Journal of Ovarian Research最新文献

{"title":"A novel ITGB8 transcript variant sustains ovarian cancer cell survival through genomic instability and altered ploidy on a mutant p53 background.","authors":"Aravindan Narayanan, Ankita S More, Muskan Talreja, Avinash M Mali, Sannannagari Boya Vinay, Sharmila A Bapat","doi":"10.1186/s13048-024-01538-6","DOIUrl":"10.1186/s13048-024-01538-6","url":null,"abstract":"<p><strong>Background: </strong>Transcript variants and protein isoforms are central to unique tissue functions and maintenance of homeostasis, in addition to being associated with aberrant states such as cancer, where their crosstalk with the mutated tumor suppressor p53 may contribute to genomic instability and chromosomal rearrangements. We previously identified several novel splice variants in ovarian cancer RNA-sequencing datasets; herein, we aimed to elucidate the biological effects of the Integrin Subunit Beta 8 variant (termed pITGB8-205).</p><p><strong>Methods: </strong>Resolution of the full-length sequence of pITGB8-205 through rapid amplification of cDNA ends (RACE-PCR). Cell cycle analysis and karyotype studies were performed to further explore genomic instability. RNA-seq and proteomics analyses were used to identify the differential expression of the genes.</p><p><strong>Results: </strong>This full-length study revealed a unique 5' sequence in pITGB8-205 that differed from the reported ITGB8-205 sequence, suggesting differential regulation of this novel transcript. Under a p53 mutant background, overexpression of pITGB8-205 triggered genetic instability reminiscent of oncogene-induced replicative stress with extensive abnormal mitoses and chromosomal and nuclear aberrations indicative of chromosomal instability, leading to near whole-genome duplication that imposes energy stress on cellular resources. Micronuclei and aneuploidy are striking features of pITGB8-205-overexpressing p53-mutant cells but are not enhanced in p53 wild-type (WT) cells. RNA-seq and proteomics analyses further suggested that p53 inactivation in ovarian cancer provides a permissive intracellular molecular niche for pITGB8-205 to mediate its effects on genomic instability. This observation is pivotal considering that most high-grade serous ovarian carcinoma (HGSC) tumors express mutant p53. The resulting aneuploid clones with enhanced self-renewal and survival capabilities disrupt clonal dominance under stress yet maintain a balance between replicative stress and prosurvival advantages.</p><p><strong>Conclusion: </strong>pITGB8-205-overexpressing clones sustain ovarian tumor cell survival, achieve homeostasis and are formidable opponents of therapy.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"218"},"PeriodicalIF":3.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATF3 mediates PM2.5-induced apoptosis and inflammation in ovarian granulosa cells.","authors":"Xiandan Zhang, Xuan Wang, Hao Li, Haihong Wang, Dewei Du, Huijuan Huang","doi":"10.1186/s13048-024-01539-5","DOIUrl":"10.1186/s13048-024-01539-5","url":null,"abstract":"<p><p>Particulate matter 2.5 (PM2.5) pollution has emerged as a major global public health concern because of its adverse effects on human health. Our group has previously demonstrated that PM2.5 exposure can seriously impair ovarian function. However, the underlying mechanisms remain a mystery. This study verifies ovarian damage in mice, evidenced by inflammatory cell infiltration and follicular atresia, following 5 months of PM2.5 exposure via tracheal drip (35 µg/m³ for low dose and 150 µg/m³ for high dose). In addition, PM2.5 exposure inhibited the cell viability of human granulosa cells (KGN) and induced apoptosis at the concentrations of 50, 100, and 150 µg/mL for 24 h. The apoptosis of KGN cells induced by inflammation contributes to follicular atresia. Furthermore, we conducted RNA-sequencing analysis to identify the genes and pathways triggered by PM2.5 (100 µg/mL) exposure, which decreases the KGN cell viability. We found a significant increase in Activating Transcription Factor 3 (ATF3). Further mechanistic studies reveal a strong association between PM2.5-induced apoptosis, inflammation, and ATF3 with its downstream oxidative stress signals. In summary, the ATF3 pathway serves a vital role in the ovarian injury caused by PM2.5 exposures.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"215"},"PeriodicalIF":3.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implication of vasopressin receptor genes (AVPR1A and AVPR1B) in the susceptibility to polycystic ovary syndrome.","authors":"Pruthvi Goparaju, Claudia Gragnoli","doi":"10.1186/s13048-024-01515-z","DOIUrl":"10.1186/s13048-024-01515-z","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a complex heterogenous disorder manifesting with various reproductive, endocrine, and metabolic derangements such as insulin resistance and hyperglycemia. The arginine vasopressin peptide (AVP), also called or antidiuretic hormone (ADH), modulates metabolic functions such as glucose hemostasis, insulin sensitivity, and lipid metabolism via binding to two central and peripheral receptors (AVPR1A and AVPR1B). In the present study, we aimed to detect whether the AVPR1A and AVPR1B genes confer risk for PCOS.</p><p><strong>Methods: </strong>In peninsular Italian families, we tested 7 variants in the AVPR1B gene and 2 variants in the AVPR1A gene via Pseudomarker for linkage and linkage joint to association (i.e.., linkage disequilibrium) with PCOS.</p><p><strong>Results: </strong>We identified two risk variants in each gene, significantly associated with the risk of PCOS.</p><p><strong>Conclusion: </strong>To the best of our knowledge, this is the first study to report risk variants in AVPR1A and AVPR1B genes in association with PCOS. However, replication in other ethnic groups as well as functional studies are needed to confirm these results.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"214"},"PeriodicalIF":3.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progesterone peak influences embryonic developmental morphokinetics on trigger day? A retrospective study.","authors":"D Baldini, V M Bartoli, A Mastrorocco, D Ferri, M Dellino, A S Laganà, S Hatirnaz, G M Baldini, A Malvasi, A Vimercati, G Trojano","doi":"10.1186/s13048-024-01548-4","DOIUrl":"10.1186/s13048-024-01548-4","url":null,"abstract":"<p><strong>Objective: </strong>Premature Progesterone Rise (PPR) is characterized by elevated serum progesterone concentrations either towards the end of the follicular phase or on the trigger day, surpassing a pre-defined threshold value. Aim of the study is to evaluate the impact of PPR exceeding 1.5 ng/ml at the time of hCG-trigger on embryo morphokinetic parameters and to identify predictive biomarkers of in IntraCytoplasmic Sperm Injection (ICSI) cycles outcomes.</p><p><strong>Methods: </strong>It is a retrospective study including patients underwent ICSI cycles in the period 2020-2023. 58 patients were recruited in the study group showing P levels in the trigger day greater than or equal to 1.5 ng/ml. A matching control group of 58 patients with P levels below 1.5 ng/ml was after selected. The general characteristics of these patients, including age, Body Mass Index (BMI), antral follicle count (AFC), anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH) levels, the type of infertility and smoking/non-smoking patients, were recorded on the day of their initial visit. Subsequently, data were collected regarding the number of eggs retrieved, mature eggs, successfully fertilized eggs, and embryos reaching the blastocyst stage. Additionally, the timing of embryonic development and the quality of obtained blastocysts, as assessed by the degree of expansion and the characteristics of the inner cell mass (ICM) and trophectoderm (TE), were evaluated using Time-Lapse technology.</p><p><strong>Results: </strong>Elevated P levels exceeding 1.5 ng/ml on the trigger day were directly associated with a significantly larger number of antral follicles, consequently leading to a higher count of retrieved eggs, mature eggs, successfully fertilized eggs and embryos reaching the blastocyst stage. Furthermore, the analysis of morphokinetic parameters indicated faster division times and a notably greater number of high-grade blastocysts in the study group compared to the control group.</p><p><strong>Conclusions: </strong>P levels ≥ 1.5 ng/ml on the trigger day did not negatively impact embryonic morphokinetic parameters, instead resulting in faster embryo development in the initial stages.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"216"},"PeriodicalIF":3.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal relationship between inflammatory cytokines and polycystic ovary syndrome: a bidirectional mendelian randomization study.","authors":"Danling Tian, Jinfeng Chen, Liang Liu","doi":"10.1186/s13048-024-01525-x","DOIUrl":"10.1186/s13048-024-01525-x","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is defined as a chronic low-grade inflammatory reproductive endocrine disorder. PCOS can induce various metabolic disorders, which are associated with a state of mild and slow-acting inflammation. Nevertheless, the causal relationship between polycystic ovary syndrome and inflammatory factors is uncertain. The causality between inflammatory cytokines and PCOS was analyzed by bidirectional Mendelian randomization (MR) in this current probe. We performed an interactive MR study to assess the causal relationships between 91 inflammatory cytokines and PCOS using Genome Wide Association Study (GWAS) data. We underwent dual-sample MR analysis with inverse variance weights (IVW) as the predominant MR methodology with multiple validity and heterogeneity analyses. MR-Egger, weighted median, simple mode, weighted mode and MR-PRESSO were analyzed as multiple likelihood sensitivity analyses to enhance the final results.The results came out interleukin-1-alpha (IL-1 A) levels (odds ratio [OR] = 1.051, 95% fiducial interval [95% CI] = 1.009-1.095, P = 0.02) and oncostatin-M (OSM) levels ( [OR] = 1.041, [95% CI] = 1.001-1.082, P = 0.04) were positively associated with the development of PCOS. Moreover, interleukin-7 (IL-7) levels ([OR] = 0.935, [95% CI] = 0.884-0.989, P = 0.02); interleukin-15 receptor subunit alpha (IL15RA) levels ([OR] = 0.959, [95% CI] = 0.929-0.99, P = 0.01); and C-X-C motif chemokine 11 (CXCL11) levels ([OR] = 0.959, [95% CI] = 0.922-0.996. P = 0.03) were strongly negatively associated with PCOS. However, we did not find any strong positive results in the reverse analysis, suggesting that although inflammatory factors contribute to the pathogenesis of PCOS, PCOS itself does not trigger inflammatory factor production.Our study provides genetic evidence for the connection between systemic inflammatory regulators and PCOS. Treatments targeting specific inflammatory factors may help to mitigate the risk of PCOS. The levels of five of the 91 inflammatory factors included in this study, namely, IL1A and OSM, were associated with PCOS. IL1A and OSM contribute to the progression of PCOS while IL-7, IL15RA, and CXCL11 levels are negatively correlated with the development of PCOS.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"217"},"PeriodicalIF":3.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A simple and practical approach to elective egg freezing to control costs and expand access to care.","authors":"Raoul Orvieto, Norbert Gleicher","doi":"10.1186/s13048-024-01543-9","DOIUrl":"10.1186/s13048-024-01543-9","url":null,"abstract":"<p><p>Social elective egg freezing (EEF) is now widely used globally but in many countries is unaffordable to many women because of high costs and lacking insurance coverage. Efforts to reduce costs, therefore, are of importance. Surprisingly, a simple, well-defined and practical approach ensuring optimal outcomes for EEF has, however, so-far not been published. We, therefore, conducted a narrative review of the literature for relevant articles regarding the different steps of ovarian stimulation (OS) in the EEF process, in order to define such a standard protocol. This review revealed that in order to maximize oocyte yields with minimal number of OS cycles - while ensuring patient safety - a multiple-dose GnRH antagonist protocol with a daily gonadotropin dose of 300 IU appears best, unless patients demonstrate a polycystic ovarian phenotype, suggestive of likely high responses. The initial gonadotropin should be recFSH, while LH supplementation should be co-administered with the addition of GnRH antagonist. Final follicular maturation should be triggered by GnRH agonist trigger, with a dual trigger (1000-1500 IU hCG) considered for suboptimal responders to GnRH agonist trigger, optionally with Cabergoline to mitigate ovarian hyperstimulation syndrome (OHSS) in high responders.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"213"},"PeriodicalIF":3.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astaxanthin improves assisted reproductive technology outcomes in poor ovarian responders through alleviating oxidative stress, inflammation, and apoptosis: a randomized clinical trial.","authors":"Anahid Shafie, Ashraf Aleyasin, Mojtaba Saffari, Mojtaba Saedi, Sahar Rostami, Saeede Rezayi, Seyed Danial Mohammadi, Fardin Amidi","doi":"10.1186/s13048-024-01537-7","DOIUrl":"10.1186/s13048-024-01537-7","url":null,"abstract":"<p><strong>Background: </strong>Poor ovarian response (POR) to controlled ovarian stimulation (COS) remains challenging, especially in advanced-age women with diminished ovarian reserve, resulting in low live birth rates. Many patients prefer to conceive with their eggs, underscoring the need for improved treatments. This study explores astaxanthin potential as a COS adjuvant to improve ovarian response and assisted reproductive technology (ART) outcomes, considering its impact on oxidative stress (OS), inflammation, and apoptosis, which are key factors in POR.</p><p><strong>Methods: </strong>In this randomized, triple-blind, placebo-controlled trial, 60 infertile POR patients from POSEIDON Group 4 (the poorest prognosis category, age > 35 and poor ovarian reserve (anti-müllerian hormone < 1.2 ng/ml or antral follicle count < 5) undergoing intracytoplasmic sperm injection were enrolled. Patients were assigned to receive either 12 mg/day AST or placebo for eight weeks. All patients underwent a gonadotropin-releasing hormone antagonist regimen for COS. ART outcomes were compared between groups. Blood serum and follicular fluid (FF) were analyzed for OS markers (superoxide dismutase [SOD], total antioxidant capacity [TAC], and malondialdehyde [MDA]), and pro-inflammatory cytokines (interleukin-6 [IL-6], interleukin-8 [IL-8], and vascular endothelial growth factor [VEGF]) via enzyme-linked immunosorbent assay kits, and cell-free DNA [cfDNA] (apoptotic marker) via ALU quantitative polymerase chain reaction.</p><p><strong>Results: </strong>After the intervention, the AST group exhibited a significant elevation in serum (P = 0.013) and TAC (P = 0.030), accompanied by a significant reduction in serum MDA (P = 0.005). No significant differences between AST and placebo groups were observed in OS markers in FF. AST group showed significant reductions in the serum IL-6 (P < 0.001), IL-8 (P = 0.001), and VEGF (P = 0.002) levels following AST therapy. In the AST group, FF levels of IL-6 (P = 0 < 001), IL-8 (P = 0.036), VEGF (P = 0.006), and cfDNA (P < 0.001) were significantly lower than in the placebo group. Between-group comparisons showed significant differences in the alterations of serum SOD (P = 0.027), IL-6 (P < 0.001), and IL-8 (P = 0.035) levels between AST and placebo groups. The AST group showed significant increases in the number of retrieved oocytes (P = 0.003), MII oocytes (P = 0.004), frozen embryos (P = 0.037), and high-quality embryos (P = 0.014) compared to the placebo group.</p><p><strong>Conclusion: </strong>AST shows promise as a COS adjuvant therapy, potentially enhancing some ART outcomes in POR through alleviating OS, inflammation, and apoptosis.</p><p><strong>Trial registration: </strong>Clinical trial registration number: IRCT20230223057510N1, URL: https://irct.behdasht.gov.ir/trial/68870 , registration date: 2023 March 16.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"212"},"PeriodicalIF":3.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between smoking, excessive androgen and negative emotions in women with polycystic ovary syndrome (PCOS).","authors":"Yang Yang, Hua Zhang, Bo-Yun Huang, Yong-Hao Lu, Ii Fukuzawa, Shuhan Yang, Lifei Zhou, Liyan Luo, Chunyong Wang, Ning Ding, Sai Li, Li Shi, Hao-Lin Zhang","doi":"10.1186/s13048-024-01541-x","DOIUrl":"10.1186/s13048-024-01541-x","url":null,"abstract":"<p><strong>Background: </strong>Lifestyle intervention is the first-line treatment for PCOS. Numerous studies have investigated the effect of various lifestyle factors, including dietary habit, smoking, and alcohol consumption on PCOS women. These studies have found that such factors may be associated with physiological parameters such as androgen, and emotional states like anxiety or depression. Smoking, a harmful lifestyle habit widely recognized to contribute to various diseases, has also been found to be related to PCOS. Current research has not adequately compared the effects of smoking with other lifestyle habits on PCOS, and there is little mention of its relationship with the emotional states of patients with PCOS. To further elucidate the association between smoking and other lifestyle factors with clinical symptoms in patients with PCOS, we conducted a cross-sectional evaluation using data from Peking University Third Hospital, with a special focus on analyzing smoking habits and comparing it with a variety of lifestyle factors.</p><p><strong>Methods: </strong>This cross-sectional study included 601 PCOS women and 184 healthy controls who underwent physical examinations, hormone profiles and psychological measures. We assessed the association between smoking and the clinical symptoms in PCOS women.</p><p><strong>Results: </strong>We found a significant correlation between smoking and the degree of depression in PCOS women among the three emotional states: anxiety, depression, and stress. Smoking was also significantly associated with testosterone level in PCOS participants, suggesting that PCOS women who smoke exhibited more severe depressive symptoms and higher testosterone level. In addition, compared to the control group, PCOS women had notably higher testosterone (T) and luteinizing hormone (LH) levels. Smoke and alcohol were statistically significantly more common in women with PCOS than the Control.</p><p><strong>Conclusion: </strong>Women with PCOS who smoke were found to have elevated testosterone levels and more severe depression. These findings suggest that clinicians should monitor smoking women with PCOS for symptoms of depression and assess their hyperandrogenic status.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"211"},"PeriodicalIF":3.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk-stratified CA125 screening integrating CA125 trajectories, trajectory-specific progression and transvaginal ultrasound for ovarian cancer.","authors":"Hongyuan Duan, Xiaomin Liu, Yu Zhang, Ya Liu, Yuting Ji, Yunmeng Zhang, Zeyu Fan, Siwen Liu, Lei Yang, Tingting Xu, Jing Tian, Weiqin Li, Zhangyan Lyu, Fangfang Song, Fengju Song, Yubei Huang","doi":"10.1186/s13048-024-01535-9","DOIUrl":"10.1186/s13048-024-01535-9","url":null,"abstract":"<p><strong>Backgrounds: </strong>Cancer antigen 125 (CA125) is widely used for screening ovarian cancer (OC), yet its effectiveness remains debated. Potential factors may include ineffective cut-off value for CA125 in screening, as well as a lack of consideration for CA125 trajectories and trajectory-specific progression.</p><p><strong>Methods: </strong>Based on data from multiple rounds of CA125 tests and transvaginal ultrasound (TVU) examinations conducted on 28,456 women in the PLCO Trial, time-dependent receiver-operating-characteristic curves (ROCs) and area-under-the-curves (tdAUCs) analyses were employed to identify the optimal CA125 cut-off values for OC screening. Participants were categorized into four CA125 trajectories: stable negative CA125 (CA125_SN), loss of positive CA125 (CA125_LP), stable positive CA125 (CA125_SP), and gain of positive CA125 (CA125_GP). The associations between different CA125 trajectories, trajectory-specific progression indicators, and OC risk were explored. The effectiveness of risk-stratified CA125 screening, incorporating CA125 trajectories, trajectory-specific progression, and TVU, was evaluated using hazard ratio and 95% confidence intervals [HR (95%CIs)], with adjustments for potential confounders.</p><p><strong>Results: </strong>After a median follow-up of 14.8 years for OC incidence and 23.8 years for OC mortality, 250 OC cases and 218 OC deaths were identified. The tdAUC for 10-year OC incidence with CA125 was 0.663, with an optimal cut-off value of 13.00 U/ml. Trajectory analyses showed that both CA125_SP and CA125_GP were significantly associated with increased risks of OC incidence [HRs (95%CIs): 2.00(1.47-2.73) and 3.06(2.25-4.16)] and mortality [HRs (95%CIs):1.58(1.13-2.21) and 2.60(1.87-3.62)] compared to CA125_SN. Trajectory-specific progression analyses identified relative velocity as the optimal progression indicators for both CA125_SP and CA125_GP (tdAUCs: 0.712 and 0.767), with optimal cut-off values of 9% and 32% per year, respectively. Positive progression was associated with significantly increased risks of OC incidence [HRs (95%CI): 7.26(4.00-13.17) and 3.83(1.96-7.51) CA125_GP and CA125_SP] and mortality [HRs (95%CI): 8.03(4.15-15.56) and 6.04(2.78-13.14)] compared to negative progression. Optimized risk-stratified CA125 screening, which integrated CA125 trajectories, trajectory-specific progression, and TVU, reduced missed OC by 3.6% and improved accuracy compared to traditional screening methods.</p><p><strong>Conclusions: </strong>Incorporating CA125 trajectories and trajectory-specific progression into screening protocols enhances the identification of the population at high-risk of OC. An optimized screening strategy, which includes these factors along with TVU, is recommended to improve the effectiveness of OC screening.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"210"},"PeriodicalIF":3.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inter-cycle variability of anti-Müllerian hormone: implications for predicting controlled ovarian stimulation cycle outcomes.","authors":"Yavuz Emre Şükür, Batuhan Aslan, Necati Berk Kaplan, Musa Doğru, Batuhan Özmen, Murat Sönmezer, Bülent Berker, Cem Somer Atabekoğlu, Ruşen Aytaç","doi":"10.1186/s13048-024-01517-x","DOIUrl":"10.1186/s13048-024-01517-x","url":null,"abstract":"<p><strong>Background: </strong>Anti-Müllerian hormone (AMH) is a widely used marker for estimating ovarian reserve, and it may predict response to ovarian stimulation. While AMH is considered a stable, cycle-independent marker, studies have shown it can exhibit significant fluctuations based on factors like age, reproductive stage, and menstrual cycle phase. The fluctuations in AMH levels can make it challenging to predict individual responses accurately, particularly when the AMH is not measured in the COS cycle. The aim of this study was to assess the inter-cycle variability of serum AMH levels in two consecutive menstrual cycles and their correlation with response to controlled ovarian stimulation outcome in the latter.</p><p><strong>Methods: </strong>In this single-centre retrospective cohort study, data of normal and low responder patients who underwent intracytoplasmic sperm injection following a GnRH antagonist cycle at a university hospital infertility clinic between January 2022 and December 2023 were reviewed. Serum AMH levels were measured in the early follicular phase of two consecutive menstrual cycles with Elecsys-AMH Roche^® system (Roche Diagnostics, Meylan, France). Correlations between AMH levels and controlled ovarian stimulation outcomes, including total oocyte and mature oocyte (MII) counts, were assessed. The study included normal and poor responder women to maintain data integrity.</p><p><strong>Results: </strong>A total of 79 patients were included in the final analyses. Significant cycle-to-cycle variation in serum AMH levels was observed, with a median variation of 44.3%. Normal responders exhibited a mean change of 0.60 ± 0.46 ng/ml, while poor responders had a mean change of 0.28 ± 0.28 ng/ml. Approximately 20% of patients were reclassified between normal and poor responder categories based on the second AMH measurement. The controlled ovarian stimulation cycle AMH levels showed a stronger correlation with both total oocyte count (r = 0.871, P < 0.001) and MII oocyte count (r = 0.820, P < 0.001) compared to preceding cycle AMH levels.</p><p><strong>Conclusion: </strong>AMH levels can exhibit significant variations between consecutive cycles, potentially leading to misclassification of patients. Measuring AMH in the early follicular phase of the COS cycle provides a more accurate prediction of the numbers of total and MII oocytes collected. Consistent and repeated AMH measurements can help clinical decision-making.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"209"},"PeriodicalIF":3.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}