Human Reproduction Update最新文献

{"title":"Iron overload disorders in adults: a comprehensive review of gonadal function, reproductive, and sexual health.","authors":"Francesco Carlomagno, Marta Tenuta, Andrea Sansone, Giulia Rastrelli, Francesca Sciarra, Biagio Cangiano, Andrea M Isidori, Daniele Gianfrilli, Csilla Krausz","doi":"10.1093/humupd/dmag010","DOIUrl":"https://doi.org/10.1093/humupd/dmag010","url":null,"abstract":"<p><strong>Background: </strong>Iron overload (IO) disorders, including thalassaemias, hereditary haemochromatosis, and transfusion-dependent anaemias, represent a growing clinical challenge with widespread systemic implications. Reproductive dysfunction remains severely underappreciated despite its high prevalence. Hormonal changes due to iron toxicity are frequently reported, yet are seldom the focus of reproductive medicine, causing fragmented knowledge, inconsistent clinical approaches, and a lack of consensus guidelines.</p><p><strong>Objective and rationale: </strong>This review synthesizes evidence on the impact of IO on male and female reproductive function, including gonadal dysfunction, impaired fertility, sexual dysfunction, and endocrine-metabolic complications. By addressing gaps in study design, diagnostic criteria, and management, we aim to provide the first comprehensive, expert-driven synthesis on the topic, integrating clinical, translational, and mechanistic insights to establish a structured framework for future research and patient care.</p><p><strong>Search methods: </strong>A systematic literature search was conducted across PubMed, Scopus, and Web of Science, including studies up to May 2025. Search terms included 'iron overload', 'thalassemia', 'hemochromatosis', 'hypogonadism', 'fertility', 'spermatogenesis', 'ovarian insufficiency', and 'pregnancy'. Quantitative synthesis involved pooling data on prevalence rates of hypogonadism, semen abnormalities, primary and secondary amenorrhoea, age at menarche, and pregnancy outcomes.</p><p><strong>Outcomes: </strong>Gonadal dysfunction primarily arises from iron deposition within the hypothalamic-pituitary-gonadal axis, coupled with oxidative damage to Leydig and Sertoli cells in males, disrupting testosterone synthesis and spermatogenesis, and to ovarian follicles and granulosa cells in females, causing reduced ovarian reserve and altered hormonal signalling. Iron-induced hypogonadism is the most frequent endocrine complication, significantly impacting reproductive health and quality of life. Our analysis of 1201 men and 2134 women indicated hypogonadism, reflecting impaired testicular endocrine function, in 47.0% of men; among those specifically assessed for spermatogenesis, over half presented azoospermia (17.6%) or other sperm abnormalities (37.5%). In women, primary amenorrhoea was reported in 45.7%, secondary amenorrhoea in 20.0%, and the weighted mean age at menarche was delayed (14.4 ± 2.1 years). Sexual dysfunction, notably erectile dysfunction, commonly accompanies hypogonadism, further impairing quality of life. Female sexual health has not been investigated at all. Pregnancy is increasingly achievable, but remains clinically challenging. Across 3536 reviewed pregnancies, ART was required in ∼20%, miscarriage occurred in 11.2%, and caesarean section was used in ∼80%. Mean gestational age at delivery was 37.1 ± 3.1 weeks, and mean birth weight was 2.64 ± 0.68 kg. Besid","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":""},"PeriodicalIF":16.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846432","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":"The placental tryptophan pathway across gestation: implications for pregnancy outcomes.","authors":"Rona Karahoda, David Walker, Cilia Abad, Kasin Yadunandam Anandam, Padma Murthi, Frantisek Staud","doi":"10.1093/humupd/dmag001","DOIUrl":"10.1093/humupd/dmag001","url":null,"abstract":"<p><strong>Background: </strong>Tryptophan metabolism within the placenta generates bioactive metabolites, including serotonin (5-hydroxytryptamine; 5-HT), melatonin, and kynurenine derivatives, that regulate immune tolerance, vascular function, oxidative balance, and fetal neurodevelopment. Increasing evidence indicates that placental handling of tryptophan is dynamically regulated across gestation and is highly sensitive to maternal environmental and metabolic cues.</p><p><strong>Objective and rationale: </strong>The aim of this review is to examine placental tryptophan metabolism across gestation, with a focus on the 5-HT, melatonin, and kynurenine pathways. We address how these pathways are regulated during normal pregnancy and how maternal factors, including inflammation, hypoxia, oxidative stress, and cardiometabolic dysfunction, influence placental tryptophan handling in pregnancy complications such as early pregnancy loss, preeclampsia, fetal growth restriction, and preterm birth.</p><p><strong>Search methods: </strong>PubMed was searched using predefined terms related to placental tryptophan metabolism, 5-HT, melatonin, kynurenine, fetal programming, neurodevelopment, and pregnancy complications. Only full-text, peer-reviewed articles published in English were included. Abstracts and conference proceedings were excluded due to their limited data reliability.</p><p><strong>Outcomes: </strong>Placental tryptophan metabolism shows clear gestational stage-dependent regulation, and early pregnancy emerges as a formative period when pathway activity and metabolite balance are first established. From early pregnancy, maternal-decidual kynurenine pathway activity and placental 5-HT synthesis intersect with immune tolerance, vascular adaptation, and neurodevelopmental signaling. Across gestation, maternal inflammation, hypoxia, oxidative stress, and cardiometabolic disturbance can redirect the tryptophan flux and shift the balance between 5-HT/melatonin and downstream kynurenine metabolites. Evidence across pregnancy complications links early pathway disruption to pregnancy loss and supports the view that early metabolic perturbations contribute to vulnerability for later placental dysfunction, including preeclampsia, fetal growth restriction, and preterm birth.</p><p><strong>Wider implications: </strong>Placental tryptophan metabolism changes across gestation, making early pregnancy a critical window when pathway balance and fetal exposure to neuroactive metabolites are first set. Maternal inflammation, metabolic status, nutrition, and drug exposures may alter this balance, with the placenta acting as the key interface that transmits maternal signals to the fetus and shapes neurodevelopmental trajectories. To define the clinical relevance of altered tryptophan catabolism, longitudinal human studies are needed to link placental phenotypes with pregnancy outcomes and postnatal neurodevelopment. These should be complemented by mechanistic models th","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"356-379"},"PeriodicalIF":16.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146229882","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":"Advantages, limitations, and innovative considerations for established and emerging models of human placental syncytiotrophoblast.","authors":"Joshua J Fisher, Ashley Williams, Farhad Soheilmoghaddam, Georgia R Kafer","doi":"10.1093/humupd/dmaf034","DOIUrl":"10.1093/humupd/dmaf034","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective and rationale: </strong>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.</p><p><strong>Search method: </strong>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.</p><p><strong>Outcomes: </strong>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.</p><p><strong>Wider implications: </strong>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 i","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"333-355"},"PeriodicalIF":16.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146054884","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":"Making narrative review abstracts count.","authors":"Madelon van Wely","doi":"10.1093/humupd/dmag004","DOIUrl":"10.1093/humupd/dmag004","url":null,"abstract":"","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"262"},"PeriodicalIF":16.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260013","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":"Intrauterine human chorionic gonadotropin administration before embryo transfer (IHABT): an individual participant data meta-analysis of randomized controlled trials.","authors":"Haowen Zou,Karim S Abdallah,Barbara Wirleitner,Kathleen H Hong,Isarin Thanaboonyawat,Pitak Laokirkkiat,Maryam Hafezi,Shoji Kokeguchi,Ahmed Makhlouf,Sol Libesman,David Nguyen,Jonathan G Williams,Marian Showell,Moustafa Gadalla,Ben W J Mol,Wentao Li,Rui Wang","doi":"10.1093/humupd/dmag009","DOIUrl":"https://doi.org/10.1093/humupd/dmag009","url":null,"abstract":"BACKGROUNDIntrauterine 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.OBJECTIVE AND RATIONALETo 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.SEARCH METHODSWe 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.OUTCOMESWe 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).WIDER IMPLICATIONSOur 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.REGISTRATION NUMBERPROSPERO (CRD42020177397)","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"3 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694894","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":"The risk for the development of hypertensive complications in oocyte donation pregnancy: a systematic review and individual participant data meta-analysis (DONOR IPD)","authors":"Kim van Bentem, Marie-Louise van der Hoorn, Manish Banker, Maria de la Calle, Evangelia Elenis, Dina El Demellawy, Nathan S Fox, Yadava Jeve, Diane Korb, Hélène Letur, Yoav Yinon, Antonio Farina, Francesca Rizzello, Kenny A Rodriguez-Wallberg, Michal Simchen, Serena Simeone, Theoni Tarlatzi, Stefano Raffaele Giannubilo, Saskia Le Cessie, Eileen Lashley","doi":"10.1093/humupd/dmag006","DOIUrl":"https://doi.org/10.1093/humupd/dmag006","url":null,"abstract":"BACKGROUND Oocyte donation (OD) is an established ART involving an oocyte donor and recipient with a rising number of treatments. Previous meta-analyses highlight increased risks of hypertensive complications compared to naturally conceived (NC) and IVF/ICSI pregnancies, including pregnancy-induced hypertension (PIH) and preeclampsia (PE), but limitations exist due to study quality and heterogeneity. OBJECTIVE AND RATIONALE The DONOR (DONation of Oocytes in Reproduction) individual participant data (IPD) meta-analysis aims to generate clinically relevant and robust evidence regarding the development of hypertensive complications in OD pregnancies compared to autologous pregnancies. IPD meta-analyses offer an advantage over current meta-analyses, as bias is reduced by using IPD of original studies, allowing reliability checks, correction for confounders, and examining causes of heterogeneity by subgroup analyses. Furthermore, using IPD increases statistical power and generalizability of results. SEARCH METHODS A literature search was conducted using PubMed, EMBASE, and Cochrane up to March 2024, with a last update performed in February 2025. We included observational studies that compared a cohort of women pregnant after OD beyond 20 weeks of gestation with an autologous pregnancy cohort (NC or IVF/ICSI), and reported on hypertensive pregnancy complications. Risk of bias was assessed using the ROBINS-I tool. Authors of eligible articles were invited to share IPD. The DONOR IPD meta-analyses were executed using both a one- and two-stage approach, adjusted for maternal age, parity, and multiple gestation. Furthermore, sensitivity, meta-regression and subgroup analysis were performed. OUTCOMES IPD was requested for 48 cohorts, and provided from 16 cohorts with data of 2747 OD, 4699 IVF/ICSI, and 33 323 NC pregnancies. The one- and two-stage approach comparing OD to autologous pregnancies showed adjusted ORs of respectively 2.62 (95% CI 2.22–3.10) and 2.85 (95% CI 2.30–3.54; I2 44%; moderate certainty) for hypertensive complications in total, 2.15 (95% CI 1.73–2.68) and 1.49 (95% CI 0.80–2.80; I2 74%; low certainty) for PIH, and 2.28 (95% CI 1.88–2.78) and 2.39 (95% CI 1.94–2.94; I2 0%; high certainty) for PE. When the autologous group was split into NC and IVF/ICSI pregnancies, higher risks for hypertensive complications, including PIH and PE, persisted in the OD group. The results of the IPD meta-analyses for HELLP syndrome show a higher risk in OD pregnancy, though with a broad 95% CI. Sensitivity meta-analyses for risk of bias showed comparable results. Subgroup analyses indicated increased risks for hypertensive complications in OD pregnancy, regardless of maternal age, BMI, multiple pregnancy, parity, ethnicity, medical history, and number of transferred embryos. A potential lower risk for hypertensive complications was found when acetylsalicylic acid or heparin is used during OD pregnancy compared to both autologous and NC pregnancy. WIDER IMPL","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"19 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147586355","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 interplay between sperm and oocyte: a narrative review.","authors":"Hsin-Yi Chang, Taylor Gierke, Shaogeng Tang, Yonggang Lu","doi":"10.1093/humupd/dmag008","DOIUrl":"https://doi.org/10.1093/humupd/dmag008","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective and rationale: </strong>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.</p><p><strong>Search methods: </strong>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.</p><p><strong>Outcomes: </strong>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 interact","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":""},"PeriodicalIF":16.1,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147517017","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":"What do we mean by preconception health and preconception care in research and policy? A systematic review.","authors":"Olivia Chingara,Annabelle Sümegi,Susan Logan,Siladitya Bhattacharya,Andrea Woolner","doi":"10.1093/humupd/dmag005","DOIUrl":"https://doi.org/10.1093/humupd/dmag005","url":null,"abstract":"BACKGROUNDPreconception health (PCH) is a globally accepted strategy to reduce preventable adverse pregnancy outcomes and ultimately improve the health of the unborn child. Optimal PCH can be achieved through preconception care (PCC), which encompasses the behavioural, biomedical, and social interventions women and couples undertake and/or receive before conception. However, there is a lack of clarity on various aspects of PCH and PCC, such as what constitutes preconception risk factors, what the optimal interventions are, when the preconception period is, and who the overall target population is. Additionally, marginalised groups such as sexual and racial or ethnic minority individuals are routinely excluded from PCH research and PCC interventions. PCH and PCC are topical issues given changing societal norms worldwide, such as delayed childbirth, exponential rises in fertility treatments, and the growing trend of unplanned pregnancies. We hypothesised that the ambiguity surrounding the definition of PCH and PCC may limit their understanding and application to improve pregnancy and childhood outcomes.OBJECTIVE AND RATIONALEThis is a systematic review of existing definitions of PCH and PCC to understand the commonalities and disparities in definitions and critical components of PCH and PCC, to aid in the development of a comprehensive and globally standardised definition.SEARCH METHODSMEDLINE, PubMed, EMBASE, Cochrane Library, CINAHL, Google Scholar, PsychINFO, and Google were searched to identify published studies, guidelines, and public health websites containing definitions of PCH and PCC published between January 1993 and October 2024. No restrictions were placed on language. We searched academic databases, organisational reports, and policy documents to capture the full range of definitions across clinical, health, and policy contexts.OUTCOMESThe narrative synthesis of 176 publications showed heterogeneity in the definitions of PCH and PCC. The themes developed from the thematic analysis showed that PCC is preventative care which identifies and utilises interventions to manage individuals' preconception risk factors and aims to improve pregnancy outcomes by optimising the short- and long-term health of potential parents and their children. The analysis also showed that PCH is relevant across the entire reproductive lifespan. PCC was described as a continuum of care that occurs before conception and encompasses the health of all potential parents, not just women.WIDER IMPLICATIONSThis systematic review found there is a lack of universality in the definitions of PCH and PCC. Current definitions often narrowly focus on women planning pregnancy, which may exclude important demographics such as unintended pregnancies and fathers, and aligned health needs such as contraception in the preconception period. We propose that there is a need for a definition that captures various demographics and emphasises a life-course approach to reproductive health,","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"100 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350720","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":"Seminal plasma cytokines in fertile versus infertile men: a systematic review and meta-analysis.","authors":"Hannah E Lyons, Cristina N Arriaran Scott, Sarah A Robertson, David J Sharkey","doi":"10.1093/humupd/dmag003","DOIUrl":"https://doi.org/10.1093/humupd/dmag003","url":null,"abstract":"<p><strong>Background: </strong>Male fertility investigation is currently limited to semen analysis. However, the origins of abnormal sperm parameters are not well-understood, and normal sperm do not assure fertility in men. Improved pathophysiological and prognostic insight might be achieved utilising additional measures of male reproductive tract function. Cytokine and chemokine levels in seminal plasma (SP) may be relevant, but evidence on their clinical significance is unclear. The utility of measuring SP cytokines remains uncertain, and no consensus exists on which cytokines are most informative.</p><p><strong>Objective and rationale: </strong>To perform a systematic review and meta-analysis on the association between fertility status and concentration of seminal plasma cytokines in men. The sixth edition of the WHO laboratory manual for the examination and processing of human semen raises the prospect of evaluating cytokines in SP as part of an extended examination. We performed a systematic search and meta-analysis to assess whether the current literature is sufficient to identify cytokines present in human SP that exhibit a relationship with fertility status in men.</p><p><strong>Search methods: </strong>We searched PubMed, Web of Science, Scopus, and Embase from inception until April 2025, using keywords pertaining to seminal fluid and cytokines, restricted to humans and the English language. Original data with values reported as concentration of cytokines in SP of men clearly defined as infertile, compared to a discernible population of fertile/normozoospermic healthy control men, were included. A total of 5737 studies were identified, with 2737 duplicates removed. Title and abstract screening were performed for 3000 studies, then 291 studies underwent full-text screening, and 68 studies progressed to quality assessment using the NHLBI-NIH quality assessment tool and 52 studies underwent data extraction.</p><p><strong>Outcomes: </strong>We identified 52 research articles published from 1993 to 2025 that quantified at least one cytokine in the seminal plasma of 8153 men, after 19 studies of poor quality and/or containing serious flaws were excluded. Data on 30 cytokines in the SP of healthy control and infertile men were extracted and included in narrative synthesis. Compared to fertile controls, infertile men had elevated concentrations of IL6 (SMD 0.39, 95% CI; 0.14-0.64, I2 = 80.7%), TNFA (SMD 0.13, 95% CI; 0.00-0.25, I2 = 4.3%), and CXCL8 (SMD 0.24, 95% CI; 0.06-0.43, I2 = 0.0%) in seminal plasma. IL6 reported a high degree of heterogeneity between studies, whilst CXCL8 and TNFA reported low heterogeneity. No significant moderator effects due to study quality or composition of the control cohort were identified.</p><p><strong>Wider implications: </strong>With one in six couples experiencing infertility worldwide and a male factor identified as a primary or contributing cause in up to 50% of cases, there is a strong imperative to deve","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":""},"PeriodicalIF":16.1,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147272964","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":"Revisiting natural cycle frozen embryo transfer: a systematic review and meta-analysis.","authors":"Murat Erden, Sezcan Mumusoglu, Esra Uyanik, Irem Yarali Ozbek, Sandro C Esteves, Peter Humaidan, Hakan Yarali","doi":"10.1093/humupd/dmag002","DOIUrl":"https://doi.org/10.1093/humupd/dmag002","url":null,"abstract":"<p><strong>Background: </strong>The optimal endometrial preparation protocol for frozen embryo transfer (FET) remains a subject of ongoing investigation. HRT is the most commonly used approach, but natural cycle (NC) FET has regained attention due to potential improvements in maternal and perinatal outcomes. Despite growing observational evidence supporting NC FET, its adoption is limited by logistical challenges in cycle monitoring and scheduling. Recently, the natural proliferative phase (NPP) FET protocol has been introduced, combining the physiological benefits of a functional corpus luteum with greater scheduling flexibility.</p><p><strong>Objective and rationale: </strong>Previous systematic reviews have largely focused on luteal phase support (LPS) or have provided narrative summaries susceptible to selection bias. This systematic review aimed to evaluate the impact of different execution strategies on reproductive outcomes across true-NC and modified-NC and to compare NPP FET with other protocols.</p><p><strong>Search methods: </strong>A comprehensive search of MEDLINE, Embase, Global Health, and Cochrane Library was conducted from database inception to 10 November 2024. The search included keywords such as 'frozen embryo transfer', 'natural cycle', 'pregnancy', 'live birth', and 'delivery' with no language or filter restrictions. Reference lists of included studies were screened to identify additional relevant studies.</p><p><strong>Outcomes: </strong>A total of 70 studies were included: 8 randomized controlled trials (1 with low risk of bias and 7 with some concerns), 16 non-randomized interventional studies (with risk of bias being moderate for 4, serious for 6, and critical for another 6), and 46 observational studies (80.4% of which were good quality) assessing prognostic factors. In true-NC FET, prolonged follicular phases did not adversely affect outcomes. Ovulatory cycles were associated with significantly higher live birth rates (LBRs) than cycles with luteinized unruptured follicle (risk ratio (RR): 1.16, 95% CI: 1.04-1.29, I2 = 0%, three studies, 2907 cycles, very low-certainty evidence). Despite variability in ovulation timing methods, performing FET on serum LH surge +6 to +7 days yielded comparable reproductive outcomes. In modified-NC FET, two observational studies reported similar LBRs when triggering ovulation at follicle diameters between 13 and 22 mm, provided the endometrial thickness was >7 mm and serum progesterone was below 1.5 ng/ml. LPS with vaginal progesterone improved LBRs in true-NC compared to no LPS (RR: 1.43, 95% CI: 1.16-1.78, I2 = 0%, 923 cycles, two studies, moderate-certainty evidence), but showed no benefit in modified-NC FET (RR: 1.04, 95% CI: 0.82-1.32, I2 = 0%, 667 cycles, two studies, moderate-certainty evidence). In NPP FET, a meta-analysis showed higher LBRs compared to HRT FET (RR: 1.25, 95% CI: 1.13-1.38, I2 = 5.36%, 3397 cycles, three studies, very low-certainty evidence).</p><p><strong>Wider ","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":""},"PeriodicalIF":16.1,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146198246","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}