OBJECTIVE: To compare dydrogesterone versus levonorgestrel-releasing intrauterine system (LNG-IUS) for abnormal uterine bleeding (AUB) management with long-term follow-up and etiology-stratified analysis. METHODS: This s...OBJECTIVE: To compare dydrogesterone versus levonorgestrel-releasing intrauterine system (LNG-IUS) for abnormal uterine bleeding (AUB) management with long-term follow-up and etiology-stratified analysis. METHODS: This single-center retrospective cohort study analyzed reproductive-aged women with International Federation of Gynecology and Obstetrics (FIGO)-classified AUB receiving dydrogesterone ( = 131) or LNG-IUS ( = 118). Propensity score matching balanced baseline covariates between groups ( = 104 pairs). Primary outcomes were bleeding control rates (composite: hemoglobin increase ≥ 1.5 g/dL, ≥ 50% Pictorial Blood Loss Assessment Chart [PBAC] reduction, no rescue interventions) at 3 and 12 months. Secondary outcomes included 24-month recurrence and adverse events (AEs). RESULTS: LNG-IUS demonstrated superior 3-month bleeding control versus dydrogesterone (82.7% vs. 65.4%; relative risk [RR] 1.26, 95% confidence interval [CI] 1.08-1.48; = 0.002). At 12 months, bleeding control rates were comparable between groups (78.8% vs. 72.1%; RR 1.09, 95% CI 0.96-1.24; = 0.17). LNG-IUS significantly reduced 24-month recurrence risk (hazard ratio [HR] 0.48, 95% CI 0.32-0.72; < 0.001), particularly for structural AUB (HR 0.39, 95% CI 0.24-0.64). Subgroup analysis revealed LNG-IUS superiority in adenomyosis at 12 months (88.2% vs. 60.0%; RR 1.47, 95% CI 1.24-1.74; < 0.001) but comparable efficacy in nonstructural AUB (76.6% vs. 72.9%; RR 0.95, 95% CI 0.78-1.16; = 0.63). Dydrogesterone exhibited higher systemic AEs (28.2% vs. 13.6%; = 0.003), while LNG-IUS had device-related events including expulsion (5.1%). CONCLUSION: LNG-IUS offers superior short-term bleeding control and sustained long-term recurrence prevention, especially for structural AUB. Dydrogesterone effectively manages nonstructural etiologies but carries higher systemic adverse event rates. Treatment selection should be etiology-guided, balancing immediate symptom control versus recurrence prevention and individualized safety considerations.
Premature ovarian insufficiency (POI) is a multifactorial disease characterized by premature depletion of ovarian follicles, leading to impaired ovarian function and increased risk of systemic diseases such as osteoporos...Premature ovarian insufficiency (POI) is a multifactorial disease characterized by premature depletion of ovarian follicles, leading to impaired ovarian function and increased risk of systemic diseases such as osteoporosis and cardiovascular disease. Although POI significantly impacts women's reproductive health and increases the risk of systemic diseases, little is known about its potential mechanisms, which limits early diagnosis and treatment options. -acetyltransferase 10 (NAT10), a key regulator of RNA acetylation, plays a crucial role in gene expression, cellular homeostasis, and stress response. This review explores the role of NAT10 in POI, emphasizing its involvement in cell apoptosis, autophagy, ferroptosis, inflammation, oxidative stress, and oocyte maturation disorders. Evidence reveals the dual role of NAT10 in regulating cell damage, balancing protective antioxidant defense and pro-apoptotic/inflammatory pathways depending on the cellular context. Dysregulation of NAT10 suggests its potential utility as a biomarker for early POI diagnosis. Furthermore, NAT10 inhibitors such as Remodelin may reduce ovarian cell damage by modulating apoptosis, inflammation, and oxidative stress. While these findings highlight NAT10 as a promising diagnostic and therapeutic target, challenges remain due to the complexity of its mechanisms and the need for more specific inhibitors. Translating these insights into clinical practice requires integrating molecular and clinical research to refine NAT10-based strategies. This review underscores the pivotal role of NAT10 in the pathophysiology of POI, paving the way for precision medicine and novel therapies targeting NAT10 to address ovarian dysfunction.
BACKGROUND: Endometriosis (EMs) is a common gynecological disorder associated with infertility. EMs patients often require assisted reproductive technology (ART) but exhibit lower success rates. This study aimed to chara...BACKGROUND: Endometriosis (EMs) is a common gynecological disorder associated with infertility. EMs patients often require assisted reproductive technology (ART) but exhibit lower success rates. This study aimed to characterize the follicular fluid microbiome in EMs patients undergoing in vitro fertilization (IVF) and provide insights into mechanisms underlying lower pregnancy rates. METHODS: Follicular fluid samples were collected from EMs patients and control subjectsundergoing IVF. Microbial DNA was subjected to 16S rRNA gene sequencing. Bioinformatic analyses, including alpha and beta diversity analysis, microbial composition profiling and biomarker identification, were performed. RESULTS: The follicular fluid microbiome in EMs patients exhibited altered alpha and beta diversity compared to controls. Distinct microbial compositions were observed at various taxonomic levels. Differentially abundant taxa were identified as potential biomarkers for EMs. Microbial profiles were associated with clinical parameters such as oocyte quality and fertilization rates. Models based on microbial profiles were constructed to elucidate the relationship between EMs and IVF outcomes. Functional predictions suggested alterations in metabolic pathways in the follicular fluid microbiome of EMs patients. CONCLUSIONS: This study revealed significant alterations in the follicular fluid microbiome of EMs patients, providing a basis for further research into the role of the microbiome in EMs-related infertility.
OBJECTIVE: To evaluate the effect of intrauterine infusion of platelet-rich plasma (PRP) on luteal support and pregnancy outcomes in patients with thin endometrium undergoing frozen-thawed embryo transfer (FET). METHODS:...OBJECTIVE: To evaluate the effect of intrauterine infusion of platelet-rich plasma (PRP) on luteal support and pregnancy outcomes in patients with thin endometrium undergoing frozen-thawed embryo transfer (FET). METHODS: A total of 160 patients with thin endometrium undergoing FET from March 2023 to March 2024 were assigned to the observation group (PRP infusion, = 80) or the control group (conventional treatment, = 80). All patients underwent hormone replacement therapy cycles,with PRP infused on days 9, 11, and 13 in the observation group. Outcomes included endometrial thickness, uterine hemodynamic parameters (PI, RI), PBAC-assessed menstrual volume, pregnancy outcomes, and embryology-related variables. Logistic regression identified independent factors associated with clinical pregnancy. Adverse events were also recorded. RESULTS: Post-treatment, the observation group had greater endometrial thickness and lower PI and RI values than the control group. PBAC scores, clinical pregnancy rate (36.25% . 21.25%), and live birth rate (25.00% . 12.50%) were significantly higher, while preterm birth rate did not differ. Embryo transfer-related variables were comparable between groups. Multivariate analysis identified PRP infusion and endometrial thickness at transfer as independent protective factors for clinical pregnancy, whereas advanced age was an unfavorable factor. No obvious adverse events occurred. CONCLUSION: PRP infusion enhances endometrial receptivity by improving thickness and blood perfusion, thereby increasing pregnancy and live birth rates in thin endometrium patients undergoing FET. It is safe and may be used as an effective adjunct in endometrial preparation.
OBJECTIVE: The purpose of this systematic review and meta-analysis is to assess the association of handgrip strength (HGS) in subjects with high-normal or mildly elevated and low-normal serum uric acid (SUA) reported by...OBJECTIVE: The purpose of this systematic review and meta-analysis is to assess the association of handgrip strength (HGS) in subjects with high-normal or mildly elevated and low-normal serum uric acid (SUA) reported by quartiles. METHODS: The research protocol was registered at PROSPERO (CRD420251050351). We searched four databases to obtain relevant articles reporting HGS by SUA quartiles in subjects without gout. Outcomes were compared by combining the third and fourth SUA (higher) quartiles versus the first and second (low) quartiles. The risk of bias was assessed using the Newcastle‒Ottawa Scale, and heterogeneity with the test. The results are reported as the mean difference (MD), standardized MD (SMD), or odds ratio (OR). RESULTS: Seven cross-sectional studies, including 18,765 adult subjects with higher SUA quartiles showed significant higher HGS (SMD: 0.21, 95% confidence interval [CI]: 0.03, 0.39), body mass index (MD: 1.02 kg/m, 95% CI: 0.48, 1.55), total cholesterol (SMD: 0.14, 95% CI: 0.05, 0.24), LDL-cholesterol SMD: 0.13, 95% CI: 0.09, 0.17), and triglycerides (SMD: 0.26, 95% CI: 0.11, 0.41) than those with lower SUA quartiles. HDL-cholesterol was significantly reduced in subjects with higher SUA (SMD: -0.13, 95% CI: -0.20, -0.07). High SUA levels were associated with a drinking history (OR: 1.21, 95% CI: 1.10, 1.34) and hypertension (OR: 1.51, 95% CI: 1.15, 1.99). CONCLUSIONS: Subjects with higher normal SUA levels showed higher HGS compared to those with lower normal levels.
Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism and ovulatory dysfunction. Women with PCOS are at an increased risk for adverse pregnancy outcomes, such as miscarriage an...Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism and ovulatory dysfunction. Women with PCOS are at an increased risk for adverse pregnancy outcomes, such as miscarriage and preterm birth. Endometrial receptivity plays a pivotal role in embryo implantation. However, there has been limited review or discussion regarding potential alterations in endometrial receptivity in PCOS patients, the nature of these changes, and their underlying mechanisms. In this review, we aim to summarize the alterations in endometrial receptivity associated with PCOS, highlight the impact of PCOS on endometrial receptivity, and explore the underlying mechanisms. Abnormal expression of key receptivity markers has been observed in both PCOS patients and animal models, which may contribute to reduced endometrial receptivity. The factors leading to impaired endometrial receptivity in PCOS are multifaceted, including hormonal imbalances, metabolic disturbances, chronic inflammation, and microbiota alterations. However, the intricate mechanisms behind PCOS-related endometrial dysfunction remain poorly understood. Further research is essential to unveil these complex mechanisms and improve fertility outcomes for women with PCOS.
OBJECTIVE: To investigate the associations of the neutrophil/albumin ratio (NAR) with type 2 diabetes mellitus (T2DM) in women with a history of gestational diabetes mellitus (GDM). METHODS: We conducted a cross-sectiona...OBJECTIVE: To investigate the associations of the neutrophil/albumin ratio (NAR) with type 2 diabetes mellitus (T2DM) in women with a history of gestational diabetes mellitus (GDM). METHODS: We conducted a cross-sectional study involving 782 participants from the National Health and Nutrition Examination Survey. Logistic regression analyses were performed to explore the relationship between NAR and T2DM, adjusting for various confounding factors across different models. Interaction analyses examined the modifying effects of socio-demographic characteristics on the relationship between NAR and T2DM. Mediation analyses were utilized to investigate whether key laboratory indicators and insulin resistance indices mediated the association between NAR and T2DM. RESULTS: Higher NAR levels were positively associated with T2DM risk. (OR[95%CI]:1.649[1.181,2.309], = 0.003). Mediation analyses revealed that the effect of NAR on T2DM was entirely mediated through the regulation of red cell distribution width (RDW Coefficient[95%CI]: 0.009[0.001,0.024], = 0.020) and high-density lipoprotein cholesterol (HDL-C Coefficient[95%CI]: 0.038[0.017,0.067], < 0.001). Besides, significant interactions and differences were observed in the relationship between NAR and T2DM risk based on body mass index (BMI) (NAR*BMI: interaction coefficient: -0.651, interaction = 0.027). In individuals with 25 kg/m ≤ BMI < 30 kg/m, NAR increased the risk of T2DM by regulating the insulin resistance index (HOMA-R) ([95%CI]: 2.220[0.653,3.787], = 0.007). CONCLUSION: This study revealed that among women with GDM history, NAR may influence the risk of T2DM through the modulation of RDW and HDL-C. Furthermore, NAR and BMI had a significant interaction affecting T2DM risk, particularly prominent in women with 25 kg/m ≤ BMI < 30 kg/m. Within this subgroup, NAR elevated the risk of T2DM via HOMA-R.
OBJECTIVE: This study aimed to investigate the mechanism of the involvement of USP33 in autophagic ferroptosis in endometriosis (EMs). METHODS: Endometrial stromal cells (ESCs) were isolated from 15 healthy controls and...OBJECTIVE: This study aimed to investigate the mechanism of the involvement of USP33 in autophagic ferroptosis in endometriosis (EMs). METHODS: Endometrial stromal cells (ESCs) were isolated from 15 healthy controls and 30 patients with EMs, which were designated NESCs and EESCs, respectively. Real-time PCR and Western blotting were utilized to determine USP33 expression as well as GPX4, LC3II/LC3I, NCOA4, FTH1, LAST1, p-LAST1, YAP, and p-YAP levels. Immunofluorescence was used to detect the colocalization of ferritin and LAMP2, as well as that of LC3 and ferritin. The levels of ROS, Fe, MDA, and GSH were measured to assess ferroptosis. An LDH assay was performed to evaluate cell death. A co-IP assay was implemented to identify the interaction between USP33 and LAST1 and detect the level of LAST1 ubiquitination. The stability of the protein was also detected via a cycloheximide (CHX) assay. RESULTS: USP33 was underexpressed in EMs patients. Loss of USP33 conferred resistance to ferroptosis in EESCs, as evidenced by increased proliferation; decreased levels of ROS, Fe, and MDA; elevated levels of GPX4 and GSH; and reduced cell death. In addition, USP33, which is localized in autophagosomes, was suggested to promote the degradation of ferritin in autophagosomes. Furthermore, USP33 repressed the Hippo-YAP pathway by suppressing LATS1 ubiquitination, thereby contributing to the reduced resistance of EESCs to ferroptosis. CONCLUSION: USP33 impedes the ubiquitination of LAST1 and represses the Hippo/YAP pathway, thus facilitating ferritinophagy and ferroptosis in EMs.
OBJECTIVE: To analyze the effects of melatonin on angiogenesis in cultured granulosa cells from women undergoing in vitro fertilization, comparing those with female-factor versus male-factor infertility. METHODS: Granulo...OBJECTIVE: To analyze the effects of melatonin on angiogenesis in cultured granulosa cells from women undergoing in vitro fertilization, comparing those with female-factor versus male-factor infertility. METHODS: Granulosa cells were obtained from 47 women undergoing in vitro fertilization treatment, including 31 women with female-factor (FFG) and 16 women with male-factor infertility (MFG). Cells from both groups were cultured and divided into four treatment conditions for 96 h: a) control (culture medium without melatonin); b) vehicle (melatonin diluent-ethanol); c) 0.1 µM melatonin; and d) 10 µM melatonin. Expression of 84 genes involved in angiogenesis signaling pathway was analyzed by real-time PCR. RESULTS: Cultured granulosa cells from both groups expressed aromatase and melatonin receptors. In both groups, cell proliferation peaked at 72 h when exposed to 10 µM melatonin. Of the 84 analyzed genes, three showed significant differential mRNA expression. In the MFG, melatonin at 10 µM upregulated VEGF-B mRNA expression in granulosa cells but downregulated PDGFA and HGF mRNA expression, in contrast to the higher expression of these genes in the FFG under identical conditions. CONCLUSION: Melatonin differentially modulates angiogenesis-related gene expression in granulosa cells, indicating that its effects may depend on infertility type and melatonin dose in women undergoing in vitro fertilization.
OBJECTIVE: We aimed to identify independent predictors of ongoing pregnancy in patients undergoing mild-OS FET cycles, focusing on follicular phase characteristics and luteal support regimens. METHODS: In this multicente...OBJECTIVE: We aimed to identify independent predictors of ongoing pregnancy in patients undergoing mild-OS FET cycles, focusing on follicular phase characteristics and luteal support regimens. METHODS: In this multicenter, retrospective cohort study conducted between January 2021 and August 2024 across Bahceci fertilization (IVF) centers in Türkiye, 489 FET cycles with mild-OS using letrozole were analyzed. Biochemical and ongoing pregnancy outcomes were assessed in relation to demographic characteristics, ovarian stimulation parameters, ovulation triggering strategies, and LPS approaches. Multivariate logistic regression was used to determine independent predictors. RESULTS: The overall biochemical and ongoing pregnancy rates were 58.5% and 43.4%, respectively. Subcutaneous progesterone (with or without vaginal route) improved biochemical pregnancy rates compared to vaginal-only LPS (67.1% vs. 52.7%, = 0.008), although this did not translate into significantly higher ongoing pregnancy rates. In adjusted models, only younger female age (OR = 0.94, 95% CI: 0.90 to 0.99, = 0.01) and a higher number of embryos transferred (OR = 2.00, 95% CI: 1.16 to 3.45, = 0.01) were independently associated with ongoing pregnancy. Follicular diameter, number of follicles >10 mm, estradiol and LH levels, or triggering with hCG did not significantly impact outcomes. CONCLUSION: In mild-OS FET cycles, while subcutaneous progesterone support may improve early implantation outcomes, ongoing pregnancy is primarily influenced by female age and embryo number. These findings support a flexible approach to LPS and triggering in mild-OS protocols without compromising clinical success.
BACKGROUND: Primary Ovarian Insufficiency (POI) impacts 3.5% of women under 40, with its etiology largely unknown. Piwi-interacting RNAs (piRNAs) have emerged as potential biomarkers for gynecological conditions, includi...BACKGROUND: Primary Ovarian Insufficiency (POI) impacts 3.5% of women under 40, with its etiology largely unknown. Piwi-interacting RNAs (piRNAs) have emerged as potential biomarkers for gynecological conditions, including POI. We hypothesized that hsa-piR-775 plays a critical role in POI pathogenesis by regulating FOXG1 expression. METHODS: We performed piRNA sequencing on serum samples from POI patients and controls using the Illumina sequencing platform. Bioinformatics analysis for target prediction was conducted using TargetScan and miRanda to identify potential downstream targets of differentially expressed piRNAs (DEPs). qPCR and luciferase reporter assays for validation to explore the function and targets of DEPs, with a focus on hsa-piR-775. RESULTS: Among 43 DEPs, hsa-piR-775 was notably upregulated in POI patients. Target gene prediction and enrichment analysis implicated FOXG1, a gene associated with ovarian function, as a potential target of hsa-piR-775. validation confirmed hsa-piR-775 can influence FOXG1 mRNA, reducing FOXG1 expression. These findings suggest hsa-piR-775 influences POI progression by modulating FOXG1 levels. CONCLUSION: We demonstrate that hsa-piR-775 is upregulated in POI and regulates FOXG1 expression, revealing a novel pathogenic mechanism. This supports piRNAs' potential as biomarkers and therapeutic targets in POI. Future studies should focus on validating these findings in larger cohorts and exploring piRNA-based therapeutic interventions for POI.
OBJECTIVE: Uterine peristalsis, which originates from sub-endometrial zone of myometrium, is observed at ultrasonography as a wave-like activity of endometrium. Increased uterine peristalsis is suggested to be related to...OBJECTIVE: Uterine peristalsis, which originates from sub-endometrial zone of myometrium, is observed at ultrasonography as a wave-like activity of endometrium. Increased uterine peristalsis is suggested to be related to decreased pregnancy rates in both fresh and frozen embryo transfer cycles. The aim of this study is to compare the effects of two different frozen embryo transfer preparation protocols on the frequency of uterine peristalsis and to evaluate the effect of peristalsis on pregnancy rates. METHODS: In this observational cohort study, 3-min transvaginal ultrasound videos were recorded one hour before embryo transfer in frozen embryo transfer cycles prepared by either artificial hormone treatment or aromatase inhibitor stimulation. Peristalsis frequency was assessed by reviewing videos at triple speed. Consequent pregnancy outcomes were also analyzed. RESULTS: During the study period of four months, a total of 147 patients with 99 artificial hormone treatments and 48 aromatase inhibitor-stimulated frozen embryo transfer cycles were included. The absence of uterine peristalsis was observed in 27.1% of the aromatase inhibitor-stimulated patients and 23.2% of the artificial hormone-treated patients ( = 0.68). Among those with peristalsis, the frequency was similar between groups (0.95 ± 0.59 and 0.98 ± 0.68 for the aromatase inhibitor-stimulated and artificial hormone treatment protocols, respectively; = 0.97). Peristalsis presence or frequency was not associated with pregnancy or live birth rates. CONCLUSIONS: In this study, uterine peristalsis frequency at frozen embryo transfer cycles did not differ between endometrial preparation protocols and showed no significant association with pregnancy outcomes. Further randomized studies are warranted.
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder affecting up to 18% of reproductive-aged women globally. Women with PCOS exhibit a significantly increased risk of miscarriage, indepe...BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder affecting up to 18% of reproductive-aged women globally. Women with PCOS exhibit a significantly increased risk of miscarriage, independent of obesity and assisted reproduction variables. The etiology of PCOS-related pregnancy loss is multifactorial. Nevertheless, current clinical interventions target isolated mechanisms and demonstrate limited efficacy in reducing miscarriage rates. OBJECTIVE: This review synthesize recent evidence connecting metabolic and immune dysregulation to pregnancy loss in PCOS and evaluate novel therapeutic strategies targeting immunometabolic pathways. CONTENT: This review first presents an overview of the mechanistic pathways implicated in PCOS-related miscarriage, including endocrine-metabolic dysfunction, immune-inflammatory imbalance, oxidative stress and ferroptosis, vascular and coagulation defects, and uterine-placental abnormalities. Both translational and clinical for interventions with dual metabolic-immune effects are highlighted, such as metformin, antioxidants likeN-acetylcysteine, anti-androgens, and combination regimens including aspirin with low-molecular-weight heparin (LMWH). Agents with mechanistic promise but limited exploration, such as glucagon-like peptide-1 (GLP-1) receptor agonists, selenium nanoparticles, and stem cell-based therapies, are also discussed. Future directions for PCOS pregnancy care are outlined, emphasizing the integration of immunometabolic biomarkers, advanced animal models, and mechanism-informed combination trials. CONCLUSION: PCOS-related miscarriage is increasingly recognized as resulting from dysregulation of immune-metabolic crosstalk. Mechanism-based, multidimensional strategies targeting this dual pathology represent a promising paradigm for preventing and managing pregnancy loss in women with PCOS.
OBJECTIVE: To evaluate the effect of oral contraceptive (OC) pretreatment on in vitro fertilization (IVF) outcomes in women with polycystic ovary syndrome (PCOS) undergoing the GnRH agonist (GnRH-a) long protocol, compar...OBJECTIVE: To evaluate the effect of oral contraceptive (OC) pretreatment on in vitro fertilization (IVF) outcomes in women with polycystic ovary syndrome (PCOS) undergoing the GnRH agonist (GnRH-a) long protocol, compared with other ovarian stimulation protocols. METHODS: This retrospective study included 121 women with PCOS, diagnosed according to the Rotterdam criteria, who underwent IVF/intracytoplasmic sperm injection (IVF/ICSI) between January and September 2018 at Beijing Obstetrics and Gynecology Hospital. Patients were assigned to one of four protocols: the OC pretreatment + GnRH-a long protocol (three cycles of OC), the standard GnRH-a long protocol, the GnRH antagonist protocol, or the GnRH-a ultralong protocol. Ovarian stimulation characteristics, embryo development, and clinical outcomes were compared among the groups. RESULTS: The GnRH-a ultralong protocol required significantly higher total Gn doses and longer stimulation duration than the OC + GnRH-a long protocol. Compared with the standard GnRH-a long protocol, OC pretreatment showed trends toward lower rates of moderate-to-severe ovarian hyperstimulation syndrome (OHSS) and higher biochemical and clinical pregnancy rates, though these differences were not statistically significant. No significant differences were observed among the groups for the number of retrieved oocytes, mature oocytes, fertilized oocytes, or normally developing embryos. CONCLUSION: In PCOS patients, OC pretreatment showed trends toward higher pregnancy rates and lower OHSS, without adverse effects on clinical outcomes. These findings highlight a potentially promising approach, warranting confirmation in larger, high-quality randomized controlled trials.
OBJECTIVE: To evaluate whether hypoxia-preconditioned human umbilical cord mesenchymal stem cells (hUCMSCs) can protect frozen-thawed human ovarian tissue via in vitro co-culture. METHODS: Frozen-thawed ovarian cortical...OBJECTIVE: To evaluate whether hypoxia-preconditioned human umbilical cord mesenchymal stem cells (hUCMSCs) can protect frozen-thawed human ovarian tissue via in vitro co-culture. METHODS: Frozen-thawed ovarian cortical pieces from 10 patients were randomly divided into a control group (no co-culture), ‑MSCs group (normoxia‑preconditioned hUCMSCs co-culture), and H‑MSCs group (hypoxia‑preconditioned hUCMSCs co-culture). Tissues in the co-culture groups were subjected to 48 h indirect Transwell co-culture. Apoptosis was assessed by TUNEL. Metabolic changes in the culture medium were measured, such as glucose consumption and lactate production, and AMH levels were determined. Oxidative stress in ovarian tissue was evaluated by measuring ROS and TAC. RNA-seq was performed, and key pathways were analyzed by GSEA. The protein expression of HIF-1α, VEGFA, GDF9, AKT, and p-AKT was examined by Western blot. RESULTS: Compared with both the control and N-MSCs groups, co-culture with H‑MSCs significantly reduced follicular atresia and apoptosis, while preserving a greater proportion of resting follicles. The H‑MSCs group presented lower glucose consumption and lactate production and elevated AMH levels in the culture medium. H‑MSCs markedly decreased reactive oxygen species (ROS) and enhanced total antioxidant capacity (TAC). Transcriptomic analysis showed that H‑MSCs induced a distinct gene expression profile characterized by upregulation of the HIF‑1 signaling pathway. H‑MSCs significantly upregulated HIF‑1α, VEGFA, and phosphorylated AKT at the protein level. CONCLUSIONS: This in vitro study showed that co-culture of ovarian tissue with H-MSCs provides stronger protection than N-MSCs. This effect likely involves the HIF-1α/VEGFA pathway, with enhanced pro-angiogenic signaling, reduced apoptosis and oxidative stress, and preservation of the follicular reserve.
OBJECTIVE: To assess the effects of a 12-week combined treatment with myo-inositol (2 g) and Banaba extract (48 mg) standardized to 1% corosolic acid (MBN) on insulin resistance (HOMA-IR) and hepatic insulin extraction i...OBJECTIVE: To assess the effects of a 12-week combined treatment with myo-inositol (2 g) and Banaba extract (48 mg) standardized to 1% corosolic acid (MBN) on insulin resistance (HOMA-IR) and hepatic insulin extraction index (HIEI) in overweight and obese postmenopausal women. METHODS: We conducted a retrospective observational study including 31 postmenopausal women (mean age 51 ± 1.2 years) attending the Gynecological Endocrinology Center of Modena, Italy. All patients received daily supplementation with MBN for 12 weeks. Hormonal and metabolic parameters-including fasting glucose, insulin, C-peptide, and HOMA-IR-were assessed before and after treatment. In addition, an oral glucose tolerance test (OGTT) was performed at both time points, with glucose, insulin, and C-peptide curves measured and corresponding area under the curve (AUC) values at 240 minutes calculated. HIEI was calculated as the insulin/C-peptide ratio. Data were analyzed globally and then stratified by family history of diabetes. RESULTS: After treatment, fasting insulin, HOMA-IR, and HIEI were significantly reduced. The OGTT showed a 23.5% decrease in glucose AUC, with greater reductions in insulin AUC (-42%) compared to C-peptide AUC (-16.8%), suggesting enhanced hepatic insulin clearance. Patients with a family history of diabetes showed reductions in insulin and C-peptide, while those without showed only a decrease in insulin and HIE, with no changes in C-peptide. CONCLUSIONS: Combined MBN supplementation improved insulin sensitivity and hepatic insulin clearance in overweight and obese postmenopausal women, with particularly pronounced effects in those with a family history of diabetes. These findings underscore the potential of targeted integrative strategies to mitigate insulin resistance in this population.