Journal of Ovarian Research最新文献

With the development of modern society and prolonged education, more women choose to delay their childbearing age, which greatly increases the number of women aged older than 35 years with childbearing needs. However, with increasing age, the quantity and quality of oocytes continue to fall, especially with increasing aneuploidy, which leads to a low in vitro fertilization (IVF) success rate, high abortion rate and high teratogenesis rate in assisted reproduction in women with advanced maternal age. In addition to genetics and epigenetics, follicular metabolism homeostasis is closely related to ovarian aging and oocyte aneuploidy. Glucose, lipid, and amino acid metabolism not only provide energy for follicle genesis but also regulate oocyte development and maturation. This review focuses on the relationships among follicular metabolism, oocyte aneuploidy, and ovarian aging and discusses potential therapeutic metabolites for ovarian aging.

Objective: To evaluate the pregnancy and perinatal outcomes of different phenotypes of polycystic ovary syndrome (PCOS) patients during the frozen embryo transfer (FET) cycles. Additionally, to analyze the T cell balance in the endometrium of PCOS patients and explore its relationship with various PCOS phenotypes.

Design: Retrospective cohort study.

Setting: A single academically affiliated reproductive medicine center.

Patients: 21,074 FET cycles were included and divided into two groups based on the diagnosis of PCOS. Patients with PCOS were further categorized into four phenotypic groups: PCOM + HA + OA, PCOM + HA, PCOM + OA, and HA + OA. Endometrial biopsies from 21 PCOS patients and 26 controls were obtained to analyze T cell subsets.

Methods: Pregnancy and perinatal outcomes, as well as T cell subset abundance were compared between women with and without PCOS. Multiple logistic regression models were employed to adjust for confounding factors impacting pregnancy-related outcomes. Flow cytometry was utilized to analyze the abundance of T cell subsets.

Main outcome measures: Pregnancy and perinatal outcomes were assessed. T cell subsets including CD4⁺CD8^-T cells, CD4^-CD8⁺T cells, Th1, Th2, Th17 and Treg cells in the endometrium were determined by flow cytometry.

Results: There was a significantly increased incidence of miscarriage, hypertensive disorders of pregnancy (HDP), preterm birth (PTB), and even fetal malformations across different phenotypes of PCOS women, especially those with the hyperandrogenic phenotype. Th1 cells decreased while Th2 cells increased significantly in the PCOS endometrium.

Conclusions: The unfavorable pregnancy and perinatal outcomes in FET cycles and T cell imbalance both suggest the endometrial dysfunction of PCOS patients, especially those with the hyperandrogenic phenotype.

Background: Cyclophosphamide (CTX) often induces oocyte and granulosa cell injury, leading to fertility loss in young female cancer survivors. Deciphering the mechanisms underlying follicular cell injury could offer novel insights into fertility preservation. Granulosa cells represent the most abundant cell type within the follicles and can be generally categorized as cumulus granulosa cells (CGCs) and mural granulosa cells (MGCs). Despite the essential roles of granulosa cells in supporting ovarian function in physiological conditions, their distinct lineage-specific responses to CTX remains elusive.

Results: Here, we performed a genome-wide transcriptome analysis of murine mural and cumulus granulosa cells before and after CTX administration. Compared with MGCs, CGCs exhibited higher basal mammalian target of rapamycin (mTOR) activity and an increased DNA damage response post-injury. Pharmacological mTOR suppression or RNA interference-mediated gene silencing of Raptor, a key component of the mTORC1 complex, significantly reduced DNA damage in granulosa cells induced by 4-HC, an activated form of CTX. Notably, by examining human granulosa cells in response to 4-HC, our results uncovered a conserved role of mTOR inhibition in ovarian protection.

Conclusions: Taken together, our findings reveal that intrinsic variations in mTOR activity in CGC and MGC lineages determine their differential responses to CTX. Targeting this signaling pathway may prove beneficial in mitigating CTX-induced granulosa cell apoptosis and protecting against ovarian injury.

Background: Diminished ovarian reserve (DOR), a major cause of female infertility, is closely linked to insulin resistance (IR). Traditional Chinese Medicine (TCM) approaches, such as the Gengnianchun (GNC) formula, focus on restoring ovarian function by improving IR and regulating hormonal balance. Despite GNC's demonstrated efficacy, its precise therapeutic mechanisms remain unclear.

Objective: This study aims to elucidate the mechanisms by which GNC ameliorates IR-induced DOR through comprehensive pharmacological and experimental validation.

Methods: The study combined Liquid chromatograph mass spectrometer (LC-MS), ultra-performance liquid chromatography (UPLC-TOF-MS/MS), network pharmacology, and molecular docking to identify active components and key therapeutic targets of GNC. Functional enrichment analyses (GO and KEGG) and molecular docking studies were performed. A high-fat diet-induced mouse model of IR-DOR was established, followed by GNC treatment at varying doses. Therapeutic effects were evaluated via qRT-PCR, western blot, immunofluorescence, and histological analysis.

Results: GNC contains 219 active ingredients targeting 53 genes associated with IR-induced DOR. KEGG analysis revealed the estrogen signaling pathway as a key mechanism. High-dose GNC significantly improved IR and ovarian reserve by increasing AKT1, ESR1, and ESR2 expression, as confirmed by qRT-PCR, western blot and immunofluorescence analysis. These findings indicate that GNC enhances insulin sensitivity, promotes follicular development, and restores ovarian function.

Conclusions: This study demonstrates for the first time that GNC alleviates IR-induced DOR by modulating the estrogen signaling pathway and activating key molecular targets. These results provide a foundation for clinical research and the development of novel therapeutic strategies for DOR.

Clinical trial number: Not applicable.

Background: The relationship between Metabolic Syndrome (MetS) and ovarian dysfunction has been widely reported in observational studies, yet it remains not fully understood. This study employs genetic prediction methods and utilizes summary data from genome-wide association studies (GWAS) to investigate this causal link.

Methods: We employed a bidirectional two-sample Mendelian Randomization (MR) analysis utilizing MetS and ovarian dysfunction summary data from GWAS. Inverse variance weighted (IVW) was employed as the primary MR method, supplemented by Weighted Median, Weighted Mode, and MR-Egger methods. The robustness of the results was further assessed through sensitivity analyses including MR-Egger regression, MR-PRESSO, Cochran's Q, and leave-one-out test.

Results: Our MR analysis identified a causal relationship between genetically determined insulin resistance (OR = 0.26, 95% CI: 0.08-0.89, P = 0.03), waist circumference (OR = 2.14, 95% CI: 1.45-3.15, P < 0.001), BMI (OR = 2.1, 95% CI: 1.56-2.83, P < 0.001) and ovarian dysfunction. Conversely, reverse MR analysis confirmed causal effects of ovarian dysfunction on metabolic syndrome (OR = 0.98, 95% CI: 0.97-0.99, P < 0.001) and waist circumference (OR = 0.99, 95% CI: 0.98-0.99, P = 0.02). The results of MR-Egger regression test indicated that the whole analysis was not affected by horizontal pleiotropy. Additionally, the MR-PRESSO test identified outliers in SNPs, but after removal of outliers, results remained unchanged.

Conclusion: This study reveals a bidirectional causal connection between metabolic syndrome and ovarian dysfunction via genetic prediction methods. These findings are crucial for advancing our understanding of the interactions between these conditions and developing strategies for prevention and treatment.

Objective: Mechanism underlying the etiology of polycystic ovary syndrome (PCOS) is still debatable. Present study explores the link between iron-mediated ferroptosis and PCOS.

Methodology: Blood samples were collected from 150 PCOS females along with healthy controls. Expression analysis of FTH1, NCOA4, GPX4, HAMP, A2M and HP genes was estimated by RT-qPCR. Serum was used for estimation of lipid peroxidation, peroxidase enzyme, ferritin and total protein.

Results: Relative expression of FTH1 (P < 0.05), HAMP (P < 0.01), GPX4, A2M, HP (P < 0.001) was downregulated and NCOA4 (P < 0.001) was upregulated in PCOS group compared to control. A significant difference was observed in mRNA expression of selected genes when ≤ 30year age group PCOS was compared to > 30year age PCOS group and their respective controls. Deregulation of gene expression was prominent in PCOS group with obese and overweight BMI compared to underweight and normal BMI group. Menstrual cycle length and marital status of PCOS females had no significant association with selected gene expression. Expression deregulation in targeted genes was observed in PCOS patients with complaints of either diabetes, high blood pressure or both. Increased level of lipid peroxidation, serum ferritin and total protein, while decreased peroxidase activity was observed in PCOS group (P < 0.001) compared to control.

Conclusion: The present study postulated the role of iron overload in trigger of ferroptosis following elevated lipid peroxidation and low peroxidase activity. Moreover, unveil the association of genes related to iron-regulating metabolism with etiology of underlying PCOS mechanism.

Background: Poor ovarian response (POR) is a challenging condition in assisted reproduction technology. Oral contraceptives (OCs) are commonly used to suppress gonadotropin hormone release in POR patients to synchronize the development of antral follicles before ovarian stimulation. Nevertheless, the question of whether such approach confers advantageous outcomes has elicited inconclusive results in previous studies. Therefore, the objective of this study was to investigate the effect of OCs pretreatment in low prognosis patients stratified by Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) criteria.

Methods: This retrospective cohort study included 2,222 patients undergoing their first IVF or ICSI cycle from January 2012 to April 2022. After propensity score matching, 369 patients were in the OC pretreatment group and 879 in the control group. Patients were divided into four subgroups based on the POSEIDON criteria. Comparisons of ovarian response and clinical outcomes were conducted, and multivariable logistic regression was used to assess the association between OCs pretreatment and live birth, clinical pregnancy, and pregnancy loss rates.

Results: Patients in POSEIDON group 1 who received OCs pretreatment exhibited a significant reduction in the dose and duration of gonadotropin administration, along with an increase in the number of oocytes retrieved, 2 pronuclei, available embryos, and good quality embryos, indicating an improvement in their ovarian response to exogenous gonadotropins. Additionally, the live birth rate (P = 0.030) and clinical pregnancy rate (P = 0.012) were significantly higher in the OCs pretreatment group. Multivariate logistic regression analysis demonstrated a positive association between OCs pretreatment and live birth rate (P = 0.008) and clinical pregnancy rate (P = 0.008). However, in POSEIDON group 2 to group 4, there were no significant differences in ovarian response or clinical outcomes between the OCs pretreatment group and the control group.

Conclusions: Administering OCs as pretreatment prior to ovarian stimulation using gonadotrophin releasing hormone antagonist protocol appears to be a more favorable approach than waiting for natural menses in low prognosis patients belonging to POSEIDON group 1.

Background: This study aimed to evaluate the predictive value of Prognostic Nutritional Index (PNI), Systemic Immunoinflammatory Index (SII), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) in patients with epithelial ovarian cancer ( EOC). Also, to explore the predictive value of a new scoring system combining PNI and SII (coPNI-SII) in patients with EOC.

Methods: In this study, 154 patients with EOC were analyzed and classified according to the best cut-off values for SII, PNI, PLR, and NLR. Spearman's rank correlation was used to analyze the correlation of variables. The Kaplan-Meier survival curve and log-rank test were used to investigate the relationship between inflammatory indicators and overall survival (OS), which was then followed by a multivariate Cox proportional hazards model. All patients were categorized into three groups based on PNI-SII scores. The coPNI-SII score ranged from 1 to 3 as follows: score of 1, high PNI (≥ 48.98) and low SII(< 998.87); score of 2, high PNI and high SII or low PNI and low SII; score of 3, low PNI and high SII. To assess the prognostic value of coPNI-SII in patients with EOC.

Results: The areas under the ROC curves for SII, PNI, PLR, NLR, and coPNI-SII were 0.814, 0.814, 0.780, 0.769, and 0.860, respectively. The optimal cut-off values for SII, PNI, PLR, and NLR were 998.87, 48.98, 217.63, and 2.61, respectively. The Kaplan-Meier analysis showed that the OS of the patients in the high PNI group, low SII group, low NLR group, and low PLR group was significantly higher than that of the patients in the low PNI group, high SII group,high NLR group, and high PLR group (p < 0.01). SII (P = 0.034), PNI (P = 0.013), FIGO staging (P = 0.009), ascites (P = 0.003), CA199 (P = 0.003), HE4 (P = 0.028), residual lesions (P = 0.022), and margins of incision (P < 0.001) were found to be significant prognostic indicators of OS by multifactorial Cox regression analysis. There was a significant inverse relationship between the PNI and SII (r = -0.484; P < 0.01). EOC patients with a coPNI-SII score of 1 had a higher 5-year OS rate (P < 0.05) than EOC patients with a coPNI-SII score of 2 or 3. When taking into account both the SII and PNI, the predictive value rose.

Conclusion: Interestingly, we found that low preoperative PNI and high SII were strong indicators of poor prognosis in patients with EOC. The combination of SII and PNI can enhance the accuracy of prognosis.

Introduction: Adolescence is a critical period for health, as conditions like polycystic ovarian syndrome (PCOS) can affect long-term outcomes, including diabetes and other non-communicable diseases in adulthood. This study evaluated the effects of Nigella sativa L. extract on glycemia among adolescents with PCOS.

Materials and methods: This secondary analysis used data from a randomized controlled trial conducted between March 2022 and March 2023. One hundred sixteen adolescent girls aged 12-18 years with PCOS were randomized into two groups. The intervention group received 1000 mg/day of Nigella sativa extract for 16 weeks, while the control group received 10 mg/day of medroxyprogesterone for 10 days per menstrual cycle over the same period. Fasting plasma glucose (FPG) and one- and two-hour post-prandial glucose levels were measured at baseline and after the intervention.

Results: 103 completed the study (50 in the Nigella sativa group and 53 in the control group). At baseline, there were no significant differences in FPG (p = 0.294), though the control group had higher one-hour (p = 0.002) and two-hour (p = 0.006) post-prandial glucose levels. Post-intervention, significant interaction effects were observed for FPG (p = 0.004) and two-hour post-prandial glucose (p = 0.023), indicating more significant reductions in the Nigella sativa group compared to the control group.

Conclusions: Considering the observed effect of Nigella sativa supplementation on FPG and two-hour post-prandial glucose, it may offer a complementary approach to managing glycemia in adolescent PCOS. However, further research is warranted.

Ovarian cancer, colloquially termed the "king of gynecological cancers," presents significant diagnostic and therapeutic challenges due to its covert nature. It ranks as the deadliest gynecologic malignancy with a disheartening 5-year survival rate below 40%. Standard therapeutic protocols for newly diagnosed patients encompass cytoreductive surgery followed by neoadjuvant or adjuvant platinum-based chemotherapy. Despite initial chemotherapeutic responses, recurrence is common, affecting up to 80% of patients, with nearly all developing eventual resistance to chemotherapy regimens. This case report highlights an Aisan patient with ovarian cancer, who exhibited tolerance, recurrence, and progression after several prior lines of treatment. The application of Mirvetuximab Soravtansine, facilitated by positive FRα expression identified through IHC analysis, notably reduced tumor lesions and CA125 levels, achieving a complete response and maintaining low CA125 levels during treatment, underscoring its efficacy in treating platinum-resistant recurrent ovarian cancer.