Hanna Roos Alexander, Shamima Afrin Ruma, Shruti Jain, Eva Lundin, Per Liv, Pernilla Israelsson, Kim Pettersson, Annika Idahl
{"title":"Predictive ability of novel glycovariant biomarkers of CA125 and CA15-3 up to three years prior to ovarian cancer diagnosis: a population-based case-control study.","authors":"Hanna Roos Alexander, Shamima Afrin Ruma, Shruti Jain, Eva Lundin, Per Liv, Pernilla Israelsson, Kim Pettersson, Annika Idahl","doi":"10.1186/s13048-026-02143-5","DOIUrl":"10.1186/s13048-026-02143-5","url":null,"abstract":"<p><strong>Background: </strong>Nanoparticle immunoassays for CA125 and CA15-3 glycovariants are promising tools for epithelial ovarian cancer (EOC) and borderline ovarian tumor (BOT) early detection.</p><p><strong>Method: </strong>This retrospective population-based study utilized prospective (< 3 years) plasma samples from 110 cases and 440 controls. Sialyl-Thomsen-nouveau (STn) antibody and macrophage galactose-type lectin (MGL) to detect cancer antigen 125 (CA125) and 15 - 3 (CA15-3) glycoforms were evaluated, using CA125, CA15-3, and HE4 enzyme immunoassay (EIA) references. The area under the receiver operating characteristic curve (AUC), partial AUC (pAUC) at specificities 0.9-1.0, and sensitivity (SN) at 0.98 specificity (SP) for detecting EOC/BOT were calculated.</p><p><strong>Results: </strong>The single marker with the highest point estimate for pAUC and SN at 98% SP was CA125<sup>EIA</sup> (pAUC 0.71 (0.66, 0.76), SN at 98% SP 0.29 (0.17-0.42 combinations)). The CA15-3<sup>STn</sup> + CA125<sup>EIA</sup> and CA125<sup>EIA</sup> + HE4<sup>EIA</sup> improved the detection rate point estimates and provided the highest pAUC values (CA125<sup>EIA</sup> + CA15-3<sup>STn</sup>: 0.75 (0.70-0.80); CA125<sup>EIA</sup> + HE4<sup>EIA</sup>: 0.71 (0.66-0.77)). For 0-<1, 1-<2 and 2-<3 years lag time, CA125<sup>EIA</sup> and the CA125 glycovariants provided similar pAUC and SN at 98% SP, with largely overlapping confidence intervals.</p><p><strong>Conclusion: </strong>This case-control study, which used plasma samples collected up to three years before diagnosis of EOC or BOT, did not provide evidence of a higher discriminatory capacity of the glycovariant biomarkers compared with the clinically established biomarker CA125<sup>EIA</sup> in asymptomatic women. Increased plasma volumes and larger cohorts are suggested in future studies.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"19 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13220484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055102","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":"The central role of hyperandrogenism in driving metabolic dysfunction in polycystic ovary syndrome: from pathophysiological mechanisms to targeted therapies.","authors":"Jinghui Xu, Bing He","doi":"10.1186/s13048-026-02124-8","DOIUrl":"10.1186/s13048-026-02124-8","url":null,"abstract":"<p><p>Polycystic ovary syndrome is a prevalent endocrine disorder wherein hyperandrogenism plays a central pathogenic role that extends beyond its reproductive manifestations. This review systematically elucidates the pathophysiological mechanisms through which hyperandrogenism, acting in a vicious cycle with insulin resistance, drives systemic metabolic dysfunction. We synthesize evidence demonstrating that hyperandrogenism promotes organ-specific lipotoxicity and insulin resistance. This contributes to visceral adiposity, hepatic steatosis (and its progression to metabolic dysfunction-associated steatotic liver disease), and skeletal muscle dysfunction. Furthermore, we explore the detrimental effects of hyperandrogenism on cardiovascular integrity and gut microbial homeostasis. Based on this mechanistic framework, we evaluate current therapeutic strategies, drawing a key distinction between metabolic-focused interventions (e.g., lifestyle modifications, insulin-sensitizing agents) that disrupt the hyperandrogenism-insulin resistance cycle, and androgen-lowering therapies (e.g., combined oral contraceptives) that primarily alleviate symptoms with limited metabolic benefits. We conclude that redefining hyperandrogenism as a primary metabolic driver is crucial for developing targeted strategies that mitigate the long-term metabolic risks associated with polycystic ovary syndrome.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148031669","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":"Distinct pregnancy challenges in PCOS women undergoing IVF/ICSI with singleton and twin births: a propensity-matched analysis.","authors":"Zhekun Zhao, Minyue Tang, Shan Wan, Sisi Wang, Bingbin Xu, Yimin Zhu","doi":"10.1186/s13048-026-02147-1","DOIUrl":"10.1186/s13048-026-02147-1","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) has been associated with adverse pregnancy outcomes; however, current literature presents inconsistent findings, probably due to varying feotal numbers included in previous research. This study sought to evaluate pregnancy outcomes in women with PCOS undergoing assisted reproductive technology (ART), with a specific focus on differentiating between singleton and twin births.</p><p><strong>Methods: </strong>This cohort study included women who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and maintained pregnancies beyond 20 weeks of gestation. Participants with PCOS or tubal factors were matched using 1:2 propensity score matching (PSM) separately within singleton and twin birth cohorts. Maternal and neonatal outcomes were collected from 95 hospitals and analysed using conditional logistic regression with cluster-robust standard errors (CRSEs) at hospital levels. Mediation analysis was further conducted to identify pathways between PCOS and several adverse outcomes.</p><p><strong>Results: </strong>From 1 June 2017 to 31 May 2022, 696 PCOS women and 1392 controls with singleton births, as well as 201 PCOS women and 402 controls with twin births, were matched for final analysis. In singleton birth cohort, PCOS women were associated with hypertensive diseases of pregnancy [HDP; crude odds ratio (OR) = 1.91, P adjusted for multiple comparisons < 0.001, the same below], pre-eclampsia (PE; OR = 1.67, P < 0.01), and cervical incompetence (CIC; OR = 3.84, P < 0.001). In twin birth cohort, PCOS women had increased odds of gestational diabetes mellitus (GDM; OR = 2.23, P < 0.001) and very preterm birth (VPTB; OR = 2.08, P < 0.01), compared to their counterparts. No significant between-group differences were observed for preterm premature rupture of membranes (PPROM). The findings were consistent after regression adjustments, multiple comparison correction, subgroup analyses, and sensitivity analyses. Subsequent mediation analysis highlighted preconception BMI and insulin resistance (IR) as key mediators to PCOS-related HDP and PE for women with singleton births. Further exploratory analysis indicated several preconception prognostic factors of adverse pregnancy outcomes in PCOS, especially metabolic indicators.</p><p><strong>Conclusions: </strong>In this study, women with PCOS who had singleton births demonstrated a higher incidence of hypertension and CIC compared to those with tubal factors. Among women with twin births, increased risks of GDM and VPTB were noted in addition to the inherent risks of twin gestation. Our findings contribute to the body of evidence regarding the differential pregnancy outcomes based on foetal number in PCOS women undergoing ART, highlighting the necessity of individual reproductive and obstetric management in clinical practice.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148031585","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}
Xingzhe Liu, Dan Liu, Zikun Peng, Jianqing Zhu, Weidong Zhao, Yi Huang, Ruifang An, Hong Zheng, Pengpeng Qu, Li Wang, Qi Zhou, Danbo Wang, Ge Lou, Jing Wang, John Low, Beihua Kong, Rutie Yin, Xing Xie, Jihong Liu, Wei Sun, Rongyu Zang, Ding Ma, Qinglei Gao
{"title":"Overall survival and long-term safety of olaparib maintenance in patients with platinum-sensitive relapsed ovarian cancer: final analyses of phase III L-MOCA trial.","authors":"Xingzhe Liu, Dan Liu, Zikun Peng, Jianqing Zhu, Weidong Zhao, Yi Huang, Ruifang An, Hong Zheng, Pengpeng Qu, Li Wang, Qi Zhou, Danbo Wang, Ge Lou, Jing Wang, John Low, Beihua Kong, Rutie Yin, Xing Xie, Jihong Liu, Wei Sun, Rongyu Zang, Ding Ma, Qinglei Gao","doi":"10.1186/s13048-026-02144-4","DOIUrl":"10.1186/s13048-026-02144-4","url":null,"abstract":"<p><strong>Background: </strong>The indications for Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy in platinum-sensitive recurrent ovarian cancer (PSROC) patients varies across nations. The lack of clinical trial evidence and detailed biomarker analysis in the Asian population results in uncertain clinical benefits. Additionally, the absence of long-term safety monitoring data limits the assessment of tolerance to prolonged PARP inhibitor use.</p><p><strong>Methods: </strong>This prospective, open-label, single-arm, phase IIIb L-MOCA study enrolled Asian patients with high-grade epithelial PSROC across China and Malaysia. Patients received oral olaparib (300 mg) twice daily until disease progression or unacceptable toxicity. The primary endpoint of progression-free survival has been reported previously. A prespecified final OS analysis was conducted at approximately 60% data maturity.</p><p><strong>Results: </strong>After a median follow-up of 73.4 months, the median OS (mOS) reached 51.0 months (95% CI, 42.7 to 56.1). The mOS was 64.4 months (49.9 to not reach [NR]) in BRCA-mutated patients and 40.9 months (33.3 to 51.0) in BRCA wild-type patients. The mOS was 54.4 months (42.5 to NE) in HRD-positive patients and 34.8 months (28.3 to 46.6) in HRD-negative patients. No new safety signals were identified compared to the primary L-MOCA report. Myelodysplastic syndrome and acute myeloid leukemia (MDS/AML) occurred in 1.3% of patients, and no additional cases were identified after approximately four additional years of follow-up beyond the primary analysis.</p><p><strong>Conclusion: </strong>Long-term follow-up data from L-MOCA indicates that olaparib maintenance monotherapy shows promising overall survival and tolerable safety profile in Asian PSROC patients, regardless of BRCA or HRD status.</p><p><strong>Trial registration: </strong>Registry: ClinicalTrials.gov.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148016159","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":"The crosslink between autophagy and ferroptosis in polycystic ovary syndrome: from synergistic pathogenesis to targeted therapy.","authors":"Xujin Wu, Jiarui Li, Xuesong Zhang, Huili Huang, Tianjiao Li, Mingyue Kong, Ziqi Dai, Yihan Yang, Xin Chen","doi":"10.1186/s13048-026-02146-2","DOIUrl":"10.1186/s13048-026-02146-2","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a highly heterogeneous endocrine-metabolic disorder whose core pathological features-follicular atresia and ovulatory dysfunction-are attributed to functional failure of ovarian granulosa cells (GCs). Although autophagy (a cellular quality-control mechanism) and ferroptosis (iron-dependent lipid peroxidation-driven cell death) have been shown to independently contribute to the pathophysiology of PCOS, their interactive networks and regulatory mechanisms within specific pathological microenvironments remain to be systematically elucidated. This review aims to systematically unravel this overlooked micro-pathogenic network. The dysfunction of GCs in PCOS is not an isolated event involving a single mode of cell death, but rather a pathological crosstalk arising from the disruption of the dynamic equilibrium between autophagy and ferroptosis. This paper elucidates the pathological mechanisms driving this cascade of disturbances through four distinct pathways: the intracellular stress hub formed by the synergistic action of oxidative stress (OS) and endoplasmic reticulum stress (ERS) serves as the initiating factor. This is compounded by the gut-ovarian axis's long-range amplification effect, mediated by gut microbiome (GM) dysregulation and low-grade chronic inflammation (LGI), collectively disrupting cellular homeostasis. while circadian rhythm disruption and epigenetic reprogramming, respectively, cement this imbalance at the temporal and molecular memory levels. Moreover, we have elucidated the specific execution pathways of autophagy-dependent ferroptosis, namely how selective autophagy (e.g., ferritinophagy and mitophagy) acts as a key amplifier of ferroptosis by exacerbating iron overload and energy collapse. On this basis, this paper explores therapeutic strategies ranging from upstream restoration of signal homeostasis to downstream precise inhibition of autophagy-ferroptosis interaction nodes. This review aims to provide novel theoretical perspectives for fundamentally reversing follicular atresia in PCOS and improving patients' reproductive outcomes by re-examining these lethal interactions at the microscopic level.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13383518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148016142","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}
Hui Teng, Qijun Xie, Cheng Zhou, Rujun Ma, Xie Ge, Jun Jing, Zhichuan Zou, Yuming Feng, Li Chen, Bing Yao
{"title":"Intraperitoneal ZP123 improves aged oocyte quality by restoring granulosa cell gap junctions and improving mitochondrial function.","authors":"Hui Teng, Qijun Xie, Cheng Zhou, Rujun Ma, Xie Ge, Jun Jing, Zhichuan Zou, Yuming Feng, Li Chen, Bing Yao","doi":"10.1186/s13048-026-02139-1","DOIUrl":"10.1186/s13048-026-02139-1","url":null,"abstract":"<p><strong>Background: </strong>Female reproductive aging is the most critical determinant of decreased fertility because the quality of oocytes gradually deteriorates with age, leading to poor embryo development, increased miscarriage rates, and reduced live births. Oocyte growth and maturation depend on bidirectional communication with surrounding granulosa cells through gap junctions, which are composed mainly of connexin 43 (CX43). Although intercellular communication mediated by CX43 is essential for folliculogenesis, how it becomes altered in the context of ovarian aging and drives oocyte deterioration remains largely unclear. This study aimed to clarify age-related alterations in gap junction communication and investigate whether augmenting CX43-mediated coupling via the peptide ZP123 might restore oocyte competence and enhance fertility outcomes in older females.</p><p><strong>Results: </strong>Our data demonstrated that CX43 expression in mouse ovaries and granulosa cells markedly decreased in an age-dependent manner, and this reduction was evident at both the protein and mRNA levels. The level of phosphorylated CX43 at Ser373 decreased markedly, indicating that total CX43 loss was the primary contributor to impaired gap junction communication. In vitro, our study revealed that ZP123 treatment significantly enhanced dye transfer between KGN cells but did not increase CX43 expression, suggesting an improvement in gap junction intercellular communication without increasing CX43 protein abundance. In vivo, chronic ZP123 administration to aged mice restored the normal gap junction between granulosa cells, improved follicle development. Functionally, ZP123 enhanced oocyte maturation (GVBD and MII rates), corrected spindle abnormalities, improved mitochondrial distribution, and increased ATP production while reducing ROS accumulation. Moreover, the mitochondrial membrane potential and Ca²⁺ homeostasis were restored, and excessive opening of the mitochondrial permeability transition pore was prevented. Consistent with these cellular improvements, ZP123-treated aged mice presented increased ovulation numbers and enhanced preimplantation embryo development, including increased blastocyst formation rates.</p><p><strong>Conclusions: </strong>This study revealed that disrupted CX43-mediated communication is a key mechanism underlying the decrease in oocyte quality during ovarian aging. Pharmacological enhancement of gap junctions with ZP123 effectively restored ovarian function, oocyte competence, and developmental potential, highlighting gap junction modulation as a novel and promising therapeutic avenue to mitigate age-related fertility decline in women of advanced maternal age.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13377967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005531","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}
Chaofeng Wei, Hsun-Ming Chang, Chenggang Wang, Peter C K Leung, Fang Lian
{"title":"Reevaluating statistical methods for proportion-based laboratory outcomes in assisted reproduction.","authors":"Chaofeng Wei, Hsun-Ming Chang, Chenggang Wang, Peter C K Leung, Fang Lian","doi":"10.1186/s13048-026-02131-9","DOIUrl":"10.1186/s13048-026-02131-9","url":null,"abstract":"<p><strong>Background: </strong>Proportion-based laboratory outcomes in assisted reproductive technology (ART), including two-pronuclear fertilization rate, good-quality embryo rate, and blastocyst formation rate, are widely used to evaluate treatment effectiveness and laboratory performance. These outcomes are bounded between 0 and 1, frequently skewed, and arise from hierarchical data structures in which oocytes or embryos are nested within cycles and patients. Inappropriate statistical handling of such data can lead to biased inference and misinterpretation of treatment effects. This narrative review aimed to identify common methodological misuses in the analysis of proportion-based ART laboratory outcomes and to summarize appropriate statistical approaches.</p><p><strong>Methods: </strong>This narrative review examined methodological and applied ART studies published between 2000 and 2025. Statistical practices were extracted and categorized according to data reporting (numerator-denominator structure), modeling strategies, and handling of clustering and boundary values. Recommended analytical frameworks were synthesized for binary outcomes reported either as a proportion or a count.</p><p><strong>Results: </strong>Common analytical issues included pooling embryo- or oocyte-level observations and applying chi-square tests, reporting absolute counts without denominators, describing skewed proportion outcomes using mean ± standard deviation and linear models, and failing to account for intra-patient or intra-cycle clustering. Appropriate approaches depended on data structure. Beta regression was suitable for continuous proportions within the open interval (0,1), while zero-one-inflated beta models accommodated observed boundary values. When numerator and denominator counts were available, binomial generalized linear mixed models (GLMMs) and generalized estimating equations (GEEs) preserved denominator information and accounted for hierarchical clustering.</p><p><strong>Conclusions: </strong>Misapplication of statistical methods to proportion-based ART laboratory outcomes remains common and may compromise reproducibility and clinical interpretation. Adoption of model-data alignment and transparent reporting practices will improve the validity of ART laboratory research and support evidence-based decision-making in reproductive medicine.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13377682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005580","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}
Xun Su, Qi Zheng, Dongyang Zhang, Qian Li, Hua Zhang, Yiqing Fan, Tao Yin, Weiwei Zou, Lei Zhang, Jie Zhang, Zhaolian Wei, Yunxia Cao, Chunmei Liang, Dongmei Ji
{"title":"Luteinizing hormone change trajectories in gonadotropin-releasing hormone antagonist protocols are associated with assisted reproductive outcomes: results from a retrospective cohort study.","authors":"Xun Su, Qi Zheng, Dongyang Zhang, Qian Li, Hua Zhang, Yiqing Fan, Tao Yin, Weiwei Zou, Lei Zhang, Jie Zhang, Zhaolian Wei, Yunxia Cao, Chunmei Liang, Dongmei Ji","doi":"10.1186/s13048-026-02140-8","DOIUrl":"10.1186/s13048-026-02140-8","url":null,"abstract":"<p><strong>Context: </strong>Luteinizing hormone (LH) plays an integral role in follicular development. In gonadotropin-releasing hormone (GnRH) antagonist protocols, LH levels have been demonstrated to affect assisted reproductive technology (ART) outcomes. However, the exact nature of this relationship remains unclear, and LH measurements at a single time point may not be sufficient to capture it fully.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study on 4,953 infertile women who underwent their first ART cycle with the GnRH antagonist protocol. Four LH measurements (basal status, antagonist administration day and 24 h later, and ovulation trigger day) were obtain for all participants. We used group-based trajectory modeling (GBTM) to characterize the trajectories of LH level changes during antagonist protocol implementation. Factors influencing the different LH trajectories were explored. Associations between LH levels at different time points and their trajectories with the number of obtained oocytes and ART outcomes in embryo transfer (ET) cycles were analyzed.</p><p><strong>Results: </strong>Based on the statistical criteria, the model with 4 trajectories were selected as the best-fitting model, and the LH change trajectories during antagonist protocol can be grouped into stable (77.0%), rising (11.0%), decreasing (6.2%) and fluctuating (5.8%) types. Different trajectory groups exhibited significant differences in the number of retrieved oocytes. Compared with that in the stable trajectory group, the oocyte yield in the rising trajectory group decreased and that in the fluctuating trajectory group increased. Of these participants, 884 underwent fresh ET cycles, with no significant differences in pregnancy outcomes between the different trajectory groups. On ovulation trigger day, high LH levels predicted better pregnancy outcomes, indicating significant positive associations with the odds of biochemical pregnancy, clinical pregnancy and live birth.</p><p><strong>Conclusion: </strong>Oocyte yield differed significantly among the LH trajectory groups, suggesting that LH dynamics during antagonist controlled ovarian stimulation may be relevant to treatment outcomes. For individuals with risk factors for a rising trajectory (e.g., advanced age, higher body mass index), closer monitoring of LH profiles may be warranted. For fresh ET cycles, trigger-day LH levels may merit heightened clinical attention.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005589","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}
Xuan Sha, Yan Zhang, Xun Xia, Haitian Ding, Yuqian Li, Guotong Li, Rong Hua, Kuokuo Li, Rui Guo, Danli Du, Yuping Xu, Yunxia Cao, Huan Wu, Yingchun Liu
{"title":"Two compound heterozygous MEIOSIN (likely) pathogenic variants cause female infertility with premature ovarian insufficiency through the disruption of meiosis-related gene transcription.","authors":"Xuan Sha, Yan Zhang, Xun Xia, Haitian Ding, Yuqian Li, Guotong Li, Rong Hua, Kuokuo Li, Rui Guo, Danli Du, Yuping Xu, Yunxia Cao, Huan Wu, Yingchun Liu","doi":"10.1186/s13048-026-02129-3","DOIUrl":"10.1186/s13048-026-02129-3","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian insufficiency (POI) is a major contributor to female infertility; however, its genetic basis remains insufficiently understood. MEIOSIN is crucial for initiating meiosis by activating a subset of key meiotic genes that regulate the transition from mitosis to meiosis in mammalian germ cells. Recent studies suggest that biallelic MEIOSIN variant may contribute to POI in humans, yet further analysis is required to confirm and clarify this role.</p><p><strong>Methods: </strong>To identify potential pathogenic variants associated with POI, whole-exome sequencing was conducted in the affected individuals, followed by Sanger sequencing for variant validation. To evaluate the functional consequences of these variants, a series of in vitro assays was performed, including Western blotting, immunostaining, and structural modeling of mutant proteins. Additionally, a dual-luciferase reporter assay was utilized to assess whether the identified variants influenced the transcriptional activity of MEIOSIN.</p><p><strong>Results: </strong>Two compound heterozygous variants in MEIOSIN-c.980T > C (p.Leu327Pro) and c.1068_1092del (p.His356fs*14)-were identified in two affected sisters, with the latter representing a novel variant. Sanger sequencing confirmed that the two variants were inherited from each parent, thereby establishing compound heterozygosity. Functional characterization revealed that the frameshift variant resulted in a truncated MEIOSIN protein with aberrant intracellular localization. While the missense variant did not impact MEIOSIN expression or localization, it disrupted the protein's 3D structure. Furthermore, dual-luciferase assays demonstrated that both variants impaired MEIOSIN's transcriptional regulation of downstream meiotic genes. According to the ACMG/AMP guidelines, the frameshift variant was classified as pathogenic, while the missense variant was classified as likely pathogenic.</p><p><strong>Conclusion: </strong>These findings provide compelling evidence that pathogenic biallelic variants in MEIOSIN represent a recurrent genetic cause of POI in humans.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13377809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005558","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":"Impact of salpingectomy on ovarian response to hormonal stimulation in in vitro fertilization (IVF) cycles.","authors":"Yohan Benchimol, Stéphane Sanchez, Catherine Racowsky, Rossana Cicinelli, Achraf Benammar, Jean-Marc Ayoubi","doi":"10.1186/s13048-026-02114-w","DOIUrl":"10.1186/s13048-026-02114-w","url":null,"abstract":"<p><strong>Background: </strong>The coagulation-section of the mesosalpinx during the salpingectomy can lead to injuries on the ovarian vascularization, and thus to the ovarian response to hormonal stimulation. Does salpingectomy affect negatively the follicles recruitment in in vitro fertilization (IVF) cycles? We conducted a monocentric retrospective case-control study including all patients undergoing IVF cycle with a history of unilateral salpingectomy for hydrosalpinx (HSX) or ectopic pregnancy (EP) (Group S), and each of them was matched to two controls (Group C) treated in the same month, according to their: age, AMH level, and BMI. The difference in follicle recruitment the day of trigger between the two ovaries of each patient was calculated. The primary endpoint was the difference between the two groups in the total number of follicles with a diameter ≥ 13 mm. Secondary endpoints were the difference between groups regarding the number of (1) mature follicles (diameter ≥ 16 mm) and intermediate follicles [13.0-15.5 mm]; (2) cycle cancellation rate; and (3) total number of oocytes and mature oocytes retrieved. The same comparisons were also carried out on subgroups according to the indication for salpingectomy (HSX or EP).</p><p><strong>Results: </strong>114 and 228 patients were included in Groups S and C, respectively. Compared to Group C, Group S patients showed a greater difference between ovaries in the total number of follicles recruited (0.76 ± 3.95 vs. -0.18 ± 3.37, p = 0.002) and in the number of mature follicles (0.51 ± 2.91 vs. -0.14 ± 2.85, p = 0.05). No significant differences were observed for the number of intermediate follicles, or the total number of oocytes or mature oocytes retrieved. However, the cycle cancellation rate was significantly higher in Group S (13.2% vs. 3.1%, p < 0.001). Subgroup analysis revealed no significant differences between each of the Group S subgroups (HSX and EP) regarding follicular recruitment. Nevertheless, both subgroups had significantly more cancelled cycles compared with their respective controls (HSX: 12.5% vs. 4.4%, p < 0.001; EP: 8.8% vs. 1.8%, p = 0.004).</p><p><strong>Conclusion: </strong>Salpingectomy has a negative impact on follicles recruitement in IVF cycles. This risk must be taken into consideration when scheduling this surgery.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005493","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}