Human reproduction最新文献

{"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":"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}

{"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":"Road to in vitro maturation (IVM), from basic science to an informed clinical practice.","authors":"Sofia Makieva, Juan J Fraire-Zamora, Omar Farhan Ammar, George Liperis, Flor Sanchez, Christian C Kramme, Lan N Vuong, Robert B Gilchrist, Pietro Bortoletto, Claudia Massarotti","doi":"10.1093/humrep/deae182","DOIUrl":"10.1093/humrep/deae182","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":"141901577","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":"A multicentre, randomized, double-blind, placebo-controlled trial of topical oestradiol gel for endometrial regeneration after induced abortion.","authors":"C Y Li, L R Teng, X X Jiang, L Shan, L Q Wang, X J Dong, Q F Li, C C Ren, Y Lin, J Jiang, X Y Gu, W Huang, Q Li, P Peng, Y Che, X Y Liu","doi":"10.1093/humrep/deae227","DOIUrl":"10.1093/humrep/deae227","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Is topical oestradiol gel effective in promoting endometrial regeneration after a surgical abortion?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Topical oestradiol gel is effective in promoting endometrial regeneration after a surgical abortion with few side-effects.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Oestrogen is effective in promoting endometrial regeneration. Transdermal oestrogen has been widely used in clinical practice for endometrial regeneration after induced abortion, but high-level evidence is limited.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;We conducted a multicentre, superiority, randomized, double-blind, placebo-controlled trial. Between 9 March 2022 and 21 February 2023, 200 women were assigned in a 1:1 ratio to receive either oestradiol gel (treatment) and or oestradiol gel simulant (control) for 28 days. The participants were scheduled to have their endometrial thickness (mm) measured by ultrasonographic scan at 21-23 days post-abortion. The trial was blinded for participants, investigators, medical staff, and statistical analysts until final unblinding.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;Participants were women undergoing induced abortion within 10 weeks of gestation. A total of 200 participants were enrolled, with 100 in each group. Eighty-eight (88%) in the treatment group and 82 (82%) in the control group completed the study as per the protocol and were included in the per-protocol set (PPS). The intent-to-treat (ITT) analysis included all participants randomized to the study groups and used inverse probability weighting to account for loss to follow-up.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;The ITT analysis showed revealed significantly greater endometrial thickness in the treatment group (mean 8.1 ± 2.5 mm) compared to the control group (mean 6.9 ± 2.1 mm) 21-23 days postabortion (mean difference 1.2 mm, 95% CI 0.7 to 1.9; P &lt; 0.001). The median time to menstrual return was shorter in the treatment group (34 days, inter-quartile range [IQR] 30-38) than in the control group (35 days, IQR 32-42), with a difference of -1 day (95% CI -2.3 to -0.9; P = 0.036). No differences were observed in the timing or volume of bleeding in the first post-abortion cycle. The PPS analysis mirrored the ITT findings. Adverse events were minimal (6% versus 8%), and the blood profile, liver, kidney and coagulation test results were comparable between groups (all P &gt; 0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations, reasons for caution: &lt;/strong&gt;Loss to follow-up was 11% in the treatment group and 15% of controls, with no significant difference (P &gt; 0.05). Inconsistencies in the timing of the ultrasonographic scans may have affected the accuracy of endometrial thickness measurements.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong&gt;Our findings suggest that topical oestrogen supplementation immediately after abortion within the first 10 weeks of gest","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":"142345717","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":"CDC42 deficiency leads to endometrial stromal cell senescence in recurrent implantation failure.","authors":"Xinyi Tang, Yingchun Zhu, Zhiwen Cao, Xiaoying Wang, Xinyu Cai, Yurun Tang, Jidong Zhou, Min Wu, Xin Zhen, Lijun Ding, Guijun Yan, Haibin Wang, Haixiang Sun, Ruiwei Jiang","doi":"10.1093/humrep/deae246","DOIUrl":"https://doi.org/10.1093/humrep/deae246","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Does the downregulation of cell division cycle 42 (CDC42) protein in endometrial stroma lead to endometrial senescence in patients with recurrent implantation failure (RIF), and what is the potential mechanism?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;CDC42 deficiency causes endometrial stromal senescence and decidualization defects, impairing uterine receptivity of RIF patients, via activation of Wnt signaling pathway.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Uterine aging is unique due to the cyclic remodeling and decidualization of endometrial tissue. Several transcriptomic studies have reported increased senescence in the endometrium in young patients with RIF. Our previous transcriptomic sequencing study discovered that endometrium from women with RIF showed downregulation of CDC42, which is an essential molecule affected by various senescence-related diseases.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;The endometrial samples of a total of 71 fertile control patients and 37 RIF patients were collected to verify the association between CDC42 expression and endometrial senescence of RIF patients. Primary endometrial stromal cells (EnSCs) were isolated from endometrial biopsies taken from patients without any endometrial complications and planning to undergo IVF, then subjected to adenovirus-mediated CDC42 knockdown and decidualization induction to explore the detailed mechanism by which CDC42 governs stromal senescence and decidualization. Wnt inhibitor XAV-939 was used to correct the endometrial senescence and decidualization defect.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;Senescence was determined by cell cycle arrest markers (e.g. P16, P21, and P53), SASP molecules (e.g. IL6 and CXCL8), and SA-β-gal staining. Masson's staining and Sirius Red staining were used to detect the endometrial fibrosis. Decidualization was evaluated by the mRNA expression and protein secretion of PRL and IGFBP1, F-actin immunostaining, and the BeWo spheroids 'in vitro implantation' model. Methods used to assess cell function included adenovirus transduction, RNA-sequencing, bioinformatic analysis, western blotting, RT-qPCR, ELISA, and immunofluorescence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Here, we observed remarkably increased levels of stromal senescence and fibrosis, along with stromal CDC42 deficiency, in the endometrium of patients with RIF (P &lt; 0.001). Knockdown of CDC42 effectively induced premature senescence in EnSCs, leading to aberrant accumulation of senescent EnSCs and collagen deposition during decidualization. CDC42 deficiency in EnSCs restrained the decidualization differentiation and receptivity to trophoblast cells. Transcriptomic analysis revealed Wnt signaling activation as a critical downstream alteration in CDC42-deficient EnSCs. Mechanistically, CDC42 interacted with AKT competitively to impede the binding of GSK3β to AKT. Knockdown of CDC42 inc","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":"142564371","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}