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Supraphysiological estradiol levels on the hCG trigger day are associated with SGA for singletons born from fresh embryo transfer

Published online by Cambridge University Press:  11 May 2021

Junwei Zhang ,
Mingze Du  and
Lijun Sun Open the ORCID record for Lijun Sun [Opens in a new window]
Junwei Zhang
Affiliation:
The Reproduction Center, The Third Affiliated Hospital of Zhengzhou University, 7 Kangfuqian Road, Zhengzhou, 450052, Henan, People’s Republic of China
Mingze Du
Affiliation:
The Reproduction Center, The Third Affiliated Hospital of Zhengzhou University, 7 Kangfuqian Road, Zhengzhou, 450052, Henan, People’s Republic of China
Lijun Sun*
Affiliation:
The Reproduction Center, The Third Affiliated Hospital of Zhengzhou University, 7 Kangfuqian Road, Zhengzhou, 450052, Henan, People’s Republic of China
*
Address for correspondence: Lijun Sun, The Reproduction Center, The Third Affiliated Hospital of Zhengzhou University, 7 Kangfuqian Road, Zhengzhou, 450052, Henan, People’s Republic of China. Email: workzhangjw@163.com
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Abstract

The effects of supraphysiological estradiol (E2) on neonatal outcomes and the significance of specific E2 concentrations remain unclear. The purpose of this study was to investigate whether supraphysiological E2 levels on the human chorionic gonadotropin (hCG) trigger day are associated with small size for gestational age (SGA) in singletons born from fresh embryo transfer (ET) cycles. Patients with singleton pregnancies who delivered after the transfer of fresh embryos, during the period from July 2012 to December 2017, at our center were included. We excluded cycles involving a vanishing twin, maternal age >35 years, basal follicle-stimulating hormone ≥10 mIU/ml, or anti-Müllerian hormone ≤1 ng/ml. We then divided all cycles into five groups by E2 level on trigger day: group A, <2000 pg/ml (reference group); group B, 2000 pg/ml≤E2<2999 pg/ml; group C, 3000 pg/ml≤E2<3999 pg/ml; group D, 4000 pg/ml≤E2<4999 pg/ml; and group E, ≥5000 pg/ml. The prevalence of SGA among singletons from fresh ET was the primary outcome. The SGA rate significantly increased when the E2 level was ≥4000 pg/ml, as observed by comparing groups D (odds ratio [OR]: 1·79, 95% confidence interval [CI]: 1·16–2·76, P = 0·01) and E (OR: 1·68, 95% CI: 1·10–2·56, P = 0·02) with the reference group. Multivariate logistic regression indicated that a serum E2 level of at least 4000 pg/ml on the hCG trigger day was associated with increased SGA and with significant differences for groups D (adjusted OR [AOR]: 1·65, 95% CI: 1·05–2·59, P = 0·03) and E (AOR: 1·60, 95% CI: 1·03–2·53, P = 0·04) relative to the reference group. In conclusion, in fresh ET cycles, the supraphysiological E2 ≥4000 pg/ml on the hCG trigger day increases the risk of SGA.

Keywords

Fresh embryo transferserum estradiolsmall for gestational agelow birth weight
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 13 , Issue 2 , April 2022 , pp. 244 - 251
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Copyright
© The Author(s), 2021. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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Footnotes

†

The first two authors should be considered similar in author order.

References

Pereira, N, Rosenwaks, Z. A fresh(er) perspective on frozen embryo transfers. Fertil Steril. 2016; 106(2), 257–258.CrossRefGoogle ScholarPubMed
Gliozheni, O, Calhaz-Jorge, C, De Geyter, C, et al. Assisted reproductive technology in Europe, 2013: results generated from European registers by ESHRE. Hum Reprod. 2017; 32(10), 1957–1973.Google Scholar
Rienzi, L, Gracia, C, Maggiulli, R, et al. Oocyte, embryo and blastocyst cryopreservation in ART: systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for the development of global guidance. Hum Reprod Update. 2017; 23(2), 139–155.Google ScholarPubMed
Zhang, J, Du, M, Li, Z, et al. Fresh versus frozen embryo transfer for full-term singleton birth: a retrospective cohort study. J Ovarian Res. 2018; 11(1), 59.CrossRefGoogle ScholarPubMed
Sazonova, A, Kallen, K, Thurin-Kjellberg, A, Wennerholm, UB, Bergh, C. Obstetric outcome in singletons after in vitro fertilization with cryopreserved/thawed embryos. Hum Reprod. 2012; 27(5), 1343–1350.CrossRefGoogle ScholarPubMed
Kansal Kalra, S, Ratcliffe, SJ, Milman, L, Gracia, CR, Coutifaris, C, Barnhart, KT. Perinatal morbidity after in vitro fertilization is lower with frozen embryo transfer. Fertil Steril. 2011; 95(2), 548–553.CrossRefGoogle ScholarPubMed
Wennerholm, UB, Henningsen, AK, Romundstad, LB, et al. Perinatal outcomes of children born after frozen-thawed embryo transfer: a Nordic cohort study from the CoNARTaS group. Hum Reprod. 2013; 28(9), 2545–2553.CrossRefGoogle ScholarPubMed
Kalra, SK, Ratcliffe, SJ, Coutifaris, C, Molinaro, T, Barnhart, KT. Ovarian stimulation and low birth weight in newborns conceived through in vitro fertilization. Obstet Gynecol. 2011; 118(4), 863–871.CrossRefGoogle ScholarPubMed
Imudia, AN, Awonuga, AO, Doyle, JO, et al. 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. Fertil Steril. 2012; 97(6), 1374–1379.CrossRefGoogle ScholarPubMed
Imudia, AN, Awonuga, AO, Kaimal, AJ, Wright, DL, Styer, AK, Toth, TL. Elective cryopreservation of all embryos with subsequent cryothaw embryo transfer in patients at risk for ovarian hyperstimulation syndrome reduces the risk of adverse obstetric outcomes: a preliminary study. Fertil Steril. 2013; 99(1), 168–173.CrossRefGoogle ScholarPubMed
Pereira, N, Reichman, DE, Goldschlag, DE, Lekovich, JP, Rosenwaks, Z. Impact of elevated peak serum estradiol levels during controlled ovarian hyperstimulation on the birth weight of term singletons from fresh IVF-ET cycles. J Assist Reprod Gen. 2015; 32(4), 527–532.CrossRefGoogle ScholarPubMed
Liu, S, Kuang, Y, Wu, Y, et al. High oestradiol concentration after ovarian stimulation is associated with lower maternal serum beta-HCG concentration and neonatal birth weight. Reprod Biomed Online. 2017; 35(2), 189–196.CrossRefGoogle ScholarPubMed
Pereira, N, Elias, RT, Christos, PJ, et al. Supraphysiologic estradiol is an independent predictor of low birth weight in full-term singletons born after fresh embryo transfer. Hum Reprod. 2017; 32(7), 1410–1417.CrossRefGoogle ScholarPubMed
Wang, M, Hao, C, Bao, H, 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. 2016; 295(2), 407–414.CrossRefGoogle Scholar
Dunne, C, Cho, K, Shan, A, et al. Peak serum estradiol level during controlled ovarian stimulation is not associated with lower levels of pregnancy-associated plasma protein-a or small for gestational age infants: a cohort study. J Obstet Gynaecol Canada. 2017; 39(10), 870–879.CrossRefGoogle ScholarPubMed
Dai, L, Deng, C, Li, Y, et al. Birth weight reference percentiles for Chinese. PloS One. 2014; 9(8), e104779.CrossRefGoogle ScholarPubMed
Schieve, LA, Meikle, SF, Ferre, C, Peterson, HB, Jeng, G, Wilcox, LS. Low and very low birth weight in infants conceived with use of assisted reproductive technology. N Engl J Med. 2002; 346(10), 731–737.CrossRefGoogle ScholarPubMed
Hansen, M, Kurinczuk, JJ, Bower, C, Webb, S. The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N Engl J Med. 2002; 346(10), 725–730.CrossRefGoogle ScholarPubMed
Wisborg, K, Ingerslev, HJ, Henriksen, TB. In vitro fertilization and preterm delivery, low birth weight, and admission to the neonatal intensive care unit: a prospective follow-up study. Fertil Steril. 2010; 94(6), 2102–2106.CrossRefGoogle Scholar
McDonald, SD, Han, Z, Mulla, S, Ohlsson, A, Beyene, J, Murphy, KE. Preterm birth and low birth weight among in vitro fertilization twins: a systematic review and meta-analyses. Eur J Obstet Gynecol Reprod Biol. 2010; 148(2), 105–113.CrossRefGoogle ScholarPubMed
Schieve, LA, Rasmussen, SA, Buck, GM, Schendel, DE, Reynolds, MA, Wright, VC. Are children born after assisted reproductive technology at increased risk for adverse health outcomes? Obstet Gynecol. 2004; 103(6), 1154–1163.CrossRefGoogle ScholarPubMed
Conti, E, Mazzotti, S, Calderoni, S, Saviozzi, I, Guzzetta, A. Are children born after assisted reproductive technology at increased risk of autism spectrum disorders? A systematic review. Hum Reprod. 2013; 28(12), 3316–3327.CrossRefGoogle ScholarPubMed
Bohlmann, MK, Fritzsching, B, Luedders, DW, et al. Impact of assisted reproduction on obstetrics and neonatology. Zeitschrift fur Geburtshilfe und Neonatologie. 2009; 213(6), 221–227.CrossRefGoogle ScholarPubMed
Shih, W, Rushford, DD, Bourne, H, et al. Factors affecting low birthweight after assisted reproduction technology: difference between transfer of fresh and cryopreserved embryos suggests an adverse effect of oocyte collection. Hum Reprod. 2008; 23(7), 1644–1653.CrossRefGoogle ScholarPubMed
Hu, XL, Feng, C, Lin, XH, et al. High maternal serum estradiol environment in the first trimester is associated with the increased risk of small-for-gestational-age birth. J Clin Endocrinol Metab. 2014; 99(6), 2217–2224.CrossRefGoogle ScholarPubMed
Wu, Z, Li, R, Ma, Y, et al. Effect of HCG-day serum progesterone and oestradiol concentrations on pregnancy outcomes in GnRH agonist cycles. Reprod Biomed Online. 2012; 24(5), 511–520.CrossRefGoogle ScholarPubMed
Yen, TA, Yang, HI, Hsieh, WS, et al. Preeclampsia and the risk of bronchopulmonary dysplasia in VLBW infants: a population based study. PloS One. 2013; 8(9), e75168.CrossRefGoogle ScholarPubMed
Chan, PY, Morris, JM, Leslie, GI, Kelly, PJ, Gallery, ED. The long-term effects of prematurity and intrauterine growth restriction on cardiovascular, renal, and metabolic function. Int J Pediat. 2010; 2010, 280402.CrossRefGoogle ScholarPubMed
Valbuena, D, Martin, J, de Pablo, JL, Remohi, J, Pellicer, A, Simon, C. Increasing levels of estradiol are deleterious to embryonic implantation because they directly affect the embryo. Fertil Steril. 2001; 76(5), 962–968.CrossRefGoogle ScholarPubMed
Ertzeid, G, Storeng, R. The impact of ovarian stimulation on implantation and fetal development in mice. Hum Reprod. 2001; 16(2), 221–225.CrossRefGoogle ScholarPubMed
Bittner, AK, Horsthemke, B, Winterhager, E, Grummer, R. Hormone-induced delayed ovulation affects early embryonic development. Fertil Steril. 2011; 95(7), 2390–2394.CrossRefGoogle ScholarPubMed
Albrecht, ED, Bonagura, TW, Burleigh, DW, Enders, AC, Aberdeen, GW, Pepe, GJ. Suppression of extravillous trophoblast invasion of uterine spiral arteries by estrogen during early baboon pregnancy. Placenta. 2006; 27(4–5), 483–490.CrossRefGoogle ScholarPubMed
Bonagura, TW, Babischkin, JS, Aberdeen, GW, Pepe, GJ, Albrecht, ED. Prematurely elevating estradiol in early baboon pregnancy suppresses uterine artery remodeling and expression of extravillous placental vascular endothelial growth factor and alpha1beta1 and alpha5beta1 integrins. Endocrinology. 2012; 153(6), 2897–2906.CrossRefGoogle ScholarPubMed
Simon, C, Cano, F, Valbuena, D, Remohi, J, Pellicer, A. Clinical evidence for a detrimental effect on uterine receptivity of high serum oestradiol concentrations in high and normal responder patients. Hum Reprod. 1995; 10(9), 2432–2437.CrossRefGoogle ScholarPubMed
Haouzi, D, Assou, S, Mahmoud, K, et al. Gene expression profile of human endometrial receptivity: comparison between natural and stimulated cycles for the same patients. Hum Reprod. 2009; 24(6), 1436–1445.CrossRefGoogle ScholarPubMed
Horcajadas, JA, Riesewijk, A, Polman, J, et al. Effect of controlled ovarian hyperstimulation in IVF on endometrial gene expression profiles. Mol Hum Reprod. 2005; 11(3), 195–205.CrossRefGoogle ScholarPubMed
Ng, EH, Chan, CC, Tang, OS, Yeung, WS, Ho, PC. Comparison of endometrial and subendometrial blood flow measured by three-dimensional power Doppler ultrasound between stimulated and natural cycles in the same patients. Hum Reprod. 2004; 19(10), 2385–2390.CrossRefGoogle ScholarPubMed
Kolibianakis, E, Bourgain, C, Albano, C, et al. Effect of ovarian stimulation with recombinant follicle-stimulating hormone, gonadotropin releasing hormone antagonists, and human chorionic gonadotropin on endometrial maturation on the day of oocyte pick-up. Fertil Steril. 2002; 78(5), 1025–1029.CrossRefGoogle ScholarPubMed
McCowan, LM, Roberts, CT, Dekker, GA, et al. Risk factors for small-for-gestational-age infants by customised birthweight centiles: data from an international prospective cohort study. BJOG: Int J Obstet Gynaecol. 2010; 117(13), 1599–1607.CrossRefGoogle ScholarPubMed
Spada, E, Chiossi, G, Coscia, A, Monari, F, Facchinetti, F. Effect of maternal age, height, BMI and ethnicity on birth weight: an Italian multicenter study. J Perinat Med. 2017. doi: 10.1515/jpm-2017-0102.CrossRefGoogle Scholar