Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 6 appraisals
PloS one
Determinants of dropout from lifestyle interventions for overweight polycystic ovary syndrome: An exploratory analysis of randomized controlled trial.
OBJECTIVE: This exploratory analysis of a randomized controlled trial aimed to identify baseline predictors of dropout in overweight women with polycystic ovary syndrome (PCOS) participating in a lifestyle intervention program. METHODS: An exploratory analysis was conducted using data from a randomized controlled trial involving overweight or insulin-resistant women with PCOS aged 18-45. All participants received cyclic progestin, metformin, and a structured lifestyle intervention. Dropout was defined as proactive withdrawal, missing two consecutive visits, or loss of contact for more than six months. Univariate and adjusted multivariable logistic regression models were used to identify factors associated with dropout. RESULTS: Among the participants, 61.06% (n = 69) dropped out within one year. No significant differences were observed in baseline demographic, clinical, biochemical, psychological, or dietary characteristics between completers and dropouts. However, baseline physical activity level (PAL), objectively measured using an accelerometer, was identified as the strongest predictor of dropout. Each 0.3-unit increase in PAL was associated with a 29.6% reduction in the likelihood of dropout. CONCLUSION: Baseline PAL is strongly associated with the risk of dropout. Screening for PAL in women with PCOS is recommended, and those with lower PAL should receive personalized support in addition to lifestyle interventions to improve adherence and promote weight loss.
28 June 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 →PloS one
Distinct endometrial protein profiles in spontaneous and stimulated cycles in women with poor ovarian response: A prospective case-crossover clinical trial
The window of implantation is a critical period for embryo implantation. Ovarian stimulation can disrupt endometrial receptivity, potentially through altered gene expression and downstream protein profiles. However, the impact on the endometrial proteome remains underexplored. Identifying biomarkers of endometrial receptivity may provide an opportunity to develop targeted interventions aimed at improving implantation outcomes. This prospective, case-crossover, open-label study was conducted at the Department of Human Reproduction, Division of Obstetrics and Gynecology, University Medical Centre Ljubljana, Slovenia, from September 2023 to June 2024. The study included 15 women aged <43 years with primary infertility and poor ovarian response. Endometrial samples were collected using a pipelle biopsy during the window of implantation in spontaneous and stimulated cycles and analyzed using protein microarrays targeting 1,466 proteins. Differential protein abundance was assessed using a multi-factorial linear model, including patient-specific effects as an additional factor to account for the paired case-crossover design. Effect sizes are reported as log2-fold changes with corresponding 95% confidence intervals. Differential abundance was defined a priori as |log2FC| > 0.5 with FDR-adjusted p-value < 0.05. Comparison of endometrial samples from spontaneous and stimulated cycles revealed 114 antibodies with differential abundance. Key proteins were associated with immune response (IL-8, proteins S100-A8 and S100-A9, CAMP) and extracellular matrix remodeling (MMP-9). Exploratory KEGG pathway mapping suggested involvement of immune and inflammatory pathways, including cytokine-cytokine receptor interaction and IL-17 signaling. Cluster analysis demonstrated distinct proteomic patterns, with all stimulated-cycle samples showing alterations and a subset of stimulated-cycle samples (40%) exhibiting more pronounced changes. The findings indicate that ovarian stimulation is associated with measurable alterations in the endometrial proteomic profile during the window of implantation. These changes may be relevant to biological pathways involved in endometrial receptivity and implantation. Further studies in larger cohorts are needed to validate the identified candidate markers and determine their clinical relevance for implantation outcomes. Trial registration: ClinicalTrials.gov NCT06804174.
22 May 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Lifestyle intervention before and during fertility treatment in women with obesity or with overweight and PCOS-a RCT
CONTEXT: Lifestyle interventions are recommended for women with obesity and infertility, but trial evidence is scarce, and studies have not investigated interventions that continue during fertility treatment. OBJECTIVE: Evaluate effectiveness of a lifestyle intervention compared with usual care on fertility outcomes in women with obesity and infertility. DESIGN: The Obesity-Fertility randomized controlled trial (RCT), at an academic fertility clinic, included 127 women aged 18 to 40 years with infertility and obesity (body mass index ≥30 kg/m2, or ≥27 kg/m2 with polycystic ovary syndrome [PCOS]), excluding those unlikely to conceive naturally. The intervention group (IG) received a 6-month lifestyle intervention alone (individual follow-up with a dietician and kinesiologist, and group sessions) before adding fertility treatments. The control group (CG) received usual fertility care directly. Rate of live birth conceived within 18 months of randomization was analyzed. RESULTS: Compared to CG, the IG lost more weight (-3.21% ± 4.73% vs -0.40% ± 3.66%, P = .003) and waist circumference (-2.62 ± 4.46 cm vs -0.23 ± 3.81 cm, P = .01) at 6 months. The live-birth rate was 44.4% in the IG (n = 63) vs 35.9% in the CG (n = 64) (risk ratio [RR] = 1.24 [95% CI 0.81-1.90]). In IG vs CG, clinical pregnancy rates were 52.4% vs 37.5% (RR = 1.40 [0.94-2.07]) and natural pregnancy rates were 27.0% vs 12.5% (RR = 2.16 [1.01-4.64]). CONCLUSION: Compared with usual care, a lifestyle intervention alone for 6 months and then combined with fertility treatments did not increase the 18-month rate of pregnancies leading to a live birth, but significantly increased natural pregnancy rates, potentially reducing the need for costly assisted reproduction in this population.
19 May 2026
Read appraisal →Journal of ethnopharmacology
Tianjing Zelan formula improves polycystic ovary syndrome by regulating steroid biosynthesis and arachidonic acid metabolism
ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a set of symptoms related to menstrual irregularities that can cause infertility in women of reproductive age. Unfortunately, there are currently no authorized treatment medications for PCOS. The Tianjing Zelan (TJZL) formula, a herbal formulation developed from the ancient Chinese medical classic Beiji Qianjin Yaofang in Tang Dynasty, is employed in the clinical management of menstrual irregularities and amenorrhea. However, its clinical characteristics and mechanism have not been systematically evaluated. AIM OF THE STUDY: To reveal the clinical characteristics and mechanisms of TJZL in treating PCOS. MATERIALS AND METHODS: A multicenter and single-arm clinical trial, and two PCOS models were used to evaluate the effectiveness of TJZL. The chemical constituents of TJZL were analyzed by UHPLC-QTOF-MS/MS. In addition, a combination of untargeted metabolomics and transcriptomics was used to reveal the complex therapeutic mechanisms of TJZL on PCOS. Subsequently, a metabolite-gene network analysis was performed to reveal potential differentially expressed genes associated with metabolites in PCOS patients. Key targets and pathways were further validated using quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry in PCOS mice. Finally, molecular docking analysis was employed to explore the potential active ingredients of TJZL. RESULTS: Clinical trials provided evidence that TJZL significantly improved the menstrual cycle, sex hormone levels, and hyperandrogenic phenotypes, and reduced insulin resistance in PCOS patients. TJZL significantly improved the fertility, estrous cycle, ovarian morphology, sex hormone levels, and oral glucose tolerance in PCOS model. Transcriptomic and metabolomics results show that TJZL has a significant regulatory effect on metabolites and gene expression profiles in pathways such as steroid synthesis, arachidonic acid metabolism, and fatty acid metabolism. Utilizing metabolite-gene association analysis, We further verified that TJZL significantly improved the expression of genes and proteins related to the ovarian steroidogenesis and arachidonic acid metabolism pathways, including CYP17A1, CYP19A1, HSD17B3 and PTGS2. Furthermore, molecular docking results showed that berberine, rosmarinic acid and glycyrrhizinic acid in TJZL had strong affinity with PTGS2 in arachidonic acid metabolism, and hesperidin, naringin and liquiritin have strong affinity with CYP19A1 in steroid synthesis. CONCLUSION: TJZL exerts beneficial therapeutic effects on PCOS in both clinical and laboratory studies. TJZL improves PCOS by regulating multiple endogenous metabolites and correcting abnormal steroid synthesis and arachidonic acid metabolism in the ovaries. Our research provides a promising therapeutic agent for PCOS patients.
25 Apr 2026
Read appraisal →African journal of reproductive health
The therapeutic potential of exosomes derived from mesenchymal stem cells for premature ovarian failure: A systematic review
This review evaluates mesenchymal stem cell-derived exosomes (MSC-Exos) for treating premature ovarian failure (POF). A comprehensive search was conducted across five databases, including PubMed, Embase, and Web of Science (WoS), yielding 17 English-language studies published between 2016 and 2025. Studies primarily using animal and in vitro models assessed the therapeutic effects and mechanisms of MSC-Exos from diverse sources. MSC-Exos significantly elevated estrogen levels, reduced follicle-stimulating hormone (FSH), increased antral follicle counts, and restored estrous cyclicity. Specifically, BMSC-Exos activated the PI3K/AKT pathway via miRNAs to suppress granulosa cell apoptosis; hUCMSC-Exos mitigated cellular senescence and autophagy; ADSC-Exos promoted follicular development through SMAD and SIRT1/FOXO1; PMSC-Exos attenuated ROS damage by improving mitochondrial function; AFSC-Exos together with MenSC-Exos enhanced oocyte maturation via the P53 pathway. Notably, perinatal exosomes showed 18-32% greater efficacy in functional recovery than adult-tissue counterparts with fewer doses. MSC-Exos present a promising therapeutic strategy for POF by targeting apoptosis, autophagy, angiogenesis, and oxidative stress. Perinatal-derived exosomes offer superior potential due to their non-invasive collection and minimal ethical concerns. Nonetheless, challenges pertaining to heterogeneity, long-term safety, and standardized manufacturing necessitate resolution through multicenter clinical trials to advance clinical applicability.. Cette revue évalue l’utilisation d’exosomes dérivés de cellules souches mésenchymateuses (MSC-Exos) pour le traitement de l’insuffisance ovarienne prématurée (IOP). Une recherche exhaustive a été menée dans cinq bases de données, notamment PubMed, Embase et Web of Science (WoS), et a permis d’identifier 17 études publiées en anglais entre 2016 et 2025. Les études, reposant principalement sur des modèles animaux et in vitro, ont examiné les effets thérapeutiques et les mécanismes d’action des MSC-Exos issus de différentes sources. Les MSC-Exos ont significativement augmenté les taux d’œstrogènes, réduit l’hormone folliculostimulante (FSH), accru le nombre de follicules antraux et rétabli la cyclicité œstrale. Plus précisément, les exosomes dérivés de cellules souches mésenchymateuses de la moelle osseuse (BMSC-Exos) ont activé la voie PI3K/AKT via des miARN afin de supprimer l’apoptose des cellules de la granulosa ; les exosomes dérivés de cellules souches mésenchymateuses du cordon ombilical humain (hUCMSC-Exos) ont atténué la sénescence cellulaire et modulé l’autophagie ; les exosomes dérivés de cellules souches mésenchymateuses du tissu adipeux (ADSC-Exos) ont favorisé le développement folliculaire via les voies SMAD et SIRT1/FOXO1 ; les exosomes dérivés de cellules souches mésenchymateuses placentaires (PMSC-Exos) ont réduit les dommages liés aux espèces réactives de l’oxygène (ROS) en améliorant la fonction mitochondriale ; les exosomes dérivés de cellules souches du liquide amniotique (AFSC-Exos), associés aux exosomes dérivés de cellules souches mésenchymateuses menstruelles (MenSC-Exos), ont amélioré la maturation ovocytaire via la voie P53. Il est à noter que les exosomes d’origine périnatale ont montré une efficacité de récupération fonctionnelle supérieure de 18 à 32 % à celle des exosomes issus de tissus adultes, et ce avec un nombre de doses plus faible. Les MSC-Exos constituent une stratégie thérapeutique prometteuse pour l’IOP en ciblant l’apoptose, l’autophagie, l’angiogenèse et le stress oxydatif. Les exosomes d’origine périnatale offrent un potentiel supérieur grâce à un prélèvement non invasif et à des préoccupations éthiques limitées. Néanmoins, des défis liés à l’hétérogénéité, à la sécurité à long terme et à la standardisation de la fabrication doivent être résolus au moyen d’essais cliniques multicentriques afin de favoriser une application clinique. Cette revue évalue l’utilisation d’exosomes dérivés de cellules souches mésenchymateuses (MSC-Exos) pour le traitement de l’insuffisance ovarienne prématurée (IOP). Une recherche exhaustive a été menée dans cinq bases de données, notamment PubMed, Embase et Web of Science (WoS), et a permis d’identifier 17 études publiées en anglais entre 2016 et 2025. Les études, reposant principalement sur des modèles animaux et in vitro, ont examiné les effets thérapeutiques et les mécanismes d’action des MSC-Exos issus de différentes sources. Les MSC-Exos ont significativement augmenté les taux d’œstrogènes, réduit l’hormone folliculostimulante (FSH), accru le nombre de follicules antraux et rétabli la cyclicité œstrale. Plus précisément, les exosomes dérivés de cellules souches mésenchymateuses de la moelle osseuse (BMSC-Exos) ont activé la voie PI3K/AKT via des miARN afin de supprimer l’apoptose des cellules de la granulosa ; les exosomes dérivés de cellules souches mésenchymateuses du cordon ombilical humain (hUCMSC-Exos) ont atténué la sénescence cellulaire et modulé l’autophagie ; les exosomes dérivés de cellules souches mésenchymateuses du tissu adipeux (ADSC-Exos) ont favorisé le développement folliculaire via les voies SMAD et SIRT1/FOXO1 ; les exosomes dérivés de cellules souches mésenchymateuses placentaires (PMSC-Exos) ont réduit les dommages liés aux espèces réactives de l’oxygène (ROS) en améliorant la fonction mitochondriale ; les exosomes dérivés de cellules souches du liquide amniotique (AFSC-Exos), associés aux exosomes dérivés de cellules souches mésenchymateuses menstruelles (MenSC-Exos), ont amélioré la maturation ovocytaire via la voie P53. Il est à noter que les exosomes d’origine périnatale ont montré une efficacité de récupération fonctionnelle supérieure de 18 à 32 % à celle des exosomes issus de tissus adultes, et ce avec un nombre de doses plus faible. Les MSC-Exos constituent une stratégie thérapeutique prometteuse pour l’IOP en ciblant l’apoptose, l’autophagie, l’angiogenèse et le stress oxydatif. Les exosomes d’origine périnatale offrent un potentiel supérieur grâce à un prélèvement non invasif et à des préoccupations éthiques limitées. Néanmoins, des défis liés à l’hétérogénéité, à la sécurité à long terme et à la standardisation de la fabrication doivent être résolus au moyen d’essais cliniques multicentriques afin de favoriser une application clinique.
15 Apr 2026
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