Brendan J Houston, Lachlan M Cauchi, Jessica E M Dunleavy, Richard Burke, Gary R Hime, Moira K O'Bryan
<p><strong>Background: </strong>Spermatogenesis is a dynamic process that involves the co-ordinated development of millions of cells, from stem cells to highly polarized sperm capable of motility and fertility. It is, therefore, not surprising that many thousand genes are required for male fertility. Mutant mouse models are routinely employed to test the function of these genes as well as to validate genetic variants that may be causing human male infertility. The use of mice and other animal models has led to significant knowledge gain regarding the genetic regulation of mammalian male fertility. However, due to the sheer number of genes and genetic variants to be tested these approaches are expensive and time-consuming. We and others have investigated the use of alternate model organisms to expedite validation approaches, including the utility of the fruit fly Drosophila melanogaster.</p><p><strong>Objective and rationale: </strong>This review explores the conserved mechanisms of sperm production between mammals and flies, with a focus on the human setting where possible.</p><p><strong>Search methods: </strong>Studies were identified via PubMed using searches including keywords related to the focus of this review, including human, mammalian, and fly or Drosophila spermatogenesis and male fertility. Follow-up searches including using search terms for specific structures and processes for comparison between species included, but were not limited to, male reproductive tract, spermatogenesis, spermatogonia and stem cell niche, meiosis, spermiogenesis and its sub-processes, and sperm/spermatozoa. No time frame or species restrictions were placed on searches.</p><p><strong>Outcomes: </strong>We identify key phases of spermatogenesis that are highly conserved between humans and flies, including the early germ cell divisions and the ratio of haploid germ cells generated for each spermatogonial stem cell, allowing their use as a model organism to explore such processes. Some processes are moderately well conserved between mammals and flies, including meiosis with the notable absence of 'crossing over' in flies. We also identify some processes that are poorly conserved, such as a divergence in sperm tail accessory structures, for which flies are not likely a suitable model organism to decipher human biology or for mammals broadly. Examples of where the fly has been or could be useful to study mammalian gene function in male fertility have also been described.</p><p><strong>Wider implications: </strong>Drosophila melanogaster is undoubtedly a useful model organism for studying a wide range of human diseases with genetic origins, including male infertility. Both humans and flies possess a pair of testes with the primary role of generating sperm. The formation of cysts in Drosophila testes allows germ cells to constantly proliferate and stay synchronized at the respective maturation phase, as is the case for humans. While both organisms use a method of sper
{"title":"A comparison of spermatogenesis between flies and men-conserved processes of male gamete production.","authors":"Brendan J Houston, Lachlan M Cauchi, Jessica E M Dunleavy, Richard Burke, Gary R Hime, Moira K O'Bryan","doi":"10.1093/humupd/dmaf018","DOIUrl":"10.1093/humupd/dmaf018","url":null,"abstract":"<p><strong>Background: </strong>Spermatogenesis is a dynamic process that involves the co-ordinated development of millions of cells, from stem cells to highly polarized sperm capable of motility and fertility. It is, therefore, not surprising that many thousand genes are required for male fertility. Mutant mouse models are routinely employed to test the function of these genes as well as to validate genetic variants that may be causing human male infertility. The use of mice and other animal models has led to significant knowledge gain regarding the genetic regulation of mammalian male fertility. However, due to the sheer number of genes and genetic variants to be tested these approaches are expensive and time-consuming. We and others have investigated the use of alternate model organisms to expedite validation approaches, including the utility of the fruit fly Drosophila melanogaster.</p><p><strong>Objective and rationale: </strong>This review explores the conserved mechanisms of sperm production between mammals and flies, with a focus on the human setting where possible.</p><p><strong>Search methods: </strong>Studies were identified via PubMed using searches including keywords related to the focus of this review, including human, mammalian, and fly or Drosophila spermatogenesis and male fertility. Follow-up searches including using search terms for specific structures and processes for comparison between species included, but were not limited to, male reproductive tract, spermatogenesis, spermatogonia and stem cell niche, meiosis, spermiogenesis and its sub-processes, and sperm/spermatozoa. No time frame or species restrictions were placed on searches.</p><p><strong>Outcomes: </strong>We identify key phases of spermatogenesis that are highly conserved between humans and flies, including the early germ cell divisions and the ratio of haploid germ cells generated for each spermatogonial stem cell, allowing their use as a model organism to explore such processes. Some processes are moderately well conserved between mammals and flies, including meiosis with the notable absence of 'crossing over' in flies. We also identify some processes that are poorly conserved, such as a divergence in sperm tail accessory structures, for which flies are not likely a suitable model organism to decipher human biology or for mammals broadly. Examples of where the fly has been or could be useful to study mammalian gene function in male fertility have also been described.</p><p><strong>Wider implications: </strong>Drosophila melanogaster is undoubtedly a useful model organism for studying a wide range of human diseases with genetic origins, including male infertility. Both humans and flies possess a pair of testes with the primary role of generating sperm. The formation of cysts in Drosophila testes allows germ cells to constantly proliferate and stay synchronized at the respective maturation phase, as is the case for humans. While both organisms use a method of sper","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"533-558"},"PeriodicalIF":16.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12584897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849686","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}
Andrew Peel, Hannah Lyons, Cathryn A Tully, Andrew D Vincent, David Jesudason, Gary Wittert, Nicole O McPherson
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
背景：肥胖是男性因素性不育症的一个普遍的可改变的原因。孕前指南建议男性保持健康的体重；然而，对于男性肥胖患者的减肥方法或减肥量，它们提供的指导有限。减肥的一线干预措施包括生活方式优化（健康饮食和运动），其次是药物治疗或严重情况下的减肥手术。每种方式都有不同的减肥潜力和并发症，其生殖影响目前尚不清楚。目的与理由综合现有的关于肥胖干预对男性肥胖患者生殖影响的证据。在可能的情况下，评估观察到的效果是否取决于体重减轻的程度。检索方法使用PubMed、Web of Science、Embase、Cochrane Central Register of Controlled Trials和Scopus检索从研究开始到2024年12月发表的英文文章，使用与四类相关的预设关键词：男性、超重/肥胖、体重减轻（减肥手术、营养、饮食、生活方式、运动、药物治疗）和生育（受孕、辅助生殖、精子、精液）。研究纳入了在干预前后反复评估生殖能力（精液分析、受孕率、辅助生殖结果）的育龄男性（18-50岁），这些男性接受了肥胖干预，确定了减肥效果。当两项或两项以上相同模态的研究以适合荟萃分析的方式评估结果时，进行荟萃分析。当有五个或更多合适的研究可用时，进行考虑体重减轻的meta回归。出现了不适合meta分析的叙述性综述。32项研究纳入分析，其中一项研究评估了生活方式干预和药物治疗。受孕率和辅助生殖的评估在所有模式中都是有限的。在几乎所有的病例中，肥胖干预对精液质量的影响作为生殖能力的替代指标进行了检查，证据的确定性很低。18项研究对减肥手术进行了评估，包括12项准实验研究、1项随机对照试验、1项病例系列和4项病例报告。随机对照试验的固定效应和随机效应荟萃分析发现，在任何干预中，对照组和干预组之间的精子参数没有差异，尽管小样本量限制了可解释性。对减肥手术前后结果的随机效应荟萃分析发现，在减肥手术后，没有临床显著的精液参数或DNA损伤变化。药物治疗（二甲双胍和利拉鲁肽）在5项研究中进行评估，包括4项准实验研究和1例病例报告。关于这些药物对生育结果的影响，没有足够的数据得出明确的结论。生活方式干预在10项研究中进行评估，包括5项准实验研究和5项随机对照试验。固定效应荟萃分析发现，生活方式干预后，精子正常形态改善（平均差异= 0.59%，95%可信区间=[0.23,0.94]），进步性改善（10.56%[8.97,12.15]）。关于减肥干预和男性生育能力的数据主要局限于检查精液质量的观察性研究。生活方式干预后精液质量的改善提示了优化营养和体育活动的潜在益处，而减肥手术的有限变化表明，肥胖相关的精子功能障碍不会以剂量依赖的方式随着体重减轻和/或快速减肥的负面影响而解决。发现了大量的知识空白，包括有限的随机试验，对受孕结果的检查不足和对GLP-1激动剂作用的评估有限。注册号CRD 42022349665。
{"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}
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.
{"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}
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,
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
{"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}
Lucile Ferreux, Bastien Ducreux, Julie Firmin, Ahmed Chargui, Khaled Pocate-Cheriet, Chloé Maignien, Pietro Santulli, Maud Borensztein, Patricia Fauque, Catherine Patrat
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
{"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}
Nathalie Søderhamn Bülow, Marie Louise Wissing, Nick Macklon, Anja Pinborg, Kristine Løssl
<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
背景：全球范围内冻融胚胎移植（FET）周期的增加导致了对子宫内膜制备方法的批判性评估。虽然目前临床使用的各种方法，如自然或改良自然周期FET，使用来曲唑（LTZ）和/或促性腺激素的刺激FET，以及人工周期（AC） FET，但最佳方案仍不清楚，特别是对于低排卵或多囊卵巢综合征（PCOS）的女性。本系统综述和荟萃分析比较了LTZ FET和AC FET在这些人群的生殖、产科和新生儿结局方面的差异。目的和理由：目的是确定与AC FET相比，LTZ FET是否能改善排卵障碍和/或PCOS妇女的生殖、产科和新生儿结局。检索方法：对MEDLINE、Cochrane和ClinicalTrials.gov数据库进行全面检索，直至2024年6月。符合条件的研究包括有排卵障碍和/或多囊卵巢综合征的妇女，比较LTZ FET和AC FET。数据提取重点关注活产率（LBR）、持续妊娠率、临床妊娠率、妊娠丢失率、妊娠高血压疾病（HDP）、妊娠期糖尿病（GDM）、出生体重、小胎龄（SGA）、大胎龄（LGA）、先天性畸形。结果：纳入74项研究，包括15项观察性研究和2项随机对照试验（rct）；研究共纳入8307名接受LTZ FET治疗的女性（±额外的促性腺激素）和16940名接受AC FET治疗的女性。将LTZ FET与AC FET进行比较的荟萃分析显示，LB的几率有适度但统计学上显著的增加（OR 1.37, 95% CI 1.21-1.56），对应于8%的风险差异（95% CI 4%-11%）。报告LB的一项RCT对LTZ FET和AC FET产生了相似的LBR，因此不支持LTZ FET后的更好结果。将LTZ FET和AC FET的妊娠损失（定义为血清hCG阳性或临床妊娠后的妊娠损失）进行比较。荟萃分析显示LTZ FET可降低PL的发生率（OR 0.63, 95% CI 0.51-0.78）。然而，报道这一结果的两项随机对照试验显示出高度异质性，引入了结果的不确定性。LTZ FET与HDP （OR 0.70, 95% CI 0.58-0.84）和LGA （OR 0.75, 95% CI 0.67-0.85）的风险较低相关，但与GDM或SGA的风险无显著差异。对于所有结果，证据的确定性都很低。更广泛的影响：与AC FET相比，LTZ FET可以适度改善生殖结果，降低一些产科并发症的风险，特别是在排卵不足的妇女中。然而，证据的质量仍然很低，需要更多设计良好的随机对照试验来证实这些发现。在等待进一步数据的同时，LTZ FET可能被推荐为有排卵障碍的妇女替代AC FET的可行方法。注册号：PROSPERO-CRD42023395117。
{"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}
Madelon van Wely, Julie M Hastings, Basil C Tarlatzis, Rui Wang
{"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}
<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
背景：能够从保留生育能力中受益的人数正在增加。然而，由于卫生保健提供者（HCPs）缺乏认识和误解，获得生育保留服务受到阻碍。有必要考虑到医护人员的看法和需求的多方面的教育计划。系统地了解影响HCPs对使用生育保护的认识和态度的因素可以帮助确定课程中要包含的主题和最需要这些项目的专业。目的与理由：本研究旨在对影响医护人员保留生育能力意识和态度的因素进行定量分析，确定医护人员应考虑的细分领域（即职业群体和专业），并评估其保留生育能力的适应症和主题。检索方法：根据PRISMA范围审查扩展（PRISMA- scr）：清单和说明进行方案和范围审查。文献检索在PubMed®、Web of Science™和PsycINFO®三个数据库中进行。原始的经验，同行评议，和完整的定量或混合方法的文章包括对生育保护的意识和态度的HCPs。涉及本科生、实习生、住院医师和研究员的研究没有被考虑在内，也没有定性数据。使用个性化数据图表工具提取感兴趣的变量，并使用MS Excel电子表格绘制数据图表。结果：纳入的研究包括54项定量研究和6项混合方法研究，主要来自美国、亚洲国家（中国、日本、土耳其、印度、伊朗）和欧洲国家（荷兰、法国、英国）。研究参与者主要由肿瘤学、妇产科和儿科领域的专业医生和/或护理专业人员组成。几乎所有的研究都评估了在肿瘤疾病和卵母细胞冷冻的背景下，HCPs对保留生育能力的认识和态度。在文献中讨论的主要主题是信息需求和提供以及护理和实践的组织。其他主题包括法律方面，获取和覆盖范围，以及生育保护干预措施。结果表明，HCPs对保留生育能力的认识和态度倾向于受其职业轨迹相关因素（与同伴和患者参与保留生育能力问题的程度、接受治疗的患者数量和高级培训）的影响，而不是其社会人口统计学特征或对患者特征的看法。更广泛的影响：需要进一步的实证研究，包括涉及在初级卫生保健机构工作的医务人员和专门从事社会心理护理的医务人员的研究，以及关于因生殖老龄化和性别转换原因而保持生育能力的研究。有必要投资于向各种保健医务人员提供关于保留生育能力的教育，而不仅仅是涉及肿瘤学的专业医务人员。实施包括法律方面、获取途径、覆盖范围和生育保护干预措施在内的教育项目，可以提高HCPs对生育保护的认识和态度。需要改变政策和宣传，以支持更好地将保留生育能力作为患者生殖健康旅程中的一种工具。注册号：osf.io/h56ds。
{"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}
Ying Gao, Yikun Zhou, Zhidan Hong, Binyu Ma, Xiaojie Wang, Linhang Nie, Ling Ma, Yuanzhen Zhang, Ming Zhang, Mei Wang
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
{"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}
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
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
{"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 &lt; 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}
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