Search Results (414)

Background/Objectives: Although anti-Müllerian hormone (AMH) is a strong biomarker of ovarian reserve and oocyte pools, it is unknown whether high AMH levels can be a reliable predictor of oocyte quality, ovulation, and embryo quality. We aimed to determine whether there is any AMH threshold value that can be used to predict treatment success in women with clomiphene citrate (CC) resistance or failure in polycystic ovary syndrome (PCOS). Methods: This retrospective cohort study included 93 infertile women with PCOS who had been previously diagnosed with CC failure or CC resistance between May 2017 and June 2018. Prior to treatment, AMH concentration was measured in all women. The participants were divided into 2 groups according to their conception after ovulation induction (OI) and intrauterine insemination (IUI). At the end of a one-year period, the medical files were assessed retrospectively. Those with and without pregnancy were compared in terms of treatment protocols, infertility periods, laboratory parameters and AMH levels. Results: Clinical and biochemical characteristics of 36 pregnant women were compared with those of 57 non-pregnant women. The results showed that the pregnant group had significantly shorter infertility periods and longer ovarian stimulations than the non-pregnant group (p < 0.05). Serum AMH levels > 4.5 ng/mL can predict OI and IUI outcome in this specific patient population, with a sensitivity of 56% and a specificity of 69%. Multivariate logistic regression analysis showed that only AMH was identified as an independent predictor of pregnancy [OR = 1.151 (95% CI: 1.034–1.280), p = 0.010]. Conclusions: Serum AMH may serve as an adjunct predictor of OI and IUI outcomes in infertile women with PCOS who failed to conceive after ≥3 cycles of CC. However, its predictive value appears to be context-dependent and should be interpreted cautiously in clinical practice. Given the distinct clinical characteristics of this patient population, individualized treatment strategies and consideration of earlier alternative therapeutic approaches may be warranted to optimize reproductive outcomes. Full article

Background: The use of HFNC (High Flow Nasal Cannula) in the management of acute respiratory failure has been fully established in clinical practice. Conversely, less data is available supporting its use in chronic hypoxemic–hypercapnic respiratory failure. The aim of the present study is to evaluate the efficacy of HFNC in chronic hypercapnic respiratory failure associated with stable COPD. Methods: In this retrospective single-center longitudinal observational study, 40 patients treated with HFNC at home followed at the COPD Clinic of Respiratory Diseases (University of Campania L. Vanvitelli Monaldi Hospital, Naples) were included. All patients are re-assessed at our clinic at T0, T3, T6 and T12 months through functional respiratory tests and blood gas analysis. Results: After 12 months, significant reductions in pCO₂ (arterial partial pressure of carbon dioxide) (from 58.5 to 48.0 mmHg) and lactates (from 1.60 to 0.90 mmol/L) were observed, and MIP and MEP improved significantly. Patients receiving HFNC flows ≥50 L/min experienced greater reductions in pCO₂ and fewer exacerbations. Multivariate analysis identified HFNC flow rate (p = 0.0046), hours of use/day (p = 0.0157), lactate levels (p = 0.0301), and FEV₁ (forced expiratory volume in 1 s) (p = 0.0491) as independent predictors of reduction in PaCO₂. Higher BMI and greater airway obstruction were associated with a reduced response. Conclusions: Treatment with HFNC represents a reasonable therapeutic choice to reduce AEs-COPD and reduce PaCO₂ and lactates in stable COPD patients. Full article

Background/Objectives: In this study, we aimed to evaluate whether neonatal ischemia-modified albumin (IMA) and umbilical venous cord blood gas parameters are associated with antenatal markers of fetal well-being, including the umbilical coiling index (UCI) and umbilical artery (UA) and middle cerebral artery (MCA) Doppler indices. Methods: For this prospective observational study, sixty-five low-risk term pregnancies (≥37 weeks) were included. Prenatal ultrasound was used to measure the UCI and UA/MCA Doppler indices. At delivery, umbilical venous cord blood gas and serum IMA analyses were performed. Maternal and neonatal data (birth weight, 5 min Apgar score, NICU admission, sex, and delivery mode) were recorded, and correlations and group comparisons were performed (p < 0.05). Results: The UCI ranged from 0.210 to 0.471 coil/cm (mean 0.337). The UA and MCA Doppler indices were within the reference ranges. The UCI showed no significant correlation with umbilical venous blood gas values, IMA, UA/MCA Doppler indices, gestational age/weeks, or 5 min Apgar score. The UA S/D ratio and UA resistive index (RI) were negatively correlated with birth weight (p < 0.05). Umbilical venous pH was positively correlated with the 5 min Apgar score, whereas venous pCO₂ was negatively correlated with the 5 min Apgar score (both p < 0.05). Newborns with venous pH < 7.32 had higher cesarean delivery rates and higher rooming-in rates. Newborns admitted to the NICU had higher mean UA systolic velocity/diastolic velocity (S/D) and UA pulsatility index (PI) and lower venous pH. Conclusions: In low-risk term pregnancies, the UCI was not associated with cord blood gas parameters, IMA, or UA/MCA Doppler indices. These results suggest that the UCI may have limited clinical utility as a predictor of early neonatal acidosis or oxidative stress in a strictly low-risk population. Full article

Background/Objectives: Geographical differences exist in the clinical presentation of polycystic ovary syndrome (PCOS). The degree to which ovarian morphology contributes to this variability is unknown. Methods: This study compared ovarian ultrasound features between women with PCOS residing in two geographical regions (India and the United States) using stored de-identified ultrasound scans from 331 women with PCOS. Sonographic markers of interest included follicle number per ovary (FNPO), follicle number per cross-section (FNPS), ovarian volume (OV), ovarian area (OA), stromal area (SA), and stromal-to-ovarian area ratio (S/A). Results: Most participants in both regions met the accepted criteria for polycystic ovarian morphology (India 87% vs. U.S. 83%). The U.S.-based group had a higher prevalence of follicle excess (41% in U.S. vs. 29% in India; p = 0.037), whereas the prevalence of ovarian enlargement was similar across groups (India 37% vs. U.S. 31%, p = 0.252). FNPS was higher in the U.S.-based group (p = 0.046), while the India-based group had higher OV (p = 0.010). SA and S/A did not differ between groups, albeit OA was slightly larger in women with PCOS from India (p = 0.022). Associations between ovarian morphology and menstrual cycle length (ρ = 0.16–0.25), hirsutism score (ρ = 0.19–0.23), and total testosterone (ρ = −0.33–0.42) were noted in both groups (p < 0.05). Conclusions: Some variation in ovarian morphology may exist across geographic regions. However, the degree of variability is unlikely to warrant regional definitions for polycystic ovarian morphology at this time. Full article

Polycystic ovary syndrome (PCOS) is an endocrine condition affecting 8–13% of reproductive-aged women globally. Psychological features of PCOS are often overlooked despite their association with mental health complications. This systematic review synthesises existing evidence of psychological interventions for women with PCOS. Database searches returned 4982 articles, of which 20 papers were eligible; 12 studies were meta-analysed. Compared to control, psychological interventions had statistically beneficial effects on change from baseline values for depression, PCOS-specific quality of life, general health, and body image. Significant improvements were found in all PCOS Questionnaire (PCOSQ) domains except acne, yet the importance of these differences in clinical practice was indeterminable. Despite statistical effects, the quality of evidence was judged as low/very-low due to between study heterogeneity, risk of bias, and imprecision in effect estimates. Future studies should focus on rigorously designed, well-reported trials, in order to address the uncertainty around the effectiveness of psychological interventions. The protocol of this systematic review was prospectively registered on the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023472417). Full article

Background/Objectives: Lifestyle interventions are first-line treatment for women with polycystic ovary syndrome (PCOS) to improve metabolic health. Impacts on reproductive function are less clear. Previous research has been limited by inconsistencies in evaluation of ovulatory function and lack of comparisons between women with and without PCOS. Methods: The present study implemented a prospective clinical trial of 28 women (PCOS, N = 10 and Non-PCOS Control, N = 18) undergoing a 1-month baseline assessment followed by a 6-month hypocaloric dietary intervention. Results: Both groups reached clinically meaningful weight loss with the intervention (PCOS group: 6.5 ± 5.5%; Non-PCOS Control group: 10.0 ± 4.7%). Largest follicle diameter and growth rate of ovulatory dominant follicle, menstrual cycle length and luteal phase length did not change during the intervention in either group (all p > 0.05). The Non-PCOS Control group had increased mid-luteal phase progesterone levels and secretory phase maximum endometrial thickness during the intervention (all p < 0.05), whereas the PCOS group showed a reduction in follicular phase length (p < 0.05). Additionally, changes in ovulatory function and endometrial development were not associated with the rate of weight loss (all p > 0.05). Conclusions: This study demonstrates that women with PCOS are unlikely to experience changes in menstrual cyclicity and endometrial development with a short-term hypocaloric dietary intervention. The shortening of the follicular phase suggests that women with PCOS may need a longer intervention to achieve clinically meaningful improvements in ovulatory function and endometrial health. Full article

Female infertility diseases such as polycystic ovary syndrome (PCOS), endometriosis, diminished ovarian reserve (DOR), and recurrent implantation failure (RIF) have different clinical phenotypes. However, they might be epigenetically convergent, and thus the therapeutic targets may be potential. This study utilized transcriptome data, microRNA (miRNA), and DNA methylation data from the granulosa cells of four Gene Expression Omnibus (GEO) datasets, GSE138518, GSE105765, GSE232306, and GSE92324, to conduct integrated bioinformatics analysis. We focused on differentially expressed genes (DEGs), constructed a miRNA–mRNA network, performed ROC curve analysis, and conducted function enrichment and drug repurposing studies. Our findings identified eight dysregulated genes (H19, SULT1A4, HCK, SPI1, CARD16, NFE2, LST1, and KRT8) common to PCOS, DOR, and RIF, which may serve to distinguish PCOS specifically. Moreover, these DEGs are associated with pathways such as innate immune activation, inflammatory responses, the NOD-like receptor signaling pathway, and Fc gamma R-mediated phagocytosis. Notably, MiRNAs differentially expressed in endometriosis (specifically hsa-miR-202-5p and hsa-miR-141-3p) were found to directly target this gene set, highlighting the role of epigenetic regulation across infertility diseases. Additionally, our drug repurposing analysis identified several FDA-approved drugs, including Abacavir and Peginterferon Alfa-2b, suggesting that the HCK gene may be a viable target for drug development to address female infertility. Furthermore, we identified 192 genes that correlated with DNA methylation and expression levels in PCOS. Thus, this study underscores the epigenetic convergence of different female infertility diseases and highlights potential biomarkers and therapeutic options that could enhance treatment in reproductive medicine. Full article

Fatty acid amide hydrolase (FAAH) is a central component of the endocannabinoid system (ECS), where it primarily regulates intracellular levels of anandamide (AEA) through enzymatic hydrolysis. Although FAAH has been extensively studied in neural and immune contexts, its involvement in female reproductive physiology is receiving increasing attention. Accumulating evidence indicates that FAAH participates in several important ovarian processes, including follicular development, steroid hormone synthesis, ovulation, and luteal function. In this review, we outline the biochemical properties of FAAH and its spatial distribution in ovarian tissues, with a particular focus on how FAAH-mediated AEA metabolism contributes to intraovarian signaling. Furthermore, we highlight the potential implications of altered FAAH activity in ovarian disorders such as polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), and infertility. By integrating molecular observations with clinical findings, this work provides updated perspectives on FAAH as both a physiological regulator and a potential therapeutic target in reproductive medicine. Full article

Background/Objectives: Cryopreservation technology used in assisted reproductive technology (ART) has significantly improved live birth rates by enabling multiple embryo transfers with frozen embryos from a single ovarian stimulation cycle. However, there is conflicting data on the effect of prolonged cryopreservation of human blastocysts. Methods: This Danish nationwide cohort study includes all frozen embryo transfers (FETs) from 1 January 2012 to 31 March 2019. Biochemical pregnancy, clinical pregnancy, and live births were analyzed based on blastocyst storage time. Blastocyst storage time was stratified into five groups, ≤3 month, 4–6 months, 7–12 months, 13–24 months, and ≥25 months, with the shortest (≤3 months) as the reference. We also examined the risk of preterm birth, small and large for gestational age (SGA and LGA), and congenital malformations among live-born children. Multivariable analysis was used to estimate the odd ratios of the reproductive outcomes, accounting for potential confounders. Results: We identified 7042 women with 12,599 FETs. Characteristics of women at embryo transfer did not vary significantly by storage time, except for polycystic ovarian syndrome (PCOS), which increased from 2.6% in the reference group to 6.7% in the ≥25-month group. The clinical pregnancy rate was 35.7%. Blastocyst storage time did not significantly affect biochemical pregnancy rates, with adjusted odds ratios (aORs) of 0.94 (95% CI: 0.80–1.11) to 0.96 (95% CI: 0.82–1.12) for the 13–24-month and ≥25-month groups, respectively. Clinical pregnancy rates also did not decrease with storage time (aOR 0.96, 95% CI: 0.82–1.13) for ≥25 months. The live birth rate was 28.6%, with no significant decrease during storage (aOR 0.89, 95% CI: 0.75–1.06). However, the risk of LGA was slightly, but non-significantly, increased (aOR: 1.42, 95% CI: 0.84–2.42) in the ≥25-month group, whereas the aOR of SGA and congenital malformations was not increased. Conclusions: Our data indicates that storing blastocysts for a period of 25 months does not significantly affect pregnancy chances following assisted reproductive technology treatment. Full article

Background: Optimizing pregnancy outcomes while minimizing gonadotropin exposure and treatment burden remains a major goal in ovulation induction for intrauterine insemination (IUI), particularly for patients with polycystic ovary syndrome (PCOS) or high ovarian reserve. Sequential protocols combining early letrozole with late-onset recombinant FSH (rFSH) have been proposed to enhance efficiency while reducing medication requirements. However, real-world comparative data adjusting for baseline differences are limited. Methods: This retrospective comparative cohort study included 764 IUI cycles performed between January 2022 and October 2025. Cycles were stimulated either with conventional rFSH (n = 372) or letrozole plus late-onset rFSH (n = 392). The primary outcome was pregnancy per cycle, defined by a positive serum β-hCG. Secondary outcomes included clinical pregnancy, total gonadotropin dose, endometrial thickness, cycle cancelation, and obstetric outcomes. Confounding was addressed using multivariable logistic regression, propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and doubly robust estimation. Results: The crude pregnancy rate was higher in the letrozole plus late rFSH group compared with conventional rFSH (14.8% vs. 9.9%, p = 0.042). Women in the sequential stimulation group had higher AMH levels, higher antral follicle counts, and a higher prevalence of PCOS (32.4% vs. 16.3%, p = 0.001). After adjustment for age, ovarian reserve, and other baseline characteristics using regression, PSM, and IPTW, the stimulation protocol was not independently associated with pregnancy (adjusted OR 1.09, 95% CI 0.68–1.74; p = 0.657). Female age remained the strongest predictor of pregnancy (adjusted OR 0.70 per year increase; p < 0.001). The sequential protocol required a significantly lower total gonadotropin dose (median 375 IU vs. 750 IU; p < 0.001) while maintaining comparable cycle cancellation and safety outcomes. Conclusions: Sequential stimulation with letrozole plus late-onset rFSH achieves pregnancy outcomes comparable to conventional rFSH stimulation while significantly reducing gonadotropin requirements. After adjustment for PCOS status and ovarian reserve, the protocol itself did not independently influence pregnancy, suggesting that crude differences reflected baseline imbalances rather than true treatment effects. This approach represents a clinically efficient, gonadotropin-sparing option for IUI, particularly in patients at risk for excessive ovarian response. Full article

Background: Ovarian granulosa cells (GCs) play a pivotal role in folliculogenesis, and their dysfunction is central to disorders such as polycystic ovary syndrome (PCOS) and premature ovarian failure (POF). MicroRNAs (miRNAs) have emerged as crucial post-transcriptional regulators of GC homeostasis. Method: This review synthesizes current evidence by systematically analyzing relevant studies, integrating data from in vitro GC models, animal experiments, human cell lines, and clinical samples to elucidate the specific mechanisms by which miRNAs regulate GCs. Results: miRNAs precisely modulate GC proliferation, apoptosis, steroidogenesis, and oxidative stress responses by targeting key signaling pathways (e.g., PI3K/AKT/mTOR, TGF-β/SMAD) and functional genes (e.g., TP53, CYP19A1). Exosomal miRNAs serve as vital mediators of communication within the follicular microenvironment. To date, nearly 200 miRNAs have been associated with PCOS. Conclusions: miRNAs constitute a decisive regulatory network governing GC fate, offering promising therapeutic targets for PCOS and POF. However, significant challenges remain, primarily miRNA pleiotropy and the lack of follicle-specific delivery systems. Future clinical translation requires rigorous validation in human-relevant models. Full article

Polycystic Ovary Syndrome (PCOS) is characterized by a self-perpetuating vicious cycle between insulin resistance (IR) and hyperandrogenism (HA). While lifestyle management remains the internationally recommended first-line treatment, current clinical management, primarily relying on combined oral contraceptives and metformin, offers symptomatic relief or “masking” of the phenotype but fails to adequately disrupt this core pathophysiological loop, while also carrying potential intergenerational safety concerns. This review systematically evaluates the paradigm shift toward mechanism-based precision medicine. First, we analyze emerging precision-targeted therapies that intervene in specific pathological nodes: (1) metabolic regulators (e.g., GLP-1RAs, SGLT2i, and brown adipose tissue (BAT) activators) that target systemic glucotoxicity and the novel “BAT-Ovarian axis”; (2) neuroendocrine modulators (e.g., NK3R antagonists) that act as negative modulators of the hyperactive GnRH pulse generator; and (3) innovative androgen synthesis inhibitors (e.g., Artemisinins) that utilize a degradation-at-source mechanism. Complementing these, we explore the strategic value of Natural Products through the lens of “Network Pharmacology”, highlighting their ability to restore systemic homeostasis via multi-target modulation. Finally, we address critical translational challenges, specifically the need to establish long-term reproductive and offspring safety, providing a roadmap for developing true disease-modifying treatments for PCOS. Distinct from reviews limited to isolated therapeutic modalities, this article uniquely bridges current clinical management with emerging organ-specific precision targets and natural product networks. Full article

Objectives: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder with diverse pathogenetic mechanisms and clinical manifestations. Phenotype D PCOS is characterized by oligomenorrhoea and polycystic ovaries without hyperandrogenism. Altered adipokine profiles may contribute to reproductive and metabolic disturbances. Chemerin is an adipokine involved in inflammatory and metabolic processes. It remains unclear whether altered chemerin levels in PCOS reflect metabolic dysfunction alone or are directly associated with hyperandrogenism. The aim of this study was to compare serum chemerin levels in women with normoandrogenic PCOS and a control group. Methods: This cross-sectional preliminary study included 49 women with phenotype D PCOS and 40 healthy, age- and body mass index (BMI)-matched controls. Anthropometric, biochemical, hormonal parameters, and serum chemerin concentrations were assessed. Results: Serum chemerin concentrations did not differ significantly between the groups. In the PCOS group, the 95% confidence interval ranged from 198.61 to 234.37, while in the controls, it ranged from 187.13 to 216.21. In women with PCOS, chemerin showed significant positive correlations with weight, BMI, waist and hip circumference, total adipose tissue, and both gynoid and android fat content. Positive correlations were also observed with highly sensitive C-reactive protein (hs-CRP), insulin, glucose, triglycerides, and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and a negative correlation was found with high-density lipoprotein (HDL) cholesterol. Chemerin was weakly negatively correlated with sex hormone binding globulin (SHBG) and positively correlated with the free androgen index (FAI). In the control group, chemerin correlated positively with CRP, insulin, triglycerides, total and gynoid adipose tissue, and negatively correlated with HDL cholesterol and SHBG. Conclusions Although chemerin levels did not differ from controls, chemerin was associated with metabolic and inflammatory markers in both groups. These findings should be considered preliminary due to the limited sample size. Chemerin may reflect metabolic and inflammatory status rather than hyperandrogenism in normoandrogenic PCOS. Full article

Women of reproductive age, especially those with polycystic ovarian syndrome (PCOS), often use glucagon-like peptide-1 receptor agonists (GLP-1RAs) to improve their metabolic functions. A growing body of evidence suggests that GLP-1R signaling may directly affect ovarian physiology, influencing granulosa cell proliferation, survival pathways, and steroidogenic production, in addition to its systemic metabolic effects. Nonetheless, there is a limited comprehension of the molecular mechanisms that regulate these activities and their correlation with menstrual function, reproductive potential, and assisted reproduction. This comprehensive review focuses on ovarian biology, granulosa cell signaling networks, steroidogenesis, and translational fertility outcomes, integrating clinical, in vivo, and in vitro information to elucidate the effects of GLP-1 receptor agonists on reproductive health. We conducted a thorough search of PubMed, Scopus, and Web of Science for randomized trials, prospective studies, animal models, and cellular experiments evaluating the effects of GLP-1RA on reproductive or ovarian outcomes, in accordance with PRISMA criteria. The retrieved data included metabolic changes, androgen levels, monthly regularity, ovarian structure, granulosa cell growth and death, FOXO1 signaling, FSH-cAMP-BMP pathway activity, and fertility or IVF results. Clinical trials shown that GLP-1 receptor agonists improve menstrual regularity, decrease body weight and central adiposity, increase sex hormone-binding globulin levels, and lower free testosterone in overweight and obese women with PCOS. Liraglutide, when combined with metformin, significantly improved IVF pregnancy rates, whereas exenatide increased natural conception rates. Mechanistic studies demonstrate that GLP-1R activation affects FOXO1 phosphorylation, hence promoting granulosa cell proliferation and anti-apoptotic processes. Incretin signaling altered steroidogenesis by reducing the levels of StAR, P450scc, and 3β-HSD, so inhibiting FSH-induced progesterone synthesis, while simultaneously enhancing BMP-Smad signaling. Animal studies demonstrated both beneficial (enhanced follicular growth, anti-apoptotic effects) and detrimental results (oxidative stress, granulosa cell death, uterine inflammation), indicating a context- and dose-dependent response. GLP-1 receptor agonists influence female reproductive biology by altering overall physiological processes and specifically impacting the ovaries via FOXO1 regulation, steroidogenic enzyme expression, and BMP-mediated FSH signaling. Preliminary clinical data indicate improved reproductive function in PCOS, as seen by increased pregnancy rates in both natural and IVF cycles; nevertheless, animal studies reveal a potential risk of ovarian and endometrial damage. These results highlight the need for controlled human research to clarify reproductive safety, molecular pathways, and optimum therapy timing, particularly in non-PCOS patients and IVF settings. Full article

Background: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder, with a prevalence of approximately 16% in Saudi Arabia. PCOS is associated with various health complications. Assessing the quality of life (QoL) of women with PCOS is crucial for effective management. Objectives: This study aims to translate and validate the Polycystic Ovary Syndrome Quality of Life scale (PCOSQOL) into Arabic for use among Arabic-speaking women. The study was designed to evaluate the psychometric properties of the Arabic PCOSQOL, including its reliability, validity, and responsiveness. Methods: A cross-sectional study was conducted among 207 Saudi women diagnosed with PCOS. Participants were recruited from family medicine and obstetrics and gynecology clinics at King Saud University Medical City, Riyadh, through an online survey. The PCOSQOL was translated into Arabic following the World Health Organization’s (WHO) forward–backward translation protocol. Psychometric evaluation included internal consistency, test–retest reliability (ICC), and construct validity. Results: The Arabic PCOSQOL demonstrated excellent psychometric performance, with high internal consistency (Cronbach’s α = 0.951) and good-to-excellent test–retest reliability (ICC = 0.760–0.885). Construct validity was supported by a four-factor structure explaining 62.5% of the total variance (KMO = 0.92; Bartlett’s p < 0.001). The subscales showed strong factor loadings (0.49–0.97). Older women (>25 years), married participants, and residents of the western and central regions reported significantly better quality of life (p < 0.05). Conclusions: The Arabic version of the PCOSQOL demonstrated excellent reliability, validity, and stability, confirming its suitability for assessing quality of life among Arabic-speaking women with PCOS. This validated tool can support both clinical practice and future research across Arabic populations. Full article