Seminars in reproductive medicine最新文献

{"title":"Genetics in Reproduction.","authors":"Kathleen M Hoeger, Terhi T Piltonen","doi":"10.1055/s-0046-1816053","DOIUrl":"https://doi.org/10.1055/s-0046-1816053","url":null,"abstract":"","PeriodicalId":21661,"journal":{"name":"Seminars in reproductive medicine","volume":"43 4","pages":"239-240"},"PeriodicalIF":1.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Testing for Genetic Conditions.","authors":"Hyung-Goo Kim, Sumia Brakta, Afif Ben-Mahmoud, Soo-Hyun Kim, Lawrence C Layman","doi":"10.1055/a-2812-9577","DOIUrl":"10.1055/a-2812-9577","url":null,"abstract":"<p><p>Clinical genetics in reproductive medicine has moved from cytogenetic assessment to integrated, genome-wide diagnostics that resolve both sequence-level and structural variation. For patients facing infertility, recurrent pregnancy loss, fetal structural anomalies, or early onset pediatric disease, contemporary care follows a reflexive pathway that links karyotyping, chromosomal microarray (CMA), and exome or genome sequencing (GS) with advanced structural platforms including optical genome mapping (OGM) and long-read sequencing. Karyotyping remains indispensable for aneuploidy and balanced rearrangements. CMA outperforms karyotyping for submicroscopic copy number variants and is guideline-endorsed in prenatal diagnosis. Trio exome or GS increases diagnostic yield and clinical utility in fetuses with anomalies and in children with neurodevelopmental disorders or other congenital anomalies. Professional societies now recommend exome or GS as first-tier test in many pediatric scenarios. Long-read sequencing resolves repeats and complex structural variants. OGM provides a single assay, genome wide structural view with strong multisite clinical concordance, including prenatal validations. We present a pragmatic algorithm that orders structure- and sequence-based tests to shorten time, reduce serial testing, and improve counseling and reproductive planning. Together, these modalities support precise diagnoses, tighter recurrence risk estimates, and alignment of care with patient values.</p>","PeriodicalId":21661,"journal":{"name":"Seminars in reproductive medicine","volume":" ","pages":"254-263"},"PeriodicalIF":1.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147435302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Genetics in Reproductive Medicine: Variant Classification, Medically Actionable Genes, and Carrier Screening.","authors":"Anastasia Navitski, Lawrence C Layman","doi":"10.1055/a-2781-8392","DOIUrl":"10.1055/a-2781-8392","url":null,"abstract":"<p><p>As genomic sequencing becomes more prevalent in reproductive medicine, clinicians must remain knowledgeable about the purpose of each ordered test, the principles of variant classification, and how to interpret and integrate findings into clinical decision-making. This review outlines the American College of Medical Genetics and Genomics (ACMG) standardized guidelines for sequence variant interpretation and highlights anticipated updates in the forthcoming v4.0 framework. When next-generation sequencing is performed for a clinical condition, incidental findings of pathogenic and likely pathogenic variants in medically actionable genes (MAGs) may be identified. Conditions included on the ACMG MAG list are typically highly penetrant, primarily autosomal dominant or X-linked, and have established interventions that can alter disease trajectory. Carrier screening enables the identification of autosomal recessive and X-linked variants in prospective parents that predispose them to genetic disease in their children. The ACMG's tier-based recommendations support universal Tier 3 screening, targeting conditions with a carrier frequency of at least 1 in 200 and moderate/severe phenotypes, while Tier 4 screening is reserved for individuals with consanguinity or significant family history. While technical genomic advances enhance the delivery of precision medicine, they introduce challenges, including higher rates of uncertain findings and the need for more careful clinical interpretation.</p>","PeriodicalId":21661,"journal":{"name":"Seminars in reproductive medicine","volume":" ","pages":"243-253"},"PeriodicalIF":1.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetics in Reproduction.","authors":"Lawrence C Layman","doi":"10.1055/s-0046-1817158","DOIUrl":"https://doi.org/10.1055/s-0046-1817158","url":null,"abstract":"","PeriodicalId":21661,"journal":{"name":"Seminars in reproductive medicine","volume":"43 4","pages":"241-242"},"PeriodicalIF":1.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using Preimplantation Genetic Testing for Aneuploidy (PGT-A) Validation Data to Inform Clinical In Vitro Fertilization (IVF) Practice.","authors":"Andria Besser, Mina Popovic, Eric Forman, Chaim Jalas, Emily Mounts","doi":"10.1055/a-2806-2756","DOIUrl":"10.1055/a-2806-2756","url":null,"abstract":"<p><p>Preimplantation genetic testing for aneuploidy (PGT-A) has become a widely adopted component of in vitro fertilization (IVF) practice. However, PGT-A is not a single, uniform test; its predictive value and clinical utility remain highly dependent on test performance and interpretation, both of which vary substantially between laboratories and platforms. This article aims to define the intended goals of PGT-A, evaluate methods for proper test validation, and explore how validation data impacts clinical counseling and decision-making. Particular attention is given to newer diagnostic categories such as mosaicism and segmental aneuploidy, for which clinical validation is limited and inter-laboratory variability is high. While PGT-A can reduce futile embryo transfers and support elective single embryo transfer, misapplication of unvalidated results may reduce IVF success rates. To ensure responsible use of PGT-A, clinicians must demand transparent, assay-specific validation data and use this information to guide evidence-based counseling for embryo transfer, storage, and disposition.</p>","PeriodicalId":21661,"journal":{"name":"Seminars in reproductive medicine","volume":" ","pages":"275-281"},"PeriodicalIF":1.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding PGT-M: A Guide for Clinicians.","authors":"Amy Hill, Alice Poulton, Tristan Hardy","doi":"10.1055/s-0046-1819623","DOIUrl":"https://doi.org/10.1055/s-0046-1819623","url":null,"abstract":"<p><p>Preimplantation genetic testing for monogenic conditions (PGT-M) is the process of testing embryos created in vitro to screen for specific monogenic conditions. Embryos unaffected by the condition of interest can then be selectively transferred to the uterus to establish a pregnancy. PGT-M is a reproductive option for individuals with an increased chance of having a child with a monogenic condition. By enabling the selection of unaffected embryos, it reduces the likelihood of transmitting the condition. It also enables the conception of a biologically related child, while minimizing the potential need to consider termination of pregnancy. For these reasons, PGT-M often emerges as the preferred reproductive option for individuals in this indication group. As uptake of PGT-M continues to grow, clinicians are increasingly required to navigate the range of technical, clinical, practical, and ethical considerations involved in its provision. This review offers a practical overview of PGT-M-covering its definition, regulatory frameworks, and technical development, through to laboratory work-up and clinical application. It also explores the limitations, ethical challenges, and experiences of PGT-M users, with the aim of supporting clinicians in the delivery of PGT-M care.</p>","PeriodicalId":21661,"journal":{"name":"Seminars in reproductive medicine","volume":"43 4","pages":"264-274"},"PeriodicalIF":1.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Basis and Heterogeneity of Congenital Hypogonadotropic Hypogonadism.","authors":"Leticia Ferreira Gontijo Silveira, Carlos Eduardo Seraphim, Ana Claudia Latronico","doi":"10.1055/a-2806-2848","DOIUrl":"10.1055/a-2806-2848","url":null,"abstract":"<p><p>Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder characterized by absent or incomplete pubertal development due to impaired production, secretion, or action of gonadotropin-releasing hormone (GnRH). When associated with anosmia or hyposmia, it is termed Kallmann syndrome. CHH exhibits striking clinical and genetic heterogeneity, encompassing either sporadic or familial cases, with inheritance patterns that include X-linked, autosomal dominant, and autosomal recessive transmission. Over the past few decades, major advances uncovered the molecular basis of CHH, shedding light on the intricate neuroendocrine regulation of human reproduction. A growing repertoire of genes has been implicated in CHH molecular pathogenesis, encoding proteins involved in the ontogeny and function of GnRH neurons. Notably, pathogenic variants in genes typically associated with complex syndromes have also been identified in patients with isolated CHH or subtle syndromic manifestations, suggesting a wide spectrum of expressivity and incomplete penetrance. Furthermore, spontaneous hypogonadism reversal, either permanent or temporary, may occur in some patients, suggesting a potential neuroplasticity within the GnRH neuronal network. This review summarizes recent advances in the molecular genetics of CHH, emphasizing the expanding spectrum of causative genes and their inheritance patterns. · Congenital hypogonadotropic hypogonadism (CHH) is a rare reproductive disorder caused by impaired production, secretion, or action of gonadotropin-releasing hormone (GnRH). When CHH is associated with olfactory defects (hyposmia or anosmia), it is termed Kallmann syndrome.. · CHH is a complex clinical and genetic heterogeneous condition with both sporadic and familial cases. Inheritance can be X-linked, autosomal recessive, or dominant.. · Although more than 60 genes have been implicated in the molecular pathogenesis of CHH, approximately 50% of cases remain without molecular diagnosis.. · CHH-associated genes encode proteins involved either in GnRH neuron ontogeny and migration or in GnRH synthesis, secretion, or action.. · Digenic or oligogenic inheritance accounts for up to 20% of CHH cases and may explain the high phenotypic variability observed among affected families.. · Pathogenic variants in genes associated with complex syndromes have been identified in cases of isolated CHH or in cases with only one additional phenotypic feature, resembling mild or incomplete forms of the original syndrome.. · Spontaneous recovery of reproductive function may occur in 10 to 20% of patients with CHH, including those harboring rare pathogenic variants in typical CHH-associated genes..</p>","PeriodicalId":21661,"journal":{"name":"Seminars in reproductive medicine","volume":" ","pages":"282-295"},"PeriodicalIF":1.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147345099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetics of Primary Ovarian Insufficiency.","authors":"Svetlana A Yatsenko, Aleksandar Rajkovic","doi":"10.1055/a-2806-2597","DOIUrl":"10.1055/a-2806-2597","url":null,"abstract":"<p><p>Primary ovarian insufficiency (POI) is a heterogeneous condition that worldwide affects up to 3.7% of women under 40 years of age. POI manifestations are diverse, ranging from ovarian dysgenesis and primary amenorrhea to a later onset ovarian dysfunction, secondary amenorrhea, and diminished ovarian reserve. These conditions result in infertility and elevated risk for osteoporosis and cardiovascular disease. Over the past decade, substantial progress has been made in understanding the complexities of ovarian biology and oocyte development, particularly in identifying involved pathways, etiology, underlying mechanisms, and POI-associated genes. In this review, we focus on chromosomal and monogenic causes of POI leading to syndromic and isolated forms in humans. We provide an updated summary on 272 genes reported in at least two unrelated individuals with a clinical diagnosis of POI. This information supports healthcare professionals in making informed decisions regarding genetic testing and genetic counseling. This review underlines the critical role of molecular diagnosis in understanding and managing POI, highlighting both the current progress and the existing limitations in translating genetic findings and knowledge into effective diagnostic practice.</p>","PeriodicalId":21661,"journal":{"name":"Seminars in reproductive medicine","volume":" ","pages":"296-322"},"PeriodicalIF":1.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147345145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endometriosis and Fertility: Where Do We Draw the Line?","authors":"Natalie E Rivera, Sadikah Behbehani","doi":"10.1055/s-0045-1811510","DOIUrl":"10.1055/s-0045-1811510","url":null,"abstract":"<p><p>Endometriosis affects millions of women around the world, yet it remains a complex and often misunderstood condition, with limited funding available for research. Although much about this enigmatic disease is still unknown, emerging data continue to shed light on its mechanisms, leading to improved understanding and better management options for patients. While advances have been made in understanding the symptoms and pathophysiology of endometriosis, one critical area remains underexplored: its impact on fertility. It is now well established that endometriosis can significantly impair fertility, posing additional challenges for women trying to conceive. This study explores current theories on how endometriosis affects reproductive function and highlights the latest research on both medical and surgical approaches to managing infertility in these patients. It will also examine the implications of endometriosis on natural conception as well as outcomes related to assisted reproductive technologies.</p>","PeriodicalId":21661,"journal":{"name":"Seminars in reproductive medicine","volume":" ","pages":"214-220"},"PeriodicalIF":1.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144967275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Hysterectomy in the Management of Endometriosis.","authors":"Nicole Afuape","doi":"10.1055/s-0045-1813017","DOIUrl":"10.1055/s-0045-1813017","url":null,"abstract":"<p><p>Endometriosis is a complex, chronic disorder that has the potential to produce long-term negative impact on the life and function of patients who carry this diagnosis. Endometriosis is thought to impact up to 10 to 15% of women across the globe and up to 90% of patients with pelvic pain. Yet, many questions remain regarding the true pathogenesis of this disease, as well as the best approach to surveillance and treatment. What we do know is that, as there remains no cure for endometriosis, management of this disease is best achieved with a longitudinal approach, with consideration of immediate disease features and other potential sequelae. The ideal treatment approach typically involves more conservative lifestyle changes, including dietary modifications, and incorporation of medication therapy, typically at the very least involving some form of hormone suppression therapy. The role of surgery remains dependent on both the patient's clinical course and the provider. Here, we explore both the known and the unknown in endometriosis management, with key updates on the potential implications of hysterectomy.</p>","PeriodicalId":21661,"journal":{"name":"Seminars in reproductive medicine","volume":" ","pages":"231-238"},"PeriodicalIF":1.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}