{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T14:23:49Z","timestamp":1781619829507,"version":"3.54.5"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\nBackground<\/jats:title>\nThreatened abortion is a common obstetric complication where early risk stratification is crucial for clinical management. CA125, a glycoprotein biomarker produced by endometrial and trophoblastic tissues, may serve as a valuable prognostic indicator as its elevated levels often reflect placental inflammation or detachment in this condition. To systematically assess its clinical value, we conducted a meta-analysis evaluating the prognostic accuracy of serum CA125 levels for miscarriage risk in patients with threatened abortion.<\/jats:p>\n<\/jats:sec>\n\nMethods<\/jats:title>\nWe systematically searched Web of Science, Medline via PubMed, ScienceDirect, EMBASE, Geenmedical, Cochrane Library, and Wiley databases from inception to May 30, 2024 for studies evaluating either CA125\u2019s prognostic value for miscarriage risk in threatened abortion, or serum markers\u2019 prognostic value for pregnancy outcomes. Two researchers independently screened literature and extracted data. Study quality and evidence certainty were assessed using QUAPAS and GRADE frameworks respectively. Meta-analyses were performed using Stata 17 and Review Manager 5.3.<\/jats:p>\n<\/jats:sec>\n\nResults<\/jats:title>\nA total of 13 studies involving 1166 patients with threatened abortion were included in this meta-analysis. The pooled estimates demonstrated that CA125 exhibited the following prognostic performance for predicting miscarriage risk in patients with threatened abortion: sensitivity, 89% (95% CI: 83\u201393%); specificity, 91% (95% CI: 84\u201395%); positive likelihood ratio (PLR), 10.2 (95% CI: 5.4\u201319.3); negative likelihood ratio (NLR), 0.13 (95% CI: 0.08\u20130.19); diagnostic odds ratio (DOR), 82 (95% CI: 31\u2013212); and area under the summary receiver operating characteristic curve (SROC AUC), 0.95 (95% CI: 0.92\u20130.96). Elevated serum CA125 levels were significantly associated with an increased risk of miscarriage. According to the GRADE assessment, the certainty of evidence was moderate for sensitivity but low for other parameters, primarily due to heterogeneity, risk of bias, and other confounding factors.<\/jats:p>\n<\/jats:sec>\n\nConclusion<\/jats:title>\nCurrent evidence with moderate certainty indicates that serum CA125 demonstrates high prognostic value for assessing miscarriage risk in threatened abortion, particularly for identifying high-risk patients. However, due to low-certainty specificity findings, caution is warranted when using CA125 to rule out miscarriage. While these results support CA125\u2019s potential as a complementary tool to ultrasound, further studies are required to establish standardized cut-off values for clinical implementation.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0326384","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T17:34:18Z","timestamp":1750786458000},"page":"e0326384","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Assessment of the prognostic value of CA125 for miscarriage risk in patients with threatened abortion: A systematic review and meta-analysis"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3182-9095","authenticated-orcid":true,"given":"Yurong","family":"Cao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linna","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"issue":"3","key":"pone.0326384.ref001","doi-asserted-by":"crossref","first-page":"284","DOI":"10.5582\/bst.2019.01155","article-title":"New thoughts in exploring the pathogenesis, diagnosis, and treatment of threatened abortion","volume":"13","author":"J Zhou","year":"2019","journal-title":"Biosci Trends"},{"issue":"7458","key":"pone.0326384.ref002","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1136\/bmj.329.7458.152","article-title":"Threatened miscarriage: evaluation and management","volume":"329","author":"A Sotiriadis","year":"2004","journal-title":"BMJ"},{"issue":"4","key":"pone.0326384.ref003","first-page":"233","article-title":"Management of threatened abortion","volume":"2","author":"I Szab\u00f3","year":"1996","journal-title":"Early Pregnancy"},{"key":"pone.0326384.ref004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jad.2018.04.012","article-title":"Threatened miscarriage and depressive and anxiety symptoms among women and partners in early pregnancy","volume":"237","author":"CS Zhu","year":"2018","journal-title":"J Affect Disord"},{"issue":"4","key":"pone.0326384.ref005","first-page":"34","article-title":"Left and right uterine artery doppler as early skreening test of threatened abortion outcome","volume":"55","author":"I Traianov","year":"2016","journal-title":"Akush Ginekol (Sofiia)"},{"issue":"1","key":"pone.0326384.ref006","doi-asserted-by":"crossref","first-page":"23","DOI":"10.23938\/ASSN.0933","article-title":"Predictive value of hyperglycosylated human chorionic gonadotropin for pregnancy outcomes in threatened abortion in first-trimester viable pregnancies","volume":"44","author":"A Salas","year":"2021","journal-title":"An Sist Sanit Navar"},{"key":"pone.0326384.ref007","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/0002-9378(95)90596-0","article-title":"Serum CA 125 levels and spontaneous abortion","volume":"172","author":"MD Hornstein","year":"1995","journal-title":"Am J Obstet Gynecol"},{"issue":"2","key":"pone.0326384.ref008","doi-asserted-by":"crossref","first-page":"188503","DOI":"10.1016\/j.bbcan.2021.188503","article-title":"Roles of CA125 in diagnosis, prediction, and oncogenesis of ovarian cancer","volume":"1875","author":"M Zhang","year":"2021","journal-title":"Biochim Biophys Acta Rev Cancer"},{"issue":"1","key":"pone.0326384.ref009","doi-asserted-by":"crossref","first-page":"21694","DOI":"10.1038\/s41598-021-01263-w","article-title":"Serum HE4 and CA125 combined to predict and monitor recurrence of type II endometrial carcinoma","volume":"11","author":"Q Quan","year":"2021","journal-title":"Sci Rep"},{"key":"pone.0326384.ref010","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.ejogrb.2017.01.017","article-title":"Ratios of biochemical markers in peritoneal fluid to those in venous blood for the diagnosis of ruptured tubal pregnancy: a prospective study","volume":"210","author":"X-L Zhu","year":"2017","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"issue":"5","key":"pone.0326384.ref011","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1097\/AOG.0000000000002900","article-title":"ACOG practice bulletin no. 200 summary: early pregnancy loss","volume":"132","year":"2018","journal-title":"Obstet Gynecol"},{"key":"pone.0326384.ref012","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"MJ Page","year":"2021","journal-title":"BMJ"},{"issue":"7","key":"pone.0326384.ref013","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.7326\/M22-0276","article-title":"QUAPAS: an adaptation of the QUADAS-2 tool to assess prognostic accuracy studies","volume":"175","author":"J Lee","year":"2022","journal-title":"Ann Intern Med"},{"key":"pone.0326384.ref014","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/0028-2243(92)90258-Z","article-title":"The prognostic significance of maternal serum CA125 measurement in threatened abortion","volume":"46","author":"F O\u00e7er","year":"1992","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"issue":"3","key":"pone.0326384.ref015","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/0020-7292(95)02371-I","article-title":"Serum CA 125 and first trimester abortion","volume":"49","author":"F Scarpellini","year":"1995","journal-title":"Int J Gynaecol Obstet"},{"issue":"2","key":"pone.0326384.ref016","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0020-7292(97)00114-8","article-title":"The prognostic predictive value of maternal serum CA 125 levels in threatened abortion","volume":"59","author":"OA Leylek","year":"1997","journal-title":"Int J Gynaecol Obstet"},{"issue":"1","key":"pone.0326384.ref017","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1080\/01443610063507","article-title":"Can a single serum CA125 assay predict the outcome of threatened abortion?","volume":"20","author":"LS Sherif","year":"2000","journal-title":"J Obstet Gynaecol"},{"issue":"12","key":"pone.0326384.ref018","first-page":"982","article-title":"Clinical value of a single serum CA-125 level in women with symptoms of imminent abortion during the first trimester of pregnancy","volume":"48","author":"P Fiegler","year":"2003","journal-title":"J Reprod Med"},{"issue":"3","key":"pone.0326384.ref019","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.mefs.2013.04.001","article-title":"Biochemical and ultrasonographic predictors of outcome in threatened abortion","volume":"18","author":"AM Maged","year":"2013","journal-title":"Middle East Fertil Soc J"},{"issue":"2","key":"pone.0326384.ref020","doi-asserted-by":"crossref","first-page":"186","DOI":"10.12891\/ceog14862014","article-title":"Prediction of pregnancy outcomes with combined ultrasound scanning of yolk sacs and serum CA125 determinations in early threatened abortion","volume":"41","author":"YJ Xie","year":"2014","journal-title":"Clin Exp Obstet Gynecol"},{"issue":"1","key":"pone.0326384.ref021","first-page":"1077","article-title":"Serum CA-125 for early prediction of miscarriage","volume":"4","author":"MS Sweed","year":"2016","journal-title":"Med J Obstet Gynecol"},{"issue":"4","key":"pone.0326384.ref022","first-page":"506","article-title":"Correlation of serum CA-125 and progesterone levels with ultrasound markers in the prediction of pregnancy outcome in threatened miscarriage","volume":"9","author":"M Al Mohamady","year":"2016","journal-title":"Int J Fertil Steril"},{"issue":"2","key":"pone.0326384.ref023","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1002\/ijgo.12631","article-title":"Doppler and biochemical assessment for the prediction of early pregnancy outcome in patients experiencing threatened spontaneous abortion","volume":"143","author":"NAA Shehata","year":"2018","journal-title":"Int J Gynaecol Obstet"},{"issue":"1","key":"pone.0326384.ref024","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.recli.2017.03.003","article-title":"CA125, progesterone & \u03b2-hCG in prediction of first trimester abortion","volume":"32","author":"AA Mansy","year":"2017","journal-title":"Reprod Climat\u00e9rio"},{"issue":"7","key":"pone.0326384.ref025","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1515\/jpm-2019-0097","article-title":"The predictive value of serum cancer antigen 125 (CA125) levels on pregnancy outcome in threatened miscarriages","volume":"47","author":"MA Adeku","year":"2019","journal-title":"J Perinat Med"},{"key":"pone.0326384.ref026","first-page":"1258","article-title":"Role of CA-125 and ultrasound in early prediction of outcome of threatened miscarriage","volume":"33","author":"M Anter","year":"2020","journal-title":"Menoufia Med J"},{"issue":"10285","key":"pone.0326384.ref027","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1016\/S0140-6736(21)00682-6","article-title":"Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss","volume":"397","author":"S Quenby","year":"2021","journal-title":"Lancet"},{"issue":"08","key":"pone.0326384.ref028","doi-asserted-by":"crossref","DOI":"10.4172\/2161-0932.1000481","article-title":"Ultrasonography and pregnancy outcome in threatened abortion: a prospective observational study","volume":"08","author":"AM Farag","year":"2018","journal-title":"Gynecol Obstet"},{"key":"pone.0326384.ref029","doi-asserted-by":"crossref","unstructured":"Sarmalkar M, Singh S, Nayak A. Maternal and perinatal outcome in women with threatened abortion in first trimester. 2016.","DOI":"10.18203\/2320-1770.ijrcog20161301"},{"issue":"5","key":"pone.0326384.ref030","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1016\/j.radi.2024.07.022","article-title":"Assessing the predictive value of first trimester ultrasound and biochemical markers in miscarriage: a scoping review","volume":"30","author":"L Sammut","year":"2024","journal-title":"Radiography (Lond)"},{"issue":"9","key":"pone.0326384.ref031","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1111\/aogs.14829","article-title":"Progestogens in women with threatened miscarriage or recurrent miscarriage: a meta-analysis","volume":"103","author":"Y Zhao","year":"2024","journal-title":"Acta Obstet Gynecol Scand"},{"issue":"9","key":"pone.0326384.ref032","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1002\/jum.15282","article-title":"Clinical and ultrasound evaluation of early threatened miscarriage to predict pregnancy continuation up to 28\u2009weeks: a prospective cohort study","volume":"39","author":"AH Shaamash","year":"2020","journal-title":"J Ultrasound Med"},{"issue":"3","key":"pone.0326384.ref033","article-title":"Diagnostic biomarkers for predicting adverse early pregnancy outcomes: scientific impact paper no. 58","volume":"126","author":"Royal College of Obstetricians and Gynaecologists","year":"2019","journal-title":"BJOG"},{"issue":"2","key":"pone.0326384.ref034","first-page":"228","article-title":"Role of serum biomarkers in the prediction of outcome in women with threatened miscarriage: a systematic review and diagnostic accuracy meta-analysis","volume":"22","author":"RN Pillai","year":"2016","journal-title":"Hum Reprod Update"},{"issue":"5","key":"pone.0326384.ref035","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/S0015-0282(16)49812-2","article-title":"The use of CA-125 in the diagnosis and management of endometriosis","volume":"46","author":"DE Pittaway","year":"1986","journal-title":"Fertil Steril"},{"issue":"5","key":"pone.0326384.ref036","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1172\/JCI110380","article-title":"Reactivity of a monoclonal antibody with human ovarian carcinoma","volume":"68","author":"RC Bast","year":"1981","journal-title":"J Clin Invest"},{"issue":"7","key":"pone.0326384.ref037","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1093\/oxfordjournals.humrep.a136445","article-title":"Cancer antigen 125 is produced by human endometrial stromal cells","volume":"1","author":"P Bischof","year":"1986","journal-title":"Hum Reprod"},{"issue":"19","key":"pone.0326384.ref038","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.3390\/cancers16193295","article-title":"The predictive value of the fibrinogen-albumin-ratio index on surgical outcomes in patients with advanced high-grade serous ovarian cancer","volume":"16","author":"M Postl","year":"2024","journal-title":"Cancers (Basel)"},{"issue":"1","key":"pone.0326384.ref039","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1186\/s12905-024-03227-4","article-title":"The coagulation status in women of endometriosis with stage IV","volume":"24","author":"L Wang","year":"2024","journal-title":"BMC Womens Health"},{"key":"pone.0326384.ref040","doi-asserted-by":"crossref","first-page":"1442814","DOI":"10.3389\/fonc.2024.1442814","article-title":"Evaluating pretreatment serum CA-125 levels as prognostic biomarkers in endometrial cancer: a comprehensive meta-analysis","volume":"14","author":"Z Yu","year":"2024","journal-title":"Front Oncol"},{"issue":"11","key":"pone.0326384.ref041","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1111\/jog.13764","article-title":"Serum levels of human epididymis protein 4 are more stable than cancer antigen 125 in early and mid-term pregnancy","volume":"44","author":"Z Wang","year":"2018","journal-title":"J Obstet Gynaecol Res"},{"key":"pone.0326384.ref042","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.placenta.2023.08.003","article-title":"Serum CA-125 as a predictor in the early diagnosis of ectopic pregnancy in Vietnam - a case-control study","volume":"140","author":"NBT Tran","year":"2023","journal-title":"Placenta"},{"issue":"3","key":"pone.0326384.ref043","first-page":"2902","article-title":"Evaluation of serum biomarkers and efficacy of MTX in women with ectopic pregnancy","volume":"20","author":"H Li","year":"2019","journal-title":"Mol Med Rep"},{"issue":"5","key":"pone.0326384.ref044","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s00404-008-0798-x","article-title":"Predictive power of serum CA-125 and LDH in the outcome of first trimester pregnancies with human chorionic gonadotropin levels below discriminatory zone","volume":"279","author":"Y Madendag","year":"2009","journal-title":"Arch Gynecol Obstet"},{"issue":"2","key":"pone.0326384.ref045","first-page":"159","article-title":"Serum maternal carcinoembryonic antigen-125 (CA-125) levels in first trimester threatened abortion with demonstrable fetal heart activity","volume":"6","author":"D Vavilis","year":"2001","journal-title":"Middle East Fertil Soc J"},{"issue":"5","key":"pone.0326384.ref046","first-page":"345","article-title":"Serum levels of CA-125 antigen during the first trimester of pregnancy complications and the risk of miscarriage","volume":"74","author":"P Fiegler","year":"2003","journal-title":"Ginekol Pol"},{"issue":"1","key":"pone.0326384.ref047","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18203\/2320-1770.ijrcog20215068","article-title":"Maternal serum CA-125 repeated measurement during pregnancy and how to use as a prognostic factor of first trimester pregnancy outcome","volume":"11","author":"NS Badr","year":"2021","journal-title":"Int J Reprod Contracept Obstet Gynecol"},{"key":"pone.0326384.ref048","article-title":"The comparison of CA125 levels in the normal pregnancy and threatened abortion","author":"E Barooti","year":"2022","journal-title":"J Obstet Gynecol Cancer Res"},{"issue":"1","key":"pone.0326384.ref049","doi-asserted-by":"crossref","first-page":"59","DOI":"10.21608\/amj.2020.67537","article-title":"Predictive value of serum CA-125 versus serum progesterone in predicting risk of pregnancy loss in cases of first trimesteric threatened abortion","volume":"49","author":"AE-M Zakaria","year":"2020","journal-title":"Al-Azhar Med J"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0326384","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T17:34:32Z","timestamp":1750786472000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0326384"}},"subtitle":[],"editor":[{"given":"Ahmed Mohamed","family":"Maged","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,6,24]]},"references-count":49,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0326384","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,24]]}}}