{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T04:46:10Z","timestamp":1793853970348,"version":"4.6.1"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:00:00Z","timestamp":1694736000000},"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><jats:title>Introduction<\/jats:title><jats:p>The failure of remodeling the spiral arteries is associated with the pathogenesis of preeclampsia. Estradiol (E2) plays a crucial role in placentation and may be involved in the development of preeclampsia. However, there is a lack of data in this area. This study aims to assess the association between serum estradiol levels in early pregnancy and the risk of preeclampsia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a retrospective cohort study on patients who conceived after frozen embryo transfer (FET) using data from a database at a university-affiliated <jats:italic>in vitro<\/jats:italic> fertilization center. The study period spanned from January 1, 2010, to December 31, 2020. Multivariable logistic regression analyses were performed to determine the adjusted effect of E2 levels on the risk of preeclampsia. We compared the odds ratios of preeclampsia across quartiles of E2 levels and assessed their significance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Serum E2 levels at the fifth gestational week were significantly different between women with and without preeclampsia after FET programmed cycles (607.5 \u00b1 245.4 vs. 545.6 \u00b1 294.4 pg\/ml, p=0.009). A multivariable logistic regression model demonstrated that E2 levels in early pregnancy were independent risk factors for preeclampsia. We observed an increased odds ratio of preeclampsia with increasing quartiles of estradiol levels after adjusting for potential confounders in FET programmed cycles. When comparing quartiles 3 and 4 (E2 &amp;gt; 493 pg\/ml at the fifth gestational week) to quartiles 1 and 2, the odds ratios of preeclampsia were significantly higher.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We found that serum E2 levels in early pregnancy may impact the risk of preeclampsia, particularly following FET programmed cycles. The association between E2 levels in early pregnancy and preeclampsia deserves further investigation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1223181","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T08:49:06Z","timestamp":1695113346000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Association between estradiol levels in early pregnancy and risk of preeclampsia after frozen embryo transfer"],"prefix":"10.3389","volume":"14","author":[{"given":"Yun-Chiao","family":"Hsieh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Ching","family":"Kao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ih-Jane","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Kai","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang-Han","family":"Chao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Jou","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jehn-Hsiahn","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shee-Uan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60279-6","article-title":"Pre-eclampsia","volume":"376","author":"Steegers","year":"2010","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.10.014","article-title":"Vessel remodelling, pregnancy hormones and extravillous trophoblast function","volume":"349","author":"Chen","year":"2012","journal-title":"Mol Cell Endocrinol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.steroids.2019.01.005","article-title":"Estrogen metabolism pathways in preeclampsia and normal pregnancy","volume":"144","author":"Cantonwine","year":"2019","journal-title":"Steroids"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1210\/er.2016-1065","article-title":"From pregnancy to preeclampsia: A key role for estrogens","volume":"38","author":"Berkane","year":"2017","journal-title":"Endocr Rev"},{"key":"B5","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/j.etp.2012.09.002","article-title":"Effect of estrogen on rat placental development depending on gestation stage","volume":"65","author":"Furukawa","year":"2013","journal-title":"Exp Toxicol Pathol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1161\/hc1102.105267","article-title":"Nongenomic mechanisms of endothelial nitric oxide synthase activation by the selective estrogen receptor modulator raloxifene","volume":"105","author":"Simoncini","year":"2002","journal-title":"Circulation"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.06184","article-title":"Regulation of the vascular endothelial growth factor (VEGF) receptor Flk-1\/KDR by estradiol through VEGF in uterus","volume":"188","author":"Herv\u00e9","year":"2006","journal-title":"J Endocrinol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-006-0012-5","article-title":"Effects of estradiol-17beta on expression of mRNA for seven angiogenic factors and their receptors in the endometrium of ovariectomized (OVX) ewes","volume":"30","author":"Johnson","year":"2006","journal-title":"Endocrine"},{"key":"B9","volume-title":"Assisted Reproductive Technology National Summary Report","year":"2018"},{"key":"B10","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.mce.2011.05.034","article-title":"The effects of human chorionic gonadotrophin, progesterone and oestradiol on trophoblast function","volume":"342","author":"Chen","year":"2011","journal-title":"Mol Cell Endocrinol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1210\/endo.133.2.8344219","article-title":"Vascular endothelial growth factor\/vascular permeability factor expression in the rat uterus: rapid stimulation by estrogen correlates with estrogen-induced increases in uterine capillary permeability and growth","volume":"133","author":"Cullinan-Bove","year":"1993","journal-title":"Endocrinology"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.81.5.885","article-title":"17 beta-estradiol regulation of human endothelial cell basal nitric oxide release, independent of cytosolic Ca2+ mobilization","volume":"81","author":"Caulin-Glaser","year":"1997","journal-title":"Circ Res"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0116","article-title":"Suppression of extravillous trophoblast vascular endothelial growth factor expression and uterine spiral artery invasion by estrogen during early baboon pregnancy","volume":"149","author":"Bonagura","year":"2008","journal-title":"Endocrinology"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-1141","article-title":"Prematurely elevating estradiol in early baboon pregnancy suppresses uterine artery remodeling and expression of extravillous placental vascular endothelial growth factor and \u03b11\u03b21 and \u03b15\u03b21 integrins","volume":"153","author":"Bonagura","year":"2012","journal-title":"Endocrinology"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2005.04.005","article-title":"Suppression of extravillous trophoblast invasion of uterine spiral arteries by estrogen during early baboon pregnancy","volume":"27","author":"Albrecht","year":"2006","journal-title":"Placenta"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2012.03.028","article-title":"Peak serum estradiol level during controlled ovarian hyperstimulation is associated with increased risk of small for gestational age and preeclampsia in singleton pregnancies after in vitro fertilization","volume":"97","author":"Imudia","year":"2012","journal-title":"Fertil Steril"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2010.04.022","article-title":"High serum oestradiol concentrations in IVF cycles increase the risk of pregnancy complications related to abnormal placentation","volume":"21","author":"Farhi","year":"2010","journal-title":"Reprod BioMed Online"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00590.2011","article-title":"Suppression of trophoblast uterine spiral artery remodeling by estrogen during baboon pregnancy: impact on uterine and fetal blood flow dynamics","volume":"302","author":"Aberdeen","year":"2012","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2019.03.010","article-title":"Neonatal and maternal outcome after frozen embryo transfer: Increased risks in programmed cycles","volume":"221","author":"Ginstr\u00f6m Ernstad","year":"2019","journal-title":"Am J Obstet Gynecol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-019-01420-1","article-title":"Increased pregnancy complications following frozen-thawed embryo transfer during an artificial cycle","volume":"36","author":"Jing","year":"2019","journal-title":"J Assist Reprod Genet"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dez079","article-title":"Endometrial preparation methods for frozen-thawed embryo transfer are associated with altered risks of hypertensive disorders of pregnancy, placenta accreta, and gestational diabetes mellitus","volume":"34","author":"Saito","year":"2019","journal-title":"Hum Reprod"},{"key":"B22","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s12958-020-00601-3","article-title":"Increased risk of maternal and neonatal complications in hormone replacement therapy cycles in frozen embryo transfer","volume":"18","author":"Zong","year":"2020","journal-title":"Reprod Biol Endocrinol Reprod Biol Endocrinol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.10.039","article-title":"Adverse obstetric and perinatal outcomes in 1,136 singleton pregnancies conceived after programmed frozen embryo transfer (FET) compared with natural cycle FET","volume":"115","author":"Asserh\u00f8j","year":"2021","journal-title":"Fertil Steril"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2012.01.020","article-title":"Human placentation from nidation to 5 weeks of gestation. Part I: What do we know about formative placental development following implantation","volume":"33","author":"James","year":"2012","journal-title":"Placenta"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1223181\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T08:49:08Z","timestamp":1695113348000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1223181\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,15]]},"references-count":24,"alternative-id":["10.3389\/fendo.2023.1223181"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1223181","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,15]]},"article-number":"1223181"}}