Human reproduction最新文献

{"title":"Upregulated let-7 expression in the follicular fluid of patients with endometriomas leads to dysfunction of granulosa cells through targeting of IGF1R","authors":"Libing Shi, Hanqi Ying, Yongdong Dai, Yan Rong, Jianmin Chen, Feng Zhou, Shasha Wang, Shiqian Xu, Xiaomei Tong, Songying Zhang","doi":"10.1093/humrep/deae247","DOIUrl":"https://doi.org/10.1093/humrep/deae247","url":null,"abstract":"STUDY QUESTION What molecular mechanisms underlie the decline in ovarian reserve as the number and quality of oocytes decrease in patients with ovarian endometriomas (OEM)? SUMMARY ANSWER Elevated expression of the let-7 micro(mi)RNAs in the follicular microenvironment of OEM-affected ovaries targets the expression of type 1 insulin-like growth factor receptor (IGF1R) in granulosa cell (GC) and disrupts their proliferation, steroid hormone secretion levels, adenosine triphosphate (ATP) energy metabolism, and reactive oxygen species (ROS) oxidative stress levels. WHAT IS KNOWN ALREADY Patients with OEM exhibit diminished ovarian reserve, characterized by reduced oocyte quantity and quality. Fibrotic changes in the ovarian tissue surrounding the OEM create a disruptive microenvironment for follicular growth and development. STUDY DESIGN, SIZE, DURATION This is a cross-sectional study aimed to elucidate the molecular mechanisms underlying the impact of OEM on follicular development. Initially, miRNA expression profiles in follicular fluid (FF) samples were sequenced from patients with infertility related to OEM (N = 3) and male factor (MF) infertility (N = 3), with the latter serving as the control group. Differentially expressed miRNAs were validated in additional samples from each group (N = 55 in OEM group and N = 45 in MF group) to confirm candidate miRNAs. The study also investigated indicators associated with GCs dysfunction in vitro on rat GCs. Subsequently, rat models of OEM were established through endometrial allogeneic transplantation, and fertility experiments were conducted to assess the let-7/IGF1R axis response to OEM in vivo. Patient samples were collected between May 2018 and April 2019, and the mechanistic study was conducted over the subsequent three years. PARTICIPANTS/MATERIALS, SETTING, METHODS FF and GC samples were obtained from infertile patients undergoing IVF treatment for OEM and MF related infertility. miRNA expression profiles in FF samples were analyzed using second-generation high-throughput sequencing technology, and candidate miRNAs were validated through quantitative PCR (qPCR). In the in vitro experiments conducted with rat GCs, cell proliferation was assessed using the CCK-8 assay, while steroid hormone concentrations were measured using chemiluminescence. ATP content was determined with an ATP assay kit, and levels of ROS were quantified using flow cytometry. A dual luciferase reporter gene assay was employed to identify the target gene of let-7 based on the construction of a IGF1R reporter gene plasmid using 293T cells. Western blotting was utilized to evaluate the expression of IGF1R in GCs, as well as its downstream proteins, and changes in signaling pathways following let-7 agomir/antagomir transfection and/or Igf1r silencing. In the in vivo OEM rat models, alterations in ovarian structure and cyst morphology were observed using hematoxylin and eosin staining. The expressions of let-7 and Igf1r in GCs were e","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reproductive factors and biological aging: the association with all-cause and cause-specific premature mortality","authors":"Gaojie Fan, Qing Liu, Jianing Bi, Qing Fang, Fei Luo, Xiaofeng Huang, Heng Li, Wenwen Guo, Binghai Liu, Lianyan Yan, Youjie Wang, Lulu Song","doi":"10.1093/humrep/deae250","DOIUrl":"https://doi.org/10.1093/humrep/deae250","url":null,"abstract":"STUDY QUESTION Are reproductive factors associated with biological aging, and does biological aging mediate the associations of reproductive factors with premature mortality? SUMMARY ANSWER Multiple reproductive factors are related to phenotypic age acceleration (PhenoAge-Accel), while adherence to a healthy lifestyle mitigates these harmful effects; PhenoAge-Accel mediated the associations between reproductive factors and premature mortality. WHAT IS KNOWN ALREADY Accelerated aging is a key contributor to mortality, but knowledge about the effect of reproductive factors on aging is limited. STUDY DESIGN, SIZE, DURATION This prospective cohort study included 223 729 women aged 40–69 years from the UK biobank in 2006–2010 and followed up until 12 November 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS Reproductive factors were collected through a touchscreen questionnaire. Biological aging was assessed through PhenoAge-Accel. Multiple linear regression models were used to examine the relationships of reproductive factors with PhenoAge-Accel and estimate the modified effect of a healthy lifestyle. Furthermore, we applied mediation analysis to explore the mediating role of PhenoAge-Accel in the associations between reproductive factors and premature mortality. MAIN RESULTS AND THE ROLE OF CHANCE Early menarche (<12 years vs 13 years, β: 0.37, 95% CI: 0.30, 0.44), late menarche (≥15 years vs 13 years, β: 0.18, 95% CI: 0.11, 0.25), early menopause (<45 years vs 50–51 years, β: 0.62, 95% CI: 0.51, 0.72), short reproductive lifespan (<30 years vs 35–39 years, β: 0.81, 95% CI: 0.70, 0.92), nulliparity (vs two live births, β: 0.36, 95% CI: 0.30, 0.43), high parity (≥4 vs 2 live births, β: 0.49, 95% CI: 0.40, 0.59), early age at first live birth (<20 years vs 25–29 years, β: 0.66, 95% CI: 0.56, 0.75), and stillbirth (β: 0.51, 95% CI: 0.36, 0.65) were associated with increased PhenoAge-Accel. Furthermore, PhenoAge-Accel mediated 6.0%–29.7% of the associations between reproductive factors and premature mortality. Women with an unfavorable lifestyle and reproductive risk factors had the highest PhenoAge-Accel compared to those with a favorable lifestyle and without reproductive risk factors. LIMITATIONS, REASONS FOR CAUTION The participants in the UK Biobank were predominantly of White ethnicity; thus, caution is warranted when generalizing these findings to other ethnic groups. WIDER IMPLICATIONS OF THE FINDINGS Our findings reveal the harmful effects of multiple reproductive factors on biological aging and the mediating role of biological aging in the associations between reproductive factors and premature mortality. They highlight the significance of adhering to a healthy lifestyle to slow biological aging as a potential way to reduce premature mortality among women with reproductive risk factors. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the National Natural Science Foundation of China (82003479, 82073660, 72","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of state-of-the-art IVF care as a marker of societal development","authors":"Alexander M Quaas, Eli Y Adashi, Richard J Paulson","doi":"10.1093/humrep/deae238","DOIUrl":"https://doi.org/10.1093/humrep/deae238","url":null,"abstract":"Access to state-of-the-art ART can be viewed as a marker of societal development. The recent Alabama Supreme Court ruling represents a major local setback in the access to state-of-the-art ART. If this isolated local incident becomes a national trend, the USA will lose ground in this emerging area of healthcare, and its citizens will be left with substandard treatment options for the redress of infertility.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Embryo multinucleation: detection, possible origins, and implications for treatment.","authors":"Giovanni Coticchio, Cristina Lagalla, Marilena Taggi, Danilo Cimadomo, Laura Rienzi","doi":"10.1093/humrep/deae186","DOIUrl":"10.1093/humrep/deae186","url":null,"abstract":"<p><p>Cell cycle regulation is crucial to assure expansion of a cell population, while preserving genome integrity. This notion is especially relevant to fertilization and early embryo development, a time when the cell cycle transforms from meiotic into mitotic cycles. Zygote-to-embryo transition is acutely error-prone, causing major developmental perturbations, including cleavage delays, tri- and multi-chotomous cleavages, and cell fragmentation. Another such alteration is bi- and multinucleation, consisting of the simultaneous formation of two or more nuclei at interphase. Indeed, multinucleation affects a large proportion of early human embryos, typically at the two-cell stage. Mechanistically, several factors, including spindle dysfunction, failed cleavage, and cell fusion, may generate this cell anomaly. In assisted reproduction treatment, multinucleation is associated with reduced developmental rates and lower implantation rates in Days 2-3 embryo transfers. However, many multinucleated embryos can develop to the blastocyst stage. In blastocyst transfers, the current evidence does not suggest a major impact of a previous history of multinucleation on the odds of euploidy or successful treatment outcomes. Human embryo multinucleation remains a not-fully-understood but developmentally relevant and intriguing phenomenon which requires further research of its generative mechanisms and clinical implications.</p>","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Müllerian hormone signaling in the ovary involves stromal fibroblasts: a study in humans and mice provides novel insights into the role of ovarian stroma.","authors":"Itay Spector, Sanaz Derech-Haim, Ilana Boustanai, Myriam Safrai, Dror Meirow","doi":"10.1093/humrep/deae221","DOIUrl":"10.1093/humrep/deae221","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;What is the involvement of ovarian stroma in the anti-Müllerian hormone (AMH) signaling pathway and which stromal cells are involved?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Mouse and human ovaries show high expression of AMH receptor II (AMHR2) in the stromal fibroblasts surrounding the follicles and activation of the post-AMHR2 pathway by recombinant AMH was evidenced by increased phosphorylation of SMAD1,5 and 9, increased expression AMHR2 and upregulation of αSMA, suggesting fibroblast activation to initiate myofibroblast differentiation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;AMH secreted by small growing follicles, regulates ovarian activity. It suppresses initial primordial follicle (PMF) recruitment and FSH-dependent growth. AMH signal transduction is mediated by AMHR2, activating intracellular SMAD proteins and other signaling cascades to induce target-gene expression. Although AMHR2 expression has been reported within the follicle unit, there is evidence suggesting it may be identified in the stroma as well.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;Fresh murine ovaries were extracted from BALB/c mice (6 weeks old; n = 12 and 21 days old; n = 56). Frozen-thawed ovarian fragments were obtained from 10 women, aged 18-35, who had undergone ovarian tissue cryopreservation and donated frozen ovarian tissue for research.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;Murine (6 weeks old) and human donor ovaries were immunostained for AMHR2 and Collagen 1α/αSMA/VCAM1, with additional vimentin staining in mice. Murine (21 days old) and human donor ovaries were used for fibroblast isolation and subsequent 7-day cultures. Prior to assessing AMH effects on isolated fibroblast culture, purity validation tests were implemented to ensure the absence of epithelial, immune, endothel, granulosa, and theca ovarian cell populations. The fibroblast culture's homogeneity was validated by RT-qPCR and western-blot assays, confirming negativity for E-cadherin, CD31, aromatase, CYP17A1, and positivity for αSMA and vimentin. Fibroblasts were then subjected to rAMH treatment in vitro (200 ng/ml) for 0-72 h, with an additional time point of 96 h for human samples, followed by RT-qPCR, western blot, and immunocytochemistry (ICC) for AMHR2 expression. AMHR2 post-receptor signaling was examined by pSMAD1,5,9 levels via western blot. Activated fibroblast marker, αSMA, was assessed via western blot and ICC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Immunostaining of mouse and human ovarian tissue showed that stromal cells around follicles at all developmental stages exhibit high AMHR2 expression, while granulosa cells of growing follicles show considerably lower levels. The majority of these AMHR2-positive stromal cells were identified as fibroblasts (Collagen1α in mice and human; vimentin in mice). RT-qPCR, western blot, and immunostaining were performed on cultured mouse and huma","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term culture of human Sertoli cells from adult Klinefelter patients as a first step to develop new tools for unravelling the testicular physiopathology.","authors":"Maria Grazia Giudice, Marc Kanbar, Jonathan Poels, Armelle Duquenne, Christine Wyns","doi":"10.1093/humrep/deae201","DOIUrl":"10.1093/humrep/deae201","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Are Sertoli cells (SCs) from adult Klinefelter men (47,XXY) capable of proliferating in vitro and maintaining their main phenotypical and functional characteristics as do SCs from adult 46,XY patients?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Isolated SCs from patients with Klinefelter syndrome (KS) can be expanded in vitro while maintaining their characteristics and a stable karyotype, similar to SCs from 46,XY patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;The mechanism leading to testicular tissue degeneration in KS is still unknown. A few recent studies highlight the main role played by SCs in the physiopathology of the disease, but new study models based on co-culture or testicular organoids are needed to further understand the SC's involvement in the mechanism of testicular degeneration and fibrosis, and to find therapeutical targets. KS SC expansion could be the first step towards developing such in vitro study models. SCs have been isolated from 46,XY men and expanded in vitro while maintaining the expression of phenotypical and functional markers, but propagation of SCs from KS men has not been achieved yet.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;Testicular tissue was obtained during a testicular sperm extraction procedure for infertility treatment between 2019 and 2021 from three azoospermic adult KS (47,XXY) men (33±3.6 years old) and from three control patients (46,XY) (36±2 years old) presenting with obstructive azoospermia. SCs isolated from frozen-thawed tissue of KS and 46,XY patients were cultured for 60 days and compared. All patients signed an informed consent according to the ethical board approval of the study protocol.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;Testicular biopsies obtained from KS (n = 3) and 46,XY (n = 3) adult patients were slow-frozen. After tissue thawing SCs were isolated using a double-step enzymatic digestion and differential plating, and cultured for 60 days in DMEM medium containing FBS. Analyses were performed at different culture times (passages 5 (P5) and 10 (P10)). Quantification of cells using immunofluorescence (IF) for cell type-specific markers (Sox9, GATA4, ACTA2, INSL3, MAGEA4), SCs characterization using both IF and quantitative real-time PCR for GDNF, BMP4, AR and CLDN11 and cells karyotyping were performed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;We demonstrate for the first time that a small population of human SCs isolated from frozen-thawed testis of adult KS patients can be expanded in vitro while retaining expression of characteristic markers of SCs and the 47,XXY karyotype, and exhibiting cell-specific functional proteins and gene expression (GDNF, BMP4, AR, and CLDN11) after 60 days in culture. At P10, 83.39 ± 4.2% of cultured cells from KS men and 85.34 ± 4.1% from 46,XY men expressed Sox9, and 88.8 ± 3.9% of KS cells versus 82.9 ± 3.2% of the control cells were positive for GATA4 ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of prior hysterosalpingo-foam sonography or hysterosalpingography on tubal patency: a secondary analysis of a randomized controlled trial.","authors":"Danah Kamphuis, Nienke van Welie, Joukje van Rijswijk, Marcel H A van Hooff, Jan-Peter de Bruin, Harold R Verhoeve, Femke Mol, Wilhelmina M van Baal, Cornelis B Lambalk, Jaap Stoker, Madelon van Wely, Patrick M M Bossuyt, Ben Willem J Mol, Kim Dreyer, Velja Mijatovic","doi":"10.1093/humrep/deae194","DOIUrl":"10.1093/humrep/deae194","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Does hysterosalpingo-foam sonography (HyFoSy) prior to hysterosalpingography (HSG) or HSG prior to HyFoSy affect visible tubal patency when compared HSG or HyFoSy alone?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Undergoing either HyFoSy or HSG prior to tubal patency testing by the alternative method does not demonstrate a significant difference in visible tubal patency when compared to HyFoSy or HSG alone.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;HyFoSy and HSG are two commonly used visual tubal patency tests with a high and comparable diagnostic accuracy for evaluating tubal patency. These tests may also improve fertility, although the underlying mechanism is still not fully understood. One of the hypotheses points to a dislodgment of mucus plugs that may have disrupted the patency of the Fallopian tubes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;This is a secondary analysis of the randomized controlled FOAM study, in which women underwent tubal patency testing by HyFoSy and HSG, randomized for order of the procedure. Participants either had HyFoSy first and then HSG, or vice versa. Here, we evaluate the relative effectiveness of tubal patency testing by HyFoSy or HSG prior to the alternative tubal patency testing method on visible tubal patency, compared to each method alone.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;Infertile women aged between 18 and 41 years scheduled for tubal patency testing were eligible for participating in the FOAM study. Women with anovulatory cycles, endometriosis, or with a partner with male infertility were excluded. To evaluate the effect HyFoSy on tubal patency, we relied on HSG results by comparing the proportion of women with bilateral tubal patency visible on HSG in those who underwent and who did not undergo HyFoSy prior to their HSG (HyFoSy prior to HSG versus HSG alone). To evaluate the effect of HSG on tubal patency, we relied on HyFoSy results by comparing the proportion of women with bilateral tubal patency visible on HyFoSy in those who underwent and who did not undergo HSG prior to their HyFoSy (HSG prior to HyFoSy versus HyFoSy alone).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Between May 2015 and January 2019, we randomized 1160 women (576 underwent HyFoSy first followed by HSG, and 584 underwent HSG first followed by HyFoSy). Among the women randomized to HyFoSy prior to HSG, bilateral tubal patency was visible on HSG in 467/537 (87%) women, compared with 472/544 (87%) women who underwent HSG alone (risk difference 0.2%; 95% CI: -3.8% to 4.2%). Among the women randomized to HSG prior to HyFoSy, bilateral tubal patency was visible on HyFoSy in 394/471 (84%) women, compared with 428/486 (88%) women who underwent HyFoSy alone (risk difference -4.4%; 95% CI: -8.8% to 0.0%).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations, reasons for caution: &lt;/strong&gt;The results of this secondary analysis should be interpreted as exploratory and cannot ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: Missing the target.","authors":"J Donnez, C Becker, H S Taylor, F Carmona Herrera, F Petraglia, S P Renner, M M Dolmans","doi":"10.1093/humrep/deae223","DOIUrl":"10.1093/humrep/deae223","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytoplasmic strings in human blastocysts: hypotheses of their role and implications for embryo selection.","authors":"Anabella Marconetto, Federica Innocenti, Gaia Saturno, Marilena Taggi, Viviana Chiappetta, Samuele Trio, Felicia De Falco, Laura Albricci, Giovanni Coticchio, Aisling Ahlström, Giulia Fiorentino, Roberta Maggiulli, Alberto Vaiarelli, Maurizio Zuccotti, Laura Rienzi, Danilo Cimadomo","doi":"10.1093/humrep/deae226","DOIUrl":"10.1093/humrep/deae226","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;What are the implications of the presence cytoplasmic strings (Cyt-S) and their quantity and dynamics for the pre-implantation development of human blastocysts?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Cyt-S are common in human embryos and are associated with faster blastocyst development, larger expansion, and better morphological quality.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Cyt-S are dynamic cellular projections connecting inner cell mass and trophectoderm (TE) cells, that can be observed during blastocyst expansion. Their prevalence in human embryos has been estimated to be between 44% and 93%. Data relevant to their clinical implications and role in development are lacking, limited, or controversial.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;Retrospective study conducted at a single IVF center between May 2013 and November 2014 and involving 124 pre-implantation genetic testing for aneuploidy cycles in a time-lapse incubator with ≥1 blastocyst biopsied and vitrified (N = 370 embryos assessed). These cycles resulted in 87 vitrified-warmed single-euploid blastocyst transfers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;ICSI, continuous blastocyst culture (Days 5-7), TE biopsy of fully expanded blastocysts without Day 3 zona pellucida drilling, qPCR to assess uniform full-chromosome aneuploidies, and vitrification were all performed. Only vitrified-warmed euploid single-embryo-transfers were conducted. Blastocyst morphological quality was defined according to Gardner's criteria. The AI-based software CHLOE™ (Fairtility) automatically registered timings from time of starting blastulation (tSB) to biopsy (t-biopsy, i.e. blastocyst full-expansion) as hours-post-insemination (hpi), embryo area (including zona pellucida in µm2), and spontaneous blastocyst collapses. One senior embryologist manually annotated Cyt-S presence, quantity, timings, and type (thick cell-to-cell connections and/or threads). All significant associations were confirmed through regression analyses. All couples', cycles', and embryos' main features were also tested for associations with Cyt-S presence, quantity, and dynamics.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;About 94.3% of the patients (N = 117/124) had ≥1 embryo with Cyt-S. Out of a total of 370 blastocysts, 55 degenerated between blastulation and full-expansion (N = 55/370, 14.9%). The degeneration rate among embryos with ≥1 Cyt-S was 10.8% (N = 33/304), significantly lower than that of embryos without Cyt-S (33.3%, N = 22/66, P &lt; 0.01). Of the remaining 315 viable blastocysts analyzed, 86% (N = 271/315; P &lt; 0.01) had ≥1 Cyt-S, on average 3.5 ± 2.1 per embryo ranging 1-13. The first Cyt-S per viable embryo appeared at 115.3 ± 12.5 hpi (85.7-157.7), corresponding to 10.5 ± 5.8 h (0.5-31) after tSB. Overall, we analyzed 937 Cyt-S showing a mean duration of 3.8 ± 2.7 h (0.3-20.9). Cyt-S were mostly threads (N = 508/937, 54.2%) o","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One fresh cleavage-stage single embryo transfer (SET) plus one frozen-thawed blastocyst-stage SET or one fresh cleavage-stage double embryo transfer? A retrospective matched cohort study.","authors":"Zheng Wang, Fang Liu, Kailun Hu, Tian Tian, Rui Yang, Yuanyuan Wang, Rong Li, Ben W Mol, Jie Qiao","doi":"10.1093/humrep/deae245","DOIUrl":"https://doi.org/10.1093/humrep/deae245","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Are there significant differences in fertility outcomes between transferring two cleavage-stage embryos in a single fresh cycle and transferring one cleavage-stage embryo in a fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;In women aged &lt;38 years with two embryos available, transferring one cleavage-stage embryo in a fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle increased live birth rates and decreased multiple live birth rates compared to transferring two cleavage-stage embryos in a single fresh cycle.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;The strategy of repeated single embryo transfer (SET) has emerged as a solution to address the reduced live birth rates associated with SET per cycle. There is substantial evidence indicating that the cumulative live birth rate after repeated SET is comparable to that of double embryo transfer (DET), while significantly reducing the incidence of multiple pregnancies. Evidence regarding the outcomes of transferring two cleavage-stage embryos in a single fresh cycle versus transferring one cleavage-stage embryo in one fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle is scarce.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;This study is a retrospective matched cohort study, where data were gathered from the clinical database of women who underwent IVF treatment at the Reproductive Center of Peking University Third Hospital between January 2011 and December 2019, with follow-up extending until December 2021.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;The study group included cycles with a fresh cleavage-stage SET and a subsequent frozen-thawed blastocyst-stage SET (2xSET, N = 976). Fresh cleavage-stage DET was the control group (DET, N = 976). Included cycles were divided into subgroups based on age (≥38 years vs &lt;38 years) and total number of utilizable (transferred or cryopreserved) embryos (=2 vs &gt;2).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;The duration of infertility, prevalence of unexplained infertility, and controlled ovarian stimulation regimes differed significantly between the two groups and were adjusted for in the further analysis. We observed a significant increase in clinical pregnancies (55.5% vs 42%, adjusted odds ratio (OR) 1.87 [1.55-2.26]) and live births (44.8% vs 34.5%, adjusted OR 1.63 [1.35-1.97]) in favor of the 2xSET group. The preterm birth rate was lower in the study group (adjusted OR 0.64 [0.42-0.96]). Neonatal birth weight of singletons was similar between the two groups (adjusted B 4.94 g [-84.5 to 94.4]). The beneficial effect on the live birth rate disappeared in cases where aged 38 years and older or when only two embryos were utilizable.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations, reasons for caution: &lt;/strong&gt;This study is limited by differences in baseline chara","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}