{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T04:45:07Z","timestamp":1793853907894,"version":"4.6.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the association between early pregnancy estradiol (E2)\u00a0trajectory patterns and the risk of early miscarriage in women with natural conception.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study included 527 women aged 18\u201345 years with natural conception and at least three E2 measurements within the first 12 gestational weeks, from March 2023 to August 2024. Group-based trajectory modeling identified four distinct E2 trajectories. Demographic and clinical data were extracted from medical records, and pregnancy outcomes were obtained through follow-up. Multivariate logistic regression and subgroup analyses were performed to evaluate the association between E2 trajectories and early miscarriage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among the four identified E2 trajectories, women in Trajectory 3 (\u201cHigh Level with Steady Increase\u201d) showed a significantly reduced risk of early miscarriage compared to those in Trajectory 2 (\u201cLow Level with Slow Increase\u201d) (adjusted OR = 0.24, 95% CI: 0.12\u20130.46, p &amp;lt; 0.001). Subgroup analyses stratified by age and number of previous miscarriages confirmed the robustness of this association, while no significant associations were found for the other trajectories. The highest miscarriage rate (42.03%) and lowest baseline E2 level (300.29 \u00b1 194.23) were observed in Trajectory 2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A steadily increasing high estradiol trajectory in early pregnancy is associated with a lower risk of early miscarriage, highlighting the potential value of E2 monitoring for early pregnancy risk assessment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1657453","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T05:17:30Z","timestamp":1763356650000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Estradiol trajectories and early pregnancy loss: a retrospective study"],"prefix":"10.3389","volume":"16","author":[{"given":"Yanling","family":"Wei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangxiang","family":"Mu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"Cd007223","DOI":"10.1002\/14651858.CD007223.pub4","article-title":"Medical treatments for incomplete miscarriage","volume":"1","author":"Kim","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"B2","doi-asserted-by":"publisher","first-page":"hoad002","DOI":"10.1093\/hropen\/hoad002","article-title":"ESHRE guideline: recurrent pregnancy loss: an update in 2022","volume":"2023","author":"Bender Atik","year":"2023","journal-title":"Hum Reprod Open"},{"key":"B3","doi-asserted-by":"publisher","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":"Quenby","year":"2021","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"Cd003511","DOI":"10.1002\/14651858.CD003511.pub4","article-title":"Progestogen for preventing miscarriage in women with recurrent miscarriage of unclear etiology","volume":"10","author":"Haas","year":"2018","journal-title":". Cochrane Database Syst Rev"},{"key":"B5","doi-asserted-by":"publisher","first-page":"Cd009278","DOI":"10.1002\/14651858.CD009278.pub2","article-title":"Combined oestrogen and progesterone for preventing miscarriage","volume":"2013","author":"Lim","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"B6","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s10815-013-0117-8","article-title":"The impact of supraphysiologic serum estradiol levels on peri-implantation embryo development and early pregnancy outcome following in vitro fertilization cycles","volume":"31","author":"Imudia","year":"2014","journal-title":"J Assist Reprod Genet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-006-9089-2","article-title":"Is estradiol mandatory for an adequate follicular and embryo development? A mouse model using aromatase inhibitor (anastrozole)","volume":"23","author":"Fatum","year":"2006","journal-title":"J Assist Reprod Genet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/1477-7827-7-124","article-title":"Regulated expression of matrix metalloproteinases, inflammatory mediators, and endometrial matrix remodeling by 17beta-estradiol in the immature rat uterus","volume":"7","author":"Russo","year":"2009","journal-title":"Reprod Biol Endocrinol"},{"key":"B9","article-title":"FoxM1 influences embryo implantation and is regulated by 17 beta-estradiol and progesterone in mouse uteri and endometrium cells","volume":"7","author":"Xie","year":"2014","journal-title":"Int J Clin Exp Pathol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-1133","article-title":"Regulation of progesterone receptor expression by estradiol is dependent on age, sex and region in the rat brain","volume":"149","author":"Quadros","year":"2008","journal-title":"Endocrinology"},{"key":"B11","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s13063-021-05953-8","article-title":"Does serum progesterone level impact the ongoing pregnancy rate in frozen embryo transfer under artificial preparation with vaginal progesterone? Study protocol for a randomized controlled trial","volume":"23","author":"Haiyan","year":"2022","journal-title":"Trials"},{"key":"B12","doi-asserted-by":"publisher","first-page":"3000605251327478","DOI":"10.1177\/03000605251327478","article-title":"Weekly changes in serum \u03b2-human chorionic gonadotropin, estradiol, and progesterone levels for pregnancy assessment in women with unexplained recurrent miscarriage","volume":"53","author":"Su","year":"2025","journal-title":"J Int Med Res"},{"key":"B13","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/s12884-021-04158-w","article-title":"Prediction of miscarriage in first trimester by serum estradiol, progesterone and \u03b2-human chorionic gonadotropin within 9\u2009weeks of gestation","volume":"22","author":"Deng","year":"2022","journal-title":"BMC Pregnancy Childbirth"},{"key":"B14","doi-asserted-by":"publisher","first-page":"107942","DOI":"10.1016\/j.maturitas.2024.107942","article-title":"The role of estrogen receptor gene polymorphisms in menopausal symptoms and estradiol levels in perimenopausal women - Findings from the Swiss Perimenopause Study","volume":"183","author":"Grub","year":"2024","journal-title":"Maturitas"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s10940-010-9113-7","article-title":"Group-based trajectory modeling (Nearly) two decades later","volume":"26","author":"Nagin","year":"2010","journal-title":"J Quant Criminol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"3472","DOI":"10.3390\/ijerph16183472","article-title":"Exploration of medical trajectories of stroke patients based on group-based trajectory modeling","volume":"16","author":"Chien","year":"2019","journal-title":"Int J Environ Res Public Health"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1159\/000360229","article-title":"Group-based trajectory modeling: an overview","volume":"65","author":"Nagin","year":"2014","journal-title":"Ann Nutr Metab"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2017.05.002","article-title":"The significance of estradiol metabolites in human corpus luteum physiology","volume":"123","author":"Devoto","year":"2017","journal-title":"Steroids"},{"key":"B19","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.repbio.2013.12.002","article-title":"Estrogen hormone physiology: reproductive findings from estrogen receptor mutant mice","volume":"14","author":"Hamilton","year":"2014","journal-title":"Reprod Biol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.5935\/1518-0557.20210076","article-title":"In vitro growth of the ovarian follicle: taking stock of advances in research","volume":"26","author":"Taghizabet","year":"2022","journal-title":"JBRA Assist Reprod"},{"key":"B21","doi-asserted-by":"publisher","first-page":"170491","DOI":"10.1155\/2009\/170491","article-title":"Combined application of 17beta-estradiol and progesterone enhance vascular endothelial growth factor and surfactant protein expression in cultured embryonic lung cells of mice","volume":"2009","author":"Trotter","year":"2009","journal-title":"Int J Pediatr"},{"key":"B22","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.tice.2018.03.008","article-title":"Effects of estradiol and progesterone on secretion of epidermal growth factor and insulin-like growth factor-1 in cultured yak endometrial epithelial cells","volume":"52","author":"Jiang","year":"2018","journal-title":"Tissue Cell"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-023-01323-8","article-title":"A novel approach to predicting early pregnancy outcomes dynamically in a prospective cohort using repeated ultrasound and serum biomarkers","volume":"30","author":"Petersen","year":"2023","journal-title":"Reprod Sci"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.827724","article-title":"Estrogen receptor function: impact on the human endometrium","volume":"13","author":"Yu","year":"2022","journal-title":"Front Endocrinol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1093\/humupd\/dmad016","article-title":"The pathophysiological role of estrogens in the initial stages of pregnancy: molecular mechanisms and clinical implications for pregnancy outcome from the periconceptional period to end of the first trimester","volume":"29","author":"Parisi","year":"2023","journal-title":"Hum Reprod Update"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.23559","article-title":"Significance of dynamically monitoring serum estrogen and \u03b2-human chorionic gonadotropin in early pregnancy assessment","volume":"35","author":"Li","year":"2021","journal-title":"J Clin Lab Anal"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/frph.2023.1321284","article-title":"Restoration of serum estradiol and reduced incidence of miscarriage in patients with low serum estradiol during pregnancy: a retrospective cohort study using a multifactorial protocol including DHEA","volume":"5","author":"Boyle","year":"2023","journal-title":"Front Reprod Health"},{"key":"B28","doi-asserted-by":"publisher","first-page":"3674","DOI":"10.3390\/nu14183674","article-title":"Maternal passive smoking, vitamin D deficiency and risk of spontaneous abortion","volume":"14","author":"Lin","year":"2022","journal-title":"Nutrients"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/fsn3.4412","article-title":"Dietary factors and risk for adverse pregnancy outcome: A Mendelian randomization analysis","volume":"12","author":"Mu","year":"2024","journal-title":"Food Sci Nutr"},{"key":"B30","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s12955-021-01703-1","article-title":"Anxiety and depression are risk factors for recurrent pregnancy loss: a nested case-control study","volume":"19","author":"Wang","year":"2021","journal-title":"Health Qual Life Outcomes"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2017.09.037","article-title":"Ambient air pollution and the risk of pregnancy loss: a prospective cohort study","volume":"109","author":"Ha","year":"2018","journal-title":"Fertil Steril"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1657453\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T05:17:31Z","timestamp":1763356651000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1657453\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,17]]},"references-count":31,"alternative-id":["10.3389\/fendo.2025.1657453"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1657453","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,17]]},"article-number":"1657453"}}