<p><strong>Study question: </strong>Does sperm cryopreservation serve as a feasible and effective method for preserving fertility in adult male patients with cancer?</p><p><strong>Summary answer: </strong>Sperm cryopreservation is an effective fertility preservation method and may benefit patients with cancer.</p><p><strong>What is known already: </strong>Sperm cryopreservation is the only way to efficiently preserve male fertility. It is an important procedure in ART. Recently, due to remarkable advances in cancer treatment, an increasing number of studies have reported the outcomes of sperm cryopreservation in patients with cancer.</p><p><strong>Study design size duration: </strong>We conducted an extensive literature search for relevant studies published through to 31 December 2021, in the following databases: CENTRAL, CNKI, Cochrane Systematic Reviews, EMBASE, MEDLINE, PUBMED, and Web of Science. The search terms used were '(cryopreservation OR freeze OR freezing OR banking OR cryostorage OR storage) AND (sperm OR semen OR spermatozoon) AND (cancer OR tumor OR malignancy OR neoplasm)'.</p><p><strong>Participants/materials setting methods: </strong>We included all studies that reported offering or attempting to cryopreserve sperm before or during cancer treatment in male patients considered at risk of treatment-related fertility impairment. We evaluated the eligibility of all data in each study. The major exclusion criteria were as follows: non-cancer patients; pediatric and adolescent cancer patients; not reporting the use of cryopreserved sperm; use of fresh semen for ART; not reporting the number of patients with cancer offered sperm cryopreservation or attempting to do so before or during treatment; using an experimental fertility preservation technique such as preservation of testicular tissue or spermatogonial stem cells; duplicate data; abstracts, case report, comments, reviews, or editorials; insufficient data reported. The quality of the included studies was assessed using the Newcastle-Ottawa scale and the Methodological Index for Non-Randomized Studies.</p><p><strong>Main results and the role of chance: </strong>This meta-analysis included 69 non-randomized studies, with 32 234 patients referred for sperm analysis and 23 178 patients cryopreserving at least one sperm sample. The pooled failed-to-cryopreserve rate was 10% (95% CI, 8-12%), and the sperm disposal and sperm use rates were 23% (95% CI, 16-30%) and 9% (95% CI, 8-10%), respectively. The pregnancy, miscarriage, and delivery rates were 28% (95% CI, 22-33%), 13% (95% CI, 10-17%), and 20% (95% CI, 15-25%), respectively. Subgroup analysis showed higher pregnancy and delivery rates, as well as a lower failed-to-cryopreserve rate, in recent studies compared to those released a decade ago. The studies from Asia reported higher sperm disposal and pregnancy rates than in other continents. Our analysis showed clinical pregnancy rates per cycle of 34% (27-41%), 24% (14-35%), and 9% (5
{"title":"Fertility preservation in adult male patients with cancer: a systematic review and meta-analysis.","authors":"Qing Li, Qiong-Yu Lan, Wen-Bing Zhu, Li-Qing Fan, Chuan Huang","doi":"10.1093/hropen/hoae006","DOIUrl":"10.1093/hropen/hoae006","url":null,"abstract":"<p><strong>Study question: </strong>Does sperm cryopreservation serve as a feasible and effective method for preserving fertility in adult male patients with cancer?</p><p><strong>Summary answer: </strong>Sperm cryopreservation is an effective fertility preservation method and may benefit patients with cancer.</p><p><strong>What is known already: </strong>Sperm cryopreservation is the only way to efficiently preserve male fertility. It is an important procedure in ART. Recently, due to remarkable advances in cancer treatment, an increasing number of studies have reported the outcomes of sperm cryopreservation in patients with cancer.</p><p><strong>Study design size duration: </strong>We conducted an extensive literature search for relevant studies published through to 31 December 2021, in the following databases: CENTRAL, CNKI, Cochrane Systematic Reviews, EMBASE, MEDLINE, PUBMED, and Web of Science. The search terms used were '(cryopreservation OR freeze OR freezing OR banking OR cryostorage OR storage) AND (sperm OR semen OR spermatozoon) AND (cancer OR tumor OR malignancy OR neoplasm)'.</p><p><strong>Participants/materials setting methods: </strong>We included all studies that reported offering or attempting to cryopreserve sperm before or during cancer treatment in male patients considered at risk of treatment-related fertility impairment. We evaluated the eligibility of all data in each study. The major exclusion criteria were as follows: non-cancer patients; pediatric and adolescent cancer patients; not reporting the use of cryopreserved sperm; use of fresh semen for ART; not reporting the number of patients with cancer offered sperm cryopreservation or attempting to do so before or during treatment; using an experimental fertility preservation technique such as preservation of testicular tissue or spermatogonial stem cells; duplicate data; abstracts, case report, comments, reviews, or editorials; insufficient data reported. The quality of the included studies was assessed using the Newcastle-Ottawa scale and the Methodological Index for Non-Randomized Studies.</p><p><strong>Main results and the role of chance: </strong>This meta-analysis included 69 non-randomized studies, with 32 234 patients referred for sperm analysis and 23 178 patients cryopreserving at least one sperm sample. The pooled failed-to-cryopreserve rate was 10% (95% CI, 8-12%), and the sperm disposal and sperm use rates were 23% (95% CI, 16-30%) and 9% (95% CI, 8-10%), respectively. The pregnancy, miscarriage, and delivery rates were 28% (95% CI, 22-33%), 13% (95% CI, 10-17%), and 20% (95% CI, 15-25%), respectively. Subgroup analysis showed higher pregnancy and delivery rates, as well as a lower failed-to-cryopreserve rate, in recent studies compared to those released a decade ago. The studies from Asia reported higher sperm disposal and pregnancy rates than in other continents. Our analysis showed clinical pregnancy rates per cycle of 34% (27-41%), 24% (14-35%), and 9% (5","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 1","pages":"hoae006"},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10882264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-17eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae001
Cristina Valle-Hita, Albert Salas-Huetos, María Fernández de la Puente, María Ángeles Martínez, Silvia Canudas, Antoni Palau-Galindo, Cristina Mestres, José María Manzanares, Michelle M Murphy, Montse Marquès, Jordi Salas-Salvadó, Nancy Babio
<p><strong>Study question: </strong>Is ultra-processed food (UPF) consumption associated with semen quality parameters?</p><p><strong>Summary answer: </strong>Higher UPF consumption was inversely associated with total sperm count, sperm concentration, and total motility in men of reproductive age.</p><p><strong>What is known already: </strong>The consumption of UPF, which has been rising during the last decades, has been demonstrated to be positively associated with several chronic diseases such as diabetes or cardiovascular diseases. However, the scientific evidence on its potential impact on semen quality remains notably limited.</p><p><strong>Study design size duration: </strong>A cross-sectional analysis was conducted using data from 200 healthy men (mean age 28.4 ± 5.5 years) enrolled in the Led-Fertyl (Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters) study between February 2021 and April 2023.</p><p><strong>Participants/materials setting methods: </strong>UPF consumption (% of energy from UPF) was estimated according to the NOVA classification system using a validated 143-item semi-quantitative food frequency questionnaire. Total sperm count, sperm concentration, sperm vitality, total motility, progressive motility, and normal sperm forms were set as the main outcomes. Microscopic parameters were analyzed using a phase-contrast microscope and a computer-assisted sperm analysis (CASA) system. Semen samples were collected and tested according to World Health Organization 2010 standards. Multivariable linear regression models were fitted to estimate the associations between UPF tertile and semen quality parameters.</p><p><strong>Main results and the role of chance: </strong>Sperm concentration (<i>β</i>: -1.42 × 10<sup>6</sup> spz./ml; 95% CI: -2.72 to -0.12) and motility (<i>β</i>: -7.83%; 95% CI: -15.16 to -0.51) were lower in participants in the highest tertile of UPF compared to the lowest. A similar association was observed for sperm count when UPF was analyzed per 10% increment of energy from UPF consumption (<i>β</i>: -1.50 × 10<sup>6</sup> spz.; 95% CI: -2.83 to -0.17). Theoretically replacing 10% of energy from UPF consumption with 10% of energy from unprocessed or minimally processed food consumption was associated with a higher total sperm count, sperm concentration, total motility, progressive motility, and normal sperm forms.</p><p><strong>Limitations reasons for caution: </strong>Cross-sectional studies do not permit the drawing of causal inferences. Measurement errors and reporting bias cannot be entirely ruled out.</p><p><strong>Wider implications of the findings: </strong>This work suggests that consumption of UPF may have an impact on certain semen quality parameters. Furthermore, opting for unprocessed or minimally processed foods instead of UPFs could potentially benefit semen quality. If these results are replicated in future epidemiological studies with different long-ter
研究问题：超加工食品（UPF）消费量与精液质量参数是否相关？在育龄男性中，较高的 UPF 消费量与精子总数、精子浓度和总活力成反比：过去几十年来，UPF 的摄入量一直在上升，这已被证明与多种慢性疾病（如糖尿病或心血管疾病）呈正相关。然而，有关其对精液质量潜在影响的科学证据仍然非常有限：利用 2021 年 2 月至 2023 年 4 月期间参加 Led-Fertyl（精液图和其他男性生育能力相关参数的生活方式和环境决定因素）研究的 200 名健康男性（平均年龄为 28.4 ± 5.5 岁）的数据进行了横断面分析：使用经过验证的 143 项半定量食物频率问卷，根据 NOVA 分类系统估算 UPF 消耗量（UPF 能量百分比）。主要结果包括精子总数、精子浓度、精子活力、总活力、渐进活力和正常精子形态。显微参数使用相差显微镜和计算机辅助精子分析系统（CASA）进行分析。精液样本按照世界卫生组织 2010 年标准进行采集和检测。多变量线性回归模型用于估算UPF三分位数与精液质量参数之间的关系：主要结果和偶然性的作用：与最低的参与者相比，UPF值最高的参与者的精子浓度（β：-1.42 × 106 spz./ml；95% CI：-2.72 至 -0.12）和活力（β：-7.83%；95% CI：-15.16 至 -0.51）较低。当分析 UPF 消费每增加 10%的能量时，精子数量也出现了类似的关联（β：-1.50 × 106 spz.；95% CI：-2.83 至 -0.17）。从理论上讲，用未加工或微量加工食品消费的 10%能量替代 UPF 消费的 10%能量，与较高的精子总数、精子浓度、总活力、渐进活力和正常精子形态有关：横断面研究无法得出因果推论。研究结果的广泛影响：这项研究表明，食用 UPF 可能会对某些精液质量参数产生影响。此外，选择食用未经加工或加工程度较低的食品而不食用UPF可能对精液质量有益。如果这些结果能在未来采用不同长期设计的流行病学研究中得到重复，那么这些新发现将为更新甚至设计预防和干预计划以解决育龄男性不育问题提供有价值的见解：本研究得到了西班牙政府生物医学研究官方资助机构ISCIII（通过Fondo de Investigación para la Salud (FIS)）、欧盟ERDF/ESF（"A way to make Europe"/"Investing in your future"[PI21/01447]）和塔拉戈纳省议会（2021/11-No.Exp. 8004330008-2021-0022642）的支持。J.S.-S.衷心感谢 ICREA 在 ICREA Academia 计划下提供的资助。C.V.-H. 获得了加泰罗尼亚自治区政府（2022 FI_B100108）的博士前期资助。M.Á.M. 获得了 Sara Borrell 博士后奖学金（CD21/00045-Instituto de Salud Carlos III (ISCIII)）。M.F.d.l.P.获得了罗维拉-伊-维尔吉利大学（Rovira i Virgili University）和塔拉戈纳省议会（Diputació de Tarragona）的博士前期资助（2020-PMF-PIPF-8）。所有作者均无利益冲突：不适用。
{"title":"Ultra-processed food consumption and semen quality parameters in the Led-Fertyl study.","authors":"Cristina Valle-Hita, Albert Salas-Huetos, María Fernández de la Puente, María Ángeles Martínez, Silvia Canudas, Antoni Palau-Galindo, Cristina Mestres, José María Manzanares, Michelle M Murphy, Montse Marquès, Jordi Salas-Salvadó, Nancy Babio","doi":"10.1093/hropen/hoae001","DOIUrl":"10.1093/hropen/hoae001","url":null,"abstract":"<p><strong>Study question: </strong>Is ultra-processed food (UPF) consumption associated with semen quality parameters?</p><p><strong>Summary answer: </strong>Higher UPF consumption was inversely associated with total sperm count, sperm concentration, and total motility in men of reproductive age.</p><p><strong>What is known already: </strong>The consumption of UPF, which has been rising during the last decades, has been demonstrated to be positively associated with several chronic diseases such as diabetes or cardiovascular diseases. However, the scientific evidence on its potential impact on semen quality remains notably limited.</p><p><strong>Study design size duration: </strong>A cross-sectional analysis was conducted using data from 200 healthy men (mean age 28.4 ± 5.5 years) enrolled in the Led-Fertyl (Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters) study between February 2021 and April 2023.</p><p><strong>Participants/materials setting methods: </strong>UPF consumption (% of energy from UPF) was estimated according to the NOVA classification system using a validated 143-item semi-quantitative food frequency questionnaire. Total sperm count, sperm concentration, sperm vitality, total motility, progressive motility, and normal sperm forms were set as the main outcomes. Microscopic parameters were analyzed using a phase-contrast microscope and a computer-assisted sperm analysis (CASA) system. Semen samples were collected and tested according to World Health Organization 2010 standards. Multivariable linear regression models were fitted to estimate the associations between UPF tertile and semen quality parameters.</p><p><strong>Main results and the role of chance: </strong>Sperm concentration (<i>β</i>: -1.42 × 10<sup>6</sup> spz./ml; 95% CI: -2.72 to -0.12) and motility (<i>β</i>: -7.83%; 95% CI: -15.16 to -0.51) were lower in participants in the highest tertile of UPF compared to the lowest. A similar association was observed for sperm count when UPF was analyzed per 10% increment of energy from UPF consumption (<i>β</i>: -1.50 × 10<sup>6</sup> spz.; 95% CI: -2.83 to -0.17). Theoretically replacing 10% of energy from UPF consumption with 10% of energy from unprocessed or minimally processed food consumption was associated with a higher total sperm count, sperm concentration, total motility, progressive motility, and normal sperm forms.</p><p><strong>Limitations reasons for caution: </strong>Cross-sectional studies do not permit the drawing of causal inferences. Measurement errors and reporting bias cannot be entirely ruled out.</p><p><strong>Wider implications of the findings: </strong>This work suggests that consumption of UPF may have an impact on certain semen quality parameters. Furthermore, opting for unprocessed or minimally processed foods instead of UPFs could potentially benefit semen quality. If these results are replicated in future epidemiological studies with different long-ter","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 1","pages":"hoae001"},"PeriodicalIF":8.3,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10813743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139571676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-11eCollection Date: 2024-01-01DOI: 10.1093/hropen/hoae003
Gui-Quan Meng, Yaling Wang, Chen Luo, Yu-Mei Tan, Yong Li, Chen Tan, Chaofeng Tu, Qian-Jun Zhang, Liang Hu, Huan Zhang, Lan-Lan Meng, Chun-Yu Liu, Leiyu Deng, Guang-Xiu Lu, Ge Lin, Juan Du, Yue-Qiu Tan, Yanwei Sha, Lingbo Wang, Wen-Bin He
<p><strong>Study question: </strong>Are there other pathogenic genes for asthenoteratozoospermia (AT)?</p><p><strong>Summary answer: </strong><i>DNAH3</i> is a novel candidate gene for AT in humans and mice.</p><p><strong>What is known already: </strong>AT is a major cause of male infertility. Several genes underlying AT have been reported; however, the genetic aetiology remains unknown in a majority of affected men.</p><p><strong>Study design size duration: </strong>A total of 432 patients with AT were recruited in this study. <i>DNAH3</i> mutations were identified by whole-exome sequencing (WES). <i>Dnah3</i> knockout mice were generated using the genome editing tool. The morphology and motility of sperm from <i>Dnah3</i> knockout mice were investigated. The entire study was conducted over 3 years.</p><p><strong>Participants/materials setting methods: </strong>WES was performed on 432 infertile patients with AT. In addition, two lines of <i>Dnah3</i> knockout mice were generated. Haematoxylin and eosin (H&E) staining, transmission electron microscopy (TEM), immunostaining, and computer-aided sperm analysis (CASA) were performed to investigate the morphology and motility of the spermatozoa. ICSI was used to overcome the infertility of one patient and of the <i>Dnah3</i> knockout mice.</p><p><strong>Main results and the role of chance: </strong><i>DNAH3</i> biallelic variants were identified in three patients from three unrelated families. H&E staining revealed various morphological abnormalities in the flagella of sperm from the patients, and TEM and immunostaining further showed the loss of the central pair of microtubules, a dislocated mitochondrial sheath and fibrous sheath, as well as a partial absence of the inner dynein arms. In addition, the two <i>Dnah3</i> knockout mouse lines demonstrated AT. One patient and the <i>Dnah3</i> knockout mice showed good treatment outcomes after ICSI.</p><p><strong>Large scale data: </strong>N/A.</p><p><strong>Limitations reasons for caution: </strong>This is a preliminary report suggesting that defects in <i>DNAH3</i> can lead to asthenoteratozoospermia in humans and mice. The pathogenic mechanism needs to be further examined in a future study.</p><p><strong>Wider implications of the findings: </strong>Our findings show that <i>DNAH3</i> is a novel candidate gene for AT in humans and mice and provide crucial insights into the biological underpinnings of this disorder. The findings may also be beneficial for counselling affected individuals.</p><p><strong>Study funding/competing interests: </strong>This work was supported by grants from National Natural Science Foundation of China (82201773, 82101961, 82171608, 32322017, 82071697, and 81971447), National Key Research and Development Program of China (2022YFC2702604), Scientific Research Foundation of the Health Committee of Hunan Province (B202301039323, B202301039518), Hunan Provincial Natural Science Foundation (2023JJ30716), the Medical Innovation Proje
{"title":"Bi-allelic variants in <i>DNAH3</i> cause male infertility with asthenoteratozoospermia in humans and mice.","authors":"Gui-Quan Meng, Yaling Wang, Chen Luo, Yu-Mei Tan, Yong Li, Chen Tan, Chaofeng Tu, Qian-Jun Zhang, Liang Hu, Huan Zhang, Lan-Lan Meng, Chun-Yu Liu, Leiyu Deng, Guang-Xiu Lu, Ge Lin, Juan Du, Yue-Qiu Tan, Yanwei Sha, Lingbo Wang, Wen-Bin He","doi":"10.1093/hropen/hoae003","DOIUrl":"10.1093/hropen/hoae003","url":null,"abstract":"<p><strong>Study question: </strong>Are there other pathogenic genes for asthenoteratozoospermia (AT)?</p><p><strong>Summary answer: </strong><i>DNAH3</i> is a novel candidate gene for AT in humans and mice.</p><p><strong>What is known already: </strong>AT is a major cause of male infertility. Several genes underlying AT have been reported; however, the genetic aetiology remains unknown in a majority of affected men.</p><p><strong>Study design size duration: </strong>A total of 432 patients with AT were recruited in this study. <i>DNAH3</i> mutations were identified by whole-exome sequencing (WES). <i>Dnah3</i> knockout mice were generated using the genome editing tool. The morphology and motility of sperm from <i>Dnah3</i> knockout mice were investigated. The entire study was conducted over 3 years.</p><p><strong>Participants/materials setting methods: </strong>WES was performed on 432 infertile patients with AT. In addition, two lines of <i>Dnah3</i> knockout mice were generated. Haematoxylin and eosin (H&E) staining, transmission electron microscopy (TEM), immunostaining, and computer-aided sperm analysis (CASA) were performed to investigate the morphology and motility of the spermatozoa. ICSI was used to overcome the infertility of one patient and of the <i>Dnah3</i> knockout mice.</p><p><strong>Main results and the role of chance: </strong><i>DNAH3</i> biallelic variants were identified in three patients from three unrelated families. H&E staining revealed various morphological abnormalities in the flagella of sperm from the patients, and TEM and immunostaining further showed the loss of the central pair of microtubules, a dislocated mitochondrial sheath and fibrous sheath, as well as a partial absence of the inner dynein arms. In addition, the two <i>Dnah3</i> knockout mouse lines demonstrated AT. One patient and the <i>Dnah3</i> knockout mice showed good treatment outcomes after ICSI.</p><p><strong>Large scale data: </strong>N/A.</p><p><strong>Limitations reasons for caution: </strong>This is a preliminary report suggesting that defects in <i>DNAH3</i> can lead to asthenoteratozoospermia in humans and mice. The pathogenic mechanism needs to be further examined in a future study.</p><p><strong>Wider implications of the findings: </strong>Our findings show that <i>DNAH3</i> is a novel candidate gene for AT in humans and mice and provide crucial insights into the biological underpinnings of this disorder. The findings may also be beneficial for counselling affected individuals.</p><p><strong>Study funding/competing interests: </strong>This work was supported by grants from National Natural Science Foundation of China (82201773, 82101961, 82171608, 32322017, 82071697, and 81971447), National Key Research and Development Program of China (2022YFC2702604), Scientific Research Foundation of the Health Committee of Hunan Province (B202301039323, B202301039518), Hunan Provincial Natural Science Foundation (2023JJ30716), the Medical Innovation Proje","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 1","pages":"hoae003"},"PeriodicalIF":8.3,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10834362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139682038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laszlo Nanassy, B. Schoepper, A. Schultze-Mosgau, M. Depenbusch, Tanja K Eggersmann, R. Hiller, G. Griesinger
{"title":"Double vitrification and warming does not compromise the chance of live birth—a potential invalid conclusion","authors":"Laszlo Nanassy, B. Schoepper, A. Schultze-Mosgau, M. Depenbusch, Tanja K Eggersmann, R. Hiller, G. Griesinger","doi":"10.1093/hropen/hoad049","DOIUrl":"https://doi.org/10.1093/hropen/hoad049","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139386155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Makieva, M. Sachs, Min Xie, Ana Velasco, Samia El-Hadad, D. R. Kalaitzopoulos, Ioannis Dedes, R. Stiller, B. Leeners
{"title":"Reply: Double vitrification and warming does not compromise the chance of live birth—a potential invalid conclusion","authors":"S. Makieva, M. Sachs, Min Xie, Ana Velasco, Samia El-Hadad, D. R. Kalaitzopoulos, Ioannis Dedes, R. Stiller, B. Leeners","doi":"10.1093/hropen/hoad050","DOIUrl":"https://doi.org/10.1093/hropen/hoad050","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"20 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139385374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Grubliauskaitė, H. Vlieghe, S. Moghassemi, A. Dadashzadeh, A. Camboni, Ž. Gudlevičienė, C. Amorim
Do ovarian stromal cells (OSCs) influence the viability and growth of human pre-antral follicles in vitro? A feeder layer of oSCs promotes the growth and transition of low developmental stage follicles to the primary/secondary stage while maintaining a high proportion of viable follicles. In the ovary, follicles rely on the support of ovarian cells, which secrete essential factors for their survival and development. This phenomenon has also been demonstrated in vitro through the 3D culture of isolated mouse primary and secondary follicles on a feeder layer of ovarian stromal cells. This co-culture notably enhances follicle survival and growth. Pre-antral follicles were isolated from human frozen-thawed ovarian tissue (OT) biopsies and then encapsulated in 1% alginate scaffolds. These embedded pre-antral follicles were either placed directly on the OSCs feeder layer or at the bottom of a culture dish for a 7-day in vitro culture (control). The study compared follicle viability, growth and hormone production between the different groups. Primordial/intermediate and primary follicles were isolated from frozen-thawed OT of cancer patients (n = 6). Ovarian stromal cells were then isolated from OT of post-menopausal women and cultured as a feeder layer. Follicle diameter was measured on days 0 and 7 using an inverted microscope to assess their development based on the increase in diameter. Viability was evaluated by staining a subset of follicles (n = 87) with calcein AM and ethidium homodimer-I, followed by classification into healthy/minimally damaged and damaged/dead follicles using confocal fluorescence microscopy. Additionally, estradiol levels were measured using ELISA. A total of 382 human preantral follicles (370 primordial/intermediate and 12 primary) with a mean diameter of 40.8 ± 9.9 µm (mean±SD) were isolated, embedded in 1% alginate hydrogel, and placed either on a monolayer of oSCs or directly on the plastic. By Day 7, the preantral follicles showed a significant size increase under both culture conditions (p < 0.0001 for D0 vs D7). The mean diameter of follicles (quiescent and growing) cultured on the feeder layer was 80.6 ± 11.0 μm compared to 67.3 ± 7.2 μm without it (p = 0.07). During the 7-day in vitro culture, the viability of the follicles significantly decreased only in the group without an OSCs monolayer compared to the D0 viability (p < 0.05). Additionally, more follicles transitioned to a higher developmental stage in the presence of OSCs (D0 primordial/intermediate: 184, primary: 7 vs D7 primordial/intermediate: 51, primary/secondary: 93) compared to those cultured without OSCs (D0 primordial/intermediate: 186, primary: 5 vs D7 primordial/intermediate: 84, primary/secondary: 65; p < 0.001). Specifically, 66 and 44 follicles reached the secondary stage (75 < x < 200 μm) in the presence and absence of OSCs, respectively. Moreover, the estradiol level was significantly higher (p = 0.006) i
{"title":"Influence of ovarian stromal cells on human ovarian follicle growth in a 3D environment","authors":"M. Grubliauskaitė, H. Vlieghe, S. Moghassemi, A. Dadashzadeh, A. Camboni, Ž. Gudlevičienė, C. Amorim","doi":"10.1093/hropen/hoad052","DOIUrl":"https://doi.org/10.1093/hropen/hoad052","url":null,"abstract":"\u0000 \u0000 \u0000 Do ovarian stromal cells (OSCs) influence the viability and growth of human pre-antral follicles in vitro?\u0000 \u0000 \u0000 \u0000 A feeder layer of oSCs promotes the growth and transition of low developmental stage follicles to the primary/secondary stage while maintaining a high proportion of viable follicles.\u0000 \u0000 \u0000 \u0000 In the ovary, follicles rely on the support of ovarian cells, which secrete essential factors for their survival and development. This phenomenon has also been demonstrated in vitro through the 3D culture of isolated mouse primary and secondary follicles on a feeder layer of ovarian stromal cells. This co-culture notably enhances follicle survival and growth.\u0000 \u0000 \u0000 \u0000 Pre-antral follicles were isolated from human frozen-thawed ovarian tissue (OT) biopsies and then encapsulated in 1% alginate scaffolds. These embedded pre-antral follicles were either placed directly on the OSCs feeder layer or at the bottom of a culture dish for a 7-day in vitro culture (control). The study compared follicle viability, growth and hormone production between the different groups.\u0000 \u0000 \u0000 \u0000 Primordial/intermediate and primary follicles were isolated from frozen-thawed OT of cancer patients (n = 6). Ovarian stromal cells were then isolated from OT of post-menopausal women and cultured as a feeder layer. Follicle diameter was measured on days 0 and 7 using an inverted microscope to assess their development based on the increase in diameter. Viability was evaluated by staining a subset of follicles (n = 87) with calcein AM and ethidium homodimer-I, followed by classification into healthy/minimally damaged and damaged/dead follicles using confocal fluorescence microscopy. Additionally, estradiol levels were measured using ELISA.\u0000 \u0000 \u0000 \u0000 A total of 382 human preantral follicles (370 primordial/intermediate and 12 primary) with a mean diameter of 40.8 ± 9.9 µm (mean±SD) were isolated, embedded in 1% alginate hydrogel, and placed either on a monolayer of oSCs or directly on the plastic. By Day 7, the preantral follicles showed a significant size increase under both culture conditions (p < 0.0001 for D0 vs D7). The mean diameter of follicles (quiescent and growing) cultured on the feeder layer was 80.6 ± 11.0 μm compared to 67.3 ± 7.2 μm without it (p = 0.07). During the 7-day in vitro culture, the viability of the follicles significantly decreased only in the group without an OSCs monolayer compared to the D0 viability (p < 0.05). Additionally, more follicles transitioned to a higher developmental stage in the presence of OSCs (D0 primordial/intermediate: 184, primary: 7 vs D7 primordial/intermediate: 51, primary/secondary: 93) compared to those cultured without OSCs (D0 primordial/intermediate: 186, primary: 5 vs D7 primordial/intermediate: 84, primary/secondary: 65; p < 0.001). Specifically, 66 and 44 follicles reached the secondary stage (75 < x < 200 μm) in the presence and absence of OSCs, respectively. Moreover, the estradiol level was significantly higher (p = 0.006) i","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138951660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yunhan Nie, Wenya Guo, Xi Shen, Yating Xie, Yuqi Zeng, Hongyuan Gao, Yali Liu, Li Wang
What are the odds of achieving pregnancy when adopting progestin-primed ovarian stimulation (PPOS)-related protocols combined with repetitive frozen–thawed transfer (FET) cycles in patients with different clinical characteristics? The cumulative live birth rates (CLBRs) of women undergoing different PPOS-related protocols can be significantly and consistently enhanced within six FET cycles when the female age is < 40 years (or even <45 years) and when >5 oocytes are retrieved, regardless of antral follicle count (AFC). There have been numerous studies on the live birth rate of the first FET cycle in patients with PPOS-related protocols. These studies have focused mainly on comparing pregnancy outcomes with those of other stimulation protocols. However, owing to the unique features of the PPOS-related strategy, such as its flexible timing of oocyte retrieval and repeated transfer of frozen embryos, studies using the CLBR as an overall indicator of success and investigating which types of patients would benefit from this protocol are lacking. This retrospective cohort study included 18,593 women who underwent PPOS-related protocols (dydrogesterone + hMG, medroxyprogesterone acetate + hMG, micronized progesterone + hMG treatment, and luteal-phase ovarian stimulation protocol) from 1 March 2011 to 31 September 2022 in our centre. The population was categorized by female age, number of oocytes retrieved, and AFC in the analysis of CLBR within six FET cycles. The age groups (groups 1-5, respectively) were <30, 30-34, 35-39, 40-44, and ≥45 years. The number of oocytes retrieved was grouped as 1-5, 6-10, 11-15, 16-20, and >20. AFC was grouped as < 5, 5-10, 11-15, and >15. The Kaplan–Meier analysis (optimistic method), which hypothesized that patients who did not continue treatment had the same chance of achieving a live birth as those who continued, and the competing risk method (conservative method) which hypothesized they had no chance of achieving a live birth, were applied. In further analyses, the Cox model and Fine–Gray model were adopted: the former corresponds to the optimistic scenario, and the latter corresponds to the pessimistic scenario. CLBR had a declining trend with female age over six FET cycles (groups 1-5, respectively: optimistic: 96.9%, 96.6%, 91.4%, 67.3%, and 11.7%; conservative: 87.3%, 85.0%, 74.0%, 41.3%, and 7.5%), requiring more FET cycles to achieve a success rate of at least 50% (groups 1-5, respectively: optimistic: 2, 2, 2, 4 and >6 cycles; conservative: 2, 2, 2, > 6 and > 6 cycles). CLBR showed an increasing trend with the number of oocytes retrieved (groups 1-5, respectively: optimistic: 93.8%, 94.3%, 95.8%, 96.0%, and 95.6%; conservative: 66.2%, 78.3%, 85.6%, 88.9%, and 91.0%). All groups needed the same number of FET cycles to achieve a success rate of at least 50% (groups 1-5, respectively: optimistic: 2, 2, 2, 2 and 2 cycles; conservative: 2, 2, 2, 2 and 2 cycles). Furthermore,
不同临床特征的患者在采用孕激素促排卵（PPOS）相关方案结合重复冻融移植（FET）周期时，怀孕的几率有多大？ 当女性年龄达到 5 个卵母细胞时，无论前卵泡数（AFC）如何，接受不同 PPOS 相关方案的女性在 6 个 FET 周期内的累积活产率（CLBR）均可显著且持续地提高。 关于采用 PPOS 相关方案的患者在第一个 FET 周期的活产率，已有许多研究。这些研究主要集中于比较与其他刺激方案的妊娠结果。然而，由于 PPOS 相关策略的独特性，如取回卵母细胞的时间灵活、重复移植冷冻胚胎等，将 CLBR 作为成功率的总体指标，并调查哪些类型的患者可从该方案中获益的研究还很缺乏。 这项回顾性队列研究纳入了本中心2011年3月1日至2022年9月31日期间接受PPOS相关方案（地屈孕酮+hMG、醋酸甲羟孕酮+hMG、微粒化孕酮+hMG治疗和黄体期卵巢刺激方案）的18593名女性。 研究对象按女性年龄、取卵数量和六个 FET 周期内 CLBR 分析中的 AFC 进行分类。年龄组（1-5 组）分别为 20 人。AFC分为15组。采用卡普兰-梅耶分析法（乐观法）和竞争风险法（保守法）进行分析，前者假设不继续治疗的患者与继续治疗的患者获得活产的机会相同，后者假设他们没有机会获得活产。在进一步分析中，采用了 Cox 模型和 Fine-Gray 模型：前者对应于乐观方案，后者对应于悲观方案。 在六个 FET 周期中，CLBR 随女性年龄呈下降趋势（1-5 组分别为：乐观组：96.9%、96.6%、91.4%、67.3% 和 11.7%；保守组：87.3%、85.0%、74.0%、41.3% 和 7.5%），需要更多的 FET 周期才能达到至少 50%的成功率（1-5 组分别为：乐观组：2、2、2、4 和 >6 个周期；保守组：2、2、2、>6 和 >6 个周期）。CLBR 随取回卵母细胞数量的增加而呈上升趋势（1-5 组分别为：乐观组：93.8%、94.3%、95.8%、96.0% 和 95.6%；保守组：66.2%、78.3%、85.6%、88.9% 和 91.0%）。所有组别都需要相同数量的 FET 周期才能达到至少 50%的成功率（1-5 组分别为：乐观组：2、2、2、2 和 2 个周期；保守组：2、2、2、2 和 2 个周期）。此外，6 个 FET 周期内的 CLBR 随 AFC 数量的增加而呈上升趋势（1-4 组分别为：乐观组：89.2%、94.8%、95.9% 和 96.3%；保守组：67.4%、78.2%、83.9% 和 88.1%），到第二个 FET 周期时，所有 4 组的成功率均达到至少 50%。 目前的研究因其回顾性设计和单中心性质而受到限制，这可能会限制我们研究结果的推广性。 本研究介绍了两个模型（卡普兰-梅耶分析法和竞争风险法），用于评估使用 PPOS 相关方案的患者的临床结果，这两个模型对高龄患者或卵巢储备功能减退的患者尤其有用。我们的研究结果鼓励 45 岁以下的患者，尤其是 40 岁以下的患者，以及 AFC 较低和取卵较少的患者尝试这种新方案。此外，本研究还证明了不同临床特征的患者在六个 FET 周期内 CLBR 的改善程度，为决定移植失败后是否继续进行 ART 提供了有价值的参考。 本研究得到了国家自然科学基金的资助（L.W.的基金号为 82071603，刘宇的基金号为 82001502）。无利益冲突需要声明。 不适用。
{"title":"The cumulative live birth rates of 18,593 women with progestin-primed ovarian stimulation-related protocols and frozen–thawed transfer cycles","authors":"Yunhan Nie, Wenya Guo, Xi Shen, Yating Xie, Yuqi Zeng, Hongyuan Gao, Yali Liu, Li Wang","doi":"10.1093/hropen/hoad051","DOIUrl":"https://doi.org/10.1093/hropen/hoad051","url":null,"abstract":"\u0000 \u0000 \u0000 What are the odds of achieving pregnancy when adopting progestin-primed ovarian stimulation (PPOS)-related protocols combined with repetitive frozen–thawed transfer (FET) cycles in patients with different clinical characteristics?\u0000 \u0000 \u0000 \u0000 The cumulative live birth rates (CLBRs) of women undergoing different PPOS-related protocols can be significantly and consistently enhanced within six FET cycles when the female age is < 40 years (or even <45 years) and when >5 oocytes are retrieved, regardless of antral follicle count (AFC).\u0000 \u0000 \u0000 \u0000 There have been numerous studies on the live birth rate of the first FET cycle in patients with PPOS-related protocols. These studies have focused mainly on comparing pregnancy outcomes with those of other stimulation protocols. However, owing to the unique features of the PPOS-related strategy, such as its flexible timing of oocyte retrieval and repeated transfer of frozen embryos, studies using the CLBR as an overall indicator of success and investigating which types of patients would benefit from this protocol are lacking.\u0000 \u0000 \u0000 \u0000 This retrospective cohort study included 18,593 women who underwent PPOS-related protocols (dydrogesterone + hMG, medroxyprogesterone acetate + hMG, micronized progesterone + hMG treatment, and luteal-phase ovarian stimulation protocol) from 1 March 2011 to 31 September 2022 in our centre.\u0000 \u0000 \u0000 \u0000 The population was categorized by female age, number of oocytes retrieved, and AFC in the analysis of CLBR within six FET cycles. The age groups (groups 1-5, respectively) were <30, 30-34, 35-39, 40-44, and ≥45 years. The number of oocytes retrieved was grouped as 1-5, 6-10, 11-15, 16-20, and >20. AFC was grouped as < 5, 5-10, 11-15, and >15. The Kaplan–Meier analysis (optimistic method), which hypothesized that patients who did not continue treatment had the same chance of achieving a live birth as those who continued, and the competing risk method (conservative method) which hypothesized they had no chance of achieving a live birth, were applied. In further analyses, the Cox model and Fine–Gray model were adopted: the former corresponds to the optimistic scenario, and the latter corresponds to the pessimistic scenario.\u0000 \u0000 \u0000 \u0000 CLBR had a declining trend with female age over six FET cycles (groups 1-5, respectively: optimistic: 96.9%, 96.6%, 91.4%, 67.3%, and 11.7%; conservative: 87.3%, 85.0%, 74.0%, 41.3%, and 7.5%), requiring more FET cycles to achieve a success rate of at least 50% (groups 1-5, respectively: optimistic: 2, 2, 2, 4 and >6 cycles; conservative: 2, 2, 2, > 6 and > 6 cycles). CLBR showed an increasing trend with the number of oocytes retrieved (groups 1-5, respectively: optimistic: 93.8%, 94.3%, 95.8%, 96.0%, and 95.6%; conservative: 66.2%, 78.3%, 85.6%, 88.9%, and 91.0%). All groups needed the same number of FET cycles to achieve a success rate of at least 50% (groups 1-5, respectively: optimistic: 2, 2, 2, 2 and 2 cycles; conservative: 2, 2, 2, 2 and 2 cycles). Furthermore,","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"139 39","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138953328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Is PCOS associated with higher risks of extreme birth size and/or preterm birth in mothers with different hypertension types? PCOS was associated with additional risks of preterm birth in mothers with chronic hypertension and in singleton pregnancies of mothers with pre-eclampsia, and with increased risks of offspring being large for gestational age (LGA) in mothers with gestational hypertension. Women with PCOS are more likely to develop gestational hypertension, preeclampsia, and chronic hypertension. Although adverse birth outcomes have been frequently reported in mothers with PCOS, such associations in the setting of a hypertensive disorder remain unknown. This is a population-based cohort study including all live births 2004-2014 in Finland (n = 652 732), excluding mothers with diagnoses that could cause signs and symptoms like PCOS to ensure diagnosis specificity. Maternal diagnoses of PCOS, gestational hypertension, chronic hypertension, and pre-eclampsia were identified from the Finnish national registries. Generalized estimating equation and multivariable logistic regression were used to assess the adjusted odds ratio (aOR) and 95% CIs of preterm birth, very preterm birth and offspring being small (SGA) or large (LGA) for gestational age in hypertensive mothers with or without PCOS, using normotensive mothers without PCOS as reference. Of 43 902 (6.7%) mothers with hypertensive disorders, 1709 (3.9%) had PCOS. Significant interactions were detected for PCOS with hypertension on preterm birth, very preterm birth, offspring being SGA and LGA (F = 504.1, pinteraction <0.001; F = 124.2, pinteraction <0.001; F = 99.5, pinteraction <0.001; F = 2.7, pinteraction =0.012, respectively). Using mothers with no hypertensive disorder and no PCOS as reference, the risks of preterm and very preterm birth were overrepresented in mothers with chronic hypertension and pre-eclampsia without PCOS. PCOS was associated with higher risks of preterm birth (aOR PCOS 4.02, 3.14–5.15 vs. aOR non-PCOS 2.51, 2.32–2.71) in mothers with chronic hypertension, with significant interaction between the exposures (F = 32.7, pinteraction <0.001). Comorbid PCOS was also associated with a higher risk of preterm birth in singleton pregnancies of mothers with pre-eclampsia (aOR PCOS 7.33, 5.92–9.06 vs. aOR non-PCOS 5.72, 5.43–6.03; F = 50.0, pinteraction<0.001). Furthermore, the combined associations of PCOS with chronic hypertension or pre-eclampsia persisted for spontaneous births. Moreover, the risk of offspring LGA was increased in mothers with PCOS and gestational hypertension although decreased in those with gestational hypertension alone (aOR PCOS 2.04, 1.48–2.80 vs. aOR non-PCOS 0.80, 0.72–0.89; F = 9.7, pinteraction=0.002), whereas for offspring SGA the risks were comparable between hypertensive mothers with and those without PCOS. Information on medication treatment, gestational weeks of onset for pre-eclampsia and gesta
多囊卵巢综合征与不同高血压类型母亲的极端出生尺寸和/或早产风险是否相关?多囊卵巢综合征与慢性高血压母亲的早产风险增加有关，与子痫前期母亲的单胎妊娠有关，与妊娠高血压母亲的后代大胎龄(LGA)风险增加有关。患有多囊卵巢综合征的妇女更容易发生妊娠期高血压、先兆子痫和慢性高血压。尽管PCOS母亲的不良分娩结果经常被报道，但在高血压疾病的背景下，这种关联仍然未知。这是一项基于人群的队列研究，包括2004-2014年在芬兰出生的所有活产婴儿(n = 652 732)，排除了诊断可能导致多囊卵巢综合征等体征和症状的母亲，以确保诊断的特异性。从芬兰国家登记处确定了多囊卵巢综合征、妊娠期高血压、慢性高血压和先兆子痫的母亲诊断。采用广义估计方程和多变量logistic回归方法，以无PCOS的正常血压母亲为参照，评估有PCOS或无PCOS的高血压母亲早产、极早产和胎龄小(SGA)或大(LGA)的调整优势比(aOR)和95% ci。43 902例(6.7%)患有高血压疾病的母亲中，1709例(3.9%)患有多囊卵巢综合征。PCOS合并高血压与早产、非常早产、子代SGA和LGA存在显著相互作用(F = 504.1, p相互作用<0.001;F = 124.2, p交互作用<0.001;F = 99.5, p交互作用<0.001;F = 2.7, p - interaction =0.012)。以无高血压疾病和无PCOS的母亲为对照，慢性高血压和先兆子痫无PCOS的母亲早产和非常早产的风险过高。PCOS与慢性高血压母亲的早产风险较高相关(aOR PCOS为4.02,3.14-5.15,aOR非PCOS为2.51,2.32-2.71)，暴露之间存在显著交互作用(F = 32.7, p交互作用<0.001)。合并多囊卵巢综合征(PCOS)与子痫前期母亲的单胎妊娠早产风险较高相关(aOR PCOS为7.33,5.92-9.06,aOR非PCOS为5.72,5.43-6.03;F = 50.0, p交互作用<0.001)。此外，PCOS与慢性高血压或先兆子痫的联合关联在自然分娩中持续存在。此外，PCOS合并妊娠高血压的母亲的后代LGA风险增加，而单独妊娠高血压的母亲的后代LGA风险降低(aOR PCOS为2.04,1.48-2.80,aOR非PCOS为0.80,0.72-0.89;F = 9.7, p相互作用=0.002)，而对于后代SGA的风险，高血压母亲与未患PCOS的母亲之间是相当的。没有关于药物治疗、子痫前期和妊娠期高血压发病的妊娠周数、孕期体重增加和多囊卵巢综合征表型的信息。所有诊断都是从登记处检索的，仅代表那些因其症状而寻求医疗护理的人。众所周知，1996年以前用于识别多囊卵巢综合征的ICD-9代码低估了多囊卵巢综合征的患病率，而将无排卵性不孕症纳入多囊卵巢综合征可能会引入过度代表偏差，尽管多囊卵巢综合征占无排卵性不孕症的80%。由于样本量有限，应谨慎解释与母体多囊卵巢综合征和高血压疾病相关的极早产风险。母体多囊卵巢综合征的多胎妊娠太少，无法进行亚组分析。此外，ART仅包括IVF/ICSI。其他治疗的潜在影响，如促排卵，没有被检查。多囊卵巢综合征与高血压母亲早产或后代LGA的额外风险相关，高血压类型之间存在差异。这些加剧的风险突出了妊娠咨询和高血压疾病妇女管理中多囊卵巢综合征的考虑。本研究得到山东省自然科学基金[ZR2020MH064 to X.C]，山东大学和卡罗林斯卡研究所联合研究基金[SDU-KI-2019-08 to X.C and c.l]，芬兰卫生与福利研究所:药物与妊娠项目[M.G.]、瑞典研究理事会[2022-01188 to C.L.]、斯德哥尔摩郡议会和卡罗林斯卡研究所之间的医学培训和临床研究区域协议(ALF)斯德哥尔摩郡议会[SLL20190589 to C.L.]、瑞典大脑基金会[FO2021-0412 to C.L.]。资助者在研究设计、数据收集、分析和解释、撰写报告或决定是否提交发表方面没有任何作用。作者报告没有利益冲突。不适用。
{"title":"Birth outcomes in mothers with hypertensive disorders and polycystic ovary syndrome: a population-based cohort study","authors":"Xinxia Chen, Mika Gissler, C. Lavebratt","doi":"10.1093/hropen/hoad048","DOIUrl":"https://doi.org/10.1093/hropen/hoad048","url":null,"abstract":"\u0000 \u0000 \u0000 Is PCOS associated with higher risks of extreme birth size and/or preterm birth in mothers with different hypertension types?\u0000 \u0000 \u0000 \u0000 PCOS was associated with additional risks of preterm birth in mothers with chronic hypertension and in singleton pregnancies of mothers with pre-eclampsia, and with increased risks of offspring being large for gestational age (LGA) in mothers with gestational hypertension.\u0000 \u0000 \u0000 \u0000 Women with PCOS are more likely to develop gestational hypertension, preeclampsia, and chronic hypertension. Although adverse birth outcomes have been frequently reported in mothers with PCOS, such associations in the setting of a hypertensive disorder remain unknown.\u0000 \u0000 \u0000 \u0000 This is a population-based cohort study including all live births 2004-2014 in Finland (n = 652 732), excluding mothers with diagnoses that could cause signs and symptoms like PCOS to ensure diagnosis specificity.\u0000 \u0000 \u0000 \u0000 Maternal diagnoses of PCOS, gestational hypertension, chronic hypertension, and pre-eclampsia were identified from the Finnish national registries. Generalized estimating equation and multivariable logistic regression were used to assess the adjusted odds ratio (aOR) and 95% CIs of preterm birth, very preterm birth and offspring being small (SGA) or large (LGA) for gestational age in hypertensive mothers with or without PCOS, using normotensive mothers without PCOS as reference.\u0000 \u0000 \u0000 \u0000 Of 43 902 (6.7%) mothers with hypertensive disorders, 1709 (3.9%) had PCOS. Significant interactions were detected for PCOS with hypertension on preterm birth, very preterm birth, offspring being SGA and LGA (F = 504.1, pinteraction <0.001; F = 124.2, pinteraction <0.001; F = 99.5, pinteraction <0.001; F = 2.7, pinteraction =0.012, respectively). Using mothers with no hypertensive disorder and no PCOS as reference, the risks of preterm and very preterm birth were overrepresented in mothers with chronic hypertension and pre-eclampsia without PCOS. PCOS was associated with higher risks of preterm birth (aOR PCOS 4.02, 3.14–5.15 vs. aOR non-PCOS 2.51, 2.32–2.71) in mothers with chronic hypertension, with significant interaction between the exposures (F = 32.7, pinteraction <0.001). Comorbid PCOS was also associated with a higher risk of preterm birth in singleton pregnancies of mothers with pre-eclampsia (aOR PCOS 7.33, 5.92–9.06 vs. aOR non-PCOS 5.72, 5.43–6.03; F = 50.0, pinteraction<0.001). Furthermore, the combined associations of PCOS with chronic hypertension or pre-eclampsia persisted for spontaneous births. Moreover, the risk of offspring LGA was increased in mothers with PCOS and gestational hypertension although decreased in those with gestational hypertension alone (aOR PCOS 2.04, 1.48–2.80 vs. aOR non-PCOS 0.80, 0.72–0.89; F = 9.7, pinteraction=0.002), whereas for offspring SGA the risks were comparable between hypertensive mothers with and those without PCOS.\u0000 \u0000 \u0000 \u0000 Information on medication treatment, gestational weeks of onset for pre-eclampsia and gesta","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"58 13","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138604961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. J. W. Tack, C. Brachet, V. Beauloye, C. Heinrichs, E. Boros, K. De Waele, S. van der Straaten, S. Van Aken, M. Craen, A. Lemay, A. Rochtus, K. Casteels, D. Beckers, T. Mouraux, K. Logghe, M. Van Loocke, G. Massa, K. Van de Vijver, H. Syryn, J. Van de Velde, E. De Baere, H. Verdin, M. Cools
What is the long-term outcome of individuals born with bilateral testicular regression (BTR) in relation to its underlying etiology? Statural growth and pubertal development are adequate with incremental doses of testosterone replacement therapy, however penile growth is often suboptimal, especially in those with a suspected genetic etiology (i.e. heterozygous DHX37 variants) or a micropenis at birth. BTR is a rare and poorly understood condition. Although a vascular origin has been postulated, heterozygous missense variants in DHX37 have been attributed to the phenotype as well. How these various etiologies impact the clinical phenotype, gonadal histology and outcome of BTR remains unclear. For this cross-sectional study, individuals with BTR were recruited in eight Belgian pediatric endocrinology departments, between December 2019 and December 2022. A physical exam was performed cross-sectionally in all 17 end-pubertal participants and a quality of care questionnaire was completed by 11 of them. Exome-based panel testing of 241 genes involved in gonadal development and spermatogenesis was performed along with a retrospective analysis of presentation and management. A centralized histological review of gonadal rests was done for 10 participants. A total of 35 participants (33 with male, one with female and one with non-binary gender identity), were recruited at a mean age of 15.0±5.7 years. The median age at presentation was 1.2 years [0-14 years]. Maternal gestational complications were common (38.2%), with a notably high incidence of monozygotic twin pregnancies (8.8%). Heterozygous (likely) pathogenic missense variants in DHX37 (p.Arg334Trp and p.Arg308Gln) were found in three participants. No other (likely) pathogenic variants were found. All three participants with a DHX37 variant had a microphallus at birth (leading to female sex assignment in one), while only six of the remaining 31 participants without a DHX37 variant (19.4%) had a microphallus at birth (information regarding one participant was missing). Testosterone therapy during infancy to increase penile growth was more effective in those without versus those with a DHX37 variant. The three participants with a DHX37 variant developed a male, female and non-binary gender identity, respectively; all other participants identified as males. Testosterone replacement therapy (TRT) in incremental doses had been initiated in 25 participants (median age at start 12.4 years). Final height was within the target height range in all end-pubertal participants, however, five out of 11 participants (45.5%), for whom stretched penile length (SPL) was measured, had a micropenis (mean adult SPL: 9.6 ± 2.5). Of the 11 participants who completed the questionnaire, five (45.5%) reported suboptimal understanding of the goals and effects of TRT at the time of puberty induction. Furthermore, only six (54.5%) and five (45.5%) of these 11 participants indicated they we
{"title":"Etiology, histology and long-term outcome of bilateral testicular regression: a large Belgian series","authors":"L. J. W. Tack, C. Brachet, V. Beauloye, C. Heinrichs, E. Boros, K. De Waele, S. van der Straaten, S. Van Aken, M. Craen, A. Lemay, A. Rochtus, K. Casteels, D. Beckers, T. Mouraux, K. Logghe, M. Van Loocke, G. Massa, K. Van de Vijver, H. Syryn, J. Van de Velde, E. De Baere, H. Verdin, M. Cools","doi":"10.1093/hropen/hoad047","DOIUrl":"https://doi.org/10.1093/hropen/hoad047","url":null,"abstract":"\u0000 \u0000 \u0000 What is the long-term outcome of individuals born with bilateral testicular regression (BTR) in relation to its underlying etiology?\u0000 \u0000 \u0000 \u0000 Statural growth and pubertal development are adequate with incremental doses of testosterone replacement therapy, however penile growth is often suboptimal, especially in those with a suspected genetic etiology (i.e. heterozygous DHX37 variants) or a micropenis at birth.\u0000 \u0000 \u0000 \u0000 BTR is a rare and poorly understood condition. Although a vascular origin has been postulated, heterozygous missense variants in DHX37 have been attributed to the phenotype as well. How these various etiologies impact the clinical phenotype, gonadal histology and outcome of BTR remains unclear.\u0000 \u0000 \u0000 \u0000 For this cross-sectional study, individuals with BTR were recruited in eight Belgian pediatric endocrinology departments, between December 2019 and December 2022. A physical exam was performed cross-sectionally in all 17 end-pubertal participants and a quality of care questionnaire was completed by 11 of them. Exome-based panel testing of 241 genes involved in gonadal development and spermatogenesis was performed along with a retrospective analysis of presentation and management. A centralized histological review of gonadal rests was done for 10 participants.\u0000 \u0000 \u0000 \u0000 A total of 35 participants (33 with male, one with female and one with non-binary gender identity), were recruited at a mean age of 15.0±5.7 years.\u0000 \u0000 \u0000 \u0000 The median age at presentation was 1.2 years [0-14 years]. Maternal gestational complications were common (38.2%), with a notably high incidence of monozygotic twin pregnancies (8.8%). Heterozygous (likely) pathogenic missense variants in DHX37 (p.Arg334Trp and p.Arg308Gln) were found in three participants. No other (likely) pathogenic variants were found. All three participants with a DHX37 variant had a microphallus at birth (leading to female sex assignment in one), while only six of the remaining 31 participants without a DHX37 variant (19.4%) had a microphallus at birth (information regarding one participant was missing). Testosterone therapy during infancy to increase penile growth was more effective in those without versus those with a DHX37 variant. The three participants with a DHX37 variant developed a male, female and non-binary gender identity, respectively; all other participants identified as males. Testosterone replacement therapy (TRT) in incremental doses had been initiated in 25 participants (median age at start 12.4 years). Final height was within the target height range in all end-pubertal participants, however, five out of 11 participants (45.5%), for whom stretched penile length (SPL) was measured, had a micropenis (mean adult SPL: 9.6 ± 2.5). Of the 11 participants who completed the questionnaire, five (45.5%) reported suboptimal understanding of the goals and effects of TRT at the time of puberty induction. Furthermore, only six (54.5%) and five (45.5%) of these 11 participants indicated they we","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":" 13","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138616004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-25eCollection Date: 2023-01-01DOI: 10.1093/hropen/hoad045
F Horta, M Salih, C Austin, R Warty, V Smith, D L Rolnik, S Reddy, H Rezatofighi, B Vollenhoven
{"title":"Reply: Artificial intelligence as a door opener for a new era of human reproduction.","authors":"F Horta, M Salih, C Austin, R Warty, V Smith, D L Rolnik, S Reddy, H Rezatofighi, B Vollenhoven","doi":"10.1093/hropen/hoad045","DOIUrl":"10.1093/hropen/hoad045","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2023 4","pages":"hoad045"},"PeriodicalIF":8.3,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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