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A supraphysiologic E2 level is inevitable during controlled ovarian hyper-stimulation (COH), and its effect on the outcome of IVF-ET is controversial. The aim of this retrospective study is to evaluate the association between elevated serum oestradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration and neonatal birthweight after IVF-ET cycles. The data of 3659 infertile patients with fresh IVF-ET cycles were analysed retrospectively between August 2009 and February 2017 in First Hospital of Zhengzhou University. Patients were categorized by serum E2 levels on the day of hCG administration into six groups: group 1 (serum E<jats:sub>2<\/jats:sub> levels\u2009\u2264\u20091000\u00a0pg\/mL, n\u2009=\u2009230), group 2 (serum E2 levels between 1001 and 2000\u00a0pg\/mL, n\u2009=\u2009524), group 3 (serum E<jats:sub>2<\/jats:sub> levels between 2001 and 3000\u00a0pg\/mL, n\u2009=\u2009783), group 4 (serum E<jats:sub>2<\/jats:sub> levels between 3001 and 4000\u00a0pg\/mL, n\u2009=\u2009721), group 5 (serum E2 levels between 4001 and 5000\u00a0pg\/mL, n\u2009=\u2009548\u200a), and group 6 (serum E2 levels\u2009&gt;\u20095000\u00a0pg\/mL, n\u2009=\u2009852). Univariate linear regression was used to evaluate the independent correlation between each factor and outcome index. Multiple logistic regression was used to adjust for confounding factors. The LBW rates were as follows: 3.0% (group 1), 2.9% (group 2), 1.9% (group 3), 2.9% (group 4), 2.9% (group 5), and 2.0% (group 6) (<jats:italic>P<\/jats:italic>\u2009=\u20090.629), respectively. There were no statistically significant differences in the incidences of neonatal LBW among the six groups. We did not detect an association between peak serum E2 level during ovarian stimulation and neonatal birthweight after IVF-ET. The results of this retrospective cohort study showed that serum E2 peak levels during ovarian stimulation were not associated with birth weight during IVF cycles. In addition, no association was found between higher E2 levels and increased LBW risk. Our observations suggest that the hyper-oestrogenic milieu during COS does not seem to have adverse effects on the birthweight of offspring after IVF. Although this study provides some reference, the obstetric-related factors were not included due to historical reasons. The impact of the high estrogen environment during COS on the birth weight of IVF offspring still needs future research.<\/jats:p>","DOI":"10.1038\/s41598-021-85692-7","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T11:14:42Z","timestamp":1615893282000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Association between serum oestradiol level on the hCG administration day and neonatal birthweight after IVF-ET among 3659 singleton live births"],"prefix":"10.1038","volume":"11","author":[{"given":"Yu","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,16]]},"reference":[{"key":"85692_CR1","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1016\/s0140-6736(78)92957-4","volume":"2","author":"PC Steptoe","year":"1978","unstructured":"Steptoe, P. C. & Edwards, R. G. Birth after the reimplantation of a human embryo. Lancet 2, 366. https:\/\/doi.org\/10.1016\/s0140-6736(78)92957-4 (1978).","journal-title":"Lancet"},{"key":"85692_CR2","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1016\/j.fertnstert.2018.06.039","volume":"110","author":"GD Adamson","year":"2018","unstructured":"Adamson, G. D. et al. International Committee for Monitoring Assisted Reproductive Technology: world report on assisted reproductive technology, 2011. Fertil. Steril. 110, 1067\u20131080. https:\/\/doi.org\/10.1016\/j.fertnstert.2018.06.039 (2018).","journal-title":"Fertil. Steril."},{"key":"85692_CR3","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1007\/s00404-017-4291-2","volume":"295","author":"JB Qin","year":"2017","unstructured":"Qin, J. B. et al. Worldwide prevalence of adverse pregnancy outcomes associated with in vitro fertilization\/intracytoplasmic sperm injection among multiple births: a systematic review and meta-analysis based on cohort studies. Arch. Gynecol. Obstet. 295, 577\u2013597. https:\/\/doi.org\/10.1007\/s00404-017-4291-2 (2017).","journal-title":"Arch. Gynecol. Obstet."},{"key":"85692_CR4","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1093\/humupd\/dmz001","volume":"25","author":"S Berntsen","year":"2019","unstructured":"Berntsen, S. et al. The health of children conceived by ART: \u201cthe chicken or the egg?\u201d. Hum. Reprod. Update 25, 137\u2013158. https:\/\/doi.org\/10.1093\/humupd\/dmz001 (2019).","journal-title":"Hum. Reprod. Update"},{"key":"85692_CR5","first-page":"463","volume":"60","author":"RG Steward","year":"2015","unstructured":"Steward, R. G. et al. High peak estradiol predicts higher miscarriage and lower live birth rates in high responders triggered with a GnRH Agonist in IVF\/ICSI cycles. J. Reprod. Med. 60, 463\u2013470 (2015).","journal-title":"J. Reprod. Med."},{"key":"85692_CR6","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/1477-7827-12-119","volume":"12","author":"MT Zavy","year":"2014","unstructured":"Zavy, M. T. et al. In high responding patients undergoing an initial IVF cycle, elevated estradiol on the day of hCG has no effect on live birth rate. Reprod. Biol. Endocrinol. 12, 119. https:\/\/doi.org\/10.1186\/1477-7827-12-119 (2014).","journal-title":"Reprod. Biol. Endocrinol."},{"key":"85692_CR7","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1007\/s00404-016-4242-3","volume":"295","author":"M Wang","year":"2017","unstructured":"Wang, M. et al. Effect of elevated estradiol levels on the hCG administration day on IVF pregnancy and birth outcomes in the long GnRH-agonist protocol: analysis of 3393 cycles. Arch. Gynecol. Obstet. 295, 407\u2013414. https:\/\/doi.org\/10.1007\/s00404-016-4242-3 (2017).","journal-title":"Arch. Gynecol. Obstet."},{"key":"85692_CR8","doi-asserted-by":"publisher","first-page":"2298","DOI":"10.1093\/humrep\/dex277","volume":"32","author":"MC Magnus","year":"2017","unstructured":"Magnus, M. C. et al. Vanishing twin syndrome among ART singletons and pregnancy outcomes. Hum. Reprod. 32, 2298\u20132304. https:\/\/doi.org\/10.1093\/humrep\/dex277 (2017).","journal-title":"Hum. Reprod."},{"key":"85692_CR9","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1093\/humrep\/dez262","volume":"35","author":"J Huang","year":"2020","unstructured":"Huang, J. et al. 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Progesterone elevation on the day of human chorionic gonadotropin administration adversely affects the outcome of IVF with transferred embryos at different developmental stages. Reproduct. Biol. Endocrinol. RB&E 13, 82. https:\/\/doi.org\/10.1186\/s12958-015-0075-3 (2015).","journal-title":"Reproduct. Biol. Endocrinol. RB&E"},{"key":"85692_CR12","doi-asserted-by":"publisher","first-page":"e104779","DOI":"10.1371\/journal.pone.0104779","volume":"9","author":"L Dai","year":"2014","unstructured":"Dai, L. et al. Birth weight reference percentiles for Chinese. PLoS ONE 9, e104779. https:\/\/doi.org\/10.1371\/journal.pone.0104779 (2014).","journal-title":"PLoS ONE"},{"key":"85692_CR13","doi-asserted-by":"publisher","first-page":"2193","DOI":"10.4103\/0366-6999.240808","volume":"131","author":"H Cai","year":"2018","unstructured":"Cai, H., Zhu, X. X., Li, Z. F., Zhu, Y. P. & Lang, J. H. 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Effect of HCG-day serum progesterone and oestradiol concentrations on pregnancy outcomes in GnRH agonist cycles. Reprod. Biomed. Online 24, 511\u2013520. https:\/\/doi.org\/10.1016\/j.rbmo.2012.02.003 (2012).","journal-title":"Reprod. Biomed. Online"},{"key":"85692_CR20","doi-asserted-by":"publisher","first-page":"2902","DOI":"10.1093\/humrep\/dep290","volume":"24","author":"D Kyrou","year":"2009","unstructured":"Kyrou, D. et al. Does the estradiol level on the day of human chorionic gonadotrophin administration have an impact on pregnancy rates in patients treated with rec-FSH\/GnRH antagonist?. Hum. Reprod. 24, 2902\u20132909. https:\/\/doi.org\/10.1093\/humrep\/dep290 (2009).","journal-title":"Hum. Reprod."},{"key":"85692_CR21","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1016\/s0015-0282(00)00407-6","volume":"73","author":"EH Ng","year":"2000","unstructured":"Ng, E. H. What is the threshold value for serum estradiol levels associated with adverse IVF outcomes?. 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