Human Reproduction Update最新文献

{"title":"Defects in mRNA splicing and implications for infertility: a comprehensive review and in silico analysis.","authors":"Kuokuo Li, Yuge Chen, Yuying Sheng, Dongdong Tang, Yunxia Cao, Xiaojin He","doi":"10.1093/humupd/dmae037","DOIUrl":"https://doi.org/10.1093/humupd/dmae037","url":null,"abstract":"<p><strong>Background: </strong>mRNA splicing is a fundamental process in the reproductive system, playing a pivotal role in reproductive development and endocrine function, and ensuring the proper execution of meiosis, mitosis, and gamete function. Trans-acting factors and cis-acting elements are key players in mRNA splicing whose dysfunction can potentially lead to male and female infertility. Although hundreds of trans-acting factors have been implicated in mRNA splicing, the mechanisms by which these factors influence reproductive processes are fully understood for only a subset. Furthermore, the clinical impact of variations in cis-acting elements on human infertility has not been comprehensively characterized, leading to probable omissions of pathogenic variants in standard genetic analyses.</p><p><strong>Objective and rationale: </strong>This review aimed to summarize our current understanding of the factors involved in mRNA splicing regulation and their association with infertility disorders. We introduced methods for prioritizing and functionally validating splicing variants associated with human infertility. Additionally, we explored corresponding abnormal splicing therapies that could potentially provide insight into treating human infertility.</p><p><strong>Search methods: </strong>Systematic literature searches of human and model organisms were performed in the PubMed database between May 1977 and July 2024. To identify mRNA splicing-related genes and pathogenic variants in infertility, the search terms 'splice', 'splicing', 'variant', and 'mutation' were combined with azoospermia, oligozoospermia, asthenozoospermia, multiple morphological abnormalities of the sperm flagella, acephalic spermatozoa, disorders of sex development, early embryonic arrest, reproductive endocrine disorders, oocyte maturation arrest, premature ovarian failure, primary ovarian insufficiency, zona pellucida, fertilization defects, infertile, fertile, infertility, fertility, reproduction, and reproductive.</p><p><strong>Outcomes: </strong>Our search identified 5014 publications, of which 291 were included in the final analysis. This review provided a comprehensive overview of the biological mechanisms of mRNA splicing, with a focus on the roles of trans-acting factors and cis-acting elements. We highlighted the disruption of 52 trans-acting proteins involved in spliceosome assembly and catalytic activity and recognized splicing regulatory regions and epigenetic regulation associated with infertility. The 73 functionally validated splicing variants in the cis-acting elements of 54 genes have been reported in 20 types of human infertility; 27 of them were located outside the canonical splice sites and potentially overlooked in standard genetic analysis due to likely benign or of uncertain significance. The in silico prediction of splicing can prioritize potential splicing abnormalities that may be true pathogenic mechanisms. We also summarize the methods for pri","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425790","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":"Parental conditions, modifiable lifestyle factors, and first trimester growth and development: a systematic review.","authors":"Naomi Graafland, Melek Rousian, Merle L de Zwart, Regine P M Steegers-Theunissen, Eric A P Steegers, Anke G Posthumus","doi":"10.1093/humupd/dmaf001","DOIUrl":"https://doi.org/10.1093/humupd/dmaf001","url":null,"abstract":"<p><strong>Introduction: </strong>The embryonic period in human development is the foundation of lifelong and even transgenerational health. Although previously believed to be uniform, there is increasing evidence that embryonic growth is influenced by the conditions and modifiable lifestyle factors of parents in the periconception period. In ongoing pregnancies, a delay in growth in the first trimester has been associated with miscarriages, malformations, low birth weight, preterm birth, and small for gestational age at birth. This has stimulated research on factors associated with variations in human embryonic growth. However, there is still no consensus on which parental conditions and modifiable lifestyle factors affect first trimester growth and development and to what extent.</p><p><strong>Objective and rationale: </strong>A systematic review was undertaken according to PRISMA guidelines to provide an overview of literature on the associations between parental conditions and lifestyle factors in the periconception period and first trimester growth and development, with an aim to identify existing evidence gaps.</p><p><strong>Search methods: </strong>A systematic search of the literature concerning articles on embryonic growth and lifestyle factors published between 1900 and 2024 was performed in six electronic databases. Studies were eligible for inclusion if they reported on the association between periconception parental conditions and/or modifiable lifestyle factors and an in vivo measure of first trimester growth or development (i.e. crown-rump length, embryonic volume and/or Carnegie stage) between 6 + 0 and 13 + 6 weeks gestational age in singleton pregnancies. Parental conditions and modifiable lifestyle factors were defined as ex utero determinants divided into characteristics (age, ethnicity, BMI, blood pressure), lifestyle risk factors (caffeine intake, alcohol consumption, and smoking), nutrition (dietary patterns and food groups), vitamins (vitamin B9/B11, vitamin B12, vitamin D, and supplements), and the ambient environment (air pollution, noise exposure, and neighborhood deprivation). Risk of bias of the included studies was assessed using the Newcastle-Ottawa Scale. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to assess the evidence level of the studies included in the review.</p><p><strong>Outcomes: </strong>A total of 4708 unique records were identified, of which 34 studies were included in the systematic review. The majority of studies investigating smoking and BMI suggested an inverse association with embryonic growth and development, while maternal age, folic acid supplement use, and folate levels were positively associated with embryonic growth and development. Studies on blood pressure, ethnicity, vitamin B12, vitamin D, alcohol consumption, caffeine consumption, and ambient environment were too limited to conclude an association with embryonic growth and developmen","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426003","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":"Fertility in transgender and gender diverse people: systematic review of the effects of gender-affirming hormones on reproductive organs and fertility","authors":"C De Roo, F Schneider, T H R Stolk, W L J van Vugt, D Stoop, N M van Mello","doi":"10.1093/humupd/dmae036","DOIUrl":"https://doi.org/10.1093/humupd/dmae036","url":null,"abstract":"BACKGROUND Transgender and gender diverse (TGD) people seek gender-affirming care at any age to manage gender identities or expressions that differ from their birth gender. Gender-affirming hormone treatment (GAHT) and gender-affirming surgery may alter reproductive function and/or anatomy, limiting future reproductive options to varying degrees, if individuals desire to either give birth or become a biological parent. OBJECTIVE AND RATIONALE TGD people increasingly pursue help for their reproductive questions, including fertility, fertility preservation, active desire for children, and future options. Their specific needs certainly require more insight into the effects of GAHT on gonads, gametes, and fertility. This systematic review aims to provide an overview of the current knowledge on the impact of GAHT on gonads, gametes, fertility, fertility preservation techniques, and outcomes. SEARCH METHODS This review was registered in the PROSPERO registry under number CRD42024516133. A literature search (in PubMed, Embase, and Web of Science) was performed with a medical information specialist until 15 November 2024. OUTCOMES In all TGD people using GAHT, histological changes have been reported. Using testosterone GAHT, ovarian cortical and stromal changes were reported by various studies. In most studies, persistent activity in folliculogenesis can be concluded based on the descriptions of the follicle count, distribution, and oocyte retrieval yield. However, there may be a negative effect on the fertilization rate in the presence of testosterone. Reports of successful ovarian stimulation, fertilization, pregnancies, and live births have been published, describing cases with and without testosterone discontinuation. After using oestrogen GAHT, testes are reported to be more atrophic, including smaller seminiferous tubules with heavy hyalinization and fibrosis. Spermatogenic levels varied widely from complete spermatogenesis to meiotic arrest with spermatids, to spermatogonial arrest, Sertoli cells only, or even tubular shadows. Oestrogen and anti-androgen treatment causes higher proportions of sperm abnormalities (i.e. low total sperm count, low sperm concentration, poor sperm motility) or azoospermia. However, after cessation, this may be restored. WIDER IMPLICATIONS Although knowledge of the effect of GAHT is growing, blind spots remain to be uncovered. Therefore, additional research in this specific population is needed, preferably comparing outcomes before and after the start of GAHT. This may help to reveal the pure impact of GAHT on reproductive functioning. Research suggestions also include investigations into the reversibility of the GAHT effect, especially for those who start transition at a young age. Looking carefully at the presented data on GAHT effects on gonads and gametes, the correct advice is to assess and reassess reproductive wishes and preferences repeatedly, and also to explore individual fertility preservation needs during ge","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"47 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031090","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":"Celebrating 30 years at Human Reproduction Update.","authors":"Arne S Sunde, Madelon van Wely","doi":"10.1093/humupd/dmae035","DOIUrl":"https://doi.org/10.1093/humupd/dmae035","url":null,"abstract":"","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"31 1","pages":"1"},"PeriodicalIF":14.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924088","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":"Functional hypothalamic amenorrhoea and polycystic ovarian morphology: a narrative review about an intriguing association.","authors":"Johannes Ott, Geoffroy Robin, Marlene Hager, Didier Dewailly","doi":"10.1093/humupd/dmae030","DOIUrl":"10.1093/humupd/dmae030","url":null,"abstract":"<p><strong>Background: </strong>Functional hypothalamic amenorrhoea (FHA) is responsible for 20-35% of all cases of secondary amenorrhoea and, thus, is the second most common cause of secondary amenorrhoea after polycystic ovary syndrome (PCOS). A high number of patients with FHA reveal polycystic ovarian morphology (PCOM) on ultrasound. The combination of amenorrhoea and PCOM can lead to confusion. First, amenorrhoeic women with PCOM fulfil the revised Rotterdam criteria and, thus, can easily be misdiagnosed with PCOS. Moreover, it has been claimed that some women with FHA and concomitant PCOM differ from those without PCOM in terms of endocrine regulation and metabolic traits.</p><p><strong>Objective and rationale: </strong>The main focus of this article was on studies about FHA, which differentiated between patients with or without PCOM. The aim was to estimate the prevalence of PCOM and to look if it has an impact on pathophysiologic, diagnostic and therapeutic issues as well as on long-term consequences.</p><p><strong>Search methods: </strong>Peer review original and review articles were selected from PubMed searches for this review. Searches were performed using the search terms 'polycystic AND functional hypothalamic amenorrhoea'. The reference lists of publications found were searched for relevant additional studies. The inclusion criteria for publications were: English language, patients' age ≥ 18 years, year of publication >1980, original studies, validated diagnosis of FHA, and validated diagnosis of PCOM using transvaginal ultrasound.</p><p><strong>Outcomes: </strong>The prevalence of PCOM in women with FHA varied from 41.9% to 46.7%, which is higher than in healthy non-PCOS controls. Hypothetically, the high prevalence might be due to a mixture of silent PCOM, as in the general population, and pre-existing PCOS. Several differences in metabolic and hormonal parameters were found between FHA-PCOM and FHA-non-PCOM patients. While oestrogen deficiency is common to both groups of patients, FHA-PCOM patients have a higher BMI, higher levels of anti-Müllerian hormone (AMH) and testosterone, a higher increase in LH in the course of a GnRH test, and lower sex hormone binding globulin (SHBG) levels than FHA-non-PCOM patients. The differential diagnosis between FHA-PCOM and PCOS, especially PCOS phenotype D (PCOM and oligo-/anovulation without hyperandrogenism), can be challenging. Several parameters have been suggested, which are helpful though not absolutely reliable. They include the typical causes for FHA (excessive exercise, energy deficit, and/or psychological stress), the serum levels of LH, testosterone, and SHBG, as well as the progestin challenge test. Whether FHA-PCOM has a different risk profile for long-term consequences concerning patients' metabolic and cardiovascular situation as well as their bone mass, is unclear. Concerning therapeutic aspects, there are only few data about FHA-PCOM compared to FHA-non-PCOM. To treat anovula","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"64-79"},"PeriodicalIF":14.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395365","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":"Development and validation of a gonadotropin dose selection model for optimized ovarian stimulation in IVF/ICSI: an individual participant data meta-analysis","authors":"Nienke Schouten, Rui Wang, Helen Torrance, Theodora Van Tilborg, Ercan Bastu, Christina Bergh, Thomas D’Hooghe, Jesper Friis Petersen, Kannamannadiar Jayaprakasan, Yacoub Khalaf, Ellen Klinkert, Antonio La Marca, Lan Vuong, Louise Lapensée, Sarah Lensen, Åsa Magnusson, Adolfo Allegra, Anders Nyboe Andersen, Simone Oudshoorn, Biljana Popovic-Todorovic, Ben Willem Mol, Marinus Eijkemans, Frank Broekmans","doi":"10.1093/humupd/dmae032","DOIUrl":"https://doi.org/10.1093/humupd/dmae032","url":null,"abstract":"BACKGROUND The ovarian response to gonadotropin stimulation varies widely among women, and could impact the probability of live birth as well as treatment risks. Many studies have evaluated the impact of different gonadotropin starting doses, mainly based on predictive variables like ovarian reserve tests (ORT) including anti-Müllerian hormone (AMH), antral follicle count (AFC), and basal follicle-stimulating hormone (bFSH). A Cochrane systematic review revealed that individualizing the gonadotropin starting dose does not affect efficacy in terms of ongoing pregnancy/live birth rates, but may reduce treatment risks such as the development of ovarian hyperstimulation syndrome (OHSS). An individual patient data meta-analysis (IPD-MA) offers a unique opportunity to develop and validate a universal prediction model to help choose the optimal gonadotropin starting dose to minimize treatment risks without affecting efficacy. OBJECTIVE AND RATIONALE The objective of this IPD-MA is to develop and validate a gonadotropin dose-selection model to guide the choice of a gonadotropin starting dose in IVF/ICSI, with the purpose of minimizing treatment risks without compromising live birth rates. SEARCH METHODS Electronic databases including MEDLINE, EMBASE, and CRSO were searched to identify eligible studies. The last search was performed on 13 July 2022. Randomized controlled trials (RCTs) were included if they compared different doses of gonadotropins in women undergoing IVF/ICSI, presented at least one type of ORT, and reported on live birth or ongoing pregnancy. Authors of eligible studies were contacted to share their individual participant data (IPD). IPD and information within publications were used to determine the risk of bias. Generalized linear mixed multilevel models were applied for predictor selection and model development. OUTCOMES A total of 14 RCTs with data of 3455 participants were included. After extensive modeling, women aged 39 years and over were excluded, which resulted in the definitive inclusion of 2907 women. The optimal prediction model for live birth included six predictors: age, gonadotropin starting dose, body mass index, AFC, IVF/ICSI, and AMH. This model had an area under the curve (AUC) of 0.557 (95% confidence interval (CI) from 0.536 to 0.577). The clinically feasible live birth model included age, starting dose, and AMH and had an AUC of 0.554 (95% CI from 0.530 to 0.578). Two models were selected as the optimal model for combined treatment risk, as their performance was equal. One included age, starting dose, AMH, and bFSH; the other also included gonadotropin-releasing hormone (GnRH) analog. The AUCs for both models were 0.769 (95% CI from 0.729 to 0.809). The clinically feasible model for combined treatment risk included age, starting dose, AMH, and GnRH analog, and had an AUC of 0.748 (95% CI from 0.709 to 0.787). WIDER IMPLICATIONS The aim of this study was to create a model including patient characteristics whereby gon","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"12 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867040","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 epigenetic approach of varicocele: a focus on sperm DNA and m6A-RNA methylation","authors":"Nushin Naderi, Marziyeh Tavalaee, Mohammad Hossein Nasr-Esfahani","doi":"10.1093/humupd/dmae034","DOIUrl":"https://doi.org/10.1093/humupd/dmae034","url":null,"abstract":"BACKGROUND Varicocele is an abnormal dilation and torsion of the pampiniform venous plexus in the scrotum due to venous reflux, primarily affecting the left side. It affects 15% of men and is a prevalent contributor to male infertility. Varicocele is a complex disorder influenced by genetic, epigenetic, and environmental factors. Epigenetic modifications, which regulate genome activity independently of DNA or RNA sequences, may contribute to the development and severity of varicocele. These include DNA methylation, histone modifications, and RNA modifications like N6-methyladenosine (m6A). Irregularities in DNA and m6A-RNA methylation during spermatogenesis can cause gene expression abnormalities, DNA damage, and decreased fertility in varicocele patients. OBJECTIVE AND RATIONALE The review aims to comprehensively understand the underlying mechanisms of varicocele, a condition that can significantly impact male fertility. By exploring the role of methylation modifications, specifically DNA and m6A-RNA methylation, the review aims to synthesize evidence from basic, preclinical, and clinical research to expand the existing knowledge on this subject. The ultimate goal is to identify potential avenues for developing targeted treatments that can effectively improve varicocele and ultimately increase sperm quality in affected individuals. SEARCH METHODS A thorough investigation of the scientific literature was conducted through searches in PubMed, Google Scholar, and Science Direct databases until May 2024. All studies investigating the relationship between DNA and m6A-RNA methylation and male infertility, particularly varicocele were reviewed, and the most pertinent reports were included. Keywords such as varicocele, epigenetics, DNA methylation, m6A-RNA methylation, hypermethylation, hypomethylation, spermatozoa, semen parameters, spermatogenesis, and male infertility were used during the literature search, either individually or in combination. OUTCOMES The sperm has a specialized morphology essential for successful fertilization, and its epigenome is unique, potentially playing a key role in embryogenesis. Sperm DNA and RNA methylation, major epigenetic marks, regulate the expression of testicular genes crucial for normal spermatogenesis. This review explores the role of DNA and m6A-RNA methylation, in responding to oxidative stress and how various nutrients influence their function in varicocele condition. Evidence suggests a potential link between varicocele and aberrant DNA/m6A-RNA methylation patterns, especially hypomethylation, but the body of evidence is still limited. Further studies are needed to understand how abnormal expression of DNA/m6A-RNA methylation regulators affects testicular gene expression. Thus, analyzing sperm DNA 5mC/5hmC levels and m6A-RNA methylation regulators may reveal spermatogenesis defects and predict reproductive outcomes. WIDER IMPLICATIONS Nutri-epigenomics is an emerging field that could enhance the knowledge an","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"200 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823186","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 modeling of human implantation and early placentation: achievements and perspectives","authors":"Tanya Dimova, Marina Alexandrova, Ivaylo Vangelov, Yuan You, Gil Mor","doi":"10.1093/humupd/dmae033","DOIUrl":"https://doi.org/10.1093/humupd/dmae033","url":null,"abstract":"BACKGROUND Successful implantation is a critical step for embryo survival. The major losses in natural and assisted human reproduction appeared to occur during the peri-implantation period. Because of ethical constraints, the fascinating maternal–fetal crosstalk during human implantation is difficult to study and thus, the possibility for clinical intervention is still limited. OBJECTIVE AND RATIONALE This review highlights some features of human implantation as a unique, ineffective and difficult-to-model process and summarizes the pros and cons of the most used in vivo, ex vivo and in vitro models. We point out the variety of cell line-derived models and how these data are corroborated by well-defined primary cells of the same nature. Important aspects related to the handling, standardization, validation, and modus operandi of the advanced 3D in vitro models are widely discussed. Special attention is paid to blastocyst-like models recapitulating the hybrid phenotype and HLA profile of extravillous trophoblasts, which are a unique yet poorly understood population with a major role in the successful implantation and immune mother-embryo recognition. Despite raising new ethical dilemmas, extended embryo cultures and synthetic embryo models are also in the scope of our review. SEARCH METHODS We searched the electronic database PubMed from inception until March 2024 by using a multi-stage search strategy of MeSH terms and keywords. In addition, we conducted a forward and backward reference search of authors mentioned in selected articles. OUTCOMES Primates and rodents are valuable in vivo models for human implantation research. However, the deep interstitial, glandular, and endovascular invasion accompanied by a range of human-specific factors responsible for the survival of the fetus determines the uniqueness of the human implantation and limits the cross-species extrapolation of the data. The ex vivo models are short-term cultures, not relevant to the period of implantation, and difficult to standardize. Moreover, the access to tissues from elective terminations of pregnancy raises ethical and legal concerns. Easy-to-culture cancer cell lines have many limitations such as being prone to spontaneous transformation and lacking decent tissue characteristics. The replacement of the original human explants, primary cells or cancer cell lines with cultures of immortalized cell lines with preserved stem cell characteristics appears to be superior for in vitro modeling of human implantation and early placentation. Remarkable advances in our understanding of the peri-implantation stages have also been made by advanced three dimensional (3D) models i.e. spheroids, organoids, and assembloids, as placental and endometrial surrogates. Much work remains to be done for the optimization and standardization of these integrated and complex models. The inclusion of immune components in these models would be an asset to delineate mechanisms of immune tolerance. Stem ","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"1 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823197","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 systematic review and meta-analysis of double trophectoderm biopsy and/or cryopreservation in PGT: balancing the need for a diagnosis against the risk of harm.","authors":"Letizia Li Piani, Pasquale Petrone, Mariafrancesca Brutto, Anick De Vos, Annelore Van Der Kelen, Alberto Vaiarelli, Laura Rienzi, Alessandro Conforti, Danilo Cimadomo, Willem Verpoest","doi":"10.1093/humupd/dmae031","DOIUrl":"https://doi.org/10.1093/humupd/dmae031","url":null,"abstract":"<p><strong>Background: </strong>To prevent the transfer of embryos affected by monogenic conditions and/or chromosomal defects, preimplantation genetic testing (PGT) requires trophectoderm biopsy and cryopreservation. In 2-6% of biopsies, the diagnosis may be inconclusive due to DNA amplification failure or low-quality results. In these cases, a round of re-warming, re-biopsy, and re-cryopreservation is required to obtain a genetic diagnosis. In other cases, when the IVF centre starts providing PGT and/or when the patients develop an indication because of multiple failures, miscarriages or the birth of an affected child after IVF, cryopreserved untested embryos may be warmed, biopsied, and then re-vitrified. However, it is still unclear whether multiple manipulations may reduce reproductive outcomes after PGT.</p><p><strong>Objective and rationale: </strong>This study aimed at conducting a systematic review to investigate the available evidence on the safety of double biopsy and/or double cryopreservation-warming and provide recommendations in this regard. We performed meta-analyses of the differences in the reproductive outcomes (live birth per embryo transfer [LBR per ET], clinical pregnancy rate per ET [CPR per ET], and miscarriage rate per clinical pregnancy [MR per CP]) in double cryopreservation and single biopsy (CBC) or double biopsy and double cryopreservation (BCBC) flows vs the control single biopsy and single cryopreservation (BC) flow. Cryo-survival rates before ET and gestational and perinatal outcomes were also reported.</p><p><strong>Search methods: </strong>PRISMA guidelines were followed to gather all available information from the literature (PubMed, Scopus, and Embase). We used Medical Subject Headings (MeSH) terms and a list of specific keywords relevant for the study question. We searched for original studies in humans, published in peer-reviewed journals in English up to April 2024. Four independent authors assessed the articles for inclusion. One included paper was retrieved from another source.</p><p><strong>Outcomes: </strong>A total of 4219 records were identified, and 10 studies were included in the meta-analysis. Certainty of evidence level ranged from low to moderate. Both the CBC and BCBC groups showed reduced reproductive outcomes compared to the control (BC). Specifically, live birth rates per embryo transfer were lower in the CBC group (OR: 0.56, 95% CI: 0.38-0.81, I2 = 58%; six studies) and the BCBC group (OR: 0.51, 95% CI: 0.34-0.77, I2 = 24%; six studies). CPR per ET were also lower in the CBC group (OR: 0.68, 95% CI: 0.51-0.92, I2 = 57%; seven studies) and the BCBC group (OR: 0.60, 95% CI: 0.46-0.78, I2 = 0%; seven studies). Additionally, MR per CPs were higher in both the CBC group (OR: 1.68, 95% CI: 1.02-2.77, I2 = 50%; seven studies) and the BCBC group (OR: 2.08, 95% CI: 1.13-3.83, I2 = 28%; seven studies). Cryo-survival as well as gestational and perinatal outcomes were within the expected norms in the st","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640315","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":"Infertility treatment and offspring blood pressure-a systematic review and meta-analysis.","authors":"Edwina H Yeung,Ian R Trees,Priscilla K Clayton,Kristen J Polinski,Alicia A Livinski,Diane L Putnick","doi":"10.1093/humupd/dmae029","DOIUrl":"https://doi.org/10.1093/humupd/dmae029","url":null,"abstract":"BACKGROUNDStudies have inconsistently observed that children conceived by IVF or ICSI have higher blood pressure compared to children not conceived by these ARTs.OBJECTIVE AND RATIONALEThe aim was to perform a systematic review and meta-analysis of blood pressure measures of offspring conceived by ART and those conceived naturally. Resolving the suspicion of ART as a risk factor of higher blood pressure, and therefore of heart disease, has public health and clinical implications.SEARCH METHODSA biomedical librarian searched the Embase, PubMed, and Web of Science databases. Searches were limited to records published in English since 1978. Grey literature was searched. Inclusion criteria were humans born via infertility treatment (vs no treatment) who underwent a blood pressure assessment. Exclusion criteria were non-human participants, non-quantitative studies, absence of a control group, and specialty populations (e.g. cancer patients only). Two reviewers independently screened each record's title and abstract and full text using Covidence, extracted data using Excel, and assessed bias using the National Heart, Lung, and Blood Institute's Quality Assessment Tool for cohort studies.OUTCOMESOf 5082 records identified, 79 were included in the systematic review and 36 were included in the meta-analysis of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in ART and non-ART groups. Overall, 34 reports including 40 effect sizes from 25 unique cohorts, compared blood pressure between ART (N = 5229) and non-ART (N = 8509, reference) groups with no covariate adjustment. No standardized mean differences (SMD) in SBP (0.06 per SD of mmHg, 95% CI = -0.05, 0.18) or DBP (0.11, 95% CI = -0.04, 0.25) by treatment were found, but the heterogeneity was considerable (I2=76% for SBP and 87% for DBP). Adjusted analyses were presented in 12 reports, representing 28 effect sizes from 21 unique cohorts (N = 2242 treatment vs N = 37 590 non-treatment). Studies adjusted for varied covariates including maternal (e.g. age, education, body mass index, smoking, pregnancy complications), child (e.g. sex, age, physical activity, BMI, height), and birth characteristics (e.g. birth weight and gestational age). Adjusted results similarly showed no SMD for SBP (-0.03, 95% CI = -0.13, 0.08) or DBP (0.02, 95% CI = -0.12, 0.16), though heterogeneity remained high (I2 = 64% and 86%). Funnel plots indicated a slight publication bias, but the trim and fill approach suggested no missing studies. Removal of five studies which adjusted for birth outcomes (potentially over-adjusting for mediators) made no material difference. Type of treatment (e.g. IVF vs ICSI), period effects by birth year (≤2000 vs >2000), offspring age group (<8, 8-14, 15+), or study location (e.g. Europe) did not modify the results.WIDER IMPLICATIONSIn conclusion, conception by ART was not associated with offspring blood pressure in a meta-analysis, although considerable heterogeneity was observed. Given ","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"1 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385349","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}