Human reproduction open最新文献

{"title":"The severity of meiotic aneuploidy is associated with altered morphokinetic variables of mouse oocyte maturation","authors":"Yiru Zhu, Catherine Kratka, Jeffrey Pea, Hoi Chang Lee, Caroline E. Kratka, Jia Xu, Diego Marin, Nathan R Treff, Francesca E Duncan","doi":"10.1093/hropen/hoae023","DOIUrl":"https://doi.org/10.1093/hropen/hoae023","url":null,"abstract":"\u0000 \u0000 \u0000 Is there an association between morphokinetic variables of meiotic maturation and the severity of aneuploidy following in vitro maturation (IVM) in the mouse?\u0000 \u0000 \u0000 \u0000 The severity of meiotic aneuploidy correlates with an extended time to first polar body extrusion (tPB1) and duration of meiosis I (dMI).\u0000 \u0000 \u0000 \u0000 Morphokinetic variables measured using time-lapse technology allow for the non-invasive evaluation of preimplantation embryo development within clinical assisted reproductive technology (ART). We recently applied this technology to monitor meiotic progression during IVM of mouse gametes. Whether there is a relationship between morphokinetic variables of meiotic progression and aneuploidy in the resulting egg has not been systematically examined at the resolution of specific chromosomes. Next-generation sequencing (NGS) is a robust clinical tool for determining aneuploidy status and has been reverse-translated in mouse blastocysts and oocytes. Therefore, we harnessed the technologies of time-lapse imaging and NGS to determine the relationship between the morphokinetics of meiotic progression and egg aneuploidy.\u0000 \u0000 \u0000 \u0000 Cumulus–oocyte complexes (COCs) were collected from large antral follicles from hyperstimulated CD-1 mice. Cumulus cells were removed, and spontaneous IVM was performed in the absence or presence of two doses of Nocodazole (25 nM or 50 nM) to induce a spectrum of spindle abnormalities and chromosome segregation errors during oocyte meiosis. Comprehensive chromosome screening was then performed in the resulting eggs, and morphokinetic variables and ploidy status were compared across experimental groups (control, n = 11; 25 nM Nocodazole, n = 13; 50 nM Nocodazole, n = 23).\u0000 \u0000 \u0000 \u0000 We monitored IVM in mouse oocytes using time-lapse microscopy for 16 hours, and time to germinal vesicle breakdown (tGVBD), time to first polar body extrusion (tPB1), and duration of meiosis I (dMI) were analyzed. Following IVM, comprehensive chromosome screening was performed on the eggs and their matched first polar bodies via adaptation of an NGS-based preimplantation genetic testing for aneuploidy (PGT-A) assay. Bioinformatics analysis was performed to align reads to the mouse genome and determine copy number-based predictions of aneuploidy. The concordance of each polar body–egg pair (reciprocal errors) was used to validate the results. Ploidy status was categorized as euploid, 1–3 chromosomal segregation errors, or ≥ 4 chromosomal segregation errors. Additionally, aneuploidy due to premature separation of sister chromatids versus non-disjunction was distinguished.\u0000 \u0000 \u0000 \u0000 We applied and validated state-of-the-art NGS technology to screen aneuploidy in individual mouse eggs and matched polar bodies at the chromosome-specific level. By performing IVM in the presence of different doses of Nocodazole, we induced a range of aneuploidy. No aneuploidy was observed in the absence of Nocodazole (0/11), whereas IVM in the presence of 25 nM and 50 nM Noco","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140667316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current global status of male reproductive health","authors":"C. J. De Jonge, Christopher L R Barratt, R. J. Aitken, Richard A Anderson, Peter Baker, David Y L Chan, Mark P Connolly, Michael L Eisenberg, N. Garrido, Niels Jørgensen, Sarah Kimmins, C. Krausz, Robert I. McLachlan, C. Niederberger, Moira K ÓBryan, Allan Pacey, L. Priskorn, S. Rautakallio-Hokkanen, G. Serour, J. Veltman, Donna L Vogel, M. Vazquez-Levin","doi":"10.1093/hropen/hoae017","DOIUrl":"https://doi.org/10.1093/hropen/hoae017","url":null,"abstract":"\u0000 \u0000 \u0000 The widespread interest in male reproductive health (MRH), fueled by emerging evidence, such as the global decline in sperm counts, has intensified concerns about the status of MRH. Consequently, there is a pressing requirement for a strategic, systematic approach to identify critical questions, collect pertinent information, and utilize this data to develop evidence-based strategies. The methods for addressing these questions and the pathways towards their answers will inevitably vary based on the variations in cultural, geopolitical, and health-related contexts. To address these issues, a conjoint ESHRE and Male Reproductive Health Initiative (MRHI) Campus workshop was convened.\u0000 \u0000 \u0000 \u0000 The three objectives were: first, to assess the current state of MRH around the world; second, to identify some of the key gaps in knowledge; and, third, to examine how MRH stakeholders can collaboratively generate intelligent and effective paths forward.\u0000 \u0000 \u0000 \u0000 Each expert reviewed and summarized the current literature that was subsequently used to provide a comprehensive overview of challenges related to MRH.\u0000 \u0000 \u0000 \u0000 This narrative report is an overview of the data, opinions and arguments presented during the workshop. A number of outcomes are presented and can be summarized by the following overarching themes: MRH is a serious global issue and there is a plethora of gaps in our understanding; there is a need for widespread international collaborative networks to undertake multidisciplinary research into fundamental issues, such as lifestyle/environmental exposure studies, and high quality clincial trials; and there is an urgent requirement for effective strategies to educate young people and the general public to safeguard and improve MRH across diverse population demographics and resources.\u0000 \u0000 \u0000 \u0000 This was a workshop where worldwide leading experts from a wide range of disciplines presented and discussed the evidence regarding challenges related to MRH. Whilst each expert summarised the current literature and placed it in context, the data in a number of areas is limited and/or sparse. Equally, important areas for consideration may have been missed. Moreover, there are clear gaps in our knowledge base, which makes some conclusions necessarily speculative and warranting of further study.\u0000 \u0000 \u0000 \u0000 Poor MRH is a global issue that suffers from low awareness among the public, patients and heathcare professionals. Addressing this will require a coordinated multidisciplinary approach. Addressing the significant number of knowledge gaps will require policy makers prioritizing MRH and its funding.\u0000 \u0000 \u0000 \u0000 The authors extend their gratitude to ESHRE for financial support of the Budapest Campus Workshop. PB is the Director of the not-for-profit organization Global Action on Men’s Health and receives fees and expenses for his work, (which includes the preparation of this manuscript. Conflicts of interest: CJDJ, CLRB, RAA, PB, MPC, MLE, NG, NJ, CK, AAP, MKO, SR-H, MHV-L","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140712169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The risk of type 1 diabetes in children born after ART: a nordic cohort study from the CoNARTaS group","authors":"F. Kyhl, A. L. Spangmose, Mika Gissler, K. Rönö, K. Westvik-Johari, A. Henningsen, C. Bergh, U. Wennerholm, S. Opdahl, J. Forman, Jannet Svensson, T. Clausen, D. Vassard, Anja Pinborg","doi":"10.1093/hropen/hoae021","DOIUrl":"https://doi.org/10.1093/hropen/hoae021","url":null,"abstract":"\u0000 \u0000 \u0000 Do children born after ART have a higher risk of developing type 1 diabetes (DM1) than children conceived without ART?\u0000 \u0000 \u0000 \u0000 The risk of DM1 was similar for children conceived with and without ART, and there were no clear differences in risk according to method of fertility treatment.\u0000 \u0000 \u0000 \u0000 ART is associated with higher risk of adverse perinatal outcomes, and risk depends on the method of ART. The Developmental Origins of Health and Disease theory proposes that prenatal stress can provoke changes in endocrine processes which impact health later in life.\u0000 \u0000 \u0000 \u0000 A Nordic register-based cohort study was carried out, including all children born in Denmark (birth years 1994–2014), Finland (1990–2014), and Norway (1984–2015). The study included 76 184 liveborn singletons born after ART and 4 403 419 born without ART. Median follow-up was 8.3 years and 13.7 years in the ART and non-ART group, respectively.\u0000 \u0000 \u0000 \u0000 The cohort, initiated by the Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS), was established by linking national registry data from the medical birth registries and national patient registries available in the Nordic countries. We performed multivariable logistic regression analyses for the birth year intervals 1984–1990, 1991–1995, 1996–2000, 2001–2005, 2006–2010, and 2011–2015, while adjusting for year of birth within each interval, sex of the child, parity, maternal age, maternal diabetes, and maternal smoking during pregnancy as potential confounders.\u0000 \u0000 \u0000 \u0000 During follow-up, 259 (3.4‰) children born after ART were diagnosed with DM1, while this was the case for 22 209 (5.0‰) born without ART, corresponding to an adjusted odds ratio of 0.98 (95% CI 0.86 to 1.11). Within the different birth year intervals, no significant difference in risk of DM1 between the two groups was found, except for the youngest cohort of children born 2011–2015 where ART was associated with a higher risk of DM1. We found no significant differences in risk of DM1 when comparing children born after IVF versus ICSI or fresh versus frozen embryo transfer, but with only few cases in each group.\u0000 \u0000 \u0000 \u0000 The main limitation of the study is the relatively short follow-up time. The incidence rate of DM1 peaks during ages 10–14 years, hence a longer follow-up would benefit all analyses and in particular the subgroup analyses.\u0000 \u0000 \u0000 \u0000 Overall, our findings are reassuring especially considering the concomitantly increasing number of children born from ART and the increasing incidence of DM1 globally.\u0000 \u0000 \u0000 \u0000 This Nordic registry study has been supported by the Nordic Trial Alliance/NORDFORSK and Rigshospitalets Research Foundation. The funding sources had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. None of the authors has any conflicts of interest to declare regarding this study.\u0000 \u0000 \u0000 \u0000 ISRCTN11780826\u0000","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140720029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-treatment with oral contraceptive pills in women with PCOS scheduled for IVF: a randomized clinical trial","authors":"Gao Jun, Qingyun Mai, Yiping Zhong, Miao Benyu, Minghui Chen, Luo Lu, Canquan Zhou, B. Mol, Yanwen Xu","doi":"10.1093/hropen/hoae019","DOIUrl":"https://doi.org/10.1093/hropen/hoae019","url":null,"abstract":"\u0000 \u0000 \u0000 What is the effect of pre-treatment with oral contraceptive pills (OCP) on oocyte and embryo quality and pregnancy rates in women with PCOS scheduled for IVF/ICSI cycles?\u0000 \u0000 \u0000 \u0000 In women with PCOS who underwent a first or second IVF/ICSI cycle with a GnRH antagonist protocol and were randomized to start ovarian stimulation immediately, the quality of cleavage-stage embryos was non-inferior to pretreatment with OCP.\u0000 \u0000 \u0000 \u0000 PCOS in Asian populations is characterized by high levels of circulating LH in the early follicular phase. Previous studies indicated that inappropriately high LH levels might affect oocyte maturation and fertilization rates, and impaired embryo quality, consequently resulting in higher rates of impaired pregnancy and miscarriage in women with PCOS. OCPs are frequently used as pretreatment to lower LH levels in PCOS patients.\u0000 \u0000 \u0000 \u0000 We performed a randomized controlled trial. After informed consent, women diagnosed with PCOS scheduled for their first or second IVF/ICSI cycle with a GnRH antagonist protocol were randomized to receive OCPs (OCP-group) or start ovarian stimulation immediately, regardless of the day of the menstrual cycle (non OCP-group). Using a non-inferiority hypothesis, the sample size was calculated at 242 women. The study lasted from Feb 7, 2018 to Aug 31, 2021.\u0000 \u0000 \u0000 \u0000 A total of 242 infertility patients with PCOS undergoing the first or second cycle of IVF or ICSI were enrolled and randomized into two groups. In the OCP group, recombinant FSH was started on day 7 of the washout period after pretreatment with OCP. In the non-OCP group, recombinant FSH was started immediately regardless of the day of the menstrual cycle. All participants received standardized GnRH antagonist ovarian stimulation. The freeze-all strategy was applied to all participants. Primary outcome was the number of good quality embryos on day 3 after insemination. Secondary outcomes included the rates of blastocyst formation, implantation, clinical pregnancy, and live birth from the first frozen/warmed embryo transfer cycles and cumulative live birth rates.\u0000 \u0000 \u0000 \u0000 We randomized 242 women to receive OCP (n = 121) or start immediately with ovarian stimulation (n = 121). The number of good quality embryos on day 3 in the OCP-group was non-inferior to the non OCP-group (OCP-group versus non OCP-group, 6.58 ± 4.93 versus 7.18 ± 4.39, AD − 0.61, 95% CI: −1.86 to 0.65, P = 0.34). The rates of blastocyst formation (55.4% versus 52.9%, RR 1.11, 95% CI: 0.96 to 1.28, P = 0.17), implantation (63.0% versus 65.5%, RR 0.90, 95% CI: 0.53 to 1.53, P = 0.79), clinical pregnancy (67.9% versus 68.8%, RR 0.96, 95% CI: 0.54 to 1.71, P = 1.0), and live birth rate (52.8% versus 55.1%, RR 0.92, 95% CI: 0.53 to 1.56, P = 0.79) of the first frozen/warmed embryo transfer cycles were all comparable between the OCP and non-OCP group, respectively. Cumulative live birth rates were also similar in the OCP and non-OCP groups (78.3% versus 83.5%, respectively RR 0.71,","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140745676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Tcte1 knockout on energy chain transportation and spermatogenesis: implications for male infertility","authors":"Marta Olszewska, A. Malcher, Tomasz Stokowy, N. Pollock, Andrea J Berman, S. Budkiewicz, M. Kamieniczna, Hanna Jackowiak, Joanna Suszynska-Zajczyk, Piotr Jedrzejczak, A. Yatsenko, Maciej Kurpisz","doi":"10.1093/hropen/hoae020","DOIUrl":"https://doi.org/10.1093/hropen/hoae020","url":null,"abstract":"Abstract STUDY QUESTION Is the Tcte1 mutation causative for male infertility? SUMMARY ANSWER Our collected data underline the complex and devastating effect of the single-gene mutation on the testicular molecular network, leading to male reproductive failure. WHAT IS KNOWN ALREADY Recent data have revealed mutations in genes related to axonemal dynein arms as causative for morphology and motility abnormalities in spermatozoa of infertile males, including dysplasia of fibrous sheath (DFS) and multiple morphological abnormalities in the sperm flagella (MMAF). The nexin–dynein regulatory complex (N-DRC) coordinates the dynein arm activity and is built from the DRC1–DRC7 proteins. DRC5 (TCTE1), one of the N-DRC elements, has already been reported as a candidate for abnormal sperm flagella beating; however, only in a restricted manner with no clear explanation of respective observations. STUDY DESIGN, SIZE, DURATION Using the CRISPR/Cas9 genome editing technique, a mouse Tcte1 gene knockout line was created on the basis of the C57Bl/6J strain. The mouse reproductive potential, semen characteristics, testicular gene expression levels, sperm ATP, and testis apoptosis level measurements were then assessed, followed by visualization of N-DRC proteins in sperm, and protein modeling in silico. Also, a pilot genomic sequencing study of samples from human infertile males (n = 248) was applied for screening of TCTE1 variants. PARTICIPANTS/MATERIALS, SETTING, METHODS To check the reproductive potential of KO mice, adult animals were crossed for delivery of three litters per caged pair, but for no longer than for 6 months, in various combinations of zygosity. All experiments were performed for wild-type (WT, control group), heterozygous Tcte1+/− and homozygous Tcte1−/− male mice. Gross anatomy was performed on testis and epididymis samples, followed by semen analysis. Sequencing of RNA (RNAseq; Illumina) was done for mice testis tissues. STRING interactions were checked for protein–protein interactions, based on changed expression levels of corresponding genes identified in the mouse testis RNAseq experiments. Immunofluorescence in situ staining was performed to detect the N-DRC complex proteins: Tcte1 (Drc5), Drc7, Fbxl13 (Drc6), and Eps8l1 (Drc3) in mouse spermatozoa. To determine the amount of ATP in spermatozoa, the luminescence level was measured. In addition, immunofluorescence in situ staining was performed to check the level of apoptosis via caspase 3 visualization on mouse testis samples. DNA from whole blood samples of infertile males (n = 137 with non-obstructive azoospermia or cryptozoospermia, n = 111 samples with a spectrum of oligoasthenoteratozoospermia, including n = 47 with asthenozoospermia) was extracted to perform genomic sequencing (WGS, WES, or Sanger). Protein prediction modeling of human-identified variants and the exon 3 structure deleted in the mouse knockout was also performed. MAIN RESULTS AND THE ROLE OF CHANCE No progeny at all was","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140744245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between synthetic phenols, phthalates, and placental growth/function: a longitudinal cohort with exposure assessment in early pregnancy","authors":"Nicolas Jovanovic, Vicente Mustieles, Marc Althuser, S. Lyon-Caen, Nadia Alfaidy, Cathrine Thomsen, A. Sakhi, Azemira Sabaredzovic, Sam Bayat, A. Couturier-Tarrade, R. Slama, C. Philippat","doi":"10.1093/hropen/hoae018","DOIUrl":"https://doi.org/10.1093/hropen/hoae018","url":null,"abstract":"\u0000 \u0000 \u0000 Is exposure to environmental chemicals associated with modification of placental morphology and function?\u0000 \u0000 \u0000 \u0000 Phthalates, a class of ubiquitous chemicals, showed an association with altered placental weight, placental vascular resistance and placental efficiency.\u0000 \u0000 \u0000 \u0000 Only a few epidemiological studies have assessed the effects of phenols and phthalates on placental health. Their results were affected by exposure measurement errors linked to the rapid excretion of these compounds and the reliance on a limited number of spot urine samples to assess exposure.\u0000 \u0000 \u0000 \u0000 A prospective mother-child cohort with improved exposure assessment for non-persistent chemicals, recruited participants between 2014 and 2017. Sample size ranged between 355 (placental parameters measured at birth: placental weight and placental-to-fetal weight ratio: a proxy for placental efficiency) and 426 (placental parameters measured during pregnancy: placental thickness and vascular resistance).\u0000 \u0000 \u0000 \u0000 Phenols (four parabens, two bisphenols, triclosan and benzophenone-3), 13 phthalate metabolites, and two non-phthalate plasticizer metabolites were measured in within-subject pools of repeated urine samples collected during the 2nd and 3rd trimesters of pregnancy (median = 21 samples/trimester/woman). Placental thickness and placental vascular resistance (PVR) were measured during pregnancy. The placenta was weighed at birth and the placental-to-fetal-weight ratio (PFR) was computed. Both adjusted linear regression and Bayesian Kernel Machine Regression were used to evaluate associations between phenols and phthalates (alone or as mixture) and placental parameters. Effect modification by child sex was also investigated.\u0000 \u0000 \u0000 \u0000 Several phthalate metabolites were negatively associated with placental outcomes. Monobenzyl phthalate (MBzP) concentrations, during the 2nd and 3rd trimesters of pregnancy, were associated with a decrease in both placental weight at birth (β= -20.1 g [95% CI: -37.8; -2.5] and β= -17.4 g [95% CI: -33.2; -1.6], for 2nd and 3rd trimester, respectively) and PFR (β= -0.5 [95% CI: -1, -0.1] and β=-0.5 [95% CI: -0.9, -0.1], for 2nd and 3rd trimester, respectively). Additionally, MBzP was negatively associated with PVR during the 3rd trimester (β= -0.9 [95% CI: -1.8; 0.1]). Mono-n-butyl phthalate (MnBP), was negatively associated with PVR in both trimesters (β=-1.3, 95%IC: [-2.3, -0.2], and β=-1.2, 95%IC: [-2.4, -0.03], for 2nd and 3rd trimester, respectively). After stratification for child sex, ∑ diisononyl phthalate (DiNP) (either 2nd or 3rd trimester exposures, depending on the outcomes considered) was associated with decreased PVR in the 3rd trimester, as well as decreased placental weight and PFR in males. No associations were observed for phenol biomarkers.\u0000 \u0000 \u0000 \u0000 False positives cannot be ruled out. Therefore, chemicals that were associated with multiple outcomes (MnBP and DiNP) or reported in existing literature as associated with placental outc","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140353550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognosis-based management of unexplained infertility—why not?","authors":"L. Shingshetty, Rui Wang, Qian Feng, Abha Maheshwari, B. Mol","doi":"10.1093/hropen/hoae015","DOIUrl":"https://doi.org/10.1093/hropen/hoae015","url":null,"abstract":"\u0000 Up to a half of couples seeking medical assistance for infertility are diagnosed with unexplained infertility, characterised by normal ovulation, tubal patency, and semen analysis results. This condition presents a challenge in determining the optimal treatment approach. Available treatments include IUI and IVF, but guidelines vary on when to offer each. Prognosis-based management is identified as a research priority, and various prediction models have been developed to guide treatment decisions. Prognostic factors include female age, duration of subfertility, and sperm parameters, among others. Prognosis-based strategies can enhance cost-effectiveness, safety, and patient outcomes, offering less invasive options to those with good prognoses and more aggressive interventions to those with poor prognoses. However, there is a gap between research evidence and its clinical application. In this paper we discuss the application of prognosis-based management in the context of unexplained infertility, highlighting its potential to improve clinical decision-making and patient outcomes.","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140218643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood pressure and lipid profiles in children born after ART with frozen embryo transfer","authors":"L. L. Asserhøj, I. Mizrak, A. S. Lebech Kjaer, T. D. Clausen, Eva R Hoffmann, Gorm Greisen, Katharina M Main, P. L. Madsen, Anja Pinborg, R. B. Jensen","doi":"10.1093/hropen/hoae016","DOIUrl":"https://doi.org/10.1093/hropen/hoae016","url":null,"abstract":"\u0000 \u0000 \u0000 Are blood pressure (BP) and lipid profiles different between children conceived after ART with frozen embryo transfer (FET), fresh embryo transfer (fresh-ET), and natural conception (NC)?\u0000 \u0000 \u0000 \u0000 Girls conceived after FET had significantly higher systolic BP and heart rate compared with girls born after fresh-ET; boys conceived after FET had a slightly more favourable lipid profile compared with boys born after fresh-ET and NC.\u0000 \u0000 \u0000 \u0000 Children conceived after ART with FET are more often born large for gestational age (LGA). LGA in general increases the risk of obesity, diabetes, and cardiovascular disease later in life. Studies on mice and humans on the whole ART population have raised concerns about premature vascular aging and higher BP. The cardiovascular health of children born after FET is scarcely explored and the results are diverging.\u0000 \u0000 \u0000 \u0000 This study was part of the cohort study “Health in Childhood following Assisted Reproductive Technology” (HiCART) which included 606 singletons (292 boys) born between December 2009 and December 2013: 200 children were conceived after FET; 203 children were conceived after fresh-ET; and 203 children were conceived naturally and matched for birth year and sex. The study period lasted from January 2019 to September 2021.\u0000 \u0000 \u0000 \u0000 The included children were 7-10 years of age at examination and underwent a clinical examination with anthropometric measurements, pubertal staging, and BP measurement. Additionally, a fasting blood sample was collected and analysed for cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL), and triglycerides. Systolic and diastolic BP were converted to standard deviation scores (SDS) using an appropriate reference and accounting for height (SDS) of the child. The three study groups were compared pairwise using a univariate linear regression model. Mean differences were adjusted for confounders using multiple linear regression analyses.\u0000 \u0000 \u0000 \u0000 Girls and boys conceived after FET had significantly higher birthweight (SDS) compared with naturally conceived peers (mean difference: girls: 0.35, 95% CI (0.06; 0.64), boys: 0.35, 95% CI (0.03; 0.68)). Girls conceived after FET had significantly higher systolic BP (SDS) and heart rate compared with girls conceived after fresh-ET (adjusted mean difference: systolic BP (SDS): 0.25 SDS, 95% CI (0.03; 0.47), heart rate: 4.53, 95% CI (0.94; 8.13)). Regarding lipid profile, no significant differences were found between the three groups of girls. For the boys, no significant differences were found for BP and heart rate. Lipid profiles were more favourable in boys born after FET compared with both boys conceived after fresh-ET and NC. All outcomes were adjusted for parity, maternal BMI at early pregnancy, smoking during pregnancy, educational level, birthweight, breastfeeding, child age at examination, and onset of puberty.\u0000 \u0000 \u0000 \u0000 The participation rate varied from 18 to 42% in the three groups, and therefore selection ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140228045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles secreted by human aneuploid embryos present a distinct transcriptomic profile and upregulate MUC1 transcription in decidualised endometrial stromal cells.","authors":"Sofia Makieva, Elisa Giacomini, Giulia Maria Scotti, Dejan Lazarevic, Valentina Pavone, Jessica Ottolina, Ludovica Bartiromo, Matteo Schimberni, Marco Morelli, Alessandra Alteri, Sabrina Minetto, Giovanni Tonon, Massimo Candiani, Enrico Papaleo, Paola Viganò","doi":"10.1093/hropen/hoae014","DOIUrl":"10.1093/hropen/hoae014","url":null,"abstract":"<p><strong>Study question: </strong>Do extracellular vesicles (EVs) secreted by aneuploid human embryos possess a unique transcriptomic profile that elicits a relevant transcriptomic response in decidualized primary endometrial stromal cells (dESCs)?</p><p><strong>Summary answer: </strong>Aneuploid embryo-derived EVs contain transcripts of <i>PPM1J</i>, <i>LINC00561</i>, <i>ANKRD34C</i>, and <i>TMED10</i> with differential abundance from euploid embryo-derived EVs and induce upregulation of <i>MUC1</i> transcript in dESCs.</p><p><strong>What is known already: </strong>We have previously reported that IVF embryos secrete EVs that can be internalized by ESCs, conceptualizing that successful implantation to the endometrium is facilitated by EVs. Whether these EVs may additionally serve as biomarkers of ploidy status is unknown.</p><p><strong>Study design size duration: </strong>Embryos destined for biopsy for preimplantation genetic testing for aneuploidy (PGT-A) were grown under standard conditions. Spent media (30 μl) were collected from euploid (n = 175) and aneuploid (n = 140) embryos at cleavage (Days 1-3) stage and from euploid (n = 187) and aneuploid (n = 142) embryos at blastocyst (Days 3-5) stage. Media samples from n = 35 cleavage-stage embryos were pooled in order to obtain five euploid and four aneuploid pools. Similarly, media samples from blastocysts were pooled to create one euploid and one aneuploid pool. ESCs were obtained from five women undergoing diagnostic laparoscopy.</p><p><strong>Participants/materials setting methods: </strong>EVs were isolated from pools of media by differential centrifugation and EV-RNA sequencing was performed following a single-cell approach that circumvents RNA extraction. ESCs were decidualized (estradiol: 10 nM, progesterone: 1 µM, cAMP: 0.5 mM twice every 48 h) and incubated for 24 h with EVs (50 ng/ml). RNA sequencing was performed on ESCs.</p><p><strong>Main results and the role of chance: </strong>Aneuploid cleavage stage embryos secreted EVs that were less abundant in RNA fragments originating from the genes <i>PPM1J</i> (log2fc = -5.13, <i>P</i> = 0.011), <i>LINC00561</i> (log2fc = -7.87, <i>P</i> = 0.010), and <i>ANKRD34C</i> (log2fc = -7.30, <i>P</i> = 0.017) and more abundant in <i>TMED10</i> (log2fc = 1.63, <i>P</i> = 0.025) compared to EVs of euploid embryos. Decidualization <i>per se</i> induced downregulation of <i>MUC1</i> (log2fc = -0.54, <i>P</i> = 0.0028) in ESCs as a prerequisite for the establishment of receptive endometrium. The expression of <i>MUC1</i> transcript in decidualized ESCs was significantly increased following treatment with aneuploid compared to euploid embryo-secreted EVs (log2fc = 0.85, <i>P</i> = 0.0201).</p><p><strong>Large scale data: </strong>Raw data have been uploaded to GEO (accession number GSE234338).</p><p><strong>Limitations reasons for caution: </strong>The findings of the study will require validation utilizing a second cohort of EV samples.</p><p><stro","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10980593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337893","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":"Ovarian ferroptosis induced by androgen is involved in pathogenesis of PCOS.","authors":"Xinyu Li, Yunying Lin, Xiaoyue Cheng, Guangxin Yao, Jufang Yao, Shuanggang Hu, Qinling Zhu, Yuan Wang, Ying Ding, Yao Lu, Jia Qi, Hanting Zhao, Xuejiao Bian, Yanzhi Du, Kang Sun, Hugo Vankelecom, Yun Sun","doi":"10.1093/hropen/hoae013","DOIUrl":"10.1093/hropen/hoae013","url":null,"abstract":"<p><strong>Study question: </strong>Does ovarian ferroptosis play an active role in the development of polycystic ovary syndrome (PCOS)?</p><p><strong>Summary answer: </strong>Increased ovarian ferroptosis was present in PCOS ovaries and the inhibition of ferroptosis with ferrostatin-1 (Fer-1) ameliorated polycystic ovary morphology and anovulation.</p><p><strong>What is known already: </strong>Programmed cell death plays a fundamental role in ovarian follicle development. However, the types and mechanisms of cell death involved in the ovary are yet to be elucidated. Ferroptosis is a recently discovered iron-dependent programmed cell death. Impaired iron metabolism and cell death have been observed in women with PCOS, the main cause of anovulatory infertility. Additionally, previous studies reported that an abnormal expression of noncoding RNA may promote ferroptosis in immortalized ovarian granulosa cell lines. However, little is known about whether ovarian ferroptosis is increased in PCOS, and there is insufficient direct evidence for a role of ferroptosis in PCOS, and the underlying mechanism. Moreover, the effect of the inhibition of ferroptosis with Fer-1 in PCOS remains unclear.</p><p><strong>Study design size duration: </strong>Ferroptosis was evaluated in human granulosa cells (hGCs) from non-PCOS (n = 6-16) and PCOS (n = 7-18) patients. The experimental study was completed <i>in vitro</i> using primary hGCs from women undergoing IVF. Improvements in PCOS indicators following ferroptosis inhibition with Fer-1 were investigated in a dehydroepiandrosterone (DHEA)-induced PCOS rat model (n = 8 per group).</p><p><strong>Participants/materials setting methods: </strong>Ovarian ferroptosis was evaluated in the following ways: by detecting iron concentrations via ELISA and fluorescent probes; measuring malondialdehyde (MDA) concentrations via ELISA; assessing ferroptosis-related protein abundance with western blotting; observing mitochondrial morphology with transmission electron microscopy; and determining cell viability. Primary hGCs were collected from women undergoing IVF. They were treated with dihydrotestosterone (DHT) for 24 h. The effect of DHT on ferroptosis was examined in the presence or absence of small interfering RNA-mediated knockdown of the putative receptor coregulator for signaling molecules. The role of ovarian ferroptosis in PCOS progression was explored <i>in vivo</i> in rats. The DHEA-induced PCOS rat model was treated with the ferroptosis inhibitor, Fer-1, and the oocytes and metaphase II oocytes were counted after ovarian stimulation. Additionally, rats were treated with the ferroptosis inducer, RSL3, to further explore the effect of ferroptosis. The concentrations of testosterone, FSH, and LH were assessed.</p><p><strong>Main results and the role of chance: </strong>Increased ferroptosis was detected in the ovaries of patients with PCOS and in rats with DHEA-induced PCOS. Increased concentrations of Fe²⁺ (<i>P","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10973940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320045","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}