Human Reproduction Update最新文献

{"title":"The effect of obesity interventions on male fertility: a systematic review and meta-analysis","authors":"Andrew Peel, Hannah Lyons, Cathryn A Tully, Andrew D Vincent, David Jesudason, Gary Wittert, Nicole O McPherson","doi":"10.1093/humupd/dmaf025","DOIUrl":"https://doi.org/10.1093/humupd/dmaf025","url":null,"abstract":"Background Obesity is a prevalent modifiable cause of male factor infertility. Preconception guidelines recommend men maintain a healthy weight; however, they provide limited guidance regarding methods or volume of weight loss for men with obesity. First-line interventions for weight loss involve lifestyle optimization (healthy diet and exercise), followed by pharmacotherapy or bariatric surgery in severe cases. Each modality has differing weight loss potential and complications for which the reproductive implications are currently unclear. Objective and Rationale To synthesize the available evidence regarding the reproductive effects of obesity interventions in men with obesity. Where possible, to evaluate whether the observed effects depend on the magnitude of weight loss. Search Methods Searches for articles published in English was performed using PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials and Scopus from inception until December 2024, using prespecified keywords pertaining to four categories: male, overweight/obesity, weight loss (bariatric surgery, nutrition, diet, lifestyle, exercise, pharmacotherapy) and fertility (conception, assisted reproduction, sperm, semen). Studies of reproductive-aged men (18–50 years) who underwent an obesity intervention with established weight loss benefits and undertook repeated assessment of reproduction capacity (semen analysis, conception rates, assisted reproduction outcomes) before and after the intervention were included. Meta-analysis was performed when two or more studies of the same modality assessed an outcome measure in a manner suitable for meta-analysis. A meta-regression considering weight loss achieved was performed when five or more suitable studies were available. Narrative review of studies not suitable for meta-analysis occurred. Outcomes 32 studies were included in the analysis, with one study assessing both lifestyle interventions and pharmacotherapy. Assessment of conception rates and assisted reproduction was limited across all modalities. In almost all cases, the effect of obesity interventions on semen quality was examined as a surrogate for reproductive capacity and the certainty of evidence was low. Bariatric surgery was assessed in 18 studies, including 12 quasi-experimental studies, one randomized controlled trial, one case series and four case reports. Fixed- and random-effects meta-analysis of randomized controlled trials identified no differences in sperm parameters between control and intervention arms across any intervention, although small sample size limits interpretability. Random-effects meta-analyses of pre-post outcomes identified no clinically significant semen parameters or DNA damage changes following bariatric surgery. Pharmacotherapy (metformin and liraglutide) was assessed in five studies, including four quasi-experimental studies and one case report. There were insufficient data to draw clear conclusions regarding the impact of ","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"36 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247024","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 diagnosis and management of extrauterine and uterine ectopic pregnancy.","authors":"Jessica Farren,Bassel H Al Wattar,Davor Jurkovic","doi":"10.1093/humupd/dmaf024","DOIUrl":"https://doi.org/10.1093/humupd/dmaf024","url":null,"abstract":"In the last two decades, we have consolidated our knowledge of the epidemiology and risk factors for ectopic pregnancies. Minimally invasive surgical skills are now widespread, and laparoscopic surgery is recognized as the best and safest operative treatment for extrauterine ectopic pregnancies. Based on the evidence from randomized trials published a decade ago, laparoscopic salpingectomy is accepted as the optimal surgical treatment for tubal ectopic pregnancy. However, with recent advances in surgical techniques and improvement in surgical skills, the appropriateness of tubal removal versus conservation is under increasing scrutiny. Improvements in the organization and provision of care for women presenting with early pregnancy complications, in conjunction with better quality and wider use of ultrasound imaging, have resulted in an increased ability to detect small failing ectopic pregnancies, which were impossible to diagnose in the past. Many of these pregnancies are destined to resolve spontaneously without the need for any intervention. The necessity to avoid overtreatment and the potential for iatrogenic harm in such cases has facilitated the introduction of expectant management into mainstream clinical practice. This represents one of the key developments in the care for women with ectopic pregnancies. By contrast, the efficacy of medical management with methotrexate has been questioned. Another important development in recent years has been a rapid rise in the prevalence of ectopic pregnancies that are located outside the uterine cavity but within the confines of the uterus, the largest burden of which is from Caesarean scar ectopic pregnancies. This has promoted the development of new terminology and classification of ectopic pregnancies, with the aim of raising awareness of these increasingly prevalent types and minimizing the risk of misdiagnosis. In comparison to ectopic pregnancies outside the uterus, uterine ectopic pregnancies are more difficult to diagnose and manage, and are also associated with increased maternal morbidity, mortality, and adverse reproductive outcomes. Another challenge, which is peculiar to uterine ectopic pregnancies, is their potential to progress to reach foetal viability, albeit with a high risk of extreme prematurity. This requires women and clinicians to make difficult decisions about whether these pregnancies should be terminated to protect maternal health, despite some possibility of a good foetal outcome. Herein, we provide a comprehensive review of published literature to summarize new evidence and explore emerging themes with respect to ectopic pregnancy. Our aim is to provide an overview of modern classification and diagnosis, to summarize available treatment options and recommendations, and to emphasize longer-term outcomes, including the potential psychological impact of ectopic pregnancy. We examine current knowledge gaps and outline priorities for further research.","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"213 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246568","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 epidemiology, clinical burden, and prevention of intrauterine adhesions (IUAs) related to surgically induced endometrial trauma: a systematic literature review and selective meta-analyses.","authors":"Malcolm G Munro,Christina A Salazar,Bala Bhagavath,Mark H Emanuel,Heather G Huddleston,Dhruv Sobti,Ajit K Jaiswal,Rachel Gamburg,Jatinder Kumar,Coby Martin,Angelo B Hooker, ","doi":"10.1093/humupd/dmaf019","DOIUrl":"https://doi.org/10.1093/humupd/dmaf019","url":null,"abstract":"BACKGROUNDReproductive-age women with intrauterine adhesions (IUAs) following uterine surgery may be asymptomatic or may experience light or absent menstruation, infertility, preterm delivery, and/or peripartum hemorrhage. Understanding procedure- and technique-specific risks and the available evidence on the impact of surgical adjuvants is essential to the design of future research.OBJECTIVE AND RATIONALEWhile many systematic reviews have been published, most deal with singular aspects of the problem. Consequently, a broadly scoped systematic review and selective meta-analyses identifying evidence strengths and gaps are necessary to inform future research and treatment strategies.SEARCH METHODSA systematic literature review was performed seeking evidence on IUA incidence following selected uterine procedures and the effectiveness of hysteroscopic adhesiolysis on menstrual, endometrial, fertility, and pregnancy-related outcomes. An evaluation of the impact of surgical adjuvants designed to facilitate adhesion-free endometrial repair was included. Searches were conducted in the PubMed, Embase, and Cochrane databases following PRISMA guidelines and included English-language publications from inception to 8 November 2024. Inclusion criteria restricted articles to those reporting IUA epidemiology or related clinical outcomes. Risk of bias assessment used the US NIH tools for interventional and observational studies. Meta-analyses were conducted and reported only for outcomes where there were sufficient data. Per analysis, we report on proportions (with 95% CI), heterogeneity (I2), and the risk of bias for each study included.OUTCOMESThe review identified 249 appropriate publications. The risks of new-onset IUAs following the removal of products of conception after early pregnancy loss, hysteroscopic myomectomy, and hysteroscopic metroplasty for septum correction were 17% (95% CI: 11-25%; 13 studies, I2 = 87%, poor to good evidence quality), 16% (95% CI: 6-28%; 8 studies, I2 = 93%, fair to good evidence quality), and 28% (95% CI: 13-46%; 8 studies, I2 = 91%, fair to good evidence quality), respectively. For primary IUA prevention with adjuvant intrauterine gel barriers, the relative risks were 0.45 (95% CI: 0.30-0.68; three studies, I2 = 0%, poor to good evidence quality), 0.38 (95% CI: 0.20-0.73; three studies, I2 = 0%, fair evidence quality), and 0.29 (95% CI: 0.12-0.69; three studies, I2 = 0%, fair to good evidence quality), respectively, following the above potentially adhesiogenic procedures. Following adhesiolysis without adjuvants, the IUA recurrence rate was 35% (95% CI: 24-46%; 13 studies, I2 = 95%, poor to good evidence quality), similar to the rate of 43% for both those treated adjuvantly with an intrauterine balloon (95% CI: 35-51%; 14 studies, I2 = 85%, poor to good evidence quality), or an IUD (95% CI: 27-59%; four studies, I2 = 85%, fair to good evidence quality). The recurrence rate for secondary prevention with gel barriers was 28% (9","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"12 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008730","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":"Transcript profiling and gene regulation of the human pre-implantation embryo: parental effects and impact of ARTs","authors":"Lucile Ferreux, Bastien Ducreux, Julie Firmin, Ahmed Chargui, Khaled Pocate-Cheriet, Chloé Maignien, Pietro Santulli, Maud Borensztein, Patricia Fauque, Catherine Patrat","doi":"10.1093/humupd/dmaf022","DOIUrl":"https://doi.org/10.1093/humupd/dmaf022","url":null,"abstract":"BACKGROUND Infertility is a growing global challenge, with ARTs significantly improving birth rates for infertile couples. However, ART conceptions are associated with a higher risk of negative obstetrical and perinatal outcomes, with potential long-term effects on offspring health. Many pre-implantation embryos exhibit abnormal morphokinetics, implantation failure, or arrested development. ART procedures and parental factors are suspected to perturb the embryonic transcriptome, potentially affecting molecular and epigenetic events during gametogenesis and early development. The timing and mechanisms of these perturbations remain unclear. Genome-wide transcriptomic misregulation in ART-conceived human pre-implantation embryos may provide important insights into observed differences between ART and naturally conceived offspring. OBJECTIVE AND RATIONALE This narrative review aims to explore how the transcriptome of the human pre-implantation embryo is influenced by parental characteristics, ART conditions, and embryonic factors, with the characterization of the temporal sequence of acquisition of lineage-specific markers at the blastocyst stage serving as a prerequisite. The primary objective is to compile changes in gene expression resulting from parental and intrinsic characteristics or from ART-specific interventions. A secondary aim is to identify common dysregulated molecular pathways across all factors studied. SEARCH METHODS A comprehensive PubMed search (up to December 2024) was conducted to identify studies assessing transcriptomic profiles in human blastocysts. Studies were included based on parental infertility characteristics (e.g. age, polycystic ovary syndrome (PCOS), endometriosis, diminished ovarian reserve (DOR), sperm alterations, unexplained infertility (UI), and obesity), ART interventions (e.g. hormonal stimulation, IVM, IVF, culture conditions, and vitrification), and intrinsic embryo factors (e.g. morphology, ploidy, sex, and developmental arrest). Differentially expressed genes between different embryo groups were compared across studies, and Gene Ontology analysis identified common or specific pathways. Single-cell RNA sequencing data were used to map lineage-specific transcriptomic patterns in human blastocysts, categorizing expression changes by cell lineages (epiblast, primitive endoderm, and trophectoderm). Where human data on blastocysts were limited, animal studies or other cleaved stages were discussed. OUTCOMES Maternal age was the most significant contributor to misregulated gene expression in human blastocysts, affecting metabolic and developmental processes. Variations in culture medium impacted cell cycle regulation, carbohydrate metabolism, and RNA biosynthesis. Blastocyst morphology mostly influenced metabolic process changes. Blastocyst aneuploidy induced significant changes in developmental pathways and pluripotency gene expression in the epiblast. Evidence on the effects of PCOS, endometriosis, DOR, sperm a","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"32 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930700","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":"Reproductive outcomes after letrozole stimulated versus artificial frozen-thawed embryo transfer cycles in women with PCOS and/or oligo-anovulation: a systematic review and meta-analysis.","authors":"Nathalie Søderhamn Bülow, Marie Louise Wissing, Nick Macklon, Anja Pinborg, Kristine Løssl","doi":"10.1093/humupd/dmaf011","DOIUrl":"10.1093/humupd/dmaf011","url":null,"abstract":"<p><strong>Background: </strong>The global increase in frozen-thawed embryo transfer (FET) cycles has led to a critical evaluation of endometrial preparation methods. While various approaches such as natural or modified natural cycle FET, stimulated FET by use of letrozole (LTZ) and/or gonadotrophins, and artificial cycle (AC) FET, are currently in clinical use, the optimal regimen remains unclear, particularly for women with oligo-anovulation or polycystic ovarian syndrome (PCOS). This systematic review and meta-analysis compares LTZ FET with AC FET regarding reproductive, obstetric, and neonatal outcomes in these populations.</p><p><strong>Objective and rationale: </strong>The aim was to determine whether LTZ FET improves reproductive, obstetric, and neonatal outcomes compared to AC FET in women with ovulatory disorders and/or PCOS.</p><p><strong>Search methods: </strong>A comprehensive search of MEDLINE, Cochrane, and ClinicalTrials.gov databases was conducted for studies until June 2024. Eligible studies included women with ovulatory disorders and/or PCOS, comparing LTZ FET to AC FET. Data extraction focused on the live birth rate (LBR), ongoing pregnancy rate, clinical pregnancy rate, pregnancy loss rate, hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), birth weight, small for gestational age (SGA), large for gestational age (LGA), and congenital malformations.</p><p><strong>Outcomes: </strong>The search identified 74 studies, and included 15 observational studies and two randomized controlled trials (RCTs) meeting the inclusion criteria; the studies encompassed a total of 8307 women treated with LTZ FET (±additional gonadotropin) and 16,940 women treated with AC FET. The meta-analysis comparing LTZ FET to AC FET demonstrated a modest yet statistically significant increase in the odds of LB (OR 1.37, 95% CI 1.21-1.56), corresponding to an 8% risk difference (95% CI 4%-11%). The one RCT that reported on LB yielded a similar LBR for LTZ FET and AC FET, thus did not support a better outcome after LTZ FET. Pregnancy losses, defined either as a loss following a positive serum hCG or following a clinical pregnancy, were compared between LTZ FET and AC FET. The meta-analysis indicated a reduction in the odds of PL with LTZ FET (OR 0.63, 95% CI 0.51-0.78). However, the two RCTs reporting this outcome exhibited high heterogeneity, introducing uncertainty of the result. LTZ FET was associated with lower risks of HDP (OR 0.70, 95% CI 0.58-0.84) and LGA (OR 0.75, 95% CI 0.67-0.85), but no significant differences were observed for GDM or SGA. For all outcomes, the certainty of evidence was low.</p><p><strong>Wider implications: </strong>LTZ FET may offer a modest improvement in reproductive outcomes and a lower risk of some obstetric complications compared to AC FET, particularly in women with oligo-anovulation. However, the quality of evidence remains low, and more well-designed RCTs are needed to confirm these findings. W","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"445-463"},"PeriodicalIF":16.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152726","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":"Bias busters: using the right risk-of-bias tools.","authors":"Madelon van Wely, Julie M Hastings, Basil C Tarlatzis, Rui Wang","doi":"10.1093/humupd/dmaf016","DOIUrl":"10.1093/humupd/dmaf016","url":null,"abstract":"","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"403-404"},"PeriodicalIF":16.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144509516","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":"Awareness and attitudes toward fertility preservation among healthcare providers: a scoping review of quantitative evidence.","authors":"Alla Tirsina, Cláudia de Freitas, Susana Silva","doi":"10.1093/humupd/dmaf014","DOIUrl":"10.1093/humupd/dmaf014","url":null,"abstract":"<p><strong>Background: </strong>The number of people who could benefit from fertility preservation is increasing. However, access to fertility preservation services has been hampered by a lack of awareness and misconceptions among healthcare providers (HCPs). There is a need for multifaceted educational programs that consider the perceptions and needs of HCPs. Systematic knowledge of the factors influencing the awareness and attitudes of HCPs toward the use of fertility preservation can help to identify the topics to be included in curricula and the specialties where these programs are most needed.</p><p><strong>Objective and rationale: </strong>This comprehensive scoping review aims to synthesize quantitative evidence on the factors influencing the awareness and attitudes of HCPs toward fertility preservation, identifying the segments of HCPs (i.e. occupation groups and specialties) that are considered and the fertility preservation indications and topics assessed.</p><p><strong>Search methods: </strong>The protocol and the scoping review were conducted according to the PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Literature searches were conducted in three databases: PubMed®, Web of Science™, and PsycINFO®. Original empirical, peer-reviewed, and full-length quantitative or mixed-methods articles concerning the awareness and attitudes of HCPs toward fertility preservation were included. Studies involving undergraduate students, interns, residents, and fellows were not considered, nor was qualitative data. The variables of interest were extracted using an individualized data charting tool, and an MS Excel spreadsheet was used to chart the data.</p><p><strong>Outcomes: </strong>The studies reviewed, comprising 54 quantitative studies and 6 mixed-methods studies, were primarily sourced from the USA, Asian countries (China, Japan, Turkey, India, Iran), and European countries (Netherlands, France, UK). The study participants were predominantly composed of specialist medical practitioners and/or nursing professionals with expertise in the fields of oncology, obstetrics and gynecology, and pediatrics. Almost all studies assessed the awareness and attitudes of HCPs toward fertility preservation in the context of oncologic diseases and oocyte freezing. The primary topics addressed in the literature are information needs and provision and the organization of care and practice. Additional topics include legal aspects, access and coverage, as well as fertility preservation interventions. The results suggested that awareness and attitudes of HCPs toward fertility preservation tended to be influenced by factors related to their professional trajectories (level of involvement in fertility preservation issues with peers and patients, number of patients treated, and advanced training), rather than their sociodemographic characteristics or perceptions of patient's characteristics.</p><p><strong>Wider implications: </strong>Further","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"497-511"},"PeriodicalIF":16.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531214","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 intricate dance of RNA-binding proteins: unveiling the mechanisms behind male infertility","authors":"Ying Gao, Yikun Zhou, Zhidan Hong, Binyu Ma, Xiaojie Wang, Linhang Nie, Ling Ma, Yuanzhen Zhang, Ming Zhang, Mei Wang","doi":"10.1093/humupd/dmaf023","DOIUrl":"https://doi.org/10.1093/humupd/dmaf023","url":null,"abstract":"BACKGROUND RNA-binding proteins (RBPs) are indispensable for transcriptional and post-transcriptional processes during spermatogenesis, orchestrating germ cell proliferation, differentiation, and maturation. Despite their established importance, the contributions of RBPs in male infertility remain underexplored. Recently, a seminal Science publication reported an RBP atlas of 1744 murine testicular RBPs, 22 loss-of-function variants, and 137 deleterious missense variants identified in 1046 infertile patients, providing unprecedented opportunities to investigate their molecular and clinical relevance. Variants in RBP-related genes associated with azoospermia, oligozoospermia, teratozoospermia, and asthenozoospermia highlight their potential as diagnostic biomarkers and therapeutic targets. However, comprehensive analyses that integrate genetic, functional, and clinical insights are still lacking. OBJECTIVE AND RATIONALE This review aims to systematically analyze the roles of RBPs in male infertility. Leveraging state-of-the-art datasets and experimental insights, it examines pathogenic variants and variants of uncertain significance (VUS), and elucidates the gene–disease relationships (GDRs). Furthermore, it explores known RBP functions across spermatogenesis stages and identifies candidate RBP genes. By integrating these findings, this work provides a comprehensive framework to advance the genetic understanding of RBPs, and their potential as clinical biomarkers and therapeutic targets in male infertility. SEARCH METHODS We searched the PubMed database for articles until 13 July 2025, using the keywords ‘RNA-binding protein’, ‘male infertility’, ‘spermatogenesis’, ‘sperm’, ‘genetic variant’, ‘functional analyses’, and ‘knockout mouse model’. Pathogenic variants and VUS in 1744 RBP-coding genes, retrieved from the ClinVar and PubMed databases, were systematically analyzed to classify GDRs by the International Male Infertility Genomics Consortium database. Functional data from RBP knockout mouse models were assessed to elucidate stage-specific roles in spermatogenesis. Candidate RBP genes lacking knockout mouse models were identified by mining the RBP atlas, alongside data from the Genotype-Tissue Expression, Human Protein Atlas, and Uniprot databases. The clinical potential of RBPs as diagnostic biomarkers and therapeutic targets was also discussed. OUTCOMES Our search generated ∼2000 records, and 331 relevant articles were ultimately included in the final text. Firstly, this review identified 177 pathogenic variants in 62 RBP genes and 91 VUS in 35 RBP genes, 15 of which have been confidently linked to human male infertility. Secondly, functional analyses of 124 RBP knockout mouse models revealed their stage-specific regulatory roles in spermatocytogenesis, spermatidogenesis, and spermiogenesis, offering insights into key processes such as piwi-interacting RNA biogenesis, chromatin remodeling, and RNA stability. Thirdly, 38 RBP genes lacking knoc","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"9 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899401","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":"Preconception lifestyle interventions for women—a systematic review and meta-analysis of intervention characteristics and behaviour change techniques","authors":"Sophia Torkel, Evangeline Mantzioris, Anthony Villani, Nicole J Kellow, Dhruv Bhatnagar, Elaine K Osei-Safo, Margaret McGowan, Nur K Abdul Jafar, Nadia Bogatzke, Simon Alesi, Tuba Astarcioglu, Ben W Mol, Robert J Norman, Stephanie Cowan, Rui Wang, Lisa Moran","doi":"10.1093/humupd/dmaf021","DOIUrl":"https://doi.org/10.1093/humupd/dmaf021","url":null,"abstract":"BACKGROUND The time before conception is an important opportunity to improve maternal lifestyle, and hence improve fertility and health. However, the components of effective preconception lifestyle interventions are unclear. OBJECTIVE AND RATIONALE This review aimed to assess the association of intervention characteristics and behaviour change techniques with the effect of lifestyle interventions on fertility, obstetric, foetal, anthropometric, and metabolic outcomes in women planning a pregnancy. Understanding the optimal components of preconception lifestyle interventions is essential to improve success of future interventions. SEARCH METHODS We searched Ovid MEDLINE, PsycINFO, Embase, Emcare, Scopus, Cochrane Central Register of Controlled Trials, and CINAHL (6 December 2024). We included randomized controlled trials on women planning a pregnancy which assessed the effect of lifestyle intervention compared to standard minimal care or no intervention on fertility, obstetric, foetal, anthropometric, and metabolic outcomes. We performed random-effects meta-analysis with subgroup analysis based on participant characteristics, intervention characteristics (using the Template for Intervention Description and Replication (TIDieR) framework), and behaviour change techniques (using the Behaviour Change Taxonomy v1). We assessed trustworthiness (using the Trustworthiness in Randomised Controlled Trials (TRACT) checklist), risk of bias (using the Cochrane Risk of Bias 2.0 tool), and certainty of the evidence (using the GRADE approach). OUTCOMES Following eligibility screening and trustworthiness assessments, we included 24 studies (n = 7795 women), of which the majority were conducted in high-income countries (79%) and studied women with infertility (67%). Risk of bias was low for seven studies, some concerns for 15 studies and high for two studies. Overall, there was no difference in clinical pregnancy (odds ratio [95% CI]: 1.06 [0.84, 1.35], I2 = 24.22%) or live birth (odds ratio [95% CI]: 1.17 [0.82, 1.67], I2 = 48.73%) with lifestyle intervention. Odds of clinical pregnancy were higher for interventions delivered over ≥10 sessions (2.17 [1.21, 3.86] vs 0.88 [0.72, 1.07], P = 0.004 for subgroup differences) and with the behaviour change technique Adding objects to the environment (e.g. provision of intervention-compliant food and/or exercise equipment) (3.51 [1.70, 7.23] vs 0.90 [0.75, 1.08], P < 0.001 for subgroup differences). Lifestyle interventions reduced weight (mean difference [95% CI]: −3.87 kg [−5.76, −1.97], I2 = 95.03%) and fasting blood glucose (mean difference [95% CI]: −0.15 mM [−0.25, −0.04], I2 = 0%). Greater weight loss was observed for interventions with a weight loss aim (−4.19 kg [−6.30, −1.92] vs −0.81 kg [−1.48, −0.14], P = 0.003 for subgroup differences). Greater weight loss was observed for interventions delivered solely via face-to-face (−6.02 kg [−8.96, −3.07]) compared to those delivered via a combination of face-to-f","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"125 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899402","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 meta-analysis and systematic review of advanced maternal age patients in IVF.","authors":"Hadas Ganer Herman, Ido Feferkorn, Michael H Dahan, Shauna Reinblatt, Ezgi Demirtas, William Buckett","doi":"10.1093/humupd/dmaf020","DOIUrl":"https://doi.org/10.1093/humupd/dmaf020","url":null,"abstract":"<p><strong>Background: </strong>There has been an increase in the average age of patients seeking fertility treatments over the past decades, with a significantly higher rate of advanced maternal age (AMA) patients undergoing IVF. It is unclear if different treatment strategies in IVF improve outcomes in AMA patients.</p><p><strong>Objective and rationale: </strong>The aim of this systematic review was to assess the efficacy of different interventions employed in IVF in patients of AMA.</p><p><strong>Search methods: </strong>A comprehensive search in Embase, Medline, and the Cochrane Library was performed. The search strategy included keywords related to IVF and AMA. We included all original peer-reviewed articles published in English, from January 1985 to September 2024, primarily designed to assess the efficacy of different interventions in IVF on clinical outcomes in AMA patients. Meta-analyses were performed for interventions for which sufficient randomized controlled trials existed.</p><p><strong>Outcomes: </strong>A total of 151 studies were included in the review. AMA was not consistently defined in all studies reviewed, although common to all studies was an age above 35 years. For the majority of evidence, there appeared to be no clear advantage to any stimulation protocol in AMA patients. There also appeared to be no advantage to any specific FSH medication, while a meta-analysis performed for the addition of LH to follicular stimulating hormone in stimulation demonstrated similar clinical pregnancy and live birth rates. No good evidence was found to support the routine implementation of ICSI in AMA patients, while a meta-analysis performed for assisted hatching (AH) pointed to decreased live birth rates with its implementation. Low-quality evidence demonstrated an increase in live birth rates with multiple embryos transferred with an increase in multiple pregnancies delivered. Finally, a meta-analysis performed for preimplantation genetic testing for aneuploidy (PGT-A) pointed to similar live birth rates as for no testing.</p><p><strong>Wider implications: </strong>This review failed to find an advantage to the routine implementation of treatment strategies such as specific stimulation protocols and gonadotropins, ICSI, and PGT-A, and a potential harmful effect for AH. Future high-quality randomized controlled trials are needed to affirm the majority of this review's conclusions.</p><p><strong>Registration number: </strong>PROSPERO ID: CRD42022335889.</p>","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":""},"PeriodicalIF":16.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849687","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}