Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 25 appraisals
Biology of reproduction
Noninvasive pre-transfer identification of women with recurrent implantation failure using a plasma microRNA-based machine learning model
Recurrent implantation failure (RIF) refers to patients who have undergone at least three implantation failures with several high-quality embryos. Identifying patients with RIF in advance is crucial for effective clinical managements. However, uterine biopsy, the primary research approach, is not only invasive but also poses a risk to the integrity of the endometrial microenvironment. Here, we provided a novel, safe, and immediate methodology for RIF populations identification through plasma microRNA (miRNA) profiles. Peripheral blood samples of 163 women were collected and sequenced to quantify the relative expression levels of plasma miRNAs. Through a comparative analysis of the temporal expression between patients with RIF and those with successful embryo implantation during the peri-implantation period, we determined that the RIF-associated miRNA signature was established at the early stage of the window of implantation. By global screening, we identified 217 miRNAs that were differentially expressed between groups on the ovulation day (D0), using a threshold of |fold change| ≥ 1.5. Through refining selection criteria, 10 eligible miRNAs were ultimately selected and further validated through real-time quantitative polymerase chain reaction. These miRNAs were employed to construct a logistic regression-based RIF model. The model demonstrated robust performance in the validation and test cohorts, with area under the curve of 0.947 and 0.912, respectively. We also demonstrated that miRNAs maintain relative stability within a specific phase, making them suitable as clinical biomarkers. This study provides a noninvasive methodology for identifying women with RIF and suggests a potential role in predicting RIF risk before embryo transfer.
16 July 2026
Read appraisal →ACS biomaterials science & engineering
A Review of Biomass-Derived Nanomaterials as Functional Interfaces for Advanced Electrochemical Hormone Detection
The study of high-performance sensing platforms is essential to achieve a high sensitivity for hormonal analytes, short response times, and cost-effectiveness. Nevertheless, standard analytical procedures, such as high-performance liquid chromatography, inductively coupled plasma mass spectrometry, and gas chromatography mass spectrometry (HPLC, ICP-MS, and GC-MS), are rather limited because their sensitivity is low at pM/nM concentrations, and the costs of these processes are too high. Moreover, modern sensor technology can be ill-equipped to selectively respond to intricate biological sample types, and there is no single standard used to quantify sensor signals. This review addresses these knowledge gaps by providing a comprehensive discussion on the role of biomass-derived materials as useful interfaces in electrochemical hormone sensing systems. To achieve improved results, we critically investigated the recent advances in the electrode modification process through biomass-based nanomaterials to promote electron transfer kinetics and interfacial engineering. The present article also discusses contemporary issues such as problems with stability, reproducibility, and selectivity in complex matrices. Furthermore, we highlighted some of the new approaches, such as the development of artificial intelligence, Internet of Things, and wearable point-of-care devices, to create the next generation hormone sensors. Overall, this current review is a comprehensive overview of biomass-derived materials, which have the prospect of enhancing surface modification at the advanced phase, AI integration, and the development of point-of-care diagnostics.
14 July 2026
Read appraisal →European journal of clinical pharmacology
Clomiphene citrate versus testosterone replacement therapy in male hypogonadism: a systematic review of literature and meta-analysis
INTRODUCTION: Male hypogonadism, including age-related and functional forms, is characterized by insufficient testosterone production often associated with obesity and metabolic comorbidities. Testosterone replacement therapy (TRT) increases serum testosterone but suppresses spermatogenesis and may cause adverse effects. Selective estrogen receptor modulators (SERMs), such as clomiphene citrate, have emerged as an alternative approach to restore endogenous testosterone while preserving fertility. This study aimed to compare the efficacy of clomiphene citrate versus testosterone replacement therapy (TRT) in increasing serum testosterone levels in men with hypogonadism. METHODS: We conducted a systematic review of the literature in PubMed, Embase, Scopus, The Cochrane Library, and Google Scholar to identify studies comparing clomiphene citrate and testosterone replacement therapy (TRT) in men with male hypogonadism'. The primary outcome was the change in serum testosterone levels before and after treatment. Secondary outcomes included variations in other hormonal parameters, and clinical symptom improvement assessed through standardized instruments. RESULTS: A total of 11 studies with 1512 patients were included (764 on clomiphene citrate; 748 on testosterone replacement therapy, TRT). For serum testosterone, the overall pooled effect showed no significant difference between clomiphene and TRT (MD = 6.64 ng/dL; 95% CI -35.35 to 48.63; I² = 80.6%). Subgroup analyses indicated injectable testosterone achieved higher levels than clomiphene (1 study, 62 patients; MD = -290.50; 95% CI -518.78 to -62.22), whereas gel-based TRT showed no difference (8 studies, 1012 patients; MD = 24.29; 95% CI -18.91 to 67.48; I² = 76.1%). For sexual function, three studies (199 patients; 85 on clomiphene; 114 on TRT) assessing post-treatment libido (ADAM 1-5) showed lower libido scores with clomiphene than TRT (MD = - 0.54; 95% CI - 0.87 to - 0.21; P = 0.009; I² = 18.8%). CONCLUSIONS: No statistically significant difference in serum testosterone levels was observed between clomiphene citrate and testosterone gel, although the evidence is limited by high heterogeneity and some concerns to high risk of bias. TRT was associated with greater improvements in libido. These findings should be interpreted as preliminary, and large-scale randomized trials incorporating clinical and fertility endpoints are needed.
13 July 2026
Read appraisal →European journal of nutrition
Nutrition interventions in women with polycystic ovary syndrome: a systematic review.
PURPOSE: This systematic review aimed to synthesize current evidence on the effects of various dietary interventions on anthropometric, metabolic, hormonal, inflammatory, and oxidative stress parameters in women with polycystic ovary syndrome (PCOS). METHODS: The review followed the PRISMA guidelines and was prospectively registered in PROSPERO (CRD42025641781). Searches were conducted in PubMed, Cochrane Library, EBSCO, Science Direct, Web of Science, National Thesis Center, Google Scholar, and DergiPark Academic for studies published between February 2015 and February 2025. Experimental and observational studies were included if they evaluated the independent effect of dietary interventions in adult women with PCOS. Methodological quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools. RESULTS: A total of 38 studies were included, covering interventions such as calorie-restricted diets, low-glycemic index/load diets, ketogenic diets, intermittent fasting, dietary approaches to stop hypertension, Mediterranean-style, and other diets. Most dietary interventions demonstrated beneficial effects on body weight, body mass index, and waist circumference, as well as improvements in insulin sensitivity, reproductive hormone regulation, and menstrual regularity. However, findings related to lipid metabolism, inflammatory markers, and oxidative stress outcomes were inconsistent. CONCLUSION: Current evidence indicates that dietary interventions are crucial in improving the management of metabolic, anthropometric, hormonal, and clinical outcomes in women with PCOS. Nevertheless, the heterogeneity of dietary approaches, study designs, and outcome measures highlights the need for long-term randomized controlled trials to establish more conclusive recommendations.
30 June 2026
Read appraisal →PloS one
Motherhood choice in multiple sclerosis (MoMS) - Pilot trial of web-based decision support
BACKGROUD: Uncertainty concerning motherhood is common among women with multiple sclerosis (wwMS). Therefore, we developed and pre-tested a patient decision aid (PtDA) and a nurse-led decision coaching intervention (DC) to support motherhood choice. The DC includes the PtDA, a decision guide on motherhood choice, and decision coaching. METHODS: We conducted a randomised pilot trial across Germany to test feasibility, with decisional conflict (Decisional Conflict Scale, DCS) as an exploratory endpoint. Initially, we planned a 3:1 randomisation ratio (planned; PtDA = 48, DC = 16). Due to recruitment difficulties, we switched to a 1:1 randomisation ratio to ensure an appropriate sample size (PtDA > 20, DC > 10). Women between 18 and 45 years old with relapsing-remitting MS or clinically isolated syndrome, and who had not yet decided about motherhood, were eligible. We recruited two nurses for our decision coaching training course. We used questionnaires to measure decisional conflict, programme feasibility, knowledge, and worries regarding pregnancy in MS. Interviews were conducted to gain in-depth information on the potential feasibility of the programmes. Interviews were analysed thematically and questionnaires descriptively. We conducted explorative group comparisons and merged findings using joint display analysis. RESULTS: We trained two decision coaches in the DC group and recruited 35 wwMS (PtDA = 22; DC = 13) over five months. Median DCS scores in the DC group were 49 at baseline and 15 at follow-up (range 0-100; higher scores indicate greater decisional conflict). In the PtDA group, scores were 54 (baseline) and 31 (follow-up). Explorative group comparison indicated lower decisional conflict at follow-up in the DC group than in the PtDA group (p = 0.035). Interviewees (PtDA = 5; DC = 6; nurses = 2) described both interventions as helpful for decision-making. Qualitative findings indicate greater satisfaction levels in the DC group. CONCLUSION: Both interventions appear useful for wwMS in making motherhood choices. The DC programme seems more promising in supporting decision-making. TRIAL REGISTRATION: German Clinical Trials Register (DRKS); DRKS00038534.
14 June 2026
Read appraisal →African journal of reproductive health
The role of information technology in promoting sexual and reproductive health awareness among young people in Lahore: A comparative study with Shanghai.
Information technology (IT) has transformed access to health information, yet its impact on sexual and reproductive health (SRH) awareness varies across contexts. This study investigates IT's influence on youth SRH awareness in Lahore, Pakistan, using primary data, and provides a comparative analysis with secondary data from Shanghai, China. Using a cross-sectional design in Lahore (n=250), structured questionnaires, PLS-SEM, logistic regression, and ANOVA assessed relationships between IT use, digital health literacy, trust in digital sources, cultural barriers, and awareness outcomes. Results indicate IT use (β=0.42), digital health literacy (β=0.38), and trust (β=0.26) significantly enhance awareness in Lahore, while cultural barriers exert a strong negative influence (β=-0.31). Significant mean differences (p<0.001) were found between cities. Shanghai demonstrated higher digital literacy, trust, awareness, and use of structured platforms, while Lahore exhibited substantially higher cultural barriers. Model comparisons showed stronger predictive pathways in Shanghai (R²=0.74) than Lahore (R²=0.68), reflecting advantages of institutionalized sex education and government-certified digital health applications. Overall, while IT holds considerable potential, its effectiveness is shaped by cultural norms, digital infrastructure, and institutional trust. The findings underscore Pakistan's need to develop culturally appropriate, reliable, and institutionally supported digital health platforms to improve youth access to accurate SRH information. La technologie de l'information (TI) a transformé l'accès à l'information sanitaire, mais son impact sur la sensibilisation à la santé sexuelle et reproductive (SSR) varie selon les contextes. Cette étude examine l'influence des TI sur la sensibilisation des jeunes à la SSR à Lahore, au Pakistan, avec une analyse comparative de Shanghai, en Chine. En utilisant un design transversal à Lahore (n=250), des questionnaires structurés, la PLS-SEM, la régression logistique et l'ANOVA ont évalué les relations entre l'utilisation des TI, la littératie numérique en santé, la confiance dans les sources numériques, les barrières culturelles et les résultats de sensibilisation. Les résultats indiquent que l'utilisation des TI (β=0,42), la littératie numérique en santé (β=0,38) et la confiance (β=0,26) améliorent significativement la sensibilisation à Lahore, tandis que les barrières culturelles exercent une forte influence négative (β=-0,31). Des différences moyennes significatives (p<0,001) ont été constatées entre les villes. Shanghai a démontré une littératie numérique, une confiance, une sensibilisation et une utilisation de plateformes structurées plus élevées, tandis que Lahore présentait des barrières culturelles substantiellement plus fortes. Les comparaisons de modèles ont montré des voies prédictives plus solides à Shanghai (R²=0,74) qu'à Lahore (R²=0,68), reflétant les avantages de l'éducation sexuelle institutionnalisée et des applications de santé numériques certifiées par le gouvernement. Globalement, bien que les TI aient un potentiel considérable, leur efficacité est façonnée par les normes culturelles, l'infrastructure numérique et la confiance institutionnelle. Les conclusions soulignent la nécessité pour le Pakistan de développer des plateformes de santé numériques culturellement adaptées, fiables et soutenues institutionnellement pour améliorer l'accès des jeunes à des informations précises sur la SSR.
31 May 2026
Read appraisal →African journal of reproductive health
Reproductive health in the digital and social age: AI, education, law, and community-based interventions.
Reproductive health has increasingly emerged as a complex, multidimensional field that extends far beyond clinical care into the domains of education, technology, law, culture, and socio-economic systems. This special issue of the African Journal of Reproductive Health brings together fifteen diverse yet interconnected papers that collectively illuminate how reproductive health outcomes are shaped by dynamic interactions across disciplines, geographies, and social structures. The contributions - spanning China, Spain, and Pakistan - underscore a unifying premise: that sustainable reproductive health improvements depend on integrative approaches that harness innovation while remaining grounded in cultural and social realities. La santé reproductive s'affirme de plus en plus comme un domaine complexe et multidimensionnel qui dépasse largement le cadre des soins cliniques pour englober l'éducation, la technologie, le droit, la culture et les systèmes socio-économiques. Ce numéro spécial de l'African Journal of Reproductive Health rassemble quinze articles divers mais interconnectés qui, ensemble, mettent en lumière la manière dont les résultats en matière de santé reproductive sont façonnés par des interactions dynamiques entre disciplines, territoires et structures sociales. Ces contributions, provenant de Chine, d'Espagne et du Pakistan, soulignent un principe unificateur : l'amélioration durable de la santé reproductive repose sur des approches intégratives qui exploitent l'innovation tout en restant ancrées dans les réalités culturelles et sociales.
30 May 2026
Read appraisal →African journal of reproductive health
A systematic review of pregnancy outcomes and management in polycystic ovary syndrome
Polycystic Ovary Syndrome (PCOS), affects 5-20% of women of reproductive age, it is the leading cause of anovulatory infertility accounting for 70-90% of cases and resulting in lower natural conception rates and a significant contributor to adverse pregnancy outcomes. Following PRISMA 2020 guidelines, this systematic review synthesized evidence from 2014-2025, evaluating the evolving landscape of PCOS pregnancy management. It explores the relationship between PCOS and reproductive outcomes, details specific maternal and perinatal complications, and discusses the latest evidence-based interventions and emerging therapies to improve pregnancy outcomes and the long-term health of both mother and child. The findings revealed that the syndrome's pathophysiology driven by hyperandrogenism, insulin resistance, and obesity significantly increases the risks of early pregnancy loss, gestational diabetes, and pre-eclampsia. There is a paradigm shift toward individualized, multidisciplinary care. Evidence-based strategies highlight the superiority of letrozole for ovulation induction, the metabolic benefits of metformin, and the necessity of nuanced lifestyle interventions over simple weight-loss models. Furthermore, emerging research into immune-metabolic pathways, such as Interleukin-22, suggests novel therapeutic directions. The review concludes that recognizing PCOS as a high-risk obstetric condition and integrating early metabolic screening into standard care are essential to improving maternal and neonatal outcomes. Le syndrome des ovaires polykystiques (SOPK), qui touche 5 à 20 % des femmes en âge de procréer, est la principale cause d'infertilité anovulatoire (70 à 90 % des cas). Il entraîne une diminution des taux de conception naturelle et contribue significativement aux complications de la grossesse. Conformément aux recommandations PRISMA 2020, cette revue systématique a synthétisé les données probantes de 2014 à 2025, évaluant l'évolution de la prise en charge des grossesses chez les femmes atteintes de SOPK. Elle explore la relation entre le SOPK et les issues de la reproduction, détaille les complications maternelles et périnatales spécifiques et présente les interventions fondées sur des données probantes les plus récentes ainsi que les thérapies émergentes visant à améliorer les issues de grossesse et la santé à long terme de la mère et de l'enfant. Les résultats ont révélé que la physiopathologie du syndrome, caractérisée par un hyperandrogénisme, une résistance à l'insuline et une obésité, augmente significativement les risques de fausse couche précoce, de diabète gestationnel et de prééclampsie. On observe un changement de paradigme vers une prise en charge individualisée et multidisciplinaire. Les stratégies fondées sur des données probantes soulignent la supériorité du létrozole pour l'induction de l'ovulation, les bénéfices métaboliques de la metformine et la nécessité d'interventions nuancées sur le mode de vie plutôt que de simples programmes de perte de poids. De plus, les recherches émergentes sur les voies immunométaboliques, telles que l'interleukine-22, suggèrent de nouvelles pistes thérapeutiques. Cette revue conclut que la reconnaissance du SOPK comme une pathologie obstétricale à haut risque et l'intégration d'un dépistage métabolique précoce dans les soins courants sont essentielles pour améliorer les issues maternelles et néonatales.
29 May 2026
Read appraisal →Medical education online
AI-assisted case-based learning and flipped classroom to improve clinical decision-making: a randomized controlled trial in reproductive medicine
BACKGROUND: Efficient training of reproductive medicine clinicians is critical in the context of declining global fertility and increasing infertility. Traditional lecture‑based instruction often fails to sufficiently develop clinical decision‑making skills within limited residency rotations. Innovative strategies that integrate artificial intelligence (AI) with case‑based learning (CBL) and flipped classroom (FC) formats may enhance clinical reasoning, however rigorous evidence in reproductive medicine education remains limited. METHODS: We conducted a randomized controlled trial involving 50 obstetrics and gynecology residents at the First Hospital of Jilin University. Participants were randomly assigned to an AI‑assisted CBL+FC group or a traditional lecture control group. The AI‑assisted CBL+FC group completed pre‑class interactive case work with virtual standardized patients on the DoctorU platform and case analyses on the Superstar Learning platform, followed by interactive in‑class discussions. Primary outcomes included post‑course theoretical knowledge tests, Mini‑Clinical Evaluation Exercise (Mini‑CEX), and Objective Structured Clinical Examination (OSCE) scores. Secondary outcomes assessed learner motivation, clinical thinking, self‑directed learning, and perceived course effectiveness using a 5‑point Likert scale. RESULTS: Baseline characteristics were comparable between groups. After the intervention, the AI‑assisted CBL+FC group achieved significantly higher theoretical test scores than the control group. The AI‑assisted CBL+FC group also demonstrated superior overall clinical competence in Mini‑CEX assessments and higher OSCE total scores. Participants in the AI‑assisted CBL+FC group reported greater improvements in learning motivation, clinical reasoning, self‑directed learning, and perceived course effectiveness. CONCLUSIONS: The AI‑assisted CBL+FC instructional model significantly enhances theoretical knowledge, clinical decision‑making skills, and learner engagement among reproductive medicine residents. This blended learning model offers an efficacious and generalizable methodology for training practitioners to address the evolving clinical requirements within contemporary fertility care.
28 May 2026
Read appraisal →Reproduction & fertility
Patient characteristics and lifestyle determinants of quality of life among women with endometriosis: a systematic review
ABSTRACT: Endometriosis is a chronic inflammatory disease presenting with debilitating symptoms strongly impacting patients' quality of life (QoL). Assessing QoL is crucial for understanding the full patient experience beyond clinical symptoms. This narrative systematic review specifically aimed to identify and describe non-pharmacological and non-surgical factors associated with QoL in women with endometriosis as reported in the literature. Following PRISMA guidelines, we systematically searched PubMed, MEDLINE, Web of Science, and Embase up to January 15, 2025, for case-control, cohort, randomized controlled trials, and cross-sectional studies. This study was registered in PROSPERO (registration number: CRD42023438457) Eligible studies assessed socio-demographic characteristics, lifestyle factors, symptoms, comorbidities, or coping strategies in relation to QoL among women with endometriosis. Twenty-one studies with a low risk of bias were included. A better QoL was related to favorable socioeconomic profiles (n = 3), high care satisfaction (n = 2), partner involvement (n = 1), healthier lifestyle habits (n = 1), and the use of coping therapeutic strategies. Poor QoL was associated with poor health (n = 5), more severe symptoms (n = 5), unhealthy lifestyle habits (n = 2), and ineffective use of coping strategies (n = 2). This review highlights a broad range of non-medical determinants of QoL, underscoring that clinical measures alone fail to capture the full patient experience. By consolidating evidence across diverse study designs, it offers a comprehensive overview of modifiable factors that could inform holistic, patient-centered approaches to endometriosis care. Further prospective and interventional studies are needed to clarify causal pathways and evaluate the effectiveness of targeted strategies to improve QoL. LAY SUMMARY: Endometriosis is a chronic disease affecting around 10% of women of reproductive age, associated with pain, infertility, and significant impacts on daily life. Because clinical measures alone fail to capture the full patient experience, assessing QoL is essential to understand the real burden of the disease. This review examined non-pharmacological and non-surgical factors that may be associated with QoL, such as lifestyle habits, socioeconomic conditions, health status, and coping strategies. Across 21 studies, we found that a better QoL was linked to good healthcare access, healthy habits, and effective coping mechanisms. Conversely, severe symptoms, poor health, and unhealthy lifestyles (smoking and alcohol use) were associated with worse QoL. The findings highlight the need for a more holistic approach to endometriosis care, combining psychological support, lifestyle guidance, and improved access to quality healthcare. Future research should use standardized QoL tools and robust study designs to develop evidence-based strategies that can meaningfully enhance patient well-being.
23 May 2026
Read appraisal →Apoptosis : an international journal on programmed cell death
Single-cell profiling and machine learning identify cuproptosis-related fibroblast subpopulations and fibrogenesis modulator AEBP1 in endometriosis
Endometriosis is characterized by progressive fibrosis and limited therapeutic options. Cuproptosis, a copper-dependent form of regulated cell death, has been implicated in multiple pathological conditions, but its relevance to fibroblast-mediated fibrotic progression in endometriosis remains unclear. Single-cell RNA sequencing data from normal, eutopic, and ectopic endometrial tissues were analyzed to assess cuproptosis-related gene (CRG) activity and fibroblast heterogeneity. Pseudotime analysis, cell-cell communication analysis and high-dimensional weighted gene co-expression network analysis were performed to identify disease-associated fibroblast states and candidate fibrosis-related genes. Machine learning approaches were applied to prioritize candidate hub genes. Functional validation was conducted in endometrial stromal cells, and a mouse model of endometriosis was used to assess the effects of tetrathiomolybdate (TTM), a copper chelator. Elevated CRG activity was enriched in a distinct fibroblast subpopulation with profibrotic transcriptional features. Network and machine learning analyses consistently prioritized AEBP1 as a candidate fibroblast-associated hub gene linked to cuproptosis-related signatures. In vitro, CuCl2 plus elesclomol treatment was associated with increased AEBP1 and fibrosis-related marker expression, accompanied by changes in β-catenin pathway-related proteins, whereas FDX1 or AEBP1 knockdown attenuated these effects. In vivo, TTM treatment reduced lesion burden, fibrotic marker expression and collagen deposition in ectopic lesions. Cuproptosis-related molecular alterations are associated with fibroblast activation and fibrotic progression in endometriosis. Targeting copper metabolism may have therapeutic potential in limiting lesion fibrosis.
19 May 2026
Read appraisal →International journal of cancer
Testicular cancer in intersex individuals: A systematic review for clinical practice
The objective of this systematic review was to identify the evidence of testicular cancer risk for people with intersex conditions. This assessment is hoped to help refine risk stratification tools for assessing gonadal malignancy risk and guide the development of more robust evidence-based management strategies. The literature was searched in Ovid MEDLINE, Embase, and Cumulative Index of Nursing and Allied Health using a search string developed by a multidisciplinary team. The protocol was registered at Prospective Register of Systematic Reviews as CRD42021231313. A total of 3608 articles were found. After selection, 301 publications were included (1215 individuals). The results identified significant evidence that pre-pubertal gonadectomy may be linked to lower rates of malignant gonadal changes for patients with partial gonadal dysgenesis, Turner's syndrome with Y-chromosome material, complete androgen insensitivity, partial androgen insensitivity, and patients with ovotestis/es. The evidence was not significant for patients with complete gonadal dysgenesis, Klinefelter syndrome, nor WT1-related syndromes. Specific cancer outcomes were unable to be assessed due to small sample sizes and thus it is unknown if clinically significant cancer outcomes are meaningfully altered by pre-pubertal gonadectomy. Importantly, the quality of data on the topic of gonadal malignancy in intersex patients with testicular tissue was determined to be poor overall. The quality was relatively more robust regarding the conditions of Complete Androgen Insensitivity, Klinefelter syndrome, and patients with ovotestis/es. More high-quality research is needed to draw specific conclusions on the risks and benefits of performing pre-pubertal gonadectomy for intersex patients. When counseling these patients, clinicians should be transparent regarding the paucity of data supporting pre-pubertal gonadectomy.
17 May 2026
Read appraisal →African journal of reproductive health
Evaluation of the effects of probiotic supplementation on the ecology and inflammatory factors of female vaginal flora: a systematic review and meta-analysis
This meta-analysis systematically evaluated the effects of probiotic supplementation on vaginal microbiota and inflammatory factors in women. PubMed, Embase, Web of Science, CNKI, and Wanfang were searched from inception to January 2026 for randomized and controlled studies. Outcomes included vaginal pH, Nugent score, and inflammatory cytokines (IL-4, IL-6, IL-10, TNF-α). Fifteen studies were included. Compared with controls, probiotics did not significantly reduce IL-4, IL-6, IL-10, or TNFα levels, nor did they significantly improve Nugent score. However, probiotic supplementation significantly reduced vaginal pH (OR = 0.36, 95% CI: 0.15-0.89; P = 0.03), indicating improved maintenance of a weakly acidic vaginal environment. Sensitivity analyses showed generally stable results, although heterogeneity remained substantial for several outcomes. Overall, probiotics appear effective in modulating vaginal acid-base balance but show limited evidence for improving inflammatory cytokine profiles or restoring vaginal microbiota structure. Current data are insufficient to support routine probiotic use for optimizing vaginal microbiota and inflammatory status. Further high-quality, well-designed randomized controlled trials are required to clarify their clinical benefits. Cette méta-analyse a évalué de manière systématique les effets de la supplémentation en probiotiques sur le microbiote vaginal et les facteurs inflammatoires chez les femmes. Les bases de données PubMed, Embase, Web of Science, CNKI et Wanfang ont été consultées depuis leur création jusqu’en janvier 2026 afin d’identifier des études randomisées et contrôlées. Les critères de jugement comprenaient le pH vaginal, le score de Nugent et les cytokines inflammatoires (IL-4, IL-6, IL-10, TNF-α). Quinze études ont été incluses. Comparativement aux groupes témoins, les probiotiques n’ont pas réduit significativement les concentrations d’IL4, IL-6, IL-10 ou TNF-α, ni amélioré significativement le score de Nugent. En revanche, la supplémentation en probiotiques a significativement réduit le pH vaginal (OR = 0,36 ; IC à 95 % : 0,15–0,89 ; P = 0,03), indiquant un meilleur maintien d’un environnement vaginal faiblement acide. Les analyses de sensibilité ont montré des résultats globalement stables, bien qu’une hétérogénéité substantielle persiste pour plusieurs critères. Dans l’ensemble, les probiotiques semblent efficaces pour moduler l’équilibre acido-basique vaginal, mais les preuves restent limitées quant à leur capacité à améliorer les profils cytokiniques inflammatoires ou à restaurer la structure du microbiote vaginal. Les données actuelles sont insuffisantes pour recommander l’utilisation systématique des probiotiques dans l’optimisation du microbiote vaginal et du statut inflammatoire. Des essais contrôlés randomisés de haute qualité sont nécessaires pour confirmer leurs bénéfices cliniques.
16 May 2026
Read appraisal →JMIR medical informatics
Adverse Pregnancy Outcomes in Women With Immune Abnormalities: Machine Learning Model Development and Validation Using First-Trimester Sonographic Features
BACKGROUND: The maintenance and progression of pregnancy rely on immune homeostasis at the maternal-fetal interface. However, pregnancy complicated by autoimmune abnormalities can disrupt this balance and significantly increase the risk of adverse pregnancy outcomes (APOs). OBJECTIVE: This study aimed to (1) develop an interpretable predictive tool for APOs in patients with immune abnormalities and (2) interpret the models using Shapley additive explanations (SHAP) values. METHODS: This study retrospectively analyzed clinical data from 288 patients with autoimmune abnormalities at Yichang Central People's Hospital between 2019 and 2024. Feature selection was performed using both the Boruta algorithm and Least Absolute Shrinkage and Selection Operator regression to identify optimal predictive factors associated with APOs. Nine machine learning models were developed and subsequently underwent a comprehensive comparative evaluation of their predictive performance, leading to the identification of the optimal predictive model. SHAP values were generated to provide interpretable insights into model predictions. RESULTS: A total of 288 patients were included in the study, 124 (43.06%) of whom had APOs. The extreme gradient boosting algorithm was shown to be the optimal model after a comparison of 9 different models utilizing various metrics. The SHAP analysis showed that crown-rump length at 6+0 to 8+6 weeks, the number of other drugs, the number of complications during pregnancy, gestational sac volume at 6+0 to 8+6 weeks, and yolk sac diameter change at 6+0 to 8+6 weeks were the key predictive factors affecting APOs. CONCLUSIONS: The study developed an interpretable predictive tool for APOs in patients with immune abnormalities, which may assist clinicians in making early intervention decisions.
14 May 2026
Read appraisal →Archives of gynecology and obstetrics
Clinical outcomes and practical management implications in rudimentary horn pregnancies: a systematic review and pooled analysis (2010-2025)
PURPOSE: Rudimentary horn pregnancies are rare and carry significant maternal and fetal risks. This study aims to systematically review published cases of rudimentary horn pregnancies describing data about time of diagnosis, time of rupture, and live birth rate (LBR), with exploratory comparisons between communicating (CHP) and non-communicating horn pregnancies (NCHP). METHODS: A PRISMA-guided systematic search of PubMed, MEDLINE, and Cochrane (October 1, 2025) was performed with terms "unicornuate uterus pregnancy" OR "rudimentary horn pregnancy." Case reports, series, and reviews with defined clinical data were included; abstracts and unclear reports were excluded. Three independent reviewers extracted data using a standardized protocol. Descriptive statistics (means, medians, standard deviations, and ranges) and exploratory group comparisons (Fisher's exact test, Mann-Whitney U and Student's t test with p < 0.05 denoting significance) were performed. RESULTS: From 132 articles, 190 cases were included: 27 CHP (14.2%) and 163 NCHP (85.8%). Time of diagnosis was earlier in NCHP (15.9 ± 8.9 weeks) than CHP (22.1 ± 10.0 weeks, p = 0.01). Rupture occurred in 68 cases (35.8%), similarly in CHP (48.1%) and NCHP (33.7%, p = 0.19). Time of rupture was earlier in NCHP (18.7 ± 6.6 weeks) than CHP (23.0 ± 9.2 weeks, p = 0.02). Four cases attempted to continue pregnancy; all resulted in premature rupture. Reported live births were infrequent (11.6%) and more common in published CHP (25.9%) vs. NCHP cases (9.2%; p = 0.02). CONCLUSIONS: This descriptive synthesis indicates uterine horn communication may be associated with later diagnosis/rupture and reported live births were significantly more frequent in published CHP vs. NCHP cases. However, all comparisons are exploratory and must be interpreted with extreme caution, as data limitations preclude causal inference. Exhaustive imaging and diagnosis are essential to characterize horn type. Surgical termination is advised, but if expectant management is chosen, close monitoring and multidisciplinary care, including weekly ultrasounds, are advisable to mitigate complications.
14 May 2026
Read appraisal →Reproductive biomedicine online
AI-driven paradigm shift in follicle ultrasound monitoring: from automated segmentation to clinical decision support
This commentary delineates the developmental pathway of artificial intelligence (AI) in ultrasound follicular monitoring, highlighting a paradigm shift from automated segmentation to clinical decision support. The deep learning-based CR-Unet and C-Rend models have enabled accurate follicle segmentation and measurement from two-dimensional to three-dimensional imaging, substantially improving boundary segmentation accuracy and measurement consistency. Building on this foundation, the study further establishes two-dimensional follicle area and three-dimensional follicle volume as novel biomarkers, providing quantitative criteria for predicting oocyte maturity and optimizing the timing of human chorionic gonadotrophin triggering. Through seamless integration of algorithms into the Acclarix LXK9 ultrasonography equipment, an intelligent monitoring platform with real-time analytical capabilities has been developed, demonstrating significantly superior measurement accuracy and consistency compared with manual operations. These advancements represent a transformative leap from image segmentation to AI-driven clinical decision making, offering robust technical support for standardized and precise management in assisted reproduction.
9 May 2026
Read appraisal →Neurology
Idiopathic Intracranial Hypertension Prevalence and Hormonal Contraception: A Meta-Analysis
BACKGROUND AND OBJECTIVES: Women's health advice in people living with idiopathic intracranial hypertension (IIH) is inconsistent, primarily due to an enduring concern that hormonal contraception (HC), including oral contraceptive pills (OCPs) and hormonal intrauterine devices (IUDs), might be associated with a higher prevalence of IIH. This systematic review and meta-analysis examines whether a meaningful association exists between HC use and IIH prevalence. METHODS: Systematic searches of Ovid MEDLINE, Embase, and the Cochrane Library were conducted from their inception to May 14, 2025. Gray literature and citation lists were also reviewed. Observational studies comparing HC use among women with IIH to controls without IIH were included. Noncomparative studies and pharmacovigilance analyses were excluded. Two independent reviewers conducted data extraction, assessed the quality of studies using the Newcastle-Ottawa Scale, and appraised the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation framework. A random-effects meta-analysis using the Mantel-Haenszel method in Review Manager 5.4 was conducted to evaluate the association between HC use and IIH prevalence, the primary outcome of interest, with leave-one-out sensitivity analyses and subgroup analyses stratified by HC modality. RESULTS: A total of 13 studies (nIIH = 5,351 and ncontrol = 669,260; mean age = 33.3 years; 100% female) were included. HC use was not significantly associated with IIH prevalence (odds ratio [OR] 0.93, 95% CI 0.69-1.24, p = 0.60, I2 = 82%; n = 12 studies). Subgroup analyses revealed no significant associations for OCPs (OR 0.91, 95% CI 0.72-1.16, p = 0.45, I2 = 25%; n = 6 studies), IUDs (OR 1.45, 95% CI 0.61-3.44, p = 0.39, I2 = 92%; n = 5 studies), or medroxyprogesterone acetate injections (OR 1.21, 95% CI 0.84-1.74, p = 0.30, I2 = 2%; n = 2 studies). Findings were largely robust in sensitivity analyses. Quality assessments ranged from poor to good, with the certainty of evidence rated as very low to low. DISCUSSION: The meta-analysis found no significant association between HC use and IIH prevalence, with consistent results across various HC modalities. This evidence provides confidence to reassure patients with IIH and clinicians that the directed use of HC should be continued as appropriate. The limited quality of available evidence and considerable heterogeneity highlights the necessity for large-scale, well-designed studies, particularly in diverse patient populations, to validate these findings.
3 May 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Pharmacological interventions to improve bone density in functional hypothalamic amenorrhea: a systematic review and network meta-analysis of randomized clinical trials
CONTEXT: Women with functional hypothalamic amenorrhea (FHA) are at high risk of poor bone health. When lifestyle measures fail to restore menses, pharmacological interventions are needed for bone health, but comparative efficacy remains unclear. OBJECTIVE: To compare the efficacy of available pharmacological interventions to improve bone mineral density (BMD), in women with FHA, employing network meta-analysis (NMA). DATA SOURCES: Medline, Embase, Emcare, Cochrane CENTRAL, ISRCTN, and ClinicalTrials.gov were searched up to 20 September 2025. STUDY SELECTION: Eligible randomized-controlled trials evaluated pharmacological interventions for lumbar spine (LS), femoral neck (FN), or total hip (TH) BMD in women with FHA. Two independent reviewers screened titles, abstracts, and texts. DATA EXTRACTION: Two reviewers independently extracted data following the Preferred Reporting Items for Systematic Reviews-network meta-analysis guidelines. Outcomes were expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs) using random-effects NMA. Evidence certainty was assessed with CINeMA. DATA SYNTHESIS & RESULTS: Thirteen randomized-controlled trials (n = 897 participant observations across all pharmacotherapy comparisons) were included (LS BMD: n = 897; FN BMD: n = 370; TH BMD: n = 750). Transdermal hormone replacement therapy (HRT) was superior to control (placebo or no intervention) for LS BMD with SMD: 0.34 (0.03, 0.64) and FN BMD with SMD: 0.57 (0.04, 1.10). Oral HRT and the combined oral contraceptive pill (COCP) showed no significant benefit for any BMD site. Teriparatide was superior to transdermal HRT and COCP for LS BMD with SMDs: 1.48 (0.38, 2.59) and 1.75 (0.66, 2.83), but not FN or TH BMD. CONCLUSIONS: Transdermal HRT and teriparatide improve LS BMD in women with FHA, with transdermal HRT also improving FN BMD. STUDY REGISTRATION: PROSPERO (CRD42024576872).
25 Apr 2026
Read appraisal →JMIR research protocols
Integrating Sperm Microscopy, Environmental Exposures, and Lifestyle Factors for Male Fertility Analysis: Protocol for the Nippon Semen and Environmental Exposure Database (N-SEED) Cross-Sectional Study
BACKGROUND: Conventional semen analysis does not fully capture male reproductive potential. The sperm DNA fragmentation index (DFI) may detect latent infertility, although the sperm chromatin structure assay (SCSA) is costly and technically demanding. Image-based analysis of semen microscopy, including artificial intelligence (AI), may enable lower-cost noninvasive assessment. However, progress is limited by a lack of standardized multimodal datasets linking sperm images with the DFI and relevant covariates. OBJECTIVE: This protocol describes the initial phase of the Nippon Semen and Environmental Exposure Database (N-SEED) initiative. The study aims to (1) establish standardized acquisition and quality control procedures for sperm microscopy/video and DFI measurement; (2) evaluate the feasibility and magnitude of associations between predefined image-/video-derived variables and the DFI; and (3) characterize clinical, environmental, physical, and lifestyle factors that may act as candidate correlates or confounders for subsequent image-based fertility research. METHODS: This multi-institutional cross-sectional study centralized clinical assessment and specimen collection at a single site in Japan. The prespecified group-specific enrollment targets were 25 for group 1 (a relatively homogeneous low-risk cohort for DFI quality control) and 100 for group 2 (apparently healthy community-based adult volunteers for exploratory association analyses). Microscopic sperm videos, automated semen parameters, and sperm oxidative stress data were obtained at collection. SCSA-based DFI assays are currently being performed sequentially. Group 2 participants additionally provided fasting blood and early-morning urine samples for endocrine, metabolic, environmental chemical, and elemental assays. They also underwent physical measurements and completed structured questionnaires/interviews on lifestyle, nutrition, sleep, psychological status, sexual function, and collection conditions. The primary outcome measure is the continuous DFI assessed with SCSA. Group 1 data will be used to evaluate intraday, interday, and interfacility variability and to fix flow cytometry gating settings. In groups 1 and 2, predefined image-/video-derived summary variables after standardized preprocessing will be analyzed against the continuous DFI using correlation analyses and simple linear regression to assess whether sperm microscopy data contain information relevant to sperm DNA integrity. Exploratory categorical DFI analyses will use simple logistic regression. Secondary exploratory analyses will examine candidate covariates and data completeness, including sensitivity analyses. RESULTS: The study was registered in the University Hospital Medical Information Network Clinical Trials Registry on January 18, 2026. Between January 18 and February 21, 2026, 124 unique participants were recruited (group 1: n=25; group 2: n=103; both groups: n=4). Sample and data collection were completed on February 21, 2026. Biospecimen assays and primary association analyses are expected to be completed by March 2028. CONCLUSIONS: This initial N-SEED phase will deliver a standardized, quality-controlled multimodal resource linking sperm microscopy/video data with the DFI and broader physiological and environmental measures. Its immediate contribution is not to provide an immediately deployable clinical AI tool but rather to support feasibility assessment, confounder identification, and planning for subsequent database expansion and external validation of image-based male fertility assessment methods. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000060395; https://tinyurl.com/mryfymw5. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/93803.
19 Apr 2026
Read appraisal →PloS one
Uptake and determinants of immediate and extended postpartum long-acting reversible contraceptive use in Eastern and Western Africa: A systematic review and meta-analysis
BACKGROUND: Reducing unintended pregnancies and improving maternal/child health relies heavily on postpartum family planning (PPFP). Despite their high effectiveness, the use of long-acting reversible contraceptives (LARC), such as intrauterine contraceptive device (IUCD) and implants, is inconsistent in Africa after childbirth. This systematic review and meta-analysis aimed to assess the prevalence and determinants of immediate and extended postpartum use of long-acting reversible contraceptives in Eastern and Western Africa. METHODS: We searched PubMed, the Cochrane Library, Hinari, and gray literature sources (Google Scholar) for studies published between January 1, 2015, and December 12, 2025. Eligible studies reported LARC uptake within 12 months of postpartum. Heterogeneity was assessed using the I² statistic, publication bias using Egger's test, and study quality using the JBI 2020 checklist. Data were analyzed using Stata version 17 and R version 4.5. RESULTS: Sixty-eight studies were included, most of which were from Eastern Africa. The pooled prevalence was 21.7% for immediate postpartum LARC (IPP-LARC) and 19.5% for extended postpartum LARC (EPP-LARC). Uptake was significantly associated with counseling during maternal and child health visits, partner involvement, prior family planning use, and good knowledge. Age ≥ 35 years and higher education level also favored immediate postpartum IUD use. CONCLUSION: The uptake of postpartum LARCs remains low in Eastern and Western Africa. Strengthening FP counseling during MCH services, encouraging partner involvement, and improving knowledge are critical strategies to increase coverage and reduce unmet needs. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews (ID: CRD420250577642).
19 Apr 2026
Read appraisal →African journal of reproductive health
Mapping research fronts of reproductive medicine using the NHANES database: A bibliometric and thematic analysis
Reproductive health, infertility, and perinatal diseases significantly challenge human health development and continuity, requiring multidisciplinary approaches for enhanced academic understanding and practical solutions. This study used bibliometric analysis to examine related articles in the web of science (WoS) database, employing tools including bibliometrix and VOSviewer for systematic literature analysis. To capture the broader context of high-impact research, we first analyzed 1,026 highly-cited and hot papers in reproductive medicine, which revealed evolving thematic trends and global collaboration patterns. Then we examined 232 literatures using NHANES datasets for reproductive health research to identify research gaps and opportunities for further research in this field. The analysis revealed key trends, areas of concentration, and potential knowledge gaps in the literature, while the thematic analysis of reproductive health studies utilizing the NHANES database further underscored the wealth of data amenable to multidisciplinary investigation. Future research directions to explore new dimensions of reproductive health, improving health policies and clinical practices in this field using NHANES database are also suggested. The study concludes that multidisciplinary research using comprehensive datasets like NHANES is crucial for advancing understanding of reproductive health, infertility, and perinatal outcomes. La santé reproductive, l'infertilité et les maladies périnatales constituent un défi majeur pour le développement et la continuité de la santé humaine, nécessitant des approches multidisciplinaires afin d'améliorer la compréhension académique et de proposer des solutions pratiques. Cette étude a utilisé une analyse bibliométrique pour examiner les articles pertinents dans la base de données WoS, en employant des outils tels que Bibliometrix et VOSviewer pour une analyse systématique de la littérature. Afin de saisir le contexte plus large de la recherche à fort impact, nous avons d'abord analysé 1 026 articles hautement cités et à tendance chaude en médecine reproductive, ce qui a révélé les tendances thématiques évolutives et les modèles de collaboration internationale. Nous avons ensuite examiné 232 publications utilisant les jeux de données NHANES pour la recherche sur la santé reproductive, afin d'identifier les lacunes de recherche et les opportunités pour de futures études dans ce domaine. L'analyse a mis en évidence les tendances clés, les domaines de concentration et les lacunes de connaissances potentielles dans la littérature, tandis que l'analyse thématique des études sur la santé reproductive utilisant les jeux de données NHANES a en outre souligné la richesse des données susceptibles d'être étudiées de manière multidisciplinaire. Les orientations futures de la recherche visant à explorer de nouvelles dimensions de la santé reproductive, à améliorer les politiques sanitaires et les pratiques cliniques dans ce domaine à l'aide des jeux de données NHANES sont également proposées. L'étude conclut que la recherche multidisciplinaire utilisant des jeux de données complets tels que NHANES est cruciale pour faire progresser la compréhension de la santé reproductive, de l'infertilité et des issues périnatales.
17 Apr 2026
Read appraisal →Biology of reproduction
The relationship between seminal microbiome and male reproductive wellness: a systematic review
The seminal microbiome, which is composed of different types of bacteria in semen and seminal plasma, has a significant impact on male reproductive health by changing the quality of semen and fertility. Previously regarded as sterile, the male reproductive tract contains microbes originating from the gastrointestinal tract, reproductive organs, and external sources such as sexual partners. Dysbiosis alters sperm parameters, triggers inflammation and oxidative stress, and is associated with conditions such as infertility, HPV infection, prostatitis, prostate cancer, and azoospermia. This systematic review adhered to the PRISMA 2020 guidelines (with 2025 extensions for reproducibility) and examined studies from PubMed, Scopus, and Science Direct (2015-2025, with prior context), concentrating on human, in vitro, and rodent models. Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes are among the most important phyla. Beneficial genera, such as Lactobacillus, improve sperm motility, concentration, and DNA integrity, whereas dysbiotic taxa, such as Prevotella, Pseudomonas, and Ureaplasma, are associated with declines. Sexual activity facilitates bidirectional microbial transfer, modifying diversity and fostering the dysbiosis. Inflammatory cytokines, reactive oxygen species, and metabolic disruptions are all involved in this process. Changes that are specific to a disease, such as higher levels of Fusobacterium in HPV-positive samples, worsen the situation. This review highlights how the microbiome alters sperm function and causes infertility. Standardized methods and long-term studies are needed to prove causality. Probiotics and other therapeutic interventions show promise in restoring balance and boosting fertility.
16 Apr 2026
Read appraisal →Human fertility (Cambridge, England)
The global evaluation of the effects of antioxidants on seminal outcomes in infertile men: a systematic review and meta-analysis
The aim of the current review is to summarise information from publications on the impact of antioxidants on seminal outcomes in infertile men. A systematic search was performed in the five valid databases (Scopus, PubMed, Medline, Embase, and Web of Science) utilizing two sets of keywords up to September 2025, according to the PRISMA approach. Of the 11749 papers identified, 101 papers were included in this review, for a total of 11889 infertile men. Sperm concentration, normal sperm morphology, progressive sperm motility, and total sperm motility, were considerably higher in experimental groups compared with control groups. Both sperm concentration (106 mL-1) and total motility (%) were higher in experimental groups compared to control groups with an overall pooled standardised mean difference (SMD) of 2.33 (95% CI: 1.73, 2.94) for sperm concentration and SMD of 1.62 (95% CI: 1.20, 2.04) for total motility (%). Subgroup analysis demonstrated that duration of treatments of more than 6 months were more effective than those of less than 3 months. Based on the findings of this review, no definitive recommendation can be made regarding the use of antioxidants as a therapy for male infertility, and further research is necessary.
16 Apr 2026
Read appraisal →Archives of gynecology and obstetrics
Misdiagnosis of different types of aneuploidy in preimplantation genetic testing (PGT): a systematic review and meta-analysis
PURPOSE: Recent studies have reported that embryos diagnosed as aneuploid by preimplantation genetic testing (PGT) can still result in successful live births after transfer. This suggests that, in addition to mosaic embryos, fully aneuploid embryos may also carry a risk of diagnostic error, potentially reducing the overall accuracy of PGT. Therefore, thoroughly investigating the risk and characteristics of aneuploidy misdiagnosis is crucial for optimizing PGT strategies and improving clinical outcomes in assisted reproductive technology (ART). METHODS: Relevant studies published from January 2000 to December 2024 were identified through PubMed and Web of Science. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). A diagnostic meta-analysis was conducted using a random-effects model to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs), combining sensitivity and specificity. Results were visualized using forest plots. RESULTS: A total of 22 studies were included to assess the discordance between trophectoderm (TE) biopsy and inner cell mass (ICM) or whole blastocyst (WB) results. The discordance rate for euploid embryo diagnosis was low (2.6%), whereas it was significantly higher for aneuploid embryos (9.2%). Segmental aneuploidies showed the highest discordance rate (17.4%). In the PGT-A population, misdiagnosis of segmental aneuploid embryos was particularly prominent (OR = 10.04, 95% CI: 7.60-13.27, I2 = 0%, P < 0.001). CONCLUSION: The results indicate that embryos with segmental aneuploidies have a significantly higher risk of misdiagnosis, especially in the PGT-A population. This highlights the need for caution when interpreting trophectoderm (TE) biopsy results involving segmental aneuploidies, to avoid misdiagnosis and the inadvertent discard of potentially viable embryos.
8 Apr 2026
Read appraisal →Genetics
Mapping whole-organism genetic comorbidities across model Species using unified ontologies
Understanding how genetic variation contributes to organism-wide phenotypes is critical for identifying mechanisms of disease. Here, we present a computational approach to analyze whole-organism comorbidities associated with genes underlying non-obstructive azoospermia (NOA), the most severe form of male infertility. We curated 204 mouse genes with experimentally validated spermatogenic failure and mapped their orthologs and phenotype annotations across humans, M. musculus, D. rerio, D. melanogaster, and C. elegans using a unified cross-species phenotype structure. This framework integrates a newly developed reproductive phenotype ontology with standardized whole-body phenotype categories to enable direct cross-species comparisons, using thousands of genotype-phenotype associations stored in model organism databases. Our analysis shows that most NOA genes have conserved orthologs across models, and that perturbation of these genes is frequently associated with non-reproductive phenotypes. In particular, integumentary defects and neoplastic phenotypes recur across species, supporting a shared genetic basis for epidemiological links between male infertility and systemic disease. Gene-level comorbidity patterns are partially predictable from single-cell RNA-seq, whole-body gene expression, and Gene Ontology annotations, suggesting that fundamental biological constraints shape the systemic consequences of reproductive gene dysfunction. Clustering genes by comorbidity profiles further distinguished genes with isolated reproductive effects from those with broad organismal consequences. This work demonstrates the power of ontology-based cross-species analysis for identifying pleiotropic effects of Mendelian disease mutations, and provides a resource, CoMorbidity DataBase Mapper (CoMo DBM), for joint analysis of genotype-phenotype associations in model organism databases.
6 Apr 2026
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