Human reproduction open最新文献

{"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,&nbsp;Lu Wang,&nbsp;Yanru Xing,&nbsp;Jun Qian,&nbsp;Xiao He,&nbsp;Jing Wu,&nbsp;Juan Zhou,&nbsp;Li Hai,&nbsp;Jun Wang,&nbsp;Hongya Yang,&nbsp;Jianlei Huang,&nbsp;Xingqing Gou,&nbsp;Ying Ju,&nbsp;Xiyi Wang,&nbsp;Yunan He,&nbsp;Danjie Su,&nbsp;Lingyin Kong,&nbsp;Bo Liang,&nbsp;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":null,"pages":null},"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,&nbsp;Wim Groot,&nbsp;Jelena Arsenijevic,&nbsp;Silke Dyer,&nbsp;Gitau Mburu,&nbsp;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":null,"pages":null},"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":"Low ovarian reserve and risk of miscarriage in pregnancies derived from assisted reproductive technology.","authors":"Alessandra Chinè,&nbsp;Marco Reschini,&nbsp;Gianfranco Fornelli,&nbsp;Ludovica Basili,&nbsp;Andrea Busnelli,&nbsp;Paola Viganò,&nbsp;Ludovico Muzii,&nbsp;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":null,"pages":null},"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":"Biallelic mutations in RNA-binding protein ADAD2 cause spermiogenic failure and non-obstructive azoospermia in humans.","authors":"Baolu Shi,&nbsp;Wasim Shah,&nbsp;Li Liu,&nbsp;Chenjia Gong,&nbsp;Jianteng Zhou,&nbsp;Tanveer Abbas,&nbsp;Hui Ma,&nbsp;Huan Zhang,&nbsp;Menglei Yang,&nbsp;Yuanwei Zhang,&nbsp;Nadeem Ullah,&nbsp;Zubair Mahammad,&nbsp;Mazhar Khan,&nbsp;Ghulam Murtaza,&nbsp;Asim Ali,&nbsp;Ranjha Khan,&nbsp;Jiahao Sha,&nbsp;Yan Yuan,&nbsp;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^Mut/Mut</i>) carrying mutations similar to those found in NOA patients were generated using the CRISPR/Cas9 genome editing tool. Reproductive phenotypes of <i>Adad2^Mut/Mut</i> mice were verified at 2 months of age. Round spermatids from the littermates of wild-type (WT) and <i>Adad2^Mut/Mut</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^WT/Mut</i> male mice and six <i>Adad2^WT/Mut</i> female mice. A total of 120 <i>Adad2^Mut/Mut</i>, <i>Adad2^WT/Mut</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^Mut/Mut</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":null,"pages":null},"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":"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":null,"pages":null},"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":null,"pages":null},"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}

{"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":"<p><strong>Study question: </strong>Do extracellular vesicles (EVs) from human Fallopian tubes exert an influence on early embryo development <i>in vitro</i>?</p><p><strong>Summary answer: </strong>Human Fallopian tube EVs carrying miRNAs increase murine embryo viability <i>in vitro</i>.</p><p><strong>What is known already: </strong>Oviductal EVs (oEVs) are recently identified key players in embryo-oviduct interactions that contribute to successful pregnancy <i>in vivo</i>. Their absence in current <i>in vitro</i> systems may partly explain the suboptimal embryo development observed; therefore, further knowledge is needed about their impact on early embryos.</p><p><strong>Study design size duration: </strong>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.</p><p><strong>Participants/materials setting methods: </strong>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 <i>in vitro</i> 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.</p><p><strong>Main results and the role of chance: </strong>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 (<i>P</i> < 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 (<i>P</i> < 0.05 versus untreated). The genes, <i>Actr3</i> (actin-related protein 3), <i>Eomes</i> (eomesodermin), and <i>Wnt3a</i> (Wnt family member 3A) were upregulated in blastocysts in the oEVs-treated group.</p><p><strong>Large scale data: </strong>Data are available from Gene Expression Omnibus: Accession number: GSE225122.</p><p><strong>Limitations reasons for caution: </strong>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 <i>in vitro</i> co-culture system using murine embryos was used instead of human embryos, and the findings may","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"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":"A blended preconception lifestyle programme for couples undergoing IVF: lessons learned from a multicentre randomised controlled trial","authors":"Tessy Boedt, Eline Dancet, Diane De Neubourg, Sofie Vereeck, Jan Seghers, Katleen Van der Gucht, Ben Van Calster, Carl Spiessens, Sharon Lie Fong, Christophe Matthys","doi":"10.1093/hropen/hoad036","DOIUrl":"https://doi.org/10.1093/hropen/hoad036","url":null,"abstract":"Abstract STUDY QUESTION What is the effect of a blended preconception lifestyle programme on reproductive and lifestyle outcomes of couples going through their first 12 months of IVF as compared to an attention control condition? SUMMARY ANSWER This randomized controlled trial (RCT) was stopped prematurely because of the coronavirus disease 2019 (Covid-19) pandemic but the available data did not suggest that a blended preconception lifestyle programme could meaningfully affect time to ongoing pregnancy or other reproductive and lifestyle outcomes. WHAT IS KNOWN ALREADY Increasing evidence shows associations between a healthy lifestyle and IVF success rates. Lifestyle programmes provided through a mobile phone application have yet to be evaluated by RCTs in couples undergoing IVF. STUDY DESIGN, SIZE, DURATION A multicentre RCT (1:1) was carried out. The RCT started in January 2019 and was prematurely stopped because of the Covid-19 pandemic, leading to a reduced sample size (211 couples initiating IVF) and change in primary outcome (cumulative ongoing pregnancy to time to ongoing pregnancy). PARTICIPANTS/MATERIALS, SETTING, METHODS Heterosexual couples initiating IVF in five fertility clinics were randomized between an attention control arm and an intervention arm for 12 months. The attention control arm received treatment information by mobile phone in addition to standard care. The intervention arm received the blended preconception lifestyle (PreLiFe)-programme in addition to standard care. The PreLiFe-programme included a mobile application, offering tailored advice and skills training on diet, physical activity and mindfulness, in combination with motivational interviewing over the telephone. The primary outcome was ‘time to ongoing pregnancy’. Secondary reproductive outcomes included the Core Outcome Measures for Infertility Trials and IVF discontinuation. Changes in the following secondary lifestyle outcomes over 3 and 6 months were studied in both partners: diet quality, fruit intake, vegetable intake, total moderate to vigorous physical activity, sedentary behaviour, emotional distress, quality of life, BMI, and waist circumference. Finally, in the intervention arm, acceptability of the programme was evaluated and actual use of the mobile application part of the programme was tracked. Analysis was according to intention to treat. MAIN RESULTS AND THE ROLE OF CHANCE A total of 211 couples were randomized (105 control arm, 106 intervention arm). The hazard ratio of the intervention for time to ongoing pregnancy was 0.94 (95% CI 0.63 to 1.4). Little to no effect on other reproductive or lifestyle outcomes was identified. Although acceptability of the programme was good (6/10), considerable proportions of men (38%) and 9% of women did not actively use all the modules of the mobile application (diet, physical activity, or mindfulness). LIMITATIONS, REASONS FOR CAUTION The findings of this RCT should be considered exploratory, as the Covid-19 p","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135839299","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}

{"title":"Caution is needed when communicating analyses based on an apple to orange comparison.","authors":"Birgit Alsbjerg,&nbsp;Peter Humaidan","doi":"10.1093/hropen/hoad016","DOIUrl":"https://doi.org/10.1093/hropen/hoad016","url":null,"abstract":"It was with great interest that we read ‘The effect of frozen embryo transfer regimen on the association between serum progesterone and live birth: a multi-centre prospective cohort study (ProFET)’ by Melo et al. (2022). From their data, the authors concluded that overall serum progesterone levels (P4) <7.8 ng/ml are associated with reduced odds of live birth in frozen embryo transfer (FET). Interestingly, the authors previously published a meta-analysis (Melo et al., 2021) based on several cohort studies of HRT-FET cycles using vaginal progesterone for luteal phase support and reporting a higher P4 cut-off <10 ng/ml for the reproductive outcome. Thus, in that analysis, higher serum P4 levels were associated with increased ongoing pregnancy or live birth rates (LBRs). An important question to ask in relation to the newest publication by Melo et al. (2022) would be: is this suggested new cut-off of serum P4 of 7.8 ng/ml more accurate than 10 ng/ml, and is this cut-off applicable to all FET protocols? Reading the publication carefully reveals that the present study was powered to 900 FET cycles; however, only a total of 398 cycles were included in the final analysis. Furthermore, the cohort of FET protocols was very heterogeneous, including HRT-FET, true natural cycle (t-NC), and modified natural cycle (m-NC), in which ovulation is induced with a trigger bolus of hCG. In this context, we have to bear in mind that the FET protocols mentioned are very different in terms of basic endocrinology, first and foremost when considering serum P4. Thus, the natural cycle has a circadian luteal phase progesterone pattern due to the endogenous production of progesterone from the corpus luteum and importantly, in the new Melo et al. (2022) study, a huge variation in the type of ‘NC FET’ protocols was allowed. Thus, different hCG-trigger doses (5000 vs 6500 IE) were used which will definitely have an impact on circulating luteal P4; moreover, in some cycles, no hCG trigger (t-NC) was used and some cycles had vaginal progesterone support whereas others did not. Finally, different dosing and types of vaginal micronized progesterone were used (CyclogestR , UtrogestanR ). Altogether, within a cohort of 45 ‘NC FET’, there might have been as many as nine different combinations; importantly, these differences will invariably result in significant differences in luteal P4 profiles. Furthermore, in the cohort of HRT-FET cycles, we also learn that important differences were allowed in terms of different vaginal micronized progesterone products, differences in dosing regimen and differences in no use or use of a combination of subcutaneous (s.c.) progesterone (LubionR ), 25 mg once daily or twice daily. For monitoring, the authors state that blood sampling was performed 4–6 h after the last administration of exogenous progesterone. Again, the reader might ask, what does ‘approximately’ mean? One hour, two hours—or more? Timing of luteal phase blood sampling is crucial, espe","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"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/2c/9c/hoad016.PMC10234700.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9570237","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":"Reply to: Anti-anonymity should not be taken more seriously than other positions on gamete donation.","authors":"Daniel Groll","doi":"10.1093/hropen/hoac060","DOIUrl":"https://doi.org/10.1093/hropen/hoac060","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"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/84/b3/hoac060.PMC9838311.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9100288","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}