ∼4000 children would be eligible for enrollment.</p><p><strong>Participants/materials setting methods: </strong>Eligible participants are first-trimester pregnancies (Pregnancy group) or children (Child group) born to parents who were evaluated at an infertility center in the University of California, San Francisco, CA, USA who were SC or conceived after reproductive treatments (NIFT, IVF ± ICSI, FET). Children in the Child group were conceived at UCSF and born from 2001 onwards. In the Pregnancy group, enrollment began in November of 2017.The primary outcome is the cardiometabolic health of offspring in the Child group, as measured by blood pressure and laboratory data (homeostatic model assessment for i","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 2","pages":"hoad013"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10229433/pdf/hoad013.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9568855","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}

{"title":"ESHRE guideline: recurrent pregnancy loss: an update in 2022.","authors":"Ruth Bender Atik, Ole Bjarne Christiansen, Janine Elson, Astrid Marie Kolte, Sheena Lewis, Saskia Middeldorp, Saria Mcheik, Braulio Peramo, Siobhan Quenby, Henriette Svarre Nielsen, Marie-Louise van der Hoorn, Nathalie Vermeulen, Mariëtte Goddijn","doi":"10.1093/hropen/hoad002","DOIUrl":"https://doi.org/10.1093/hropen/hoad002","url":null,"abstract":"<p><strong>Study question: </strong>What are the updates for the recommended management of women with recurrent pregnancy loss (RPL) based on the best available evidence in the literature from 2017 to 2022?</p><p><strong>Summary answer: </strong>The guideline development group (GDG) updated 11 existing recommendations on investigations and treatments for RPL, and how care should be organized, and added one new recommendation on adenomyosis investigation in women with RPL.</p><p><strong>What is known already: </strong>A previous ESHRE guideline on RPL was published in 2017 and needs to be updated.</p><p><strong>Study design size duration: </strong>The guideline was developed and updated according to the structured methodology for development and update of ESHRE guidelines. The literature searches were updated, and assessments of relevant new evidence were performed. Relevant papers published between 31 March 2017 and 28 February 2022 and written in English were included. Cumulative live birth rate, live birth rate, and pregnancy loss rate (or miscarriage rate) were considered the critical outcomes.</p><p><strong>Participants/materials setting methods: </strong>Based on the collected evidence, recommendations were updated and discussed until consensus was reached within the GDG. A stakeholder review was organized after the updated draft was finalized. The final version was approved by the GDG and the ESHRE Executive Committee.</p><p><strong>Main results and the role of chance: </strong>The new version of the guideline provides 39 recommendations on risk factors, prevention, and investigation in couples with RPL, and 38 recommendations on treatments. These includes 62 evidence-based recommendations-of which 33 were formulated as strong recommendations and 29 as conditional-and 15 good practice points. Of the evidence-based recommendations, 12 (19.4%) were supported by moderate-quality evidence. The remaining recommendations were supported by low (34 recommendations; 54.8%), or very low-quality evidence (16 recommendations; 25.8%). Owing to the lack of evidence-based investigations and treatments in RPL care, the guideline also clearly mentions those investigations and treatments that should not be used for couples with RPL.</p><p><strong>Limitations reasons for caution: </strong>The guidelines have been updated; however, several investigations and treatments currently offered to couples with RPL have not been well studied; for most of these investigations and treatments, a recommendation against using the intervention or treatment was formulated based on insufficient evidence. Future studies may require these recommendations to be revised.</p><p><strong>Wider implications of the findings: </strong>The guideline provides clinicians with clear advice on best practice in RPL, based on the best and most recent evidence available. In addition, a list of research recommendations is provided to stimulate further studies in RPL. Still, the absence of a unif","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 1","pages":"hoad002"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c4/4d/hoad002.PMC9982362.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9869742","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}

{"title":"ESHRE good practice recommendations on recurrent implantation failure.","authors":"D Cimadomo, M J de Los Santos, G Griesinger, G Lainas, N Le Clef, D J McLernon, D Montjean, B Toth, N Vermeulen, N Macklon","doi":"10.1093/hropen/hoad023","DOIUrl":"https://doi.org/10.1093/hropen/hoad023","url":null,"abstract":"<p><strong>Study question: </strong>How should recurrent implantation failure (RIF) in patients undergoing ART be defined and managed?</p><p><strong>Summary answer: </strong>This is the first ESHRE good practice recommendations paper providing a definition for RIF together with recommendations on how to investigate causes and contributing factors, and how to improve the chances of a pregnancy.</p><p><strong>What is known already: </strong>RIF is a challenge in the ART clinic, with a multitude of investigations and interventions offered and applied in clinical practice, often without biological rationale or with unequivocal evidence of benefit.</p><p><strong>Study design size duration: </strong>This document was developed according to a predefined methodology for ESHRE good practice recommendations. Recommendations are supported by data from the literature, if available, and the results of a previously published survey on clinical practice in RIF and the expertise of the working group. A literature search was performed in PubMed and Cochrane focussing on 'recurrent reproductive failure', 'recurrent implantation failure', and 'repeated implantation failure'.</p><p><strong>Participants/materials setting methods: </strong>The ESHRE Working Group on Recurrent Implantation Failure included eight members representing the ESHRE Special Interest Groups for Implantation and Early Pregnancy, Reproductive Endocrinology, and Embryology, with an independent chair and an expert in statistics. The recommendations for clinical practice were formulated based on the expert opinion of the working group, while taking into consideration the published data and results of the survey on uptake in clinical practice. The draft document was then open to ESHRE members for online peer review and was revised in light of the comments received.</p><p><strong>Main results and the role of chance: </strong>The working group recommends considering RIF as a secondary phenomenon of ART, as it can only be observed in patients undergoing IVF, and that the following description of RIF be adopted: 'RIF describes the scenario in which the transfer of embryos considered to be viable has failed to result in a positive pregnancy test sufficiently often in a specific patient to warrant consideration of further investigations and/or interventions'. It was agreed that the recommended threshold for the cumulative predicted chance of implantation to identify RIF for the purposes of initiating further investigation is 60%. When a couple have not had a successful implantation by a certain number of embryo transfers and the cumulative predicted chance of implantation associated with that number is greater than 60%, then they should be counselled on further investigation and/or treatment options. This term defines clinical RIF for which further actions should be considered. Nineteen recommendations were formulated on investigations when RIF is suspected, and 13 on interventions. Recommendations were c","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 3","pages":"hoad023"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5f/b8/hoad023.PMC10270320.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9715806","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}

{"title":"Low ovarian reserve and risk of miscarriage in pregnancies derived from assisted reproductive technology.","authors":"Alessandra Chinè, Marco Reschini, Gianfranco Fornelli, Ludovica Basili, Andrea Busnelli, Paola Viganò, Ludovico Muzii, Edgardo Somigliana","doi":"10.1093/hropen/hoad026","DOIUrl":"https://doi.org/10.1093/hropen/hoad026","url":null,"abstract":"<p><strong>Study question: </strong>Do low levels of anti-Müllerian hormone (AMH) or antral follicle count (AFC) properly predict miscarriage in young women conceiving with ART?</p><p><strong>Summary answer: </strong>Low ovarian reserve, as indicated by AMH or AFC, is not associated with miscarriage in young women conceiving with ART.</p><p><strong>What is known already: </strong>Presently, the impact of low ovarian reserve on the risk of miscarriage remains controversial. Some studies have reported an association between serum AMH levels and AFC and miscarriage, but others have failed to confirm these findings. The main limitation that undermines the reliability and consistency of the results is the confounding effect of female age. Indeed, after 35 years of age, on the one hand, the risk of miscarriage starts increasing because of impaired oocyte quality while, on the other, the physiological decline in AMH and AFC levels continues, thus hampering the possibility to properly explore the real effects of reduced ovarian reserve. Indeed, the two processes, i.e. the gradual loss of resting primordial follicles and the loss of oocyte quality, progress in parallel. In other words, the older the woman becomes, the higher is the risk of miscarriage, but one cannot distinguish between the effects of biological aging on oocyte quality and those mediated by a lower ovarian reserve.</p><p><strong>Study design size duration: </strong>The present retrospective monocentric cohort study was carried out at Fondazione IRCSS Ca Granda Ospedale Maggiore Policlinico, Milan. All women referred to the ART Unit between 2014 and 2021 and who underwent either conventional IVF (c-IVF), ICSI, or IUI were reviewed. Only women younger than 35 were eligible because, up to this age, the risk of miscarriage is steady and not strictly related to age.</p><p><strong>Participants/materials setting methods: </strong>Women younger than 35 who achieved a singleton clinical pregnancy with c-IVF, ICSI, or IUI were selected. Women with patent causes of recurrent miscarriage were excluded, as well as those undergoing pregnancy termination for fetal or medical causes. Women who did and did not have a pregnancy loss before 20 weeks' gestation were compared. Detailed information was obtained from charts of the consulting patients. ART procedures were performed according to the standardized policy of our Unit. All women underwent serum AMH measurement and a transvaginal assessment of AFC prior to initiation of treatment. AMH levels were measured by a commercially available ELISA assay. To assess AFC, all identifiable antral follicles 2-10 mm in diameter at ultrasound were recorded. The primary outcome was the risk of miscarriage for women with serum AMH levels below 5 pmol/l.</p><p><strong>Main results and the role of chance: </strong>There were 538 women were included, of whom 92 (17%) had a miscarriage. The areas under the ROC curves for prediction of miscarriage based on AMH levels and AF","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 3","pages":"hoad026"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/c4/hoad026.PMC10243845.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9971625","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}

{"title":"Dynamic peripheral blood microRNA expression landscape during the peri-implantation stage in women with successful pregnancy achieved by single frozen-thawed blastocyst transfer.","authors":"Jie Dong, Lu Wang, Yanru Xing, Jun Qian, Xiao He, Jing Wu, Juan Zhou, Li Hai, Jun Wang, Hongya Yang, Jianlei Huang, Xingqing Gou, Ying Ju, Xiyi Wang, Yunan He, Danjie Su, Lingyin Kong, Bo Liang, Xiaohong Wang","doi":"10.1093/hropen/hoad034","DOIUrl":"https://doi.org/10.1093/hropen/hoad034","url":null,"abstract":"<p><strong>Study question: </strong>What are the dynamic expression features of plasma microRNAs (miRNAs) during the peri-implantation period in women with successful pregnancy via single frozen-thawed blastocyst transfer?</p><p><strong>Summary answer: </strong>There is a significant change in the plasma miRNA expression profile before and after blastocyst transfer, during the window of implantation.</p><p><strong>What is known already: </strong>The expression of miRNAs in peripheral blood has indicative functions during the peri-implantation period. Nevertheless, the dynamic expression profile of circulating miRNAs during the peri-implantation stage in women with a successful pregnancy has not been studied.</p><p><strong>Study design size duration: </strong>Seventy-six women treated for infertility with a single frozen-thawed blastocyst transfer in a natural cycle were included in this study. Among them, 57 women had implantation success and a live birth, while 19 patients experienced implantation failure. Peripheral blood samples were collected at five different time points throughout the peri-implantation period, including D0 (ovulation day), D3, D5, D7, and D9 in this cycle of embryo transfer. The plasma miRNAs in women with blastocyst transfer were isolated, sequenced, and analyzed.</p><p><strong>Participants/materials setting methods: </strong>Peripheral blood samples were collected in EDTA tubes and stored at -80°C until further use. miRNAs were isolated from blood, cDNA libraries were constructed, and the resulting sequences were mapped to the human genome. The plasma miRNAs were initially analyzed in a screening cohort (n = 34) with successful pregnancy. Trajectory analysis, including a global test and pairwise comparisons, was performed to detect dynamic differentially expressed (DE) miRNAs. Fuzzy c-means clustering was conducted for all dynamic DE miRNAs. The correlation between DE miRNAs and clinical characteristics of patients was investigated using a linear mixed model. Target genes of the miRNAs were predicted, and functional annotation analysis was performed. The expression of DE miRNAs was also identified in a validation set consisting of women with successful (n = 23) and unsuccessful (n = 19) pregnancies.</p><p><strong>Main results and the role of chance: </strong>Following small RNA sequencing, a total of 2656 miRNAs were determined as valid read values. After trajectory analysis, 26 DE miRNAs (false discovery rate < 0.05) were identified by the global test, while pairwise comparisons in addition identified 20 DE miRNAs. A total of seven distinct clusters representing different temporal patterns of miRNA expression were discovered. Nineteen DE miRNAs were further identified to be associated with at least one clinical trait. Endometrium thickness and progesterone level showed a correlation with multiple DE miRNAs (including two of the same miRNAs, hsa-miR-1-3p and hsa-miR-6741-3p). Moreover, the 19 DE miRNAs were predicted to h","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 4","pages":"hoad034"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10493182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10295004","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}

{"title":"Financial costs of assisted reproductive technology for patients in low- and middle-income countries: a systematic review.","authors":"Purity Njagi, Wim Groot, Jelena Arsenijevic, Silke Dyer, Gitau Mburu, James Kiarie","doi":"10.1093/hropen/hoad007","DOIUrl":"https://doi.org/10.1093/hropen/hoad007","url":null,"abstract":"<p><strong>Study question: </strong>What are the direct costs of assisted reproductive technology (ART), and how affordable is it for patients in low- and middle-income countries (LMICS)?</p><p><strong>Summary answer: </strong>Direct medical costs paid by patients for infertility treatment are significantly higher than annual average income and GDP per capita, pointing to unaffordability and the risk of catastrophic expenditure for those in need.</p><p><strong>What is known already: </strong>Infertility treatment is largely inaccessible to many people in LMICs. Our analysis shows that no study in LMICs has previously compared ART medical costs across countries in international dollar terms (US$PPP) or correlated the medical costs with economic indicators, financing mechanisms, and policy regulations. Previous systematic reviews on costs have been limited to high-income countries while those in LMICs have only focussed on descriptive analyses of these costs.</p><p><strong>Study design size duration: </strong>Guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA), we searched PubMed, Web of Science, Cumulative Index of Nursing and Allied Health Literature, EconLit, PsycINFO, Latin American & Caribbean Health Sciences Literature, and grey literature for studies published in all languages from LMICs between 2001 and 2020.</p><p><strong>Participants/materials setting methods: </strong>The primary outcome of interest was direct medical costs paid by patients for one ART cycle. To gauge ART affordability, direct medical costs were correlated with the GDP per capita or average income of respective countries. ART regulations and public financing mechanisms were analyzed to provide information on the healthcare contexts in the countries. The quality of included studies was assessed using the Integrated Quality Criteria for Review of Multiple Study designs.</p><p><strong>Main results and the role of chance: </strong>Of the 4062 studies identified, 26 studies from 17 countries met the inclusion criteria. There were wide disparities across countries in the direct medical costs paid by patients for ART ranging from USD2109 to USD18 592. Relative ART costs and GDP per capita showed a negative correlation, with the costs in Africa and South-East Asia being on average up to 200% of the GDP per capita. Lower relative costs in the Americas and the Eastern Mediterranean regions were associated with the presence of ART regulations and government financing mechanisms.</p><p><strong>Limitations reasons for caution: </strong>Several included studies were not primarily designed to examine the cost of ART and thus lacked comprehensive details of the costs. However, a sensitivity analysis showed that exclusion of studies with below the minimum quality score did not change the conclusions on the outcome of interest.</p><p><strong>Wider implications of the findings: </strong>Governments in LMICs should devise appropriate ART regulatory poli","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 2","pages":"hoad007"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10029849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9409161","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}

{"title":"Biallelic mutations in RNA-binding protein ADAD2 cause spermiogenic failure and non-obstructive azoospermia in humans.","authors":"Baolu Shi, Wasim Shah, Li Liu, Chenjia Gong, Jianteng Zhou, Tanveer Abbas, Hui Ma, Huan Zhang, Menglei Yang, Yuanwei Zhang, Nadeem Ullah, Zubair Mahammad, Mazhar Khan, Ghulam Murtaza, Asim Ali, Ranjha Khan, Jiahao Sha, Yan Yuan, Qinghua Shi","doi":"10.1093/hropen/hoad022","DOIUrl":"https://doi.org/10.1093/hropen/hoad022","url":null,"abstract":"<p><strong>Study question: </strong>What are some pathogenic mutations for non-obstructive azoospermia (NOA) and their effects on spermatogenesis?</p><p><strong>Summary answer: </strong>Biallelic missense and frameshift mutations in <i>ADAD2</i> disrupt the differentiation of round spermatids to spermatozoa causing azoospermia in humans and mice.</p><p><strong>What is known already: </strong>NOA is the most severe cause of male infertility characterized by an absence of sperm in the ejaculate due to impairment of spermatogenesis. In mice, the lack of the RNA-binding protein ADAD2 leads to a complete absence of sperm in epididymides due to failure of spemiogenesis, but the spermatogenic effects of <i>ADAD2</i> mutations in human NOA-associated infertility require functional verification.</p><p><strong>Study design size duration: </strong>Six infertile male patients from three unrelated families were diagnosed with NOA at local hospitals in Pakistan based on infertility history, sex hormone levels, two semen analyses and scrotal ultrasound. Testicular biopsies were performed in two of the six patients. <i>Adad2</i> mutant mice (<i>Adad2<sup>Mut/Mut</sup></i>) carrying mutations similar to those found in NOA patients were generated using the CRISPR/Cas9 genome editing tool. Reproductive phenotypes of <i>Adad2<sup>Mut/Mut</sup></i> mice were verified at 2 months of age. Round spermatids from the littermates of wild-type (WT) and <i>Adad2<sup>Mut/Mut</sup></i> mice were randomly selected and injected into stimulated WT oocytes. This round spermatid injection (ROSI) procedure was conducted with three biological replicates and >400 ROSI-derived zygotes were evaluated. The fertility of the ROSI-derived progeny was evaluated for three months in four <i>Adad2<sup>WT/Mut</sup></i> male mice and six <i>Adad2<sup>WT/Mut</sup></i> female mice. A total of 120 <i>Adad2<sup>Mut/Mut</sup></i>, <i>Adad2<sup>WT/Mut</sup></i>, and WT mice were used in this study. The entire study was conducted over 3 years.</p><p><strong>Participants/materials setting methods: </strong>Whole-exome sequencing was performed to detect potentially pathogenic mutations in the six NOA-affected patients. The pathogenicity of the identified <i>ADAD2</i> mutations was assessed and validated in human testicular tissues and in mouse models recapitulating the mutations in the NOA patients using quantitative PCR, western blotting, hematoxylin-eosin staining, Periodic acid-Schiff staining, and immunofluorescence. Round spermatids of WT and <i>Adad2<sup>Mut/Mut</sup></i> mice were collected by fluorescence-activated cell sorting and injected into stimulated WT oocytes. The development of ROSI-derived offspring was evaluated in the embryonic and postnatal stages.</p><p><strong>Main results and the role of chance: </strong>Three recessive mutations were identified in <i>ADAD2</i> (MT1: c.G829T, p.G277C; MT2: c.G1192A, p.D398N; MT3: c.917_918del, p.Q306Rfs*43) in patients from three unrelated Pakistan","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 3","pages":"hoad022"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9657337","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}

{"title":"Extracellular vesicles from human Fallopian tubal fluid benefit embryo development <i>in vitro</i>.","authors":"Yuehan Li,&nbsp;Chang Liu,&nbsp;Na Guo,&nbsp;Lei Cai,&nbsp;Meng Wang,&nbsp;Lixia Zhu,&nbsp;Fei Li,&nbsp;Lei Jin,&nbsp;Cong Sui","doi":"10.1093/hropen/hoad006","DOIUrl":"https://doi.org/10.1093/hropen/hoad006","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Do extracellular vesicles (EVs) from human Fallopian tubes exert an influence on early embryo development &lt;i&gt;in vitro&lt;/i&gt;?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Human Fallopian tube EVs carrying miRNAs increase murine embryo viability &lt;i&gt;in vitro&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Oviductal EVs (oEVs) are recently identified key players in embryo-oviduct interactions that contribute to successful pregnancy &lt;i&gt;in vivo&lt;/i&gt;. Their absence in current &lt;i&gt;in vitro&lt;/i&gt; systems may partly explain the suboptimal embryo development observed; therefore, further knowledge is needed about their impact on early embryos.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;The oEVs were isolated from the luminal fluid of human Fallopian tubes using ultracentrifugation. We cocultured oEVs with murine two-cell embryos until the blastocyst stage. The study was conducted between August 2021 and July 2022.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;A total of 23 premenopausal women were recruited for Fallopian-tubes collection, and the oEVs were isolated. The micro RNA (miRNA) contents were detected using high-throughput sequencing and their target genes and effects were analyzed. After &lt;i&gt;in vitro&lt;/i&gt; culture with or without oEVs, the blastocyst and hatching rates were recorded. Furthermore, for the blastocysts formed, we assessed the total cell number, inner cell mass proportion, reactive oxygen species (ROS) level, number of apoptotic cells, and mRNA expression levels of genes involved in development.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;EVs were successfully isolated from the human Fallopian tubal fluid and the concentrations were evaluated. A total of 79 known miRNAs were identified from eight samples that had been sequenced, all involved in various biological processes. The blastocyst rate, hatching rate, as well as total cell number of blastocysts were significantly increased in the oEVs-treated groups (&lt;i&gt;P&lt;/i&gt; &lt; 0.05 versus untreated), while the proportion of inner cell mass showed no significant difference between groups. ROS levels and apoptotic cell proportions were decreased in the oEVs-treated groups (&lt;i&gt;P&lt;/i&gt; &lt; 0.05 versus untreated). The genes, &lt;i&gt;Actr3&lt;/i&gt; (actin-related protein 3), &lt;i&gt;Eomes&lt;/i&gt; (eomesodermin), and &lt;i&gt;Wnt3a&lt;/i&gt; (Wnt family member 3A) were upregulated in blastocysts in the oEVs-treated group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Large scale data: &lt;/strong&gt;Data are available from Gene Expression Omnibus: Accession number: GSE225122.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;The Fallopian tubes in the current study were collected from patients with uterine fibroids (the reason they underwent hysterectomy), and this pathological condition may affect the characteristics of EVs in luminal fluid. Also, owing to restrictions for ethical reasons, an &lt;i&gt;in vitro&lt;/i&gt; co-culture system using murine embryos was used instead of human embryos, and the findings may","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 2","pages":"hoad006"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/78/11/hoad006.PMC9991590.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9085878","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}

{"title":"Fertility preservation in women with benign gynaecological conditions.","authors":"Pietro Santulli,&nbsp;Christophe Blockeel,&nbsp;Mathilde Bourdon,&nbsp;Giovanni Coticchio,&nbsp;Alison Campbell,&nbsp;Michel De Vos,&nbsp;Kirsten Tryde Macklon,&nbsp;Anja Pinborg,&nbsp;Juan A Garcia-Velasco","doi":"10.1093/hropen/hoad012","DOIUrl":"https://doi.org/10.1093/hropen/hoad012","url":null,"abstract":"<p><p>Although a wealth of data has been published regarding fertility preservation (FP) in women with malignant diseases who receive gonadotoxic treatment, the role of FP in non-malignant conditions has been studied to a much lesser extent. These include benign haematological, autoimmune, and genetic disorders, as well as a multitude of benign gynaecological conditions (BGCs) that may compromise ovarian reserve and/or reproductive potential due to pathogenic mechanisms or as a result of medical or surgical treatments. Alongside accumulating data that document the reproductive potential of cryopreserved oocytes and ovarian tissue, there is potential interest in FP for women with BGCs at risk of infertility; however, there are currently insufficient data about FP in women with BGCs to develop guidelines for clinical practice. The purpose of this article is to appraise the available evidence regarding FP for BGC and discuss potential strategies for FP based on estimated ovarian impairment and on short-term and long-term reproductive goals of patients. Cost-effectiveness considerations and patients' perspectives will also be discussed.</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 2","pages":"hoad012"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a4/f0/hoad012.PMC10130191.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9392982","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}

{"title":"The thicker the endometrium, the better the neonatal outcomes?","authors":"Jing Wu,&nbsp;Jianlei Huang,&nbsp;Jie Dong,&nbsp;Xifeng Xiao,&nbsp;Mao Li,&nbsp;Xiaohong Wang","doi":"10.1093/hropen/hoad028","DOIUrl":"https://doi.org/10.1093/hropen/hoad028","url":null,"abstract":"<p><strong>Study question: </strong>Is endometrial thickness (EMT) on the hCG trigger day related to the neonatal outcome of a single birth after fresh embryo transfer (ET)?</p><p><strong>Summary answer: </strong>An EMT ≤7.8 mm was an independent predictor for greater odds of preterm delivery (PTD) of singletons born after fresh ET.</p><p><strong>What is known already: </strong>There may be a positive association between live birth rates and EMT after fresh ET. It is still unknown whether a similar association is seen for the neonatal outcomes of singletons in fresh cycles.</p><p><strong>Study design size duration: </strong>This retrospective study involved singleton live births in women undergoing autologous IVF cycles during the period from 1 October 2016 to 31 July 2021.</p><p><strong>Participants/materials setting methods: </strong>A total of 2010 women who fulfilled the inclusion criteria were included. A multivariable regression analysis was performed to detect the relationship between EMT and neonatal outcomes after controlling for potential confounders. Smooth curve fitting and threshold effect analysis were used to evaluate the accurate cutoff value of EMT.</p><p><strong>Main results and the role of chance: </strong>The results of the multivariate regression analyses showed that the odds of PTD were reduced by 45% with an EMT of 9.00-9.90 mm (adjusted odds ratio (OR): 0.55, 95% CI: 0.13 to 0.98; <i>P</i> = 0.0451), reduced by 58% with an EMT of 10.00-10.90 mm (adjusted OR: 0.42, 95% CI: 0.06 to 0.87; <i>P</i> = 0.0211) and reduced by 75% with an EMT >11 mm (adjusted OR: 0.25, 95% CI: 0.04 to 0.66; <i>P</i> = 0.0034), compared to the group with an EMT of 6.00-8.90 mm. It could also be seen from the adjusted smooth curves that the odds of PTD decreased and gestational age (GA) increased with increasing EMT. Combined with the analysis of threshold effects, the results indicated that when the EMT was ≤7.6 mm, the incidence of PTD decreased as the EMT gradually increased (adjusted OR: 0.47, 95% CI: 0.03 to 0.99; <i>P</i> = 0.0107), and when the EMT was ≤7.8 mm, the GA increased (adjusted β: 1.94, 95% CI: 1.26 to 2.63; <i>P</i> < 0.0001) as the EMT gradually increased.</p><p><strong>Limitations reasons for caution: </strong>The main limitation of our study is its retrospective design. Although we found a significant decrease in PTD as the EMT increased, in terms of GA, the magnitude of the differences was modest, which may limit the clinical relevance of the findings.</p><p><strong>Wider implications of the findings: </strong>Our data provide new insight into the relationship between EMT and neonatal outcomes by indicating that a thin endometrium of ≤7.8 mm is associated with an increased odds of PTD of singletons after fresh ET.</p><p><strong>Study funding/competing interests: </strong>This study was supported by the National Natural Science Foundation of China (grant no. 82071717). There are no conflicts of interest.</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 3","pages":"hoad028"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10363027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9867592","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}