搜索结果：Human reproduction update

Stem cell-based embryo models (SCBEMs) are clusters of pluripotent stem cells that can mimic morphological and functional aspects of early human embryos to different degrees. When cultured from human cells, SCBEMs offer technically scalable and amenable tools that can help refine, reduce, and, in the future, perhaps replace the use of animals and human embryos in fundamental and clinical research. These advantages propelled the development of SCBEMs, and several distinct types have been generated over the past decade, including gastruloids, axioloids, blastoids, and post-implantation-like embryoids. For purposes of governance, advisory reports distinguish between SCBEMs based on their presumed capacity to continuously undergo organized human development-referred to here as developmental potential. However, since functionally testing this potential by transferring human SCBEMs to a uterus would be unethical and is recommended to be prohibited, scientists lack clear or consistent ways to assess it. This narrative review aims to tackle the question of how to assess developmental potential in SCBEMs by clarifying the different ways in which it can be and is being conceptualized. We achieve this by synthesizing insights from governance, science, and ethics. First, we examine how developmental potential is described in contemporary governance frameworks, and which aspects are emphasized. Next, we discuss biological markers for developmental potential and show how their scientific basis (in embryos, let alone SCBEMs) remains poorly understood. Then, we explore how the aspects considered relevant for assessments of developmental potential in governance and science may pre-emptively hinge on underlying conceptual interpretations and lead to differing normative implications. This narrative review combines insights from both the academic and grey literature on the (ethics of) embryo models. Original and review articles were selected from PubMed and Biorxiv with the main focus on articles published since 2015. Search terms included: embryo quality, in vitro fertilization, Gardner system, blastoid, gastruloid, embryo research, potentiality argument, developmental potential, transcriptomics, epigenetics, embryo metabolism, and related terms. Additional sources were identified through snowballing. This work focuses predominantly on human SCBEMs, but references to animal models are made. Comparison of the descriptions currently recommended for governance suggests at least three criteria that are used to assess developmental potential in SCBEMs: composition, organization, and interaction. Scientifically, developmental potential is multifaceted and only partly characterized, making it necessary to measure a broader range of aspects, using human embryos as benchmarks when possible. Since the range and significance of these aspects can be shaped by underlying accounts of developmental potential, contemporary advisory reports are examined to explore if and how they connote interpretations of developmental potential as possibility, probability, and predisposition. Categorization of the regulatory and scientific criteria currently used to assess developmental potential shows that they are underpinned by distinct interpretations of the concept, revealing tensions and questions for further inquiry. By synthesizing insights from governance, science, and ethics, this review thus aims to contribute to the responsible advancement of the SCBEM field and to support its coherent and transparent governance. N/A.

The ovarian reserve is the quantity of non-growing primordial follicles (NGF) in paired ovaries. A low or high ovarian reserve at birth respectively may foreshadow early or late age at menopause. In textbooks, published papers, and internet modalities, a recurring theme is that for human females, on average, mid-gestation marks the peak supply of 7 million germ cells/NGF followed by large-scale depletion to about 1-2 million in paired ovaries at birth. We test this narrative against the evidence for germ cell quantity and degeneration reported in peer-reviewed publications. Ovary sizes, volumes/shapes are particularly variable among same-age foetuses and at birth. Coupled with genomic mechanisms determining germ cell proliferation/differentiation/survival, substantial variations of germ cell numbers are recorded within and between individual studies. Across published papers, textbooks, and webpages, germ cell numbers in foetal-newborn ovaries range from thousands to 20 million. A massive 70-85% die-off among germ cells in foetal ovaries is reported during the second half of gestation. Although germ cell degeneration is a reality, we review also the evidence for the timing and extent of germ cell death in foetal/newborn human ovaries. We cite primary publications of human embryonic, foetal/newborn ovaries where data on germ cell numbers and death are reported, and similarly for studies of ovarian volume, shape, histology, and growth in foetal-early postnatal life. Searches to September 2025 used PubMed, Google Scholar, and DOIs/URLs from published papers, textbooks, and webpages, including keywords listed below. Textbook and webpage citations are a selection and not comprehensive, serving to illustrate the widespread narrative on human ovarian development. Germ cell number estimates (oogonia, oocytes, NGF) in human embryonic, foetal, and newborn ovaries (n = 139) in seven studies from 1953 until 2011 used three different quantitation methods: (i) volumetric/model-based with correction factors, (ii) volumetric/modified stereology, and (iii) fractionator/optical dissector. In a 1963 study, germ cells in paired foetal ovaries at 20 weeks (n = 2) reported 6.8 million in total with 20% atretic, and at birth (n = 2), 2 million in total with 50% atretic, leading to the narrative that the mid-gestation human female foetus has 7 million germ cells/NGF that are subsequently depleted to 1-2 million by birth. Independent investigations of germ cell quantitation/degeneration do not confirm these findings for total numbers nor the substantial fractions reported as degenerating. In adult women, ovarian volume is strongly correlated with the numbers of NGF but an equivalent correlation between germ cell supply and ovarian volume during foetal life up to birth has not been investigated. We conclude that the narrative whereby human foetal ovaries develop millions of germ cells followed by most degenerating up to birth has not been verified. Systematic analysis of total numbers and estimates of viable versus degenerating germ cells across gestation is needed. Does it matter how many germ cells or primordial follicles are in the ovaries at birth? Yes, not only with regard to scientific authenticity but also for clinical investigations of gynaecological and reproductive conditions. These include situations where follicle numbers and growth dynamics are of consideration, such as premature ovarian insufficiency, early menopause, chemotherapy for cancer treatments, polycystic ovary syndrome, assisted conception and/or IVF particularly for poor responders to gonadotrophins and predictions of age at the menopause. For fertility counselling and for women electing to delay pregnancy, it is suggested that clinicians and health professionals be aware that the age-related ovarian reserve in adults may not necessarily be in the expected range if the NGF reserve at birth was significantly lower than the narrative of 1-2 million at that time. N/A.

Noise from human activities is a major concern for wildlife, with numerous studies demonstrating significant impacts. In 2020, Sordello and collaborators systematically mapped the literature on the impacts of anthropogenic noise on wildlife up to 2018. Since then, research on this topic has continued to grow steadily. To reflect these developments, we present an updated systematic map encompassing studies published through 2023, exclusively focused on airborne noise. The method follows the a priori protocol published by Sordello and collaborators in 2019. The present work includes literature searches by Sordello et al. (2020) and a complementary search update performed on 2020-2023. Literature from Sordello et al. (2020) was re-screened to align with the updated scope, now restricted to airborne noise. For the update, both peer-reviewed and grey literature were retrieved from Scopus, the Web of Science Core Collection, and Google Scholar. Titles, abstracts, and full texts were screened by eligibility criteria, and included articles were coded. We included all wild terrestrial or semi-aquatic taxonomic groups, and anthropogenic noise from various sources (e.g., transport, urban, recreational) was considered, along with all relevant outcomes (e.g., behaviour, reproduction, physiology). Sordello et al. (2020) provided 1,794 articles, of which 466 were retained after re-screening the full texts. The search update yielded 13,698 citations, resulting in 397 relevant articles. A total of 863 articles were included in the map (665 primary research studies, 196 reviews and meta-analyses, 2 modelling papers). Most studies have been conducted in the USA. Birds are the most studied taxonomic group (64%), followed by mammals (22%); transportation is the most studied source of noise (43%), followed by urban noise (24%); behaviour (27%) and vocal communication (25%) are the most studied outcomes. The map represents an updated state of the art on the impact of airborne anthropogenic noise on wildlife and can serve as a starting point for further syntheses of evidence. Three clusters of knowledge were identified as suitable candidates for future syntheses: (1) What is the impact of anthropogenic noise on mammals' behaviour? (2) What is the impact of anthropogenic noise on birds' reproductive success? (3) What is the impact of anthropogenic noise on species richness and diversity? In addition, the knowledge gaps identified may be used to inform future research and address the apparent imbalance in the published research: many taxonomic groups are still understudied (e.g., especially reptiles and arachnids), many potential sources of noise disturbance are neglected (e.g., recreational and military noise) and the impacts of noise are unevenly studied between taxonomic groups.

Understanding the mechanisms that promote or hinder healthy placental development and functionality is fundamental to advancing the field of fetal and reproductive medicine. Syncytiotrophoblast (STB) are highly specialized trophoblast which develop and gain functional maturity during the first trimester of pregnancy. STB are critical to many placental functions and are often implicated in the etiology of placental pathologies. Recent advancements in cell biology have facilitated the development of innovative in vitro STB model systems. However, as the variety of available in vitro STB models grows, a critical assessment of the strengths, limitations, and appropriate applications of both established and emerging model systems is important for the field. With this review, we set out to compile and synthesize current knowledge on in vitro modeling of STB. Using this information, we sought to develop a balanced and thoughtful discussion regarding the use and suitability of various in vitro STB models. Our approach is grounded in a framework that considers placental development and physiology, with a specific focus on the capability of different models to recapitulate and thus enable the study of human STB differentiation, development, function, and dysfunction. This review assessed published literature sourced through the PubMed database. Search terms included 'human placenta models,' 'syncytiotrophoblast models,' 'syncytiotrophoblast development,' 'trophoblast stem cells,' 'trophoblast organoids,' and 'trophoblast cell models.' The literature search was limited to English-language publications available up to August 2025. We provide a narrative which explores the features, potential applications, and limitations of various STB models, including explant systems, immortalized trophoblast cell lines, stem cell-derived trophoblast, and a range of established and emerging 3D culture systems. Our evaluation focuses on the potential of each model to address specific research questions and highlights the challenges associated with modeling different stages of STB development and different unique aspects of STB functionality. Moreover, while remarkable progress in developing STB models has been made, no single system fully recapitulates the complex in vivo features of STB formation and function. Rather than being exhaustive, this review seeks to provide an evidence-based perspective on STB modeling in vitro which can encourage the careful consideration of the strengths and limitations of STB models. This review provides an overview of the in vitro STB models currently available and a commentary of the knowledge that these systems have contributed to our understanding of STB biology. While the field has made significant progress, ongoing refinement of existing models is essential for advancing our understanding of STB and their role in both the health and dysfunction of the human placenta. By summarizing the unique adaptations and physiological changes of STB throughout gestation and aligning these with the capabilities of current models, we have developed a framework to guide future research and innovation in STB modeling. This framework is underscored by the importance of selecting models which align with specific research questions and simultaneously acknowledging the inherent limitations in extrapolating data from any in vitro systems to the biological context of the developing human placenta. By generating this discussion, we hope to contribute to the ongoing refinement of placental research methodologies and to inspire continued innovation in STB model systems. N/A.

Ovarian aging (OA) results from the senescence of different cell types present in the ovary, decreasing female fertility and quality of life and augmenting the risk of a variety of fertility-unrelated pathological conditions. The changes observed in the ovarian cells are accompanied by changes occurring in various elements of the hypothalamic-pituitary-ovarian (HPO) axis, the complex endocrine system that regulates the female reproductive cycle. Issues pertaining to the HPO axis have been addressed in animal models via hormonal treatments with preparations inhibiting ovarian follicular recruitment at the level of the receptors of gonadotropin-releasing hormone (GnRH)-secreting neurons, mainly acting on glutamate- and gamma-aminobutyric acid (GABA)-driven signaling. GnRH agonists and antagonists have also been used in women exposed to chemotherapeutics. HPO-independent OA can be delayed through the administration of different antioxidants and mitochondria-protecting agents, among which melatonin has been shown to be particularly useful. Other therapeutic approaches used with success in women include hormonal and growth factor (GF) modulators, such as growth hormone (GH), insulin-like growth factor 1 (IGF-1), vascular endothelial growth factors (VEGF), and dehydroepiandrosterone (DHEA), and the development of patient-tailored combination-based therapies (IGF-1 + VEGF + DHEA) has also been suggested. Intraovarian injection of autologous platelet-rich plasma (PRP), mitochondrial donation through pronuclear transfer, and ovarian tissue cryopreservation and autotransplantation have also yielded promising results in women, and their use can preserve not only fertility but also the ovarian endocrine function. Personalized mixtures of specific agents (desatinib, quercetin, rapamycin, metformin, resveratrol, melatonin, and coenzyme Q10) targeting different cell types in the ovary are currently under investigation. Overall, this review aims to present a global view of the subject, uniting the physiological and molecular background of this pathology with the history and development of potential treatment strategies and new perspectives in this domain. As such, this study may be helpful both to clinicians facing problems resulting from OA and to researchers pursuing further developments in this field.

What is the recommended management of ovarian stimulation, based on the best available evidence in the literature? This updated ESHRE guideline on ovarian stimulation for IVF/ICSI provides 121 recommendations, answering 21 key questions on ovarian stimulation for IVF/ICSI. Before the ESHRE guideline on ovarian stimulation for IVF/ICSI was published in 2019, ovarian stimulation for IVF/ICSI had only been discussed briefly in the National Institute for Health and Care Excellence guideline on fertility problems and in a statement by the Royal Australian and New Zealand College of Obstetricians and Gynaecologists. The guideline was developed according to the structured methodology for ESHRE guidelines. The 18 key questions from the 2019 version of the guideline were revised by the Guideline Development Group (GDG). This resulted in the addition of one new key question, the splitting of the key question on fertility preservation in three separate key questions (fertility preservation for women facing gonadotoxic treatment, elective oocyte cryopreservation, and oocyte donation) and several new interventions being added to the existing key questions. Papers published between 31 October 2018 and 2 February 2025 and written in English were included. The critical outcomes for this guideline were efficacy in terms of cumulative live birth rate per started cycle or live birth rate per started cycle, as well as safety in terms of the rate of occurrence of moderate and/or severe ovarian hyperstimulation syndrome (OHSS). Based on the available evidence, recommendations were formulated and discussed until consensus was reached within the GDG. Following stakeholder review of the initial draft, the final version was approved by the GDG and ultimately by the ESHRE Executive Committee. The guideline provides a total of 121 recommendations: 42 recommendations remained unchanged in 2019, 4 recommendations were reworded for better understanding, 29 recommendations were updated in view of new evidence, and 46 new recommendations for 2025 have been formulated. The guideline provides 4 recommendations on pre-stimulation evaluation, 7 recommendations on pre-treatment therapies, 50 recommendations on pituitary suppression and ovarian stimulation, 17 recommendations on monitoring, 18 recommendations on triggering of final oocyte maturation and luteal support, and 8 recommendations on the prevention of OHSS. In addition, the guideline provides 17 recommendations on fertility preservation, both oncologic and elective, and oocyte donation. These include 90 evidence-based recommendations, of which only 42 were formulated as strong recommendations and 48 as conditional, as well as 29 good practice points and 2 research-only recommendations. Of the evidence-based recommendations, none were supported by high-quality evidence, 6 by moderate-quality evidence, 36 by low-quality evidence, and 148 by very low-quality evidence. To support future research on ovarian stimulation for IVF/ICSI, a list of research recommendations was provided. Several newer interventions are not well studied yet. For most of these interventions, a recommendation against the intervention or a research-only recommendation was formulated based on insufficient evidence. Future studies may require these recommendations to be revised. The guideline provides clinicians with clear advice on best practice in ovarian stimulation, based on the best evidence available. In addition, a list of research recommendations is provided to promote further studies in ovarian stimulation. The guideline was developed by ESHRE, who funded the guideline meetings, literature searches, and dissemination of the guideline. The guideline group members did not receive any financial incentives; all work was provided voluntarily. BA reports speaker's fees from Gedeon-Richter, Ferring, IBSA, Intas, Merck, Organon, consulting fees from Merck, Organon, Oxolife, stock options from Global Fertility Solutions LLC (employee co-investment), and was chair of the Turkish Society of Reproductive Medicine. EB reports research grants from Roche Diagnostics and IBSA, consulting fees from MSD, Abbot, Gedeon-Richter, Roche, speaker's fees from IBSA, MSD, Ferring Pharmaceuticals, Abbot, Gedeon-Richter, Merck, Roche, participation in the advisory board of Ferring Pharmaceuticals, IBSA and Merck, and ownership interest from IVI-RMS Valencia. GG was part of the ESHRE working group on Recurrent Implantation Failure and the ESHRE working group on clinical KPISs, reports travel support from Merck, Organon, Ferring, Theramex, Gedeon-Richter, Abbott, consulting fees from Organon, Ferring, Merck, Gedeon-Richter, Theramex, Abbott, ReproNovo, Igyxos, OxoLife, Philipps, ReprodWissen, PregLem, Guerbet, Roche, IBSA, and Besins, speaker's fees from Organon, Ferring, Merck, Gedeon-Richter, Theramex, Abbott, ReproNovo, Igyxos, OxoLife, Philipps, ReprodWissen, PregLem, Guerbet, Roche, IBSA, and Besins, and research grants from Besin, Merck, Abbott, Ferring, Theramex. MG reports speaker's fees from Merck Serono, Ferring, and Gedeon Richter. EK reports travel/hotel expenses from Ferring, Merck SERONO, Vianex, speaker's fees from Ferring, Merck SERONO, Vianex, and is chair of the Greek Society of Fertility and Sterility. MK reports travel support and speaker's fees from Ferring. ALM reports research grants from Merck, Ferring, IBSA, Roche, Organon, Theramex, Beckman Coulter, and Gedeon-Richter, consulting fees from Merck, Ferring, IBSA, Roche, Organon, Theramex, Beckman Coulter, and Gedeon-Richter, speaker's fees from Merck, Ferring, IBSA, Roche, Organon, Theramex, Beckman Coulter, Gedeon-Richter, and participation on an advisory board of Merck, Organon, Ferring, Theramex, Gedeon Richter, and IBSA. GL reports consulting fees from Ferring and Merck, speaker's fees from Ferring, Merck, Gedeon-Richter, Organon, and Vianex, expert testimony fees from Cook, travel support from ESHRE, Ferring, Merck, Gedeon-Richter, Organon, and Vianex, is on the advisory board of Merck and Ferring, and participated in an ESHRE committee and on the Greek Fertility and Sterility Committee. NM reports research grants from IBSA, Organon, consulting fees from Organon, Merck, GE, Ferring, Abbott, and Cooper, and speaker's fees from Ferring, GE, Organon, IBSA, Merck, Theramex. NPP reports research grants from Besins Healthcare, Ferring Pharmaceutical, Merck Serono, Organon, Roche Diagnostics, and Theramex, consulting fees from Besins Healthcare, Alife, Ferring, IBSA, Merck Serono, Organon, Abbott, FertilAI, and speaker's fees from Besins Healthcare, Roche Diagnostics, Ferring Pharmaceuticals, Gedeon-Richter, IBSA, Merck Serono, Organon, and Theramex. SKS reports a research grant from Ferring, travel support from Merck and INTAS, consulting fees from Merck, and speaker's fees from Merck, MSD, INTAS, and Ferring. TT reports travel support from Merck, speaker's fees from Merck, Organon, MSD and is editor-in-chief of a Bulgarian journal, Reproductive Health. MT reports travel support from IBSA, Ferring, and Merck, consulting fees from Abbott and is a member of the board of the Finnish Endocrine Society. JU is a member of the Steering Committee of Richter Reproduction Network and received travel support from IBSA. FB reports a research grant from Besins, is on the advisory board of Merck and Abbott, reports speaker's fees from Ferring, Merck, Besins, Intas Fermaceuticals, PREIS School; he is the owner of FRANKSCHOOL RforL. The other authors have nothing to disclose. N/A. This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained.Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type.ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. (The full disclaimer is available at www.eshre.eu/guidelines.).

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. This review explores the conserved mechanisms of sperm production between mammals and flies, with a focus on the human setting where possible. 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. 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. 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 sperm storage, mammalian sperm undergo post-testicular modifications and are stored in the epididymis. In Drosophila, sperm are stored in the seminal vesicle, and do not appear to undergo any overt post-testicular modifications in this epididymis-like structure. The seminal vesicle is a separate organ in mammals that is responsible for generation of the seminal fluid. It is important to note that male fertility and thus spermatogenesis are subject to significant evolutionary pressure, and there is a degree of variation in its processes between all species. As such, the absence of a phenotype in mutants would not determine that the gene is dispensable for fertility in humans. While flies are useful for genetic studies to confirm human disease causality, we propose they should be used primarily to pre-screen and select strong candidates for further interrogation in mammalian species for translational pathways in the context of human fertility. N/A.

Fertilization ensures the transmission of genetic material across generations through a series of precisely coordinated physiological and molecular events. To fertilize an oocyte, a spermatozoon must pass through the cumulus cell layer, penetrate the zona pellucida (ZP), and ultimately adhere to and fuse with the oolemma (the oocyte plasma membrane). Upon fusion, the oocyte initiates mechanisms to block additional sperm entry at both the ZP and oolemma. These processes are highly dynamic in space and time, posing substantial technical barriers to their mechanistic dissection. Nonetheless, recent in silico, in vitro, and in vivo studies have begun to elucidate how intricate networks of intracellular signaling cascades and extracellular protein-protein interactions orchestrate successful fertilization in vertebrates. However, the extent to which these findings accurately reflect the biology of human sperm-oocyte interactions remains obscure, owing to ethical constraints on human gamete experimentation and the limited availability of patients harboring pathogenic variants in fertilization-related genes. This narrative review synthesizes current knowledge of the molecular determinants governing mammalian sperm-oocyte interactions, summarizes relevant genetic anomalies identified in infertile patients, and discusses emerging experimental approaches for the direct investigation of human fertilization. We also explore how recent mechanistic insights and technological innovations may inform the diagnosis and treatment of fertilization disorders and guide the development of novel contraceptive strategies. We searched PubMed, Google Scholar, and Scopus to identify research and review articles published in English. Studies limited to non-mammalian species and non-peer-reviewed preprints were excluded. Searches used terms related to fertilization, sperm-oocyte interactions, ZP, cumulus cells, polyspermy block, and human infertility, alone or in combination. Additional searches targeted key proteins and emerging technologies relevant to mammalian fertilization, clinical diagnostics, and contraceptive development. Our mechanistic understanding of mammalian gamete interactions has predominantly stemmed from in vitro and in vivo animal studies, which have revealed key molecular processes, such as sperm hyaluronidase-mediated cumulus matrix dispersal, translocation of sperm acrosomal membrane proteins to enable oolemma interaction, and ZP glycoprotein cleavage underlying the polyspermy block. While studies in model species remain indispensable, translating this knowledge to human biology requires meticulous validation. The integration of interdisciplinary approaches, such as humanized mouse models, artificial human oocytes, xenospecies fertilization assays, antibody inhibition studies, and high-throughput interactome screening, offers promising avenues to clarify interspecies discrepancies and generate insights more directly relevant to human gamete interactions. Advances in the mechanistic dissection of sperm-oocyte interactions are anticipated to support the development of diagnostic tools and therapeutic interventions for infertility caused by defective fertilization. In parallel, these discoveries may enable the rational design of safe, reversible contraceptives that selectively block gamete interactions without compromising other physiological processes. N/A.

Human-induced pluripotent stem cells (hiPSCs) offer immense potential in reproductive medicine, particularly for males who lack germ cells and cannot achieve biological parenthood through conventional ARTs. Early efforts to derive human germ cells from stem cells were hindered by low efficiency, subpar characterization, and the lack of standardized differentiation approaches. However, recent advancements have led to the development of defined protocols that mimic early embryonic development and allow the specification of transcriptomically and epigenetically validated human primordial germ cell-like cells (hPGCLCs). Current research focuses on maturing hPGCLCs in vitro, particularly within 3D culture systems that resemble their physiological microenvironment, with the aim of producing transplantable hiPSC-derived spermatogonial stem cells (SSCs) or differentiating them to sperm. At the same time, researchers are also testing whether hiPSCs generated from infertile patients can resume germline differentiation. This narrative review aimed to summarize the key efforts and remaining challenges in differentiating male germ cells from human pluripotent stem cells (hPSCs), with a particular focus on defined and validated protocols for hPGCLC specification. In parallel, we addressed key safety and ethical considerations that must be accounted for the development of clinical applications. A deeper understanding of the approaching therapeutic use of hiPSCs in reproductive medicine is essential for developing novel regenerative fertility strategies. PubMed, Scopus, and Web of Science were searched for studies attempting germ cell differentiation from hPSCs using relevant keywords ('stem cells', 'human pluripotent stem cells', 'human embryonic stem cells', 'human induced pluripotent stem cells', 'somatic cell reprogramming', 'infertility', 'germline', 'spermatogenesis', 'germ cells', and 'primordial germ cells'). No time period restriction was established. Studies with an exclusive focus on female germline differentiation were excluded. To maintain a human-focused perspective, only key animal studies are presented. The literature reveals a clear segregation among protocols for deriving germ cells from hPSCs, particularly between earlier studies lacking standardized differentiation conditions and characterization, and the most recent, defined protocols having transcriptomic and epigenetic validation against in vivo hPGCs. Moreover, during the last decade, the field has seen remarkable progress, with multiple efforts aimed at maturing hPGCLCs, closely recapitulating late male embryonic germline development. Additionally, hiPSCs derived from male patients at risk of infertility, particularly those without underlying genetic syndromes, generally retain the capacity for early germline commitment. While attempts at maturating patient germ cells beyond the hPGCLC state remain limited, the rapid pace of discovery and refinement in recent years suggests that further breakthroughs, including clinically applicable fertility restoration strategies, are likely to be achieved in the near future. The ability to generate hiPSCs from infertile patients and to specify them into hPGCLCs supports the feasibility of obtaining hiPSC-derived SSCs for future therapeutic use. These advances raise important ethical, regulatory, and societal questions that must be actively discussed among researchers, clinicians, policymakers, and the general public to ensure responsible and equitable access to these technologies. N/A.

To update the French national cancer institute (INCa) guidelines for the management of women with abnormal cervical cytology. In 2016, INCa published guidelines for the management of women with abnormal cervical cytology. In 2019, however, the national authority for Health (HAS) recommended that the test for human papillomavirus be used to screen for cervical cancer in women over 30. It therefore became necessary to update the initial management and follow-up of women who had a positive test followed by abnormal reflex cytology findings. We used modified Delphi methods. The 3 members of the organizing committee revised each decision tree and then presented them to 35 experts over 2 rounds, to obtain their agreement about their validity and clarity. This formalized consensus of experts allowed the creation of 17 decision trees instead of 15 previously: 13 on the diagnosis management of abnormal cytology, stratified by age, and 4 by therapeutic indications in abnormal histology. The median agreement scores were 89 % (interquartile range 81 %-97 %). These 17 decision trees present different situations encountered by various health professionals and guide them, depending on their specialties, in providing initial or follow-up management or delegating care.

Endometriosis is a chronic inflammatory condition affecting ~10% of reproductive-age individuals and contributing significantly to infertility, pain, and reduced quality of life. Since our 2020 review, new pharmacologic strategies, updated guidelines, and advances in clinical trial evidence have reshaped the therapeutic landscape. Effective, patient-centered management is essential to lessen the burden of disease. This review synthesizes current evidence-based pharmacotherapy for endometriosis, integrating 2022 European Society of Human Reproduction and Embryology recommendations and including a literature review of PubMed, with an emphasis on articles published after 2020. First-line therapies, including NSAIDs, combined oral contraceptives, and progestins such as dienogest, remain central, while GnRH agonists/antagonists and aromatase inhibitors are considered in refractory cases. Recent data highlight add-back therapy to reduce hypoestrogenic side effects. We also review postoperative regimens, fertility-preserving strategies, management in post-hysterectomy and postmenopausal populations, and therapies under investigation - including anti-inflammatory, antifibrotic, angiogenesis-modulating, and microbiome-targeting approaches. Hormonal suppression remains the cornerstone of treatment, but novel nonhormonal strategies and advances in precision medicine hold promise for more durable and individualized care. Ongoing clinical trials, artificial intelligence - assisted diagnostics, and fertility-focused pharmacotherapies represent exciting frontiers. Multimodal, patient-tailored approaches will be key to optimizing long-term outcomes in endometriosis management.

Endocrine disruptors (EDs) are a heterogeneous group of natural or synthetic chemicals capable of interfering with hormonal regulation. Widely present in plastics, cosmetics, pesticides, food packaging, and household products, they contribute to constant human exposure. Compounds such as bisphenol A, phthalates, parabens, dioxins, and certain pesticides are among the most studied. Their mechanisms of action include interaction with hormone receptors, modulation of gene expression through epigenetic changes, disruption of steroidogenesis, and interference with the hypothalamic-pituitary-gonadal axis. Evidence from animal and human studies suggests that EDs may reduce ovarian reserve, impair oocyte maturation, alter ovulation and implantation, and contribute to infertility. Associations have also been observed with polycystic ovary syndrome, endometriosis, and poorer outcomes of assisted reproductive techniques. Despite these findings, human data remain largely observational, with methodological limitations such as variable exposure assessment, lack of standardized biomarkers, and the unaddressed "cocktail effect." Strengthening preventive strategies, regulatory measures, and further research is essential to better understand and mitigate the risks EDs pose to female reproductive health.

Premature ovarian insufficiency (POI) is associated with reduced quality of life and increased health risks. While hormone therapy (HT) is standard treatment, some women seek other options to treat its sequelae. This review explores the role of complementary therapies for POI. A systematic search of four databases up to January 2024 identified randomized controlled trials, systematic reviews, meta-analyses and umbrella reviews that examined the use of complementary therapies by women with POI. Outcomes included menopausal symptoms, gonadotropins, antral follicle count, ovarian volume and quality of life. Study quality was evaluated using Cochrane Risk of Bias and A MeaSurement Tool to Assess systematic Reviews (AMSTAR 2). The search identified 1869 citations, with nine studies meeting the inclusion criteria. Findings suggest that Chinese herbal medicine and acupuncture may alleviate menopausal symptoms and regulate gonadotropins in women with POI, although evidence is very limited. There is insufficient evidence for other complementary therapies for POI. While Chinese herbal medicine may improve menopausal symptoms, there is insufficient evidence specific to POI. There is a clear need for additional and rigorous research on the efficacy and safety of complementary therapies for POI. Evidence does not support complementary medicines as replacements for HT. Review question What is the most recent and best evidence on how safe and effective complementary therapies are for women with premature ovarian insufficiency (POI)?Background Many women with POI try complementary therapies such as Chinese herbal medicine, acupuncture or nutritional supplements to help manage symptoms. It is important they have reliable information to make informed decisions about whether complementary therapies help with menopausal symptoms, hormone levels or quality of life, and whether they have any risks.Search date The evidence is up to date as of January 2024 and updates guidelines from April 2014.Study characteristics This review looked at nine studies that compare complementary therapies to hormone therapy (HT) or placebo, or used complementary therapies alongside HT.Main findings It is uncertain whether complementary therapies were beneficial for women with POI, as the current evidence is limited and very low in quality. Chinese herbal medicine, as an addition or alternative to HT, may help with management of menopausal symptoms and cholesterol markers, but the evidence is limited. Acupuncture may help reduce menopausal symptoms in POI but there was no benefit from adding acupuncture to HT. There is not enough evidence for other complementary therapies. Consequently, complementary therapies should not replace HT.Implications of the evidence There is currently insufficient evidence to recommend complementary therapies to improve POI symptoms. However, there is currently no indication that these nutrients pose any risk of significant harm.

Intrauterine administration of hCG has been considered as a promising IVF add-on before embryo transfer to improve fertility outcomes. A Cochrane review and four more recent systematic reviews all showed improved clinical pregnancy rates and/or live birth rates following intrauterine administration of hCG, however, a high unexplained heterogeneity was also present. To investigate the effectiveness and safety of intrauterine administration of hCG before embryo transfer in participants undergoing IVF. Individual participant data meta-analysis (IPD-MA) is recognized as the gold standard for evidence synthesis due to its ability to harmonize the data and to investigate treatment-covariate interactions. In addition, with recent experiences of guideline development and systematic review production raising increasing concerns about the trustworthiness of randomized controlled trials (RCTs) in women's health research, an IPD-MA provides a unique opportunity to summarize the best available and most trustworthy evidence on this topic. We searched MEDLINE, Embase, Cochrane Gynaecology and Fertility Group Specialised Register, Cochrane Central Register of Controlled Trials, PsycINFO, and clinical trial registries without language restrictions up to January 2026. Inclusion criteria included RCTs comparing intrauterine administration of hCG before embryo transfer versus placebo or no intervention in participants undergoing IVF. The IPD Integrity tool and the TRACT checklist were used to evaluate the trustworthiness of studies with and without IPD, respectively. Both one-stage and two-stage random-effect IPD meta-analyses were performed with one-stage being the primary analysis. We detected 28 RCTs, of which 7 RCTs with IPD involving 2244 participants were included. All seven RCTs with IPD met trustworthiness criteria and six RCTs had overall low risk of bias. All RCTs without IPD did not meet trustworthiness criteria. IPD-MA showed intrauterine administration of hCG before embryo transfer did not improve live birth rates (7 RCTs, 2244 participants, odds ratio [OR] 0.99, 95% CI 0.83-1.19) or clinical pregnancy rates (7 RCTs, 2244 participants, OR 1.04, 95% CI 0.83-1.31). Studies without IPD showed different results from those with IPD for live birth (1.99, 0.72-5.50, P for interaction <0.001) and clinical pregnancy (1.87 (1.48-2.35), 17 RCTs without IPD, 3152 participants, P for interaction 0.005). Our IPD-MA has shown that intrauterine administration of hCG before embryo transfer is unlikely to improve the chance of clinical pregnancy and live birth. In the comparison between studies with IPD and without IPD, we found that none of the RCTs without IPD met trustworthiness criteria but showed a significant improvement in clinical pregnancy. We therefore suggest that intrauterine administration of hCG should not be offered as an IVF add-on in practice. PROSPERO (CRD42020177397).

Although obstetrics and gynaecology (O&G) is a predominantly female specialty, previous studies have suggested that women remain under-represented in academic authorship. This study evaluates trends in female and male first and last authorship in six leading O&G journals (Human Reproduction Update, American Journal of Obstetrics and Gynecology, British Journal of Obstetrics and Gynaecology, Obstetrics and Gynecology, Gynecologic Oncology and Best Practice & Research Clinical Obstetrics & Gynaecology) between January 2013 and December 2023. A bibliometric analysis was conducted using the Web of Science database. The gender of the first and last authors was determined using Genderize.io, with a probability threshold of &#x2265;75% for classification. Binary logistic regression was performed to model the probability of authorship by gender across journals. Among 57&#x2009;310 publications, 38&#x2009;455 first (43.8% male and 56.2% female) and 38&#x2009;950 last authors (58.6% male and 41.4% female) were identified and analysed. Over the past decade, female authorship has shown a clear upward trend, with first authorship increasing from 43% (1141/2636) in 2013 to 69% (2769/4036) in 2023, and last authorship increasing from 29% (770/2700) to 54% (2180/4047). First authorship was statistically more likely to be held by women in Human Reproduction Update (1.23, 95%&#x2009;CI 1.02 to 1.48), American Journal of Obstetrics & Gynecology (1.63, 95%&#x2009;CI 1.58 to 1.70) and Obstetrics & Gynecology (2.33, 95%&#x2009;CI 2.22 to 2.45). However, female last authorship was significantly more likely only in Obstetrics & Gynecology (1.21, 95% CI 1.16 to 1.27). Despite an increasing trend in female representation in first and last authorships over the past decade, a significant gender disparity persists. While women now constitute the majority of first authors, last authorship remains disproportionately male, reflecting ongoing barriers to female leadership in O&G research. These findings highlight the need for targeted institutional efforts to promote gender equity in academic medicine.

This systematic review aimed to update a 2016 review and answer two questions: (1) Among breastfeeding women, does the use of progestogen-only contraception (POC) (ie, pills, injectables, implants, hormonal intrauterine devices) increase the risk of poor breastfeeding or infant outcomes compared with those not using POC? (2) Among breastfeeding women, does the initiation of POC before 6 weeks postpartum increase the risk of poor breastfeeding or infant outcomes compared with the initiation of POC at 6 weeks or later? We searched multiple databases (MEDLINE, EMBASE, Cochrane, ClinicalTrials.gov and CINAHL) from inception to 6 September 2023. We extracted data and assessed risk of bias (RoB) for each study and certainty of evidence for each outcome. Sixty-one articles met the inclusion criteria; 11 were newly identified since the previous review, most with high RoB. Nine new randomised and non-randomised studies assessing breastfeeding and/or infant outcomes met the inclusion criteria for Question 1. Two new randomised studies assessing breastfeeding and/or infant outcomes met the inclusion criteria for Question 2, examining early versus late initiation of the implant. One new article for each objective included preterm infants. For both questions, studies continue to find no significant adverse effects on breastfeeding (eg, continuation, supplementation, duration) or infant (eg, growth, illness) outcomes. The certainty of evidence ranged from very low to moderate across outcomes. This updated systematic review provides additional evidence for the safety of POC use during breastfeeding. Newly identified studies are consistent with the prior review in suggesting no consistent findings of adverse effects, while adding evidence for preterm infants.

Single embryo transfer is globally recommended during IVF treatments. Hence, there is a growing demand for better embryo selection. Additionally, to morphology and genetics, nutrient uptake/release and metabolome profiles in spent embryo culture media (SECM) are proposed as non-invasive biomarkers. Are they ready to be applied for clinical purposes? We reviewed methods of metabolism analysis for embryos, focusing on human SECM. Until November 2024, the Cochrane Library, PubMed, and Google Scholar were surfed for peer-reviewed English-language studies in the human, with MeSH terms and keywords: ART, IVF, ICSI, aneuploidy, embryo transfer, embryo selection, culture media, metabolome, metabolomics, metabolic profile, artificial intelligence (AI), nutrients, carbohydrates, glucose, pyruvate, lactate, amino acids (AAs), fatty acids (FAs), and spent embryo culture medium (SECM). Also, the reference lists of all relevant articles were searched. Forty-nine original publications (1989-2024) were found in which SECM samples were collected from 20 countries, focusing on preimplantation embryo metabolism single biomarker(s) of energy sources (glucose and pyruvate), AAs and free FAs (17 studies), or metabolomic analysis (32 studies). Focal points were blastocyst development, aneuploidy, embryo sex prediction, implantation, and pregnancy outcome. Eleven major companies, which supply embryo culture media, dominate the market. Nutrient composition of their culture media presents major challenges because they are not normally disclosed. In single-biomarker(s) studies, eight studies focus on glucose and pyruvate, eight on AAs, both alone and in combination with glucose or pyruvate, and their ratios. Since the absolute quantities of some AAs or glucose levels were reported in some studies, they all have the potential to become future biomarkers for clinical application. In metabolomics studies, almost all studies reported qualitative results, such as decrease/increase or the metabolite ratios. For absolute concentrations, the basal concentrations of the culture media must be considered. In sum, all differences in the experimental design, the platforms, and the results were analyzed. Establishing a unified guideline for the reporting of metabolomics studies and a specific guideline outlining the minimum information required for SECM experiment publication will ensure that future studies provide all necessary and critical information. The metabolomics studies primarily focused on implantation and pregnancy, whereas we, as a first step, preferred multi-omics studies on absolute concentrations of metabolites of good vs poor quality and euploid vs aneuploid embryos. Following this step, these quantitative approaches might lead to more convincing successes. If small numbers of predictive biomarkers were identified, a simple, rapid, and cheap test could be developed for each medium, clinically performed in the fertility center. Furthermore, further research on basal media ingredients is needed, combined with targeted metabolomics. The future could be an integration of all-primarily non-invasive-information, omics, and other, by AI. The review protocol is registered on the OSF platform: https://osf.io/mxtbg.

Progesterone plays a pivotal role in implantation and ongoing pregnancy. In the context of assisted reproductive technology (ART), and in particular frozen embryo transfer (FET), increasing evidence suggests that serum progesterone levels strongly influence reproductive outcomes. This review summarizes the latest findings regarding the optimal range of serum progesterone concentrations and their implications across different endometrial preparation protocols. Observational and interventional studies have consistently shown that suboptimal mid-luteal serum progesterone levels are associated with lower implantation and live birth rates in FET cycles. The need for exogenous supplementation varies according to the type of endometrial preparation, with hormone replacement therapy cycles being particularly sensitive to inadequate progesterone exposure. Emerging data support the concept of individualized luteal support, including serum-guided adjustments or alternative routes of administration in cases of suboptimal serum progesterone levels. Adequate serum progesterone concentrations are critical for optimizing outcomes after FET. Evidence supports a paradigm shift from empirical supplementation to precision medicine approaches based on serum thresholds and patient characteristics. Future research should aim to define universally accepted cutoff values, clarify the role of endometrial versus systemic progesterone, and refine strategies for tailoring luteal phase support in ART.

High-risk HPV (hrHPV) is the necessary cause of cervical cancer with HPV16/18 accounting for around 70% of the cases worldwide, while other non-HPV16/18 hrHPV genotypes prevail in ~95% of high-grade lesions. Understanding regional genotype distribution of hrHPV types not covered by the nonavalent vaccine is crucial for evaluating vaccine effectiveness and enhancing population-based screening (PBS). The objective of the present study is to update hrHPV genotype prevalence in a non-vaccinated cohort of 1200 hrHPV-positive women from the Dutch PBS using INNO-LiPA HPV Genotyping Extra-II to identify 32 individual HPV genotypes in self-sampled material. HrHPV prevalence for all 32 genotypes, also grouped by bivalent, quadrivalent, and nonavalent vaccine types (2vHPV, 4vHPV, and 9vHPV), was reported by histologic diagnosis and age. The most common genotypes were HPV16 (394,33%), especially in younger women, followed by HPV31 (216,18%) and HPV52 (199,17%). 2vHPV genotypes were found in 23% (n&#x2009;=&#x2009;90) of NILM cases, 27% (n&#x2009;=&#x2009;84) of CIN0/CIN1, 45% (n&#x2009;=&#x2009;74) of CIN2, 71% (n&#x2009;=&#x2009;219) of CIN3, and 92% (n&#x2009;=&#x2009;12) of cervical cancers. In comparison, 9vHPV genotypes appeared in 60% (n&#x2009;=&#x2009;240) of NILM, 69% (n&#x2009;=&#x2009;218) of CIN0/CIN1, 88% (n&#x2009;=&#x2009;145) of CIN2, 94% (n&#x2009;=&#x2009;289) of CIN3, and all cervical cancers (n&#x2009;=&#x2009;13). HrHPV types not included in 9vHPV had an overall prevalence of 19% (n&#x2009;=&#x2009;225), with 88% (197/225) found in NILM or CIN0/CIN1. This study highlights vaccine-type HPV in all cancer cases and many high-grade lesions, reinforcing the need for improved vaccination efforts and broader protection.