Human Reproduction Update最新文献

{"title":"Parental conditions, modifiable lifestyle factors, and first trimester growth and development: a systematic review.","authors":"Naomi Graafland, Melek Rousian, Merle L de Zwart, Regine P M Steegers-Theunissen, Eric A P Steegers, Anke G Posthumus","doi":"10.1093/humupd/dmaf001","DOIUrl":"10.1093/humupd/dmaf001","url":null,"abstract":"<p><strong>Introduction: </strong>The embryonic period in human development is the foundation of lifelong and even transgenerational health. Although previously believed to be uniform, there is increasing evidence that embryonic growth is influenced by the conditions and modifiable lifestyle factors of parents in the periconception period. In ongoing pregnancies, a delay in growth in the first trimester has been associated with miscarriages, malformations, low birth weight, preterm birth, and small for gestational age at birth. This has stimulated research on factors associated with variations in human embryonic growth. However, there is still no consensus on which parental conditions and modifiable lifestyle factors affect first trimester growth and development and to what extent.</p><p><strong>Objective and rationale: </strong>A systematic review was undertaken according to PRISMA guidelines to provide an overview of literature on the associations between parental conditions and lifestyle factors in the periconception period and first trimester growth and development, with an aim to identify existing evidence gaps.</p><p><strong>Search methods: </strong>A systematic search of the literature concerning articles on embryonic growth and lifestyle factors published between 1900 and 2024 was performed in six electronic databases. Studies were eligible for inclusion if they reported on the association between periconception parental conditions and/or modifiable lifestyle factors and an in vivo measure of first trimester growth or development (i.e. crown-rump length, embryonic volume and/or Carnegie stage) between 6 + 0 and 13 + 6 weeks gestational age in singleton pregnancies. Parental conditions and modifiable lifestyle factors were defined as ex utero determinants divided into characteristics (age, ethnicity, BMI, blood pressure), lifestyle risk factors (caffeine intake, alcohol consumption, and smoking), nutrition (dietary patterns and food groups), vitamins (vitamin B9/B11, vitamin B12, vitamin D, and supplements), and the ambient environment (air pollution, noise exposure, and neighborhood deprivation). Risk of bias of the included studies was assessed using the Newcastle-Ottawa Scale. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to assess the evidence level of the studies included in the review.</p><p><strong>Outcomes: </strong>A total of 4708 unique records were identified, of which 34 studies were included in the systematic review. The majority of studies investigating smoking and BMI suggested an inverse association with embryonic growth and development, while maternal age, folic acid supplement use, and folate levels were positively associated with embryonic growth and development. Studies on blood pressure, ethnicity, vitamin B12, vitamin D, alcohol consumption, caffeine consumption, and ambient environment were too limited to conclude an association with embryonic growth and developmen","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"166-182"},"PeriodicalIF":14.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remembering Professor John Collins.","authors":"","doi":"10.1093/humupd/dmaf008","DOIUrl":"10.1093/humupd/dmaf008","url":null,"abstract":"","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"165"},"PeriodicalIF":14.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Moving toward totipotency: the molecular and cellular features of totipotent and naive pluripotent stem cells.","authors":"Lingyue Hua,Yuyang Peng,Liying Yan,Peng Yuan,Jie Qiao","doi":"10.1093/humupd/dmaf006","DOIUrl":"https://doi.org/10.1093/humupd/dmaf006","url":null,"abstract":"BACKGROUNDDissecting the key molecular mechanism of embryonic development provides novel insights into embryogenesis and potential intervention strategies for clinical practices. However, the ability to study the molecular mechanisms of early embryo development in humans, such as zygotic genome activation and lineage segregation, is meaningfully constrained by methodological limitations and ethical concerns. Totipotent stem cells have an extended developmental potential to differentiate into embryonic and extraembryonic tissues, providing a suitable model for studying early embryo development. Recently, a series of ground-breaking results on stem cells have identified totipotent-like cells or induced pluripotent stem cells into totipotent-like cells.OBJECTIVE AND RATIONALEThis review followed the PRISMA guidelines, surveys the current works of literature on totipotent, naive, and formative pluripotent stem cells, introduces the molecular and biological characteristics of those stem cells, and gives advice for future research.SEARCH METHODSThe search method employed the terms 'totipotent' OR 'naive pluripotent stem cell' OR 'formative pluripotent stem cell' for unfiltered search on PubMed, Web of Science, and Cochrane Library. Papers included were those with information on totipotent stem cells, naive pluripotent stem cells, or formative pluripotent stem cells until June 2024 and were published in the English language. Articles that have no relevance to stem cells, or totipotent, naive pluripotent, or formative pluripotent cells were excluded.OUTCOMESThere were 152 records included in this review. These publications were divided into four groups according to the species of the cells included in the studies: 67 human stem cell studies, 70 mouse stem cell studies, 9 porcine stem cell studies, and 6 cynomolgus stem cell studies. Naive pluripotent stem cell models have been established in other species such as porcine and cynomolgus. Human and mouse totipotent stem cells, e.g. human 8-cell-like cells, human totipotent blastomere-like cells, and mouse 2-cell-like cells, have been successfully established and exhibit high developmental potency for both embryonic and extraembryonic contributions. However, the observed discrepancies between these cells and real embryos in terms of epigenetics and transcription suggest that further research is warranted. Our results systematically reviewed the established methods, molecular characteristics, and developmental potency of different naive, formative pluripotent, and totipotent stem cells. Furthermore, we provide a parallel comparison between animal and human models, and offer recommendations for future applications to advance early embryo research and assisted reproduction technologies.WIDER IMPLICATIONSTotipotent cell models provide a valuable resource to understand the underlying mechanisms of embryo development and forge new paths toward future treatment of infertility and regenerative medicine. However, cu","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"19 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular insights into sperm head shaping and its role in human male fertility","authors":"Jiaxin He, Xinle Lin, Chen Tan, Yong Li, Lilan Su, Ge Lin, Yue-Qiu Tan, Chaofeng Tu","doi":"10.1093/humupd/dmaf003","DOIUrl":"https://doi.org/10.1093/humupd/dmaf003","url":null,"abstract":"BACKGROUND Sperm head shaping, controlled by the acrosome-acroplaxome-manchette complex, represents a significant morphological change during spermiogenesis and involves numerous proteins expressed in a spatially and temporally specific manner. Defects in sperm head shaping frequently lead to teratozoospermia concomitant with oligozoospermia and asthenozoospermia, but the pathogenic mechanism underlying sperm head shaping, and its role in male infertility, remain poorly understood. OBJECTIVE AND RATIONALE This review aims to summarize the mechanism underlying sperm head shaping, reveal the relationship between gene defects associated with sperm head shaping and male infertility in humans and mice, and explore potential clinical improvements in ICSI treatment. SEARCH METHODS We searched the PubMed database for articles published in English using the keyword ‘sperm head shaping’ in combination with the following terms: ‘acrosome formation’, ‘proacrosomal vesicles (PAVs)’, ‘manchette’, ‘perinuclear theca (PT)’, ‘chromatin condensation’, ‘linker of nucleoskeleton and cytoskeleton (LINC) complex’, ‘histone-to-protamine (HTP) transition’, ‘male infertility’, ‘ICSI’, and ‘artificial oocyte activation (AOA)’. The selected publications until 1 August 2024 were critically summarized, integrated, and thoroughly discussed, and the irrelevant literature were excluded. OUTCOMES A total of 6823 records were retrieved. After careful screening, integrating relevant literature, and excluding articles unrelated to the topic of this review, 240 articles were ultimately included in the analysis. Firstly, we reviewed the important molecular events and structures integral to sperm head shaping, including PAV formation to fusion, acrosome attachment to the nucleus, structure and function of the manchette, PT, chromatin condensation, and HTP transition. Then, we set forth human male infertility associated with sperm head shaping and identified genes related to sperm head shaping resulting in teratozoospermia concomitant with oligozoospermia and asthenozoospermia. Finally, we summarized the outcomes of ICSI in cases of male infertility resulting from mutations in the genes associated with sperm head shaping, as well as the ICSI outcomes through AOA for infertile men with impaired sperm head. WIDER IMPLICATIONS Understanding the molecular mechanisms of sperm head shaping and its relationship with human male infertility holds profound clinical implications, which may contribute to risk prediction, genetic diagnosis, and the potential treatment of human male infertility.","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"12 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review and meta-analysis of double trophectoderm biopsy and/or cryopreservation in PGT: balancing the need for a diagnosis against the risk of harm.","authors":"Letizia Li Piani, Pasquale Petrone, Mariafrancesca Brutto, Anick De Vos, Annelore Van Der Kelen, Alberto Vaiarelli, Laura Rienzi, Alessandro Conforti, Danilo Cimadomo, Willem Verpoest","doi":"10.1093/humupd/dmae031","DOIUrl":"10.1093/humupd/dmae031","url":null,"abstract":"<p><strong>Background: </strong>To prevent the transfer of embryos affected by monogenic conditions and/or chromosomal defects, preimplantation genetic testing (PGT) requires trophectoderm biopsy and cryopreservation. In 2-6% of biopsies, the diagnosis may be inconclusive due to DNA amplification failure or low-quality results. In these cases, a round of re-warming, re-biopsy, and re-cryopreservation is required to obtain a genetic diagnosis. In other cases, when the IVF centre starts providing PGT and/or when the patients develop an indication because of multiple failures, miscarriages or the birth of an affected child after IVF, cryopreserved untested embryos may be warmed, biopsied, and then re-vitrified. However, it is still unclear whether multiple manipulations may reduce reproductive outcomes after PGT.</p><p><strong>Objective and rationale: </strong>This study aimed at conducting a systematic review to investigate the available evidence on the safety of double biopsy and/or double cryopreservation-warming and provide recommendations in this regard. We performed meta-analyses of the differences in the reproductive outcomes (live birth per embryo transfer [LBR per ET], clinical pregnancy rate per ET [CPR per ET], and miscarriage rate per clinical pregnancy [MR per CP]) in double cryopreservation and single biopsy (CBC) or double biopsy and double cryopreservation (BCBC) flows vs the control single biopsy and single cryopreservation (BC) flow. Cryo-survival rates before ET and gestational and perinatal outcomes were also reported.</p><p><strong>Search methods: </strong>PRISMA guidelines were followed to gather all available information from the literature (PubMed, Scopus, and Embase). We used Medical Subject Headings (MeSH) terms and a list of specific keywords relevant for the study question. We searched for original studies in humans, published in peer-reviewed journals in English up to April 2024. Four independent authors assessed the articles for inclusion. One included paper was retrieved from another source.</p><p><strong>Outcomes: </strong>A total of 4219 records were identified, and 10 studies were included in the meta-analysis. Certainty of evidence level ranged from low to moderate. Both the CBC and BCBC groups showed reduced reproductive outcomes compared to the control (BC). Specifically, live birth rates per embryo transfer were lower in the CBC group (OR: 0.56, 95% CI: 0.38-0.81, I2 = 58%; six studies) and the BCBC group (OR: 0.51, 95% CI: 0.34-0.77, I2 = 24%; six studies). CPR per ET were also lower in the CBC group (OR: 0.68, 95% CI: 0.51-0.92, I2 = 57%; seven studies) and the BCBC group (OR: 0.60, 95% CI: 0.46-0.78, I2 = 0%; seven studies). Additionally, MR per CPs were higher in both the CBC group (OR: 1.68, 95% CI: 1.02-2.77, I2 = 50%; seven studies) and the BCBC group (OR: 2.08, 95% CI: 1.13-3.83, I2 = 28%; seven studies). Cryo-survival as well as gestational and perinatal outcomes were within the expected norms in the st","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"102-115"},"PeriodicalIF":14.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing omics data for drug discovery and development in ovarian aging","authors":"Fengyu Zhang, Ming Zhu, Yi Chen, Guiquan Wang, Haiyan Yang, Xinmei Lu, Yan Li, Hsun-Ming Chang, Yang Wu, Yunlong Ma, Shuai Yuan, Wencheng Zhu, Xi Dong, Yue Zhao, Yang Yu, Jia Wang, Liangshan Mu","doi":"10.1093/humupd/dmaf002","DOIUrl":"https://doi.org/10.1093/humupd/dmaf002","url":null,"abstract":"BACKGROUND Ovarian aging occurs earlier than the aging of many other organs and has a lasting impact on women’s overall health and well-being. However, effective interventions to slow ovarian aging remain limited, primarily due to an incomplete understanding of the underlying molecular mechanisms and drug targets. Recent advances in omics data resources, combined with innovative computational tools, are offering deeper insight into the molecular complexities of ovarian aging, paving the way for new opportunities in drug discovery and development. OBJECTIVE AND RATIONALE This review aims to synthesize the expanding multi-omics data, spanning genome, transcriptome, proteome, metabolome, and microbiome, related to ovarian aging, from both tissue-level and single-cell perspectives. We will specially explore how the analysis of these emerging omics datasets can be leveraged to identify novel drug targets and guide therapeutic strategies for slowing and reversing ovarian aging. SEARCH METHODS We conducted a comprehensive literature search in the PubMed database using a range of relevant keywords: ovarian aging, age at natural menopause, premature ovarian insufficiency (POI), diminished ovarian reserve (DOR), genomics, transcriptomics, epigenomics, DNA methylation, RNA modification, histone modification, proteomics, metabolomics, lipidomics, microbiome, single-cell, genome-wide association studies (GWAS), whole-exome sequencing, phenome-wide association studies (PheWAS), Mendelian randomization (MR), epigenetic target, drug target, machine learning, artificial intelligence (AI), deep learning, and multi-omics. The search was restricted to English-language articles published up to September 2024. OUTCOMES Multi-omics studies have uncovered key mechanisms driving ovarian aging, including DNA damage and repair deficiencies, inflammatory and immune responses, mitochondrial dysfunction, and cell death. By integrating multi-omics data, researchers can identify critical regulatory factors and mechanisms across various biological levels, leading to the discovery of potential drug targets. Notable examples include genetic targets such as BRCA2 and TERT, epigenetic targets like Tet and FTO, metabolic targets such as sirtuins and CD38+, protein targets like BIN2 and PDGF-BB, and transcription factors such as FOXP1. WIDER IMPLICATIONS The advent of cutting-edge omics technologies, especially single-cell technologies and spatial transcriptomics, has provided valuable insights for guiding treatment decisions and has become a powerful tool in drug discovery aimed at mitigating or reversing ovarian aging. As technology advances, the integration of single-cell multi-omics data with AI models holds the potential to more accurately predict candidate drug targets. This convergence offers promising new avenues for personalized medicine and precision therapies, paving the way for tailored interventions in ovarian aging. REGISTRATION NUMBER Not applicable.","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"183 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fertility in transgender and gender diverse people: systematic review of the effects of gender-affirming hormones on reproductive organs and fertility","authors":"C De Roo, F Schneider, T H R Stolk, W L J van Vugt, D Stoop, N M van Mello","doi":"10.1093/humupd/dmae036","DOIUrl":"https://doi.org/10.1093/humupd/dmae036","url":null,"abstract":"BACKGROUND Transgender and gender diverse (TGD) people seek gender-affirming care at any age to manage gender identities or expressions that differ from their birth gender. Gender-affirming hormone treatment (GAHT) and gender-affirming surgery may alter reproductive function and/or anatomy, limiting future reproductive options to varying degrees, if individuals desire to either give birth or become a biological parent. OBJECTIVE AND RATIONALE TGD people increasingly pursue help for their reproductive questions, including fertility, fertility preservation, active desire for children, and future options. Their specific needs certainly require more insight into the effects of GAHT on gonads, gametes, and fertility. This systematic review aims to provide an overview of the current knowledge on the impact of GAHT on gonads, gametes, fertility, fertility preservation techniques, and outcomes. SEARCH METHODS This review was registered in the PROSPERO registry under number CRD42024516133. A literature search (in PubMed, Embase, and Web of Science) was performed with a medical information specialist until 15 November 2024. OUTCOMES In all TGD people using GAHT, histological changes have been reported. Using testosterone GAHT, ovarian cortical and stromal changes were reported by various studies. In most studies, persistent activity in folliculogenesis can be concluded based on the descriptions of the follicle count, distribution, and oocyte retrieval yield. However, there may be a negative effect on the fertilization rate in the presence of testosterone. Reports of successful ovarian stimulation, fertilization, pregnancies, and live births have been published, describing cases with and without testosterone discontinuation. After using oestrogen GAHT, testes are reported to be more atrophic, including smaller seminiferous tubules with heavy hyalinization and fibrosis. Spermatogenic levels varied widely from complete spermatogenesis to meiotic arrest with spermatids, to spermatogonial arrest, Sertoli cells only, or even tubular shadows. Oestrogen and anti-androgen treatment causes higher proportions of sperm abnormalities (i.e. low total sperm count, low sperm concentration, poor sperm motility) or azoospermia. However, after cessation, this may be restored. WIDER IMPLICATIONS Although knowledge of the effect of GAHT is growing, blind spots remain to be uncovered. Therefore, additional research in this specific population is needed, preferably comparing outcomes before and after the start of GAHT. This may help to reveal the pure impact of GAHT on reproductive functioning. Research suggestions also include investigations into the reversibility of the GAHT effect, especially for those who start transition at a young age. Looking carefully at the presented data on GAHT effects on gonads and gametes, the correct advice is to assess and reassess reproductive wishes and preferences repeatedly, and also to explore individual fertility preservation needs during ge","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"47 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Celebrating 30 years at Human Reproduction Update.","authors":"Arne S Sunde, Madelon van Wely","doi":"10.1093/humupd/dmae035","DOIUrl":"https://doi.org/10.1093/humupd/dmae035","url":null,"abstract":"","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"31 1","pages":"1"},"PeriodicalIF":14.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional hypothalamic amenorrhoea and polycystic ovarian morphology: a narrative review about an intriguing association.","authors":"Johannes Ott, Geoffroy Robin, Marlene Hager, Didier Dewailly","doi":"10.1093/humupd/dmae030","DOIUrl":"10.1093/humupd/dmae030","url":null,"abstract":"<p><strong>Background: </strong>Functional hypothalamic amenorrhoea (FHA) is responsible for 20-35% of all cases of secondary amenorrhoea and, thus, is the second most common cause of secondary amenorrhoea after polycystic ovary syndrome (PCOS). A high number of patients with FHA reveal polycystic ovarian morphology (PCOM) on ultrasound. The combination of amenorrhoea and PCOM can lead to confusion. First, amenorrhoeic women with PCOM fulfil the revised Rotterdam criteria and, thus, can easily be misdiagnosed with PCOS. Moreover, it has been claimed that some women with FHA and concomitant PCOM differ from those without PCOM in terms of endocrine regulation and metabolic traits.</p><p><strong>Objective and rationale: </strong>The main focus of this article was on studies about FHA, which differentiated between patients with or without PCOM. The aim was to estimate the prevalence of PCOM and to look if it has an impact on pathophysiologic, diagnostic and therapeutic issues as well as on long-term consequences.</p><p><strong>Search methods: </strong>Peer review original and review articles were selected from PubMed searches for this review. Searches were performed using the search terms 'polycystic AND functional hypothalamic amenorrhoea'. The reference lists of publications found were searched for relevant additional studies. The inclusion criteria for publications were: English language, patients' age ≥ 18 years, year of publication >1980, original studies, validated diagnosis of FHA, and validated diagnosis of PCOM using transvaginal ultrasound.</p><p><strong>Outcomes: </strong>The prevalence of PCOM in women with FHA varied from 41.9% to 46.7%, which is higher than in healthy non-PCOS controls. Hypothetically, the high prevalence might be due to a mixture of silent PCOM, as in the general population, and pre-existing PCOS. Several differences in metabolic and hormonal parameters were found between FHA-PCOM and FHA-non-PCOM patients. While oestrogen deficiency is common to both groups of patients, FHA-PCOM patients have a higher BMI, higher levels of anti-Müllerian hormone (AMH) and testosterone, a higher increase in LH in the course of a GnRH test, and lower sex hormone binding globulin (SHBG) levels than FHA-non-PCOM patients. The differential diagnosis between FHA-PCOM and PCOS, especially PCOS phenotype D (PCOM and oligo-/anovulation without hyperandrogenism), can be challenging. Several parameters have been suggested, which are helpful though not absolutely reliable. They include the typical causes for FHA (excessive exercise, energy deficit, and/or psychological stress), the serum levels of LH, testosterone, and SHBG, as well as the progestin challenge test. Whether FHA-PCOM has a different risk profile for long-term consequences concerning patients' metabolic and cardiovascular situation as well as their bone mass, is unclear. Concerning therapeutic aspects, there are only few data about FHA-PCOM compared to FHA-non-PCOM. To treat anovula","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"64-79"},"PeriodicalIF":14.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a gonadotropin dose selection model for optimized ovarian stimulation in IVF/ICSI: an individual participant data meta-analysis","authors":"Nienke Schouten, Rui Wang, Helen Torrance, Theodora Van Tilborg, Ercan Bastu, Christina Bergh, Thomas D’Hooghe, Jesper Friis Petersen, Kannamannadiar Jayaprakasan, Yacoub Khalaf, Ellen Klinkert, Antonio La Marca, Lan Vuong, Louise Lapensée, Sarah Lensen, Åsa Magnusson, Adolfo Allegra, Anders Nyboe Andersen, Simone Oudshoorn, Biljana Popovic-Todorovic, Ben Willem Mol, Marinus Eijkemans, Frank Broekmans","doi":"10.1093/humupd/dmae032","DOIUrl":"https://doi.org/10.1093/humupd/dmae032","url":null,"abstract":"BACKGROUND The ovarian response to gonadotropin stimulation varies widely among women, and could impact the probability of live birth as well as treatment risks. Many studies have evaluated the impact of different gonadotropin starting doses, mainly based on predictive variables like ovarian reserve tests (ORT) including anti-Müllerian hormone (AMH), antral follicle count (AFC), and basal follicle-stimulating hormone (bFSH). A Cochrane systematic review revealed that individualizing the gonadotropin starting dose does not affect efficacy in terms of ongoing pregnancy/live birth rates, but may reduce treatment risks such as the development of ovarian hyperstimulation syndrome (OHSS). An individual patient data meta-analysis (IPD-MA) offers a unique opportunity to develop and validate a universal prediction model to help choose the optimal gonadotropin starting dose to minimize treatment risks without affecting efficacy. OBJECTIVE AND RATIONALE The objective of this IPD-MA is to develop and validate a gonadotropin dose-selection model to guide the choice of a gonadotropin starting dose in IVF/ICSI, with the purpose of minimizing treatment risks without compromising live birth rates. SEARCH METHODS Electronic databases including MEDLINE, EMBASE, and CRSO were searched to identify eligible studies. The last search was performed on 13 July 2022. Randomized controlled trials (RCTs) were included if they compared different doses of gonadotropins in women undergoing IVF/ICSI, presented at least one type of ORT, and reported on live birth or ongoing pregnancy. Authors of eligible studies were contacted to share their individual participant data (IPD). IPD and information within publications were used to determine the risk of bias. Generalized linear mixed multilevel models were applied for predictor selection and model development. OUTCOMES A total of 14 RCTs with data of 3455 participants were included. After extensive modeling, women aged 39 years and over were excluded, which resulted in the definitive inclusion of 2907 women. The optimal prediction model for live birth included six predictors: age, gonadotropin starting dose, body mass index, AFC, IVF/ICSI, and AMH. This model had an area under the curve (AUC) of 0.557 (95% confidence interval (CI) from 0.536 to 0.577). The clinically feasible live birth model included age, starting dose, and AMH and had an AUC of 0.554 (95% CI from 0.530 to 0.578). Two models were selected as the optimal model for combined treatment risk, as their performance was equal. One included age, starting dose, AMH, and bFSH; the other also included gonadotropin-releasing hormone (GnRH) analog. The AUCs for both models were 0.769 (95% CI from 0.729 to 0.809). The clinically feasible model for combined treatment risk included age, starting dose, AMH, and GnRH analog, and had an AUC of 0.748 (95% CI from 0.709 to 0.787). WIDER IMPLICATIONS The aim of this study was to create a model including patient characteristics whereby gon","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"12 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}