Reproductive SciencesPub Date : 2025-06-01Epub Date: 2025-04-15DOI: 10.1007/s43032-025-01863-1
Natasa Z Djordjevic, Tanja R Novakovic, Zana C Dolicanin, Nikola D Jovic, Goran M Babic
{"title":"Maternal Thrombophilia Disrupts Fetal Redox Homeostasis.","authors":"Natasa Z Djordjevic, Tanja R Novakovic, Zana C Dolicanin, Nikola D Jovic, Goran M Babic","doi":"10.1007/s43032-025-01863-1","DOIUrl":"10.1007/s43032-025-01863-1","url":null,"abstract":"<p><p>Considering that the fetal redox homeostasis is a key factor for normal prenatal development, this study researched the effects of maternal thrombophilia on fetal redox homeostasis by assessing the redox profile of amniotic fluid cells and amniotic fluid during the second trimester of pregnancy. Concentration of redox biomarkers (superoxide anion, O<sub>2</sub>.<sup>-</sup>; hydrogen peroxide, H<sub>2</sub>O<sub>2</sub>; nitric oxide, NO; peroxynitrite, ONOO<sup>-</sup>; lipid peroxides, LPO, micronuclei, reduced glutathione, GSH; oxidized glutathione, GSSG) were assayed in the amniotic fluid cells and amniotic fluid of healthy pregnant women and pregnant women with thrombophilia gestational age from 16 to 18 weeks. Results of this study indicate that pregnant women with thrombophilia have significantly higher concentrations of O<sub>2</sub>.<sup>-</sup>, NO, ONOO<sup>-</sup>, and LPO but lower concentrations of H<sub>2</sub>O<sub>2</sub>, GSH, and GSSG in the amniotic fluid cells, as well as a higher concentration of GSSG in the amniotic fluid. No difference is shown in concentration of O<sub>2</sub>.<sup>-</sup>, H<sub>2</sub>O<sub>2</sub>, NO, ONOO<sup>-</sup>, LPO, and GSH in the amniotic fluid, as well as in frequency of micronuclei in the amniotic fluid cells among investigated groups of pregnant women. The present study provides the first evidence that babies born to mothers with thrombophilia in the second trimester of intrauterine life experience intense oxidative stress characterized by overproduction of O<sub>2</sub>.<sup>-</sup>, NO, ONOO<sup>-</sup>, and LPO, as well as GSH depletion.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1998-2009"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-06-01Epub Date: 2025-05-01DOI: 10.1007/s43032-025-01867-x
Cennikon Pakpahan, Natasha Susanto Utomo, Markus Christian Hartanto, Marc Torra-Massana, Andri Rezano
{"title":"Meta-correlation of Sperm Morphology and DNA Fragmentation Index.","authors":"Cennikon Pakpahan, Natasha Susanto Utomo, Markus Christian Hartanto, Marc Torra-Massana, Andri Rezano","doi":"10.1007/s43032-025-01867-x","DOIUrl":"10.1007/s43032-025-01867-x","url":null,"abstract":"<p><p>The 6th WHO guidelines for human semen examination recommend advanced semen analysis, such as the sperm DNA fragmentation index (DFI), to evaluate male factor infertility, as oxidative stress in the male reproductive system can damage sperm plasma membranes and compromise DNA integrity. Although sperm DFI was known to be associated with pregnancy probability, its examination is often limited by unavailability and high costs. In contrast, basic semen analysis, which includes sperm morphology assessment, is routinely performed, widely available, and cosf-effective. This systematic review and meta-analysis aimed to evaluate the correlation between sperm morphology and DNA Fragmentation Index (DFI) to improve diagnostic and clinical applications. Relevant studies were retrieved from MedLine, Web of Science, Scopus, EBSCO, and ProQuest, using keywords related to the correlation between sperm morphology and DFI. Correlation analyses were conducted using a random-effects model to calculate r-values for normal and abnormal sperm morphology with DFI. This meta-analysis showed an inverse correlation between normal sperm morphology and DFI with r: -0.30 and a positive correlation between abnormal sperm morphology and DFI with r: 0.39. Specifically, the head deformities had stronger correlation with DFI compared to neck and tail deformities. This study underscores the potential to predict DFI from sperm morphology results in settings where DFI testing is unavailable.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1775-1802"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-06-01Epub Date: 2025-03-19DOI: 10.1007/s43032-025-01832-8
Zeyad Hossam Atta Khalil, Omar Altayfa
{"title":"Disruption of the Wnt/β-Catenin and PI3K-AKT-mTOR Crosstalk in Endometrial Stromal Cells: A Case Report of Impaired Decidualization Leading to Recurrent Implantation Failure and Potential Pathway-Specific Therapeutic Interventions.","authors":"Zeyad Hossam Atta Khalil, Omar Altayfa","doi":"10.1007/s43032-025-01832-8","DOIUrl":"10.1007/s43032-025-01832-8","url":null,"abstract":"<p><p>A 34-year-old woman with a long-standing history of recurrent implantation failure (RIF) and unexplained infertility presented for further evaluation. Molecular analysis revealed a significant disruption in the crosstalk between the Wnt/β-catenin and PI3K-AKT-mTOR signaling pathways, both essential for regulating endometrial receptivity and successful embryo implantation. Immunohistochemical testing showed a marked reduction in β-catenin nuclear translocation and a 65% decrease in AKT phosphorylation, leading to impaired cellular processes such as proliferation and differentiation. This disruption contributed to incomplete decidualization of the endometrium, which played a central role in her repeated implantation failures. Conventional fertility treatments, including hormone therapy and in vitro fertilization (IVF), were ineffective. Consequently, we explored targeted molecular therapies aimed at restoring functionality within these signaling pathways to enhance endometrial receptivity. This case underscores the critical role of the Wnt/β-catenin and PI3K-AKT-mTOR pathways in endometrial function and highlights the potential for novel therapeutic strategies in treating RIF by addressing specific molecular defects.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1953-1958"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664466","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}
Reproductive SciencesPub Date : 2025-06-01Epub Date: 2025-04-18DOI: 10.1007/s43032-025-01861-3
Adishree Nayak, Shannon N Wood, Liisa Hantsoo
{"title":"Barriers to Diagnosis and Treatment for Premenstrual Dysphoric Disorder (PMDD): A Scoping Review.","authors":"Adishree Nayak, Shannon N Wood, Liisa Hantsoo","doi":"10.1007/s43032-025-01861-3","DOIUrl":"10.1007/s43032-025-01861-3","url":null,"abstract":"<p><p>Premenstrual dysphoric disorder (PMDD) is a significant public health challenge. While research has increased over the past decade, barriers to PMDD diagnosis and treatment persist. This paper explores the global barriers to diagnosis and treatment for PMDD. A scoping review of the literature was performed using the PubMed, PsycINFO, and CINAHL Plus databases to compile existing data on barriers to PMDD diagnosis and treatment. Eligibility criteria for articles included original research published within the last 10 years, written in English, and focused on PMDD with explicit assessment of at least one barrier to diagnosis and/or treatment. Findings were organized into four domains: individual, medical, cultural, and structural barriers. At the individual level, barriers include internalized norms and stigma that deter help-seeking; medical trauma and mistrust; feelings of fear, shame, self-blame, and confusion; and diminished autonomy and increased side effects from prescribed PMDD treatments. Medical barriers include limited provider knowledge, nonadherence to diagnostic and treatment guidelines, and negative patient-provider interactions. Cultural barriers include reproductive and mental health stigma; gender and cultural norms; and cultural preferences for alternative medicine that reduce access to pharmacological treatment. At the structural level, barriers include fragmented healthcare and limited access to health services. These findings highlight the many diagnostic and treatment barriers for individuals living with PMDD, underscoring the need for future research and intersectional approaches to improve health outcomes for this population.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1757-1767"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-06-01Epub Date: 2025-03-31DOI: 10.1007/s43032-025-01851-5
Bei Liu, Keya Tong, Yang Gao, Yi Chen, Yifan Wang, Jiaqiang Wang, Jingyu Li, Liwei Sun
{"title":"Identification of the novel homozygous whole exon deletion in MEI1 underlying azoospermia and embryonic arrest in one consanguineous family.","authors":"Bei Liu, Keya Tong, Yang Gao, Yi Chen, Yifan Wang, Jiaqiang Wang, Jingyu Li, Liwei Sun","doi":"10.1007/s43032-025-01851-5","DOIUrl":"10.1007/s43032-025-01851-5","url":null,"abstract":"<p><p>This study characterized a male infertile patient suffering from azoospermia and a female infertile patient with embryonic arrest from one consanguineous family. We aimed to elucidate the novel pathogenic mechanism and provide support for the genetic diagnosis of infertility. Mutations were detected by whole-exome sequencing (WES) and confirmed by Sanger sequencing. Effect of the mutations on mRNA level was investigated by sequencing the cDNA amplification product. Functional characterization of the mutations was investigated through transfection in HEK293T cells in vitro, and the subcellular localization and protein levels were evaluated by immunofluorescence and western blot. Preimplantation genetic testing was performed to analyze chromosomal anomalies of the arrested embryos. The novel homozygous whole exon deletion of exon 19 in MEI1 was detected by WES. Amplification and sequencing of the cDNA verified the deletion of whole exon of MEI1. Quantitative expression revealed that the deletion result in almost no detectable expression of MEI1 Exon 19 in patients, and their mother is a heterozygous carrier of this whole exon deletion. Western blotting revealed that the whole exon deletion in MEI1 result in production of truncated MEI1 protein, corresponding to the predicted premature termination at Exon 20 of MEI1. Highly chromosomal anomalies were revealed in arrested embryos with MEI1 mutation. Overall, this study reported the first exon rearrangement of MEI1, thus broadening the mutational pattern and spectrum of MEI1-associated infertility, and also revealed the aneuploidies of embryos with MEI1 mutation as a potential reason for declined developmental potency and embryonic arrest.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1968-1978"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Using Machine Learning to Predict the Prognosis of Cervical Cancer Patients with Lymph Node Metastasis: An Analysis Based on the SEER Database.","authors":"Erle Deng, Zheng Gu, Hongtao Wei, Chengdi Liu, Yiwen Dong, Junxian Yu","doi":"10.1007/s43032-025-01856-0","DOIUrl":"10.1007/s43032-025-01856-0","url":null,"abstract":"<p><p>Cervical cancer is one of the most common malignant tumors in women worldwide, and patients with lymph node metastasis have a poor prognosis. This study aimed to develop an effective machine learning model to predict the prognosis of these patients. Data from the SEER*Stat database (version: November 2021) was used, including 1016 female patients diagnosed with cervical cancer and lymph node metastasis from 2000 to 2020. Various machine learning models, including XGBoost, random forest, SVM, ANN, and the Cox proportional hazards model, were constructed and evaluated using metrics such as C-index, AUC, accuracy, and precision. Additionally, to validate model stability, a random sample of 200 patients from 8 registries between 1975 and 2019 was used as a validation set. XGBoost outperformed other models with an AUC of 0.787 in the validation set and C-index values of 0.900 and 0.773 for the training and testing sets, respectively. Cox regression analysis showed that surgery at the primary site significantly improved survival outcomes and reduced mortality. XGBoost demonstrated superior performance in predicting the prognosis of cervical cancer patients with lymph node metastasis, providing new support for personalized clinical management.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1851-1863"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-06-01Epub Date: 2025-05-13DOI: 10.1007/s43032-025-01875-x
Suresh Singh Yadav, Rohini Ravindran Nair
{"title":"Ethyl Pyruvate as a Potential Therapeutic Agent for Endometriosis: A Perspective.","authors":"Suresh Singh Yadav, Rohini Ravindran Nair","doi":"10.1007/s43032-025-01875-x","DOIUrl":"10.1007/s43032-025-01875-x","url":null,"abstract":"<p><p>Endometriosis is a disease where vascularised tissue similar to endometrium (the lining of the uterus) grows outside of the uterus. Its pathogenesis involves a complex interplay of inflammation, angiogenesis, cellular proliferation, reactive oxygen species (ROS) production, altered energy metabolism, and epithelial-to-mesenchymal transition (EMT).Even though endometriosis was described more than 150 years ago, we have been unable to find its effective therapy. Conservative treatment approaches like non-steroidal anti-inflammatory drugs or hormone therapy are available to date for the treatment of endometriosis. Anti-angiogenic inhibitors and immunomodulators like IFN-α, β, and TNF-α inhibitors are also potential treatment options. These treatments are inadequate as they either affect the symptoms only of endometriosis or target only one pathological pathway involved. Surgical excision of the endometriotic lesion is also possible, however, recurrence of the disease is reported in several cases. A single therapeutic agent targeting several pathological processes in endometriosis would always be a better option. Here we present our perspective on the pharmacological potential of Ethyl pyruvate and also propose it as a promising therapeutic agent for endometriosis as it inhibits inflammation, cell proliferation, angiogenesis, aerobic glycolysis, EMT, and ROS activity together.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1979-1986"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Association Between Annexin A5 c.-302G > T Variant and the Risk of Recurrent Pregnancy Loss: Systematic Review and Meta-analysis.","authors":"Jintuo Zhou, Yanting Zhu, Ying Liu, Hairong Zhan, Peiguang Niu, Huajiao Chen, Jinhua Zhang","doi":"10.1007/s43032-025-01848-0","DOIUrl":"10.1007/s43032-025-01848-0","url":null,"abstract":"<p><p>This study aimed to conduct a comprehensive meta-analysis of the relationship between Annexin A5 (ANXA5) c.-302G > T variant and susceptibility to recurrent pregnancy loss (RPL). We conducted a comprehensive systematic search of the literature published before June 17, 2023 using PubMed, Embase, Web of Science, and Cochrane Library. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included studies. The odds ratio was used to estimate the correlation of the ANXA5 c.-302 T > G genetic alteration with RPL susceptibility. The I squared (I<sup>2</sup>) statistic and Q statistic were used to assess the heterogeneity among the included studies. And Begg's test and Egger's regression were then conducted to evaluate publication bias. In this meta-analysis, we included seven studies comprising 1535 RPL cases and 1328 healthy pregnant women to investigate the relationship between ANXA5 c.-302G > T variants and the susceptibility of RPL. No significant publication bias was detected across different comparison models. In the overall population analysis, the ANXA5 c.-302G > T variant was positively associated with the risk of RPL under the dominant, allelic, heterozygote and homozygous models. Meta-regression analysis was performed to identify the potential source of heterogeneity, revealing that neither publication year nor country contributed to heterogeneity. Our findings provided robust evidence that the ANXA5 c.-302G > T variant was significantly associated with an increased risk of RPL, highlighting its potential as a genetic marker for identifying women at high risk of developing RPL. These results emphasized the importance of genetic screening in improving the understanding and clinical management of RPL.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2019-2026"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Decreased FTO Expression Promotes Ovarian Granulosa Cells Aging.","authors":"Jia Ying, Xuehong Zhang, Xiaoyan Sun, Qingxia Meng","doi":"10.1007/s43032-025-01873-z","DOIUrl":"10.1007/s43032-025-01873-z","url":null,"abstract":"<p><p>This study aimed to investigate the role of fat mass and obesity-associated protein (FTO), an N6-methyladenosine (m<sup>6</sup>A) demethylase, in ovarian aging by examining the effects of FTO downregulation on key biological processes in human ovarian granulosa cells (KGN), including proliferation, apoptosis regulation, senescence, and steroidogenic function. Stable FTO knockdown in KGN cells was achieved using lentivirus, complemented by modeling premature senescence with H<sub>2</sub>O<sub>2</sub> treatment. The biological functions, such as cell proliferation, apoptosis, aging, and sex hormone secretion, were assessed using RT-qPCR, WB, EdU staining, and ELISA, respectively. Silencing FTO significantly inhibited the proliferation of KGN cells, promoted apoptosis and senescence, and disrupted their endocrine function. These effects were consistent in the H<sub>2</sub>O<sub>2</sub>-induced senescence model. Our findings identify FTO as a critical regulator of ovarian homeostasis. Depletion of FTO impairs granulosa cell viability, accelerates senescence-related functional decline, and diminishes steroidogenic capacity through m<sup>6</sup>A-mediated modulation of key biosynthetic enzymes. These insights highlight FTO as a potential therapeutic target for age-related ovarian dysfunction.</p>","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"1987-1997"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reproductive SciencesPub Date : 2025-06-01Epub Date: 2025-04-24DOI: 10.1007/s43032-025-01864-0
Md Reduanul Hossain, Marina Paul, Jorge M Tolosa, Roger Smith, Jonathan W Paul
{"title":"Assessing Tocolytic Potency: Variability and Accuracy of AUC Versus Amplitude-Based Assessment of Pregnant Human Myometrial Contractions Ex Vivo.","authors":"Md Reduanul Hossain, Marina Paul, Jorge M Tolosa, Roger Smith, Jonathan W Paul","doi":"10.1007/s43032-025-01864-0","DOIUrl":"10.1007/s43032-025-01864-0","url":null,"abstract":"<p><p>The methodological approaches used to evaluate the inhibitory effects (potency determination) of tocolytic agents on human uterine contractions in ex vivo systems vary, and none of the methodologies has been subjected to scrutiny in terms of objectivity, variability, and reliability. Therefore, this study aimed to assess and compare the reliability of using area under the curve (AUC) versus amplitude alone-based assessment of contraction traces to generate concentration-response curves, which were then used to calculate the tocolytic concentrations that inhibited 25% (IC<sub>25</sub>) and 50% (IC<sub>50</sub>) of baseline contractility. The accuracy of the determined inhibitory concentrations (IC) was then scrutinized while taking into consideration the contraction parameters (amplitude, frequency, duration) affected by the different tocolytics. To do this, pregnant human myometrial strips (term, not-in-labor) were treated with cumulative concentrations of the contraction-blocking agents, nifedipine (NIF), indomethacin (IND), 2-aminoethoxydiphenyl borate (2-APB), glycyl-h-1152 (GH), aminophylline (AMP), or rolipram (ROL)). Concentration-response curves were generated using either AUC or amplitude alone as the index of contraction inhibition, from which tocolytic IC<sub>25</sub> and IC<sub>50</sub> concentrations were calculated and compared (i.e. IC<sub>25(AUC)</sub> vs. IC<sub>25(Amplitude)</sub>). The effects of each tocolytic on contraction frequency were also quantified. To assess accuracy, each tocolytic was applied to contracting strips as a single treatment at their respective IC<sub>25(AUC/Amplitude)</sub> and IC<sub>50(AUC/Amplitude)</sub>, and then the inhibitory effect re-quantified against both contraction AUC and amplitude alone. Significant differences between IC<sub>50(AUC)</sub> and IC<sub>50(Amplitude)</sub> were detected for AMP (318.5 vs. 450 µM), ROL (4.3 vs. 55 µM), and IND (59.5 vs. 75 µM), whereas AUC versus amplitude-based IC<sub>50</sub> concentrations were comparable for NIF (10 vs. 10 nM), GH (18.2 vs. 15 µM), and 2-APB (53 vs. 57 µM). Similarly, the determined IC<sub>25(AUC)</sub> and IC<sub>25(Amplitude)</sub> were again significantly different for AMP (175 vs. 277 µM), ROL (515 nM vs. 15 µM), and IND (28 vs. 42 µM), but also for 2-APB (27 vs. 40 µM). The confirmation studies revealed that a single dose of the tocolytics at their determined IC<sub>25(AUC)</sub> and IC<sub>50(AUC)</sub> concentrations consistently reduced contraction AUC by approximately 25% and 50%, respectively, whereas single doses of the IC<sub>25(Amplitude)</sub> and IC<sub>50(Amplitude)</sub> concentrations revealed inconsistent results. Of the six tocolytics, four reduced contraction amplitude by > 25% when applied as a single dose at IC<sub>25(Amplitude)</sub>, while three reduced contraction amplitude by > 50% when applied at IC<sub>50(Amplitude)</sub>. Our experimental data indicate that when determining tocolytic potency, assessment of","PeriodicalId":20920,"journal":{"name":"Reproductive Sciences","volume":" ","pages":"2027-2049"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021545","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}