Human reproduction open最新文献

{"title":"A comprehensive study of common and rare genetic variants in spermatogenesis-related loci identifies new risk factors for idiopathic severe spermatogenic failure.","authors":"Andrea Guzmán-Jiménez, Sara González-Muñoz, Miriam Cerván-Martín, Nicolás Garrido, José A Castilla, M Carmen Gonzalvo, Ana Clavero, Marta Molina, Saturnino Luján, Samuel Santos-Ribeiro, Miguel Ángel Vilches, Andrea Espuch, Vicente Maldonado, Noelia Galiano-Gutiérrez, Esther Santamaría-López, Cristina González-Ravina, Fernando Quintana-Ferraz, Susana Gómez, David Amorós, Luis Martínez-Granados, Yanira Ortega-González, Miguel Burgos, Iris Pereira-Caetano, Ozgur Bulbul, Stefano Castellano, Massimo Romano, Elena Albani, Lluís Bassas, Susana Seixas, João Gonçalves, Alexandra M Lopes, Sara Larriba, Rogelio J Palomino-Morales, F David Carmona, Lara Bossini-Castillo","doi":"10.1093/hropen/hoae069","DOIUrl":"10.1093/hropen/hoae069","url":null,"abstract":"<p><strong>Study question: </strong>Can genome-wide genotyping data be analysed using a hypothesis-driven approach to enhance the understanding of the genetic basis of severe spermatogenic failure (SPGF) in male infertility?</p><p><strong>Summary answer: </strong>Our findings revealed a significant association between SPGF and the <i>SHOC1</i> gene and identified three novel genes (<i>PCSK4</i>, <i>AP3B1</i>, and <i>DLK1</i>) along with 32 potentially pathogenic rare variants in 30 genes that contribute to this condition.</p><p><strong>What is known already: </strong>SPGF is a major cause of male infertility, often with an unknown aetiology. SPGF can be due to either multifactorial causes, including both common genetic variants in multiple genes and environmental factors, or highly damaging rare variants. Next-generation sequencing methods are useful for identifying rare mutations that explain monogenic forms of SPGF. Genome-wide association studies (GWASs) have become essential approaches for deciphering the intricate genetic landscape of complex diseases, offering a cost-effective and rapid means to genotype millions of genetic variants. Novel methods have demonstrated that GWAS datasets can be used to infer rare coding variants that are causal for male infertility phenotypes. However, this approach has not been previously applied to characterize the genetic component of a whole case-control cohort.</p><p><strong>Study design size duration: </strong>We employed a hypothesis-driven approach focusing on all genetic variation identified, using a GWAS platform and subsequent genotype imputation, encompassing over 20 million polymorphisms and a total of 1571 SPGF patients and 2431 controls. Both common (minor allele frequency, MAF > 0.01) and rare (MAF < 0.01) variants were investigated within a total of 1797 loci with a reported role in spermatogenesis. This gene panel was meticulously assembled through comprehensive searches in the literature and various databases focused on male infertility genetics.</p><p><strong>Participants/materials setting methods: </strong>This study involved a European cohort using previously and newly generated data. Our analysis consisted of three independent methods: (i) variant-wise association analyses using logistic regression models, (ii) gene-wise association analyses using combined multivariate and collapsing burden tests, and (iii) identification and characterisation of highly damaging rare coding variants showing homozygosity only in SPGF patients.</p><p><strong>Main results and the role of chance: </strong>The variant-wise analyses revealed an association between SPGF and <i>SHOC1</i>-rs12347237 (<i>P </i>=<i> </i>4.15E-06, odds ratio = 2.66), which was likely explained by an altered binding affinity of key transcription factors in regulatory regions and the disruptive effect of coding variants within the gene. Three additional genes (<i>PCSK4</i>, <i>AP3B1</i>, and <i>DLK1</i>) were identified as novel relevan","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae069"},"PeriodicalIF":8.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830969","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: Birth rate decline, COVID-19 pandemic, and vaccination programmes.","authors":"Tomáš Sobotka, Maria Winkler-Dworak, Kryštof Zeman","doi":"10.1093/hropen/hoae068","DOIUrl":"10.1093/hropen/hoae068","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae068"},"PeriodicalIF":8.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735208","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":"Birth rate decline, COVID-19 pandemic, and vaccination programmes.","authors":"Hinpetch Daungsupawong, Viroj Wiwanitkit","doi":"10.1093/hropen/hoae067","DOIUrl":"10.1093/hropen/hoae067","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae067"},"PeriodicalIF":8.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735206","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":"Lab-based semen parameters as predictors of long-term health in men-a systematic review.","authors":"Silvia Nedelcu, Srisailesh Vitthala, Abha Maheshwari","doi":"10.1093/hropen/hoae066","DOIUrl":"10.1093/hropen/hoae066","url":null,"abstract":"<p><strong>Study question: </strong>Can semen parameters predict long-term health outcomes in men?</p><p><strong>Summary answer: </strong>There is a lack of evidence to suggest a higher risk of comorbidities in men with poor semen concentration.</p><p><strong>What is known already: </strong>Male infertility has been long associated with a higher mortality risk and possibly higher chance of developing comorbidities but there has been less focus on semen analysis as a potential predictive factor.</p><p><strong>Study design size duration: </strong>We searched PubMed/MEDLINE, EMBASE, and EBM databases from inception to December 2023. MESH term strategy: heading 1 ('OR', semen analysis, sperm count, sperm parameter*, male infertility, azoospermia, aspermia, oligospermia, teratozoospermia, asthenozoospermia) 'AND' heading 2 ('OR', morbidity, mortality, diabetes, cancer, cardiovascular, death, hypertension, stroke, long-term health). We included all studies that analyzed the risk of mortality and/or future development of comorbidities in men with at least one semen analysis. Case series and reviews were excluded.</p><p><strong>Participants/materials setting methods: </strong>A narrative synthesis was done for all studies and meta-analysis where possible. Odds ratio (ORs) (95% CI, <i>P</i>-value) were calculated for all men with one suboptimal semen parameter and associated with the risk of a particular outcome. The risk of bias was assessed with QUADAS-2.</p><p><strong>Main results and the role of chance: </strong>Twenty-one studies were finally included. There was either a high or unclear risk of bias in all studies. The results only allowed for meta-analysis on categories of sperm concentration. We found a 2-fold increase in mortality risk in azoospermic men compared to oligospermic (OR 1.96, 95% CI: 1.29-2.96) and normozoospermic (OR 2.00, 95% CI: 1.23-3.25) groups, but not in oligospermic compared to normozoospermic (OR 1.04, 95% CI: 0.52-2.09). There was no difference in risk of cardiovascular disease in any of the sperm concentration groups (azoospermic-oligospermic OR 0.94, 95% CI: 0.74-1.20, azoospermic-normozoospermic OR 1.11, 95% CI: 0.71-1.75, and oligospermic-normozoospermic OR 1.12, 95% CI: 0.80-1.55). OR for diabetes in azoospermic men was higher only compared to oligospermic (OR 2.16, 95% CI: 1.55-3.01). The risk of all-site cancer was higher in azoospermic men compared to oligospermic (OR 2.16, 95% CI: 1.55-3.01) and normozoospermic (OR 2.18, 95% CI: 1.20-3.96). Only azoospermic men might be at higher risk of testicular cancer when compared to men with normal sperm concentration (OR 1.80, 95% CI: 1.12-2.89).</p><p><strong>Limitations reasons for caution: </strong>Although our pooled analysis shows an increased risk of mortality and all-site cancer risk in azoospermic men, the results show a lack of evidence to suggest a higher risk of comorbidities in men with poor semen concentration. Given the limited available data, the nature of the ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae066"},"PeriodicalIF":8.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11643900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830976","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":"Membrane-bound receptor for advanced glycation end products (RAGE) is a stable biomarker of low-quality sperm.","authors":"Jill Browning, Magda Ghanim, William Jagoe, Jennifer Cullinane, Louise E Glover, Mary Wingfield, Vincent P Kelly","doi":"10.1093/hropen/hoae064","DOIUrl":"10.1093/hropen/hoae064","url":null,"abstract":"<p><strong>Study question: </strong>Does receptor for advanced glycation end products (RAGE) on the surface membrane of the sperm cell function as a biomarker of low-quality sperm?</p><p><strong>Summary answer: </strong>Membrane-bound RAGE at a cellular level directly correlates with low sperm motility, high cell permeability, decreased mitochondrial function, DNA fragmentation, and higher levels of apoptosis.</p><p><strong>What is known already: </strong>RAGE has previously been measured by ELISA in low-quality sperm in diabetic men and has been shown to correlate with DNA fragmentation (terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay).</p><p><strong>Study design size duration: </strong>Semen samples were recovered from 60 non-obese, non-diabetic and non-smoking subjects, washed with fresh media, and analysed directly or purified further by differential gradient centrifugation (DGC) or fractionated by direct swim-up before being analysed for sperm motility and molecular health parameters, including cell membrane permeability, cell death, mitochondrial membrane potential, DNA fragmentation, and RAGE protein expression.</p><p><strong>Participants/materials setting methods: </strong>Sperm motility assessments were carried out by computer-assisted sperm analysis (CASA) on 1000 spermatozoa for washed samples and 300 spermatozoa for purified samples. Molecular sperm health parameters were evaluated using flow cytometry with the use of the following markers: DAPI for cell membrane permeability, Annexin V/DAPI for cell death (apoptosis and necrosis), MitoTracker<sup>®</sup> Red CMXRos for mitochondrial membrane potential, TUNEL assay for DNA fragmentation and 8-hydroxy-2-deoxyguanosine for identification of oxidative damage to sperm DNA, and contrasted to membrane-bound RAGE expression levels, which were evaluated using an anti-RAGE monoclonal mouse antibody.</p><p><strong>Main results and the role of chance: </strong>RAGE protein was shown to be present on the acrosomal and equatorial regions of sperm, with the levels of membrane bound receptor strongly correlating with poor sperm health across all parameters tested; motility (<i>R</i> <sup>2</sup> = 0.5441, <i>P</i> < 0.0001) and mitochondrial membrane potential (<i>R</i> <sup>2</sup> = 0.6181, <i>P</i> < 0.0001) being of particular note. The analysis was performed at a single cell level thereby removing confounding complications from soluble forms of the RAGE protein that can be found in seminal plasma. The expression of the RAGE protein was shown to be stable over time and its levels are therefore not subject to variation in sample handling or preparation time.</p><p><strong>Large scale data: </strong>N/A.</p><p><strong>Limitations reasons for caution: </strong>Inclusion criteria for this study were non-diabetic, non-obese and non-smoking participants to assess the distribution of RAGE expression in the general population, thereby excluding disease conditions that may inc","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae064"},"PeriodicalIF":8.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649741","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":"Women may not benefit from repeated frozen embryo transfers: a retrospective analysis of the cumulative live birth rate of 43 972 women.","authors":"Yuqi Zeng, Yali Liu, Yunhan Nie, Xi Shen, Tiantian Wang, Yanping Kuang, Li Wang","doi":"10.1093/hropen/hoae063","DOIUrl":"10.1093/hropen/hoae063","url":null,"abstract":"<p><strong>Study question: </strong>Which specific groups of women would not benefit from repeated frozen embryo transfers (FETs)?</p><p><strong>Summary answer: </strong>Women over 45 years of age should stop treatment after three FET attempts due to the absence of further benefits, while women aged 40-45 years and those with a diminished ovarian reserve and other causes of infertility have a lower chance of improving their cumulative live birth rate (CLBR) within five FET cycles and experience fewer advantages from repeated transfers.</p><p><strong>What is known already: </strong>In real-life scenarios of ART, women who fail to achieve a live birth often choose to undergo repeated FETs via the freeze-all strategy.</p><p><strong>Study design size duration: </strong>This retrospective study included 43 972 women who underwent 86 496 oocyte retrieval cycles and 82 022 FET cycles between January 2010 and March 2023 under the freeze-all strategy.</p><p><strong>Participants/materials setting methods: </strong>We categorized the population based on the female's age at the first oocyte pick-up (OPU) cycle (Groups 1-6: <30, 30-34, 35-39, 40-42, 43-44, and ≥45 years of age), number of retrieved oocytes at the first OPU cycle (Groups 1-5: 1-5, 6-10, 11-15, 16-20, and >20 oocytes), and causes of infertility (Groups 1-9: tubal factor, male factor, polycystic ovary syndrome, diminished ovarian reserve, endometriosis, other uterine factors, combined factors, unexplained infertility, and other infertility) to analyse their CLBRs within different FET cycles via Kaplan-Meier analysis (optimistic method) and the competing risk method (conservative method). We utilized multivariate Cox and Fine-Gray models to examine the associations between the CLBR and age, the number of retrieved oocytes, and nine causes of infertility.</p><p><strong>Main results and the role of chance: </strong>The CLBR decreased with increasing female age over five FET cycles (Groups 1-6: optimistic method: 96.4%, 94.2%, 86.0%, 50.2%, 23.1%, and 10.1%; conservative method: 87.1%, 82.0%, 67.8%, 33.9%, 13.8%, and 3.5%, respectively). Moreover, there was an increasing trend in the number of retrieved oocytes (Groups 1-5: optimistic method: 82.5%, 91.7%, 93.6%, 94.1%, and 96.2%; conservative method: 58.6%, 76.7%, 84.8%, 88.0%, and 92.5%, respectively). Furthermore, the CLBR varied across different causes of infertility (Groups 1-9: optimistic method: 91.7%, 93.1%, 96.6%, 79.2%, 89.9%, 76.1%, 90.0%, 92.9%, and 35.4%; conservative method: 77.3%, 79.4%, 88.9%, 46.7%, 72.7%, 62.1%, 74.4%, 78.8%, and 20.1%, respectively).</p><p><strong>Limitations reasons for caution: </strong>Calculating the actual CLBR for each person is difficult because some patients have remaining embryos that have not been transferred; additionally, the current statistical methodology uses both optimistic and conservative methods to calculate the CLBR, and in real life, the CLBR falls between the optimistic and conservative curve","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae063"},"PeriodicalIF":8.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633205","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":"Sperm and leukocyte telomere length are related to sperm quality parameters in healthy men from the Led-Fertyl study.","authors":"María Fernández de la Puente, Cristina Valle-Hita, Albert Salas-Huetos, María Ángeles Martínez, Elena Sánchez-Resino, Silvia Canudas, Daniel Torres-Oteros, Joana Relat, Nancy Babio, Jordi Salas-Salvadó","doi":"10.1093/hropen/hoae062","DOIUrl":"https://doi.org/10.1093/hropen/hoae062","url":null,"abstract":"<p><strong>Study question: </strong>Could sperm and leukocyte telomere length (TL) be associated with sperm quality parameters and reproductive health in men from the general population?</p><p><strong>Summary answer: </strong>A positive association between sperm and leukocyte TL with sperm concentration and total count has been demonstrated.</p><p><strong>What is known already: </strong>Male factors account for almost half of cases of couple infertility, and shorter TLs have been observed in sperm from men with impaired sperm parameters. However, evidence in men from the general population is limited.</p><p><strong>Study design size duration: </strong>A total of 200 volunteers of reproductive age were recruited between February 2021 and April 2023 to participate in the Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters (Led-Fertyl) cross-sectional study.</p><p><strong>Participants/materials setting methods: </strong>TLs in sperm and leukocytes were measured using quantitative polymerase chain reaction (qPCR) in 168 and 194 participants, respectively. Sperm parameters, including concentration, total count, motility, vitality, and morphology, were analyzed using a computer-assisted sperm analysis (CASA) SCA<sup>®</sup> system according to the World Health Organization (WHO) 2010 guidelines. Multivariable regression models were performed to assess the associations between sperm and leukocyte TL, either in tertiles or as continuous variables, and sperm quality parameters while adjusting for potential confounders.</p><p><strong>Main results and the role of chance: </strong>Participants in tertiles 2 (T2) and 3 (T3) of sperm TL showed a higher sperm concentration (β: 1.09; 95% CI: 0.09-2.09 and β: 2.06; 95% CI: 1.04-3.09 for T2 and T3, respectively; <i>P</i>-trend < 0.001), compared to those in the reference tertile (T1). Participants in the highest tertile of sperm TL showed higher total sperm count (β: 3.83; 95% CI: 2.08-5.58 for T3 vs T1; <i>P</i>-trend < 0.001). Participants in the top tertile of leukocyte TL showed higher sperm concentration (β: 1.49; 95% CI: 0.44-2.54 for T3 vs T1; <i>P</i>-trend = 0.004), and total count (β: 3.49; 95% CI: 1.62-5.35 for T3 vs T1; <i>P</i>-trend < 0.001) compared with participants in T1. These results remained consistent when sperm and leukocyte TL were modelled as continuous variables.</p><p><strong>Limitations reasons for caution: </strong>One limitation is the impossibility of establishing a cause-effect relationship due to the cross-sectional study design. Additionally, the sample size of the study cannot be considered large.</p><p><strong>Wider implications of the findings: </strong>Sperm and leukocyte TLs are associated with sperm quality parameters in the general population. Additional determinations and further studies with larger sample sizes are needed to clarify the mechanisms underlying these associations and to investigate the further implications.</p><p","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae062"},"PeriodicalIF":8.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549294","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: Emerging evidence of endometrial compaction in predicting ART outcomes.","authors":"Hannan Al-Lamee, Gayathri Delanerolle, Dharani K Hapangama, Nicola Tempest","doi":"10.1093/hropen/hoae061","DOIUrl":"10.1093/hropen/hoae061","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae061"},"PeriodicalIF":8.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514160","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":"Emerging evidence of endometrial compaction in predicting ART outcomes.","authors":"Guangyao Lin, Stella Lim Jin Yie, Lianwei Xu","doi":"10.1093/hropen/hoae060","DOIUrl":"10.1093/hropen/hoae060","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae060"},"PeriodicalIF":8.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514159","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":"Steady morphokinetic progression is an independent predictor of live birth: a descriptive reference for euploid embryos.","authors":"Aşina Bayram, Ibrahim Elkhatib, Erkan Kalafat, Andrea Abdala, Virginia Ferracuti, Laura Melado, Barbara Lawrenz, Human Fatemi, Daniela Nogueira","doi":"10.1093/hropen/hoae059","DOIUrl":"10.1093/hropen/hoae059","url":null,"abstract":"<p><strong>Study question: </strong>Can modelling the longitudinal morphokinetic pattern of euploid embryos during time-lapse monitoring (TLM) be helpful for selecting embryos with the highest live birth potential?</p><p><strong>Summary answer: </strong>Longitudinal reference ranges of morphokinetic development of euploid embryos have been identified, and embryos with steadier progression during TLM are associated with higher chances of live birth.</p><p><strong>What is known already: </strong>TLM imaging is increasingly adopted by fertility clinics as an attempt to improve the ability of selecting embryos with the highest potential for implantation. Many markers of embryonic morphokinetics have been incorporated into decision algorithms for embryo (de)selection. However, longitudinal changes during this temporal process, and the impact of such changes on embryonic competence remain unknown. Aiming to model the reference ranges of morphokinetic development of euploid embryos and using it as a single longitudinal trajectory might provide an additive value to the blastocyst morphological grade in identifying highly competent embryos.</p><p><strong>Study design size duration: </strong>This observational, retrospective cohort study was performed in a single IVF clinic between October 2017 and June 2021 and included only autologous single euploid frozen embryo transfers (seFET).</p><p><strong>Participants/materials setting methods: </strong>Reference ranges were developed from [hours post-insemination (hpi)] of the standard morphokinetic parameters of euploid embryos assessed as tPB2, tPNa, tPNf, t2-t9, tSC, tM, tSB, and tB. Variance in morphokinetic patterns was measured and reported as morphokinetic variance score (MVS). Nuclear errors (micronucleation, binucleation, and multinucleation) were annotated when present in at least one blastomere at the two- or four-cell stages. The blastocyst grade of expansion, trophectoderm (TE), and inner cell mass (ICM) were assessed immediately before biopsy using Gardner's criteria. Pre-implantation genetic diagnosis for aneuploidy (PGT-A) was performed by next-generation sequencing. All euploid embryos were singly transferred in a frozen transferred cycle and outcomes were assessed as live birth, pregnancy loss, or not pregnant. Association of MVS with live birth was investigated with regression analyses.</p><p><strong>Main results and the role of chance: </strong>TLM data from 340 seFET blastocysts were included in the study, of which 189 (55.6%) resulted in a live birth. The median time for euploid embryos to reach blastulation was 109.9 hpi (95% CI: 98.8-121.0 hpi). The MVS was calculated from the variance in time taken for the embryo to reach all morphokinetic points and reflects the total morphokinetic variability it exhibits during its development. Embryos with more erratic kinetics, i.e. higher morphokinetic variance, had higher rates of pregnancy loss (<i>P</i> = 0.004) and no pregnancy (<i>P</i> < 0.001)","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae059"},"PeriodicalIF":8.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592450","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}