Human Reproduction Update最新文献

{"title":"A fresh start for IVM: capacitating the oocyte for development using pre-IVM.","authors":"Robert B Gilchrist, Tuong M Ho, Michel De Vos, Flor Sanchez, Sergio Romero, William L Ledger, Ellen Anckaert, Lan N Vuong, Johan Smitz","doi":"10.1093/humupd/dmad023","DOIUrl":"10.1093/humupd/dmad023","url":null,"abstract":"<p><strong>Background: </strong>While oocyte IVM is practiced sporadically it has not achieved widespread clinical practice globally. However, recently there have been some seminal advances in our understanding of basic aspects of oocyte biology and ovulation from animal studies that have led to novel approaches to IVM. A significant recent advance in IVM technology is the use of biphasic IVM approaches. These involve the collection of immature oocytes from small antral follicles from minimally stimulated patients/animals (without hCG-priming) and an ∼24 h pre-culture of oocytes in an advanced culture system ('pre-IVM') prior to IVM, followed by routine IVF procedures. If safe and efficacious, this novel procedure may stand to make a significant impact on human ART practices.</p><p><strong>Objective and rationale: </strong>The objectives of this review are to examine the major scientific advances in ovarian biology with a unique focus on the development of pre-IVM methodologies, to provide an insight into biphasic IVM procedures, and to report on outcomes from animal and clinical human data, including safety data. The potential future impact of biphasic IVM on ART practice is discussed.</p><p><strong>Search methods: </strong>Peer review original and review articles were selected from PubMed and Web of Science searches for this narrative review. Searches were performed using the following keywords: oocyte IVM, pre-IVM, biphasic IVM, CAPA-IVM, hCG-triggered/primed IVM, natural cycle IVF/M, ex-vivo IVM, OTO-IVM, oocyte maturation, meiotic competence, oocyte developmental competence, oocyte capacitation, follicle size, cumulus cell (CC), granulosa cell, COC, gap-junction communication, trans-zonal process, cAMP and IVM, cGMP and IVM, CNP and IVM, EGF-like peptide and IVM, minimal stimulation ART, PCOS.</p><p><strong>Outcomes: </strong>Minimizing gonadotrophin use means IVM oocytes will be collected from small antral (pre-dominant) follicles containing oocytes that are still developing. Standard IVM yields suboptimal clinical outcomes using such oocytes, whereas pre-IVM aims to continue the oocyte's development ex vivo, prior to IVM. Pre-IVM achieves this by eliciting profound cellular changes in the oocyte's CCs, which continue to meet the oocyte's developmental needs during the pre-IVM phase. The literature contains 25 years of animal research on various pre-IVM and biphasic IVM procedures, which serves as a large knowledge base for new approaches to human IVM. A pre-IVM procedure based on c-type natriuretic peptide (named 'capacitation-IVM' (CAPA-IVM)) has undergone pre-clinical human safety and efficacy trials and its adoption into clinical practice resulted in healthy live birth rates not different from conventional IVF.</p><p><strong>Wider implications: </strong>Over many decades, improvements in clinical IVM have been gradual and incremental but there has likely been a turning of the tide in the past few years, with landmark discoveries in anim","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"3-25"},"PeriodicalIF":14.8,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10483885","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":"Transcriptomic integrity of human oocytes used in ARTs: technical and intrinsic factor effects.","authors":"Bastien Ducreux, Catherine Patrat, Jacquetta Trasler, Patricia Fauque","doi":"10.1093/humupd/dmad025","DOIUrl":"10.1093/humupd/dmad025","url":null,"abstract":"<p><strong>Background: </strong>Millions of children have been born throughout the world thanks to ARTs, the harmlessness of which has not yet been fully demonstrated. For years, efforts to evaluate the specific effects of ART have focused on the embryo; however, it is the oocyte quality that mainly dictates first and foremost the developmental potential of the future embryo. Ovarian stimulation, cryopreservation, and IVM are sometimes necessary steps to obtain a mature oocyte, but they could alter the appropriate expression of the oocyte genome. Additionally, it is likely that female infertility, environmental factors, and lifestyle have a significant influence on oocyte transcriptomic quality, which may interfere with the outcome of an ART attempt.</p><p><strong>Objective and rationale: </strong>The objective of this review is to identify transcriptomic changes in the human oocyte caused by interventions specific to ART but also intrinsic factors such as age, reproductive health issues, and lifestyle. We also provide recommendations for future good practices to be conducted when attempting ART.</p><p><strong>Search methods: </strong>An in-depth literature search was performed on PubMed to identify studies assessing the human oocyte transcriptome following ART interventions, or in the context of maternal aging, suboptimal lifestyle, or reproductive health issues.</p><p><strong>Outcomes: </strong>ART success is susceptible to external factors, maternal aging, lifestyle factors (smoking, BMI), and infertility due to endometriosis or polycystic ovary syndrome. Indeed, all of these are likely to increase oxidative stress and alter mitochondrial processes in the foreground. Concerning ART techniques themselves, there is evidence that different ovarian stimulation regimens shape the oocyte transcriptome. The perturbation of processes related to the mitochondrion, oxidative phosphorylation, and metabolism is observed with IVM. Cryopreservation might dysregulate genes belonging to transcriptional regulation, ubiquitination, cell cycle, and oocyte growth pathways. For other ART laboratory factors such as temperature, oxygen tension, air pollution, and light, the evidence remains scarce. Focusing on genes involved in chromatin-based processes such as DNA methylation, heterochromatin modulation, histone modification, and chromatin remodeling complexes, but also genomic imprinting, we observed systematic dysregulation of such genes either after ART intervention or lifestyle exposure, as well as due to internal factors such as maternal aging and reproductive diseases. Alteration in the expression of such epigenetic regulators may be a common mechanism linked to adverse oocyte environments, explaining global transcriptomic modifications.</p><p><strong>Wider implications: </strong>Many IVF factors and additional external factors have the potential to impair oocyte transcriptomic integrity, which might not be innocuous for the developing embryo. Fortunately, it","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"26-47"},"PeriodicalIF":14.8,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10211148","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":"Ultrasonographic criteria in the diagnosis of polycystic ovary syndrome: a systematic review and diagnostic meta-analysis.","authors":"Jeffrey Pea, Jahnay Bryan, Cynthia Wan, Alexis L Oldfield, Kiran Ganga, Faith E Carter, Lynn M Johnson, Marla E Lujan","doi":"10.1093/humupd/dmad027","DOIUrl":"10.1093/humupd/dmad027","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary morphology (PCOM) on ultrasonography is considered as a cardinal feature of polycystic ovarian syndrome (PCOS). Its relevance as a diagnostic criterion for PCOS was reaffirmed in the most recent International Evidence-Based Guideline for the Assessment and Management of PCOS. However, there remains a lack of clarity regarding the best practices and specific ultrasonographic markers to define PCOM.</p><p><strong>Objective and rationale: </strong>The aim of this systematic review and diagnostic meta-analysis was to assess the diagnostic accuracy of various ultrasonographic features of ovarian morphology in the diagnosis of PCOS.</p><p><strong>Search methods: </strong>Relevant studies published from 1 January 1990 to 12 June 2023 were identified by a systematic search in PubMed, Web of Science, Scopus, CINAHL, and CENTRAL. Studies that generated diagnostic accuracy measures (e.g. proposed thresholds, sensitivity, specificity) for PCOS using the following ultrasonographic markers met criteria for inclusion: follicle number per ovary (FNPO) or per single cross-section (FNPS), ovarian volume (OV), and stromal features. Studies on pregnant or post-menopausal women were excluded. Risk of bias and applicability assessment for diagnostic test accuracy studies were determined using the QUADAS-2 and QUADAS-C tool for a single index test or between multiple index tests, respectively. Diagnostic meta-analysis was conducted using a bivariate model of pooled sensitivity and specificity, and visualized using forest plots and summary receiver-operating characteristic (SROC) curves.</p><p><strong>Outcomes: </strong>From a total of 2197 records initially identified, 31 studies were included. Data from five and two studies were excluded from the meta-analysis due to duplicate study populations or limited data for the index test, leaving 24 studies. Pooled results of 20 adult studies consisted of 3883 control participants and 3859 individuals with PCOS. FNPO was the most accurate diagnostic marker (sensitivity: 84%, CI: 81-87%; specificity: 91%, CI: 86-94%; AUC: 0.905) in adult women. OV and FNPS had similar pooled sensitivities (OV: 81%, CI: 76-86%; FNPS: 81%, CI: 70-89%) but inferior pooled specificities (OV: 81%, CI: 75-86%; FNPS: 83%, CI: 75-88%) and AUCs (OV: 0.856; FNPS: 0.870) compared to FNPO. Pooled results from four adolescent studies consisting of 210 control participants and 268 girls with PCOS suggested that OV may be a robust ultrasonographic marker for PCOS diagnosis albeit the current evidence remains limited. The majority of the studies had high risk of bias for the patient selection (e.g. lack of randomized/consecutive patient selection) and index test (e.g. lack of pre-proposed thresholds for comparison) domains across all ultrasonographic markers. As such, diagnostic meta-analysis was unable to determine the most accurate cutoff for ultrasonographic markers to diagnose PCOS. Subgroup analysis suggest","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"109-130"},"PeriodicalIF":14.8,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41158428","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":"Endometrial receptivity in women of advanced age: an underrated factor in infertility.","authors":"Amruta D S Pathare, Marina Loid, Merli Saare, Sebastian Brusell Gidlöf, Masoud Zamani Esteki, Ganesh Acharya, Maire Peters, Andres Salumets","doi":"10.1093/humupd/dmad019","DOIUrl":"10.1093/humupd/dmad019","url":null,"abstract":"<p><strong>Background: </strong>Modern lifestyle has led to an increase in the age at conception. Advanced age is one of the critical risk factors for female-related infertility. It is well known that maternal age positively correlates with the deterioration of oocyte quality and chromosomal abnormalities in oocytes and embryos. The effect of age on endometrial function may be an equally important factor influencing implantation rate, pregnancy rate, and overall female fertility. However, there are only a few published studies on this topic, suggesting that this area has been under-explored. Improving our knowledge of endometrial aging from the biological (cellular, molecular, histological) and clinical perspectives would broaden our understanding of the risks of age-related female infertility.</p><p><strong>Objective and rationale: </strong>The objective of this narrative review is to critically evaluate the existing literature on endometrial aging with a focus on synthesizing the evidence for the impact of endometrial aging on conception and pregnancy success. This would provide insights into existing gaps in the clinical application of research findings and promote the development of treatment options in this field.</p><p><strong>Search methods: </strong>The review was prepared using PubMed (Medline) until February 2023 with the keywords such as 'endometrial aging', 'receptivity', 'decidualization', 'hormone', 'senescence', 'cellular', 'molecular', 'methylation', 'biological age', 'epigenetic', 'oocyte recipient', 'oocyte donation', 'embryo transfer', and 'pregnancy rate'. Articles in a language other than English were excluded.</p><p><strong>Outcomes: </strong>In the aging endometrium, alterations occur at the molecular, cellular, and histological levels suggesting that aging has a negative effect on endometrial biology and may impair endometrial receptivity. Additionally, advanced age influences cellular senescence, which plays an important role during the initial phase of implantation and is a major obstacle in the development of suitable senolytic agents for endometrial aging. Aging is also accountable for chronic conditions associated with inflammaging, which eventually can lead to increased pro-inflammation and tissue fibrosis. Furthermore, advanced age influences epigenetic regulation in the endometrium, thus altering the relation between its epigenetic and chronological age. The studies in oocyte donation cycles to determine the effect of age on endometrial receptivity with respect to the rates of implantation, clinical pregnancy, miscarriage, and live birth have revealed contradictory inferences indicating the need for future research on the mechanisms and corresponding causal effects of women's age on endometrial receptivity.</p><p><strong>Wider implications: </strong>Increasing age can be accountable for female infertility and IVF failures. Based on the complied observations and synthesized conclusions in this review, advanced age h","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"773-793"},"PeriodicalIF":14.8,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10195806","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":"The pathophysiological role of estrogens in the initial stages of pregnancy: molecular mechanisms and clinical implications for pregnancy outcome from the periconceptional period to end of the first trimester.","authors":"F Parisi, C Fenizia, A Introini, A Zavatta, C Scaccabarozzi, M Biasin, V Savasi","doi":"10.1093/humupd/dmad016","DOIUrl":"10.1093/humupd/dmad016","url":null,"abstract":"<p><strong>Background: </strong>Estrogens regulate disparate female physiological processes, thus ensuring reproduction. Altered estrogen levels and signaling have been associated with increased risks of pregnancy failure and complications, including hypertensive disorders and low birthweight babies. However, the role of estrogens in the periconceptional period and early pregnancy is still understudied.</p><p><strong>Objective and rationale: </strong>This review aims to summarize the current evidence on the role of maternal estrogens during the periconceptional period and the first trimester of pregnancies conceived naturally and following ART. Detailed molecular mechanisms and related clinical impacts are extensively described.</p><p><strong>Search methods: </strong>Data for this narrative review were independently identified by seven researchers on Pubmed and Embase databases. The following keywords were selected: 'estrogens' OR 'estrogen level(s)' OR 'serum estradiol' OR 'estradiol/estrogen concentration', AND 'early pregnancy' OR 'first trimester of pregnancy' OR 'preconceptional period' OR 'ART' OR 'In Vitro Fertilization (IVF)' OR 'Embryo Transfer' OR 'Frozen Embryo Transfer' OR 'oocyte donation' OR 'egg donation' OR 'miscarriage' OR 'pregnancy outcome' OR 'endometrium'.</p><p><strong>Outcomes: </strong>During the periconceptional period (defined here as the critical time window starting 1 month before conception), estrogens play a crucial role in endometrial receptivity, through the activation of paracrine/autocrine signaling. A derailed estrogenic milieu within this period seems to be detrimental both in natural and ART-conceived pregnancies. Low estrogen levels are associated with non-conception cycles in natural pregnancies. On the other hand, excessive supraphysiologic estrogen concentrations at time of the LH peak correlate with lower live birth rates and higher risks of pregnancy complications. In early pregnancy, estrogen plays a massive role in placentation mainly by modulating angiogenic factor expression-and in the development of an immune-tolerant uterine micro-environment by remodeling the function of uterine natural killer and T-helper cells. Lower estrogen levels are thought to trigger abnormal placentation in naturally conceived pregnancies, whereas an estrogen excess seems to worsen pregnancy development and outcomes.</p><p><strong>Wider implications: </strong>Most current evidence available endorses a relation between periconceptional and first trimester estrogen levels and pregnancy outcomes, further depicting an optimal concentration range to optimize pregnancy success. However, how estrogens co-operate with other factors in order to maintain a fine balance between local tolerance towards the developing fetus and immune responses to pathogens remains elusive. Further studies are highly warranted, also aiming to identify the determinants of estrogen response and biomarkers for personalized estrogen administration regimens","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"699-720"},"PeriodicalIF":14.8,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9677177","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":"Endometrial scratching in women undergoing IVF/ICSI: an individual participant data meta-analysis.","authors":"Nienke E van Hoogenhuijze, Gemma Lahoz Casarramona, Sarah Lensen, Cindy Farquhar, Mohan S Kamath, Aleyamma T Kunjummen, Nick Raine-Fenning, Sine Berntsen, Anja Pinborg, Shari Mackens, Zeynep Ozturk Inal, Ernest H Y Ng, Jennifer S M Mak, Sachin A Narvekar, Wellington P Martins, Mia Steengaard Olesen, Helen L Torrance, Ben W Mol, Marinus J C Eijkemans, Rui Wang, Frank J M Broekmans","doi":"10.1093/humupd/dmad014","DOIUrl":"10.1093/humupd/dmad014","url":null,"abstract":"<p><strong>Background: </strong>In IVF/ICSI treatment, the process of embryo implantation is the success rate-limiting step. Endometrial scratching has been suggested to improve this process, but it is unclear if this procedure increases the chance of implantation and live birth (LB) and, if so, for whom, and how the scratch should be performed.</p><p><strong>Objective and rationale: </strong>This individual participant data meta-analysis (IPD-MA) aims to answer the question of whether endometrial scratching in women undergoing IVF/ICSI influences the chance of a LB, and whether this effect is different in specific subgroups of women. After its incidental discovery in 2000, endometrial scratching has been suggested to improve embryo implantation. Numerous randomized controlled trials (RCTs) have been conducted, showing contradicting results. Conventional meta-analyses were limited by high within- and between-study heterogeneity, small study samples, and a high risk of bias for many of the trials. Also, the data integrity of several trials have been questioned. Thus, despite numerous RCTs and a multitude of conventional meta-analyses, no conclusion on the clinical effectiveness of endometrial scratching could be drawn. An IPD-MA approach is able to overcome many of these problems because it allows for increased uniformity of outcome definitions, can filter out studies with data integrity concerns, enables a more precise estimation of the true treatment effect thanks to adjustment for participant characteristics and not having to make the assumptions necessary in conventional meta-analyses, and because it allows for subgroup analysis.</p><p><strong>Search methods: </strong>A systematic literature search identified RCTs on endometrial scratching in women undergoing IVF/ICSI. Authors of eligible studies were invited to share original data for this IPD-MA. Studies were assessed for risk of bias (RoB) and integrity checks were performed. The primary outcome was LB, with a one-stage intention to treat (ITT) as the primary analysis. Secondary analyses included as treated (AT), and the subset of women that underwent an embryo transfer (AT+ET). Treatment-covariate interaction for specific participant characteristics was analyzed in AT+ET.</p><p><strong>Outcomes: </strong>Out of 37 published and 15 unpublished RCTs (7690 participants), 15 RCTs (14 published, one unpublished) shared data. After data integrity checks, we included 13 RCTs (12 published, one unpublished) representing 4112 participants. RoB was evaluated as 'low' for 10/13 RCTs. The one-stage ITT analysis for scratch versus no scratch/sham showed an improvement of LB rates (odds ratio (OR) 1.29 [95% CI 1.02-1.64]). AT, AT+ET, and low-RoB-sensitivity analyses yielded similar results (OR 1.22 [95% CI 0.96-1.54]; OR 1.25 [95% CI 0.99-1.57]; OR 1.26 [95% CI 1.03-1.55], respectively). Treatment-covariate interaction analysis showed no evidence of interaction with age, number of previous failed embryo","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"721-740"},"PeriodicalIF":14.8,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9667357","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":"Assessing the influence of preconception diet on female fertility: a systematic scoping review of observational studies.","authors":"Simon Alesi, Nahal Habibi, Thais Rasia Silva, Nicole Cheung, Sophia Torkel, Chau Thien Tay, Alejandra Quinteros, Hugo Winter, Helena Teede, Aya Mousa, Jessica A Grieger, Lisa J Moran","doi":"10.1093/humupd/dmad018","DOIUrl":"10.1093/humupd/dmad018","url":null,"abstract":"<p><strong>Background: </strong>Preconception diet is a proposed modifiable risk factor for infertility. However, there is no official guidance for women in the preconception period as to which dietary approaches may improve fertility.</p><p><strong>Objective and rationale: </strong>A comprehensive synthesis of the relevant evidence is key to determine the potentially effective dietary patterns and components as well as evidence gaps, and to provide information for nutritional recommendations for couples planning a pregnancy.</p><p><strong>Search methods: </strong>In this systematic scoping review, four electronic databases (Medline and EMBASE via Ovid processing, CAB Direct, and CINAHL via EBSCO) were searched for observational studies (prospective and retrospective cohort, cross-sectional, and case-control studies) from inception to 27 September 2021. Eligible studies included women of reproductive age during the preconception period, and evaluated exposures related to preconception diet and outcomes related to fertility. Results were synthesized using a descriptive approach.</p><p><strong>Outcomes: </strong>A total of 36 studies were eligible for inclusion (31 prospective, 3 cross-sectional, and 2 case-control studies) and were published between 2007 and 2022. Of the assessed dietary exposures, increased adherence to the Mediterranean diet displayed the strongest and most consistent association with improved clinical pregnancy rates. Reducing trans fatty acids (TFAs), saturated fatty acids, and discretionary food intake (fast food and sugar-sweetened beverages) were associated with improvements in live birth, clinical pregnancy rates, and related ART outcomes. The dietary components of seafood, dairy, and soy demonstrated inconsistent findings across the few included studies.</p><p><strong>Wider implications: </strong>Due to heterogeneity and the limited available literature on most exposures, there is insufficient evidence to support any specific dietary approach for improving fertility. However, following some of the dietary approaches outlined in this review (anti-inflammatory diets, reducing TFA, and discretionary food intake) are consistent with broad healthy eating guidelines, have little to no associated risk, and offer a plausible set of possible benefits. This warrants further exploration in randomized controlled trials.</p>","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"811-828"},"PeriodicalIF":14.8,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9834686","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":"Dissecting mammalian reproduction with spatial transcriptomics.","authors":"Xin Zhang, Qiqi Cao, Shreya Rajachandran, Edward J Grow, Melanie Evans, Haiqi Chen","doi":"10.1093/humupd/dmad017","DOIUrl":"10.1093/humupd/dmad017","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Mammalian reproduction requires the fusion of two specialized cells: an oocyte and a sperm. In addition to producing gametes, the reproductive system also provides the environment for the appropriate development of the embryo. Deciphering the reproductive system requires understanding the functions of each cell type and cell-cell interactions. Recent single-cell omics technologies have provided insights into the gene regulatory network in discrete cellular populations of both the male and female reproductive systems. However, these approaches cannot examine how the cellular states of the gametes or embryos are regulated through their interactions with neighboring somatic cells in the native tissue environment owing to tissue disassociations. Emerging spatial omics technologies address this challenge by preserving the spatial context of the cells to be profiled. These technologies hold the potential to revolutionize our understanding of mammalian reproduction.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective and rationale: &lt;/strong&gt;We aim to review the state-of-the-art spatial transcriptomics (ST) technologies with a focus on highlighting the novel biological insights that they have helped to reveal about the mammalian reproductive systems in the context of gametogenesis, embryogenesis, and reproductive pathologies. We also aim to discuss the current challenges of applying ST technologies in reproductive research and provide a sneak peek at what the field of spatial omics can offer for the reproduction community in the years to come.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Search methods: &lt;/strong&gt;The PubMed database was used in the search for peer-reviewed research articles and reviews using combinations of the following terms: 'spatial omics', 'fertility', 'reproduction', 'gametogenesis', 'embryogenesis', 'reproductive cancer', 'spatial transcriptomics', 'spermatogenesis', 'ovary', 'uterus', 'cervix', 'testis', and other keywords related to the subject area. All relevant publications until April 2023 were critically evaluated and discussed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Outcomes: &lt;/strong&gt;First, an overview of the ST technologies that have been applied to studying the reproductive systems was provided. The basic design principles and the advantages and limitations of these technologies were discussed and tabulated to serve as a guide for researchers to choose the best-suited technologies for their own research. Second, novel biological insights into mammalian reproduction, especially human reproduction revealed by ST analyses, were comprehensively reviewed. Three major themes were discussed. The first theme focuses on genes with non-random spatial expression patterns with specialized functions in multiple reproductive systems; The second theme centers around functionally interacting cell types which are often found to be spatially clustered in the reproductive tissues; and the thrid theme discusses pathological states in reproductive systems which are often associated with unique","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"794-810"},"PeriodicalIF":14.8,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9677176","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":"PCOS during the menopausal transition and after menopause: a systematic review and meta-analysis.","authors":"Mercedes Millán-de-Meer, Manuel Luque-Ramírez, Lía Nattero-Chávez, Héctor F Escobar-Morreale","doi":"10.1093/humupd/dmad015","DOIUrl":"10.1093/humupd/dmad015","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Current knowledge about the consequences of PCOS during the late reproductive years and after menopause is limited.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective and rationale: &lt;/strong&gt;We performed a systematic review and meta-analysis of data on the pathophysiology, clinical manifestations, diagnosis, prognosis, and treatment of women ≥45 years of age-peri- or postmenopausal-with PCOS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Search methods: &lt;/strong&gt;Studies published up to 15 April 2023, identified by Entrez-PubMed, EMBASE, and Scopus online facilities, were considered. We included cross-sectional or prospective studies that reported data from peri- or postmenopausal patients with PCOS and control women with a mean age ≥45 years. Three independent researchers performed data extraction. Meta-analyses of quantitative data used random-effects models because of the heterogeneity derived from differences in study design and criteria used to define PCOS, among other confounding factors. Sensitivity analyses restricted the meta-analyses to population-based studies, to studies including only patients diagnosed using the most widely accepted definitions of PCOS, only menopausal women or only women not submitted to ovarian surgery, and studies in which patients and controls presented with similar indexes of weight excess. Quality of evidence was assessed using the GRADE system.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Outcomes: &lt;/strong&gt;The initial search identified 1400 articles, and another six were included from the reference lists of included articles; 476 duplicates were deleted. We excluded 868 articles for different reasons, leaving 37 valid studies for the qualitative synthesis, of which 28 studies-published in 41 articles-were considered for the quantitative synthesis and meta-analyses. Another nine studies were included only in the qualitative analyses. Compared with controls, peri- and postmenopausal patients with PCOS presented increased circulating total testosterone (standardized mean difference, SMD 0.78 (0.35, 1.22)), free androgen index (SMD 1.29 (0.89, 1.68)), and androstenedione (SMD 0.58 (0.23, 0.94)), whereas their sex hormone-binding globulin was reduced (SMD -0.60 (-0.76, -0.44)). Women with PCOS showed increased BMI (SMD 0.57 (0.32, 0.75)), waist circumference (SMD 0.64 (0.42, 0.86)), and waist-to-hip ratio (SMD 0.38 (0.14, 0.61)) together with increased homeostasis model assessment of insulin resistance (SMD 0.56 (0.27, 0.84)), fasting insulin (SMD 0.61 (0.38, 0.83)), fasting glucose (SMD 0.48 (0.29, 0.68)), and odds ratios (OR, 95% CI) for diabetes (OR 3.01 (1.91, 4.73)) compared to controls. Women with PCOS versus controls showed decreased HDL concentrations (SMD -0.32 (-0.46, -0.19)) and increased triglycerides (SMD 0.31 (0.16, 0.46)), even though total cholesterol and LDL concentrations, as well as the OR for dyslipidaemia, were similar to those of controls. The OR for having hypertension was increased in women with PCOS compared with controls (OR 1.79 (1.36, 2.36)). ","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"741-772"},"PeriodicalIF":14.8,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9682916","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":"Obstetric and neonatal outcomes after natural versus artificial cycle frozen embryo transfer and the role of luteal phase support: a systematic review and meta-analysis.","authors":"T R Zaat,&nbsp;E B Kostova,&nbsp;P Korsen,&nbsp;M G Showell,&nbsp;F Mol,&nbsp;M van Wely","doi":"10.1093/humupd/dmad011","DOIUrl":"https://doi.org/10.1093/humupd/dmad011","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The number of frozen embryo transfers (FET) has increased dramatically over the past decade. Based on current evidence, there is no difference in pregnancy rates when natural cycle FET (NC-FET) is compared to artificial cycle FET (AC-FET) in subfertile women. However, NC-FET seems to be associated with lower risk of adverse obstetric and neonatal outcomes compared with AC-FET cycles. Currently, there is no consensus about whether NC-FET needs to be combined with luteal phase support (LPS) or not. The question of how to prepare the endometrium for FET has now gained even more importance and taken the dimension of safety into account as it should not simply be reduced to the basic question of effectiveness.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective and rationale: &lt;/strong&gt;The objective of this project was to determine whether NC-FET, with or without LPS, decreases the risk of adverse obstetric and neonatal outcomes compared with AC-FET.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Search methods: &lt;/strong&gt;A systematic review and meta-analysis was carried out. A literature search was performed using the following databases: CINAHL, EMBASE, and MEDLINE from inception to 10 October 2022. Observational studies, including cohort studies, and registries comparing obstetric and neonatal outcomes between singleton pregnancies after NC-FET and those after AC-FET were sought. Risk of bias was assessed using the ROBINS-I tool. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. We calculated pooled odds ratios (ORs), pooled risk differences (RDs), pooled adjusted ORs, and prevalence estimates with 95% CI using a random effect model, while heterogeneity was assessed by the I2.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Outcomes: &lt;/strong&gt;The conducted search identified 2436 studies, 890 duplicates were removed and 1546 studies were screened. Thirty studies (NC-FET n = 56 445; AC-FET n = 57 231) were included, 19 of which used LPS in NC-FET. Birthweight was lower following NC-FET versus AC-FET (mean difference 26.35 g; 95% CI 11.61-41.08, I2 = 63%). Furthermore NC-FET compared to AC-FET resulted in a lower risk of large for gestational age (OR 0.88, 95% 0.83-0.94, I2 = 54%), macrosomia (OR 0.81; 95% CI 0.71-0.93, I2 = 68%), low birthweight (OR 0.81, 95% CI 0.77-0.85, I2 = 41%), early pregnancy loss (OR 0.73; 95% CI 0.61-0.86, I2 = 70%), preterm birth (OR 0.80; 95% CI 0.75-0.85, I2 = 20%), very preterm birth (OR 0.66, 95% CI 0.53-0.84, I2 = 0%), hypertensive disorders of pregnancy (OR 0.60, 95% CI 0.50-0.65, I2 = 61%), pre-eclampsia (OR 0.50; 95% CI 0.42-0.60, I2 = 44%), placenta previa (OR 0.84, 95% CI 0.73-0.97, I2 = 0%), and postpartum hemorrhage (OR 0.43; 95% CI 0.38-0.48, I2 = 53%). Stratified analyses on LPS use in NC-FET suggested that, compared to AC-FET, NC-FET with LPS decreased preterm birth risk, while NC-FET without LPS did not (OR 0.75, 95% CI 0.70-0.81). LPS use did not modify the other outcomes. Heterogeneity varied from","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"29 5","pages":"634-654"},"PeriodicalIF":13.3,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0a/93/dmad011.PMC10477943.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10216449","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}