Skip to main content
SpringerLink
Log in

Impact of Supraphysiological Estradiol Serum Levels on Birth Weight in Singletons Born After Fresh Embryo Transfer

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

In assisted reproductive technology, high estradiol (E2) levels at trigger may increase the risk of low birth weight (LBW). Our objective was to investigate the impact of supra-physiological E2 levels at trigger, on the rate of LBW in singleton pregnancies following fresh embryo transfers (ET), in a center that typically employs the ‘freeze-all’ strategy in case of high E2 levels, to prevent ovarian hyper stimulation syndrome risk. A cohort study was conducted in a university hospital between November 2012 and January 2017. The main inclusion criterion was having a live birth (LB) singleton (≥ 24 weeks of gestation) after a fresh-ET. Four groups were defined according to the E2 level at trigger, as quartiles of the entire patient population. The main measured outcome was the rate of LBW. 497 fresh-ET led to LB. Mean E2 level was 1608.4 ± 945.5 pg/ml. The groups were allocated as follows: 124LB in the Group E2 < 25 percentile(p) (1106.5 pg/ml), 124LB in the Group E2 [25p-50p] (1106.5–1439 pg/ml), 124LB in the Group E2[50p-75p] (1440–1915 pg/ml), and 125LB in the Group E2 > 75p (>1915 pg/ml). There was no significant difference in the rate of LBW (Group E2 < 25p, n = 8/124, (6.5%); Group E2[25p-50p], n = 15/124, (12.1%); Group E2 [50p-75p], n = 13/124, (10.4%); and Group E2 > 75p, n = 10/12, (8.1%); (p = 0.43)). After multivariate analysis, E2 level at trigger was not significantly correlated to the rate of LBW. In our cohort, E2 level on the day of hCG trigger was not associated with increased odds of LBW after fresh embryo transfers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. 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):731–7.

    Article  PubMed  Google Scholar 

  2. Perri T, Chen R, Yoeli R, Merlob P, Orvieto R, Shalev Y, et al. Are singleton assisted reproductive technology pregnancies at risk of prematurity? J Assist Reprod Genet. 2001;18(5):245–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. McDonald SD, Han Z, Mulla S, Murphy KE, Beyene J, Ohlsson A, et al. Preterm birth and low birth weight among in vitro fertilization singletons: a systematic review and meta-analyses. Eur J Obstet Gynecol Reprod Biol. 2009;146(2):138–48.

    Article  PubMed  Google Scholar 

  4. Jackson RA, Gibson KA, Wu YW, Croughan MS. Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstet Gynecol. 2004;103(3):551–63.

    Article  PubMed  Google Scholar 

  5. Maheshwari A, Pandey S, Amalraj Raja E, Shetty A, Hamilton M, Bhattacharya S. Is frozen embryo transfer better for mothers and babies? Can cumulative meta-analysis provide a definitive answer? Hum Reprod Update. 2018;24(1):35–58.

    Article  PubMed  Google Scholar 

  6. Tan SL, Doyle P, Campbell S, Beral V, Rizk B, Brinsden P, et al. Obstetric outcome of in vitro fertilization pregnancies compared with normally conceived pregnancies. Am J Obstet Gynecol. 1992;167(3):778–84.

    Article  CAS  PubMed  Google Scholar 

  7. Bohlmann MK, Fritzsching B, Luedders DW, Hornemann A, Göpel W, Pöschl J, et al. Impact of assisted reproduction on obstetrics and neonatology. Z Geburtshilfe Neonatol. 2009;213(6):221–7.

    Article  CAS  PubMed  Google Scholar 

  8. Wennerholm U-B, Henningsen A-KA, Romundstad LB, Bergh C, Pinborg A, Skjaerven R, et al. Perinatal outcomes of children born after frozen-thawed embryo transfer: a Nordic cohort study from the CoNARTaS group. Hum Reprod Oxf Engl. 2013;28(9):2545–53.

    Article  Google Scholar 

  9. Pelkonen S, Koivunen R, Gissler M, Nuojua-Huttunen S, Suikkari A-M, Hydén-Granskog C, et al. Perinatal outcome of children born after frozen and fresh embryo transfer: the Finnish cohort study 1995-2006. Hum Reprod Oxf Engl. 2010;25(4):914–23.

    Article  CAS  Google Scholar 

  10. Pinborg A, Henningsen AA, Loft A, Malchau SS, Forman J, Andersen AN. Large baby syndrome in singletons born after frozen embryo transfer (FET): is it due to maternal factors or the cryotechnique? Hum Reprod Oxf Engl. 2014;29(3):618–27.

    Article  CAS  Google Scholar 

  11. Imudia AN, Awonuga AO, Doyle JO, Kaimal AJ, Wright DL, Toth TL, 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):1374–9.

    Article  CAS  PubMed  Google Scholar 

  12. Ma W, Song H, Das SK, Paria BC, Dey SK. Estrogen is a critical determinant that specifies the duration of the window of uterine receptivity for implantation. Proc Natl Acad Sci U S A. 2003;100(5):2963–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Norwitz ER. Defective implantation and placentation: laying the blueprint for pregnancy complications. Reprod Biomed Online 2007 Spec No 1:101–109.

  14. Farhi J, Ben-Haroush A, Haroush AB, Andrawus N, Pinkas H, Sapir O, et al. High serum oestradiol concentrations in IVF cycles increase the risk of pregnancy complications related to abnormal placentation. Reprod Biomed Online. 2010;21(3):331–7.

    Article  CAS  PubMed  Google Scholar 

  15. Pereira N, Elias RT, Christos PJ, Petrini AC, Hancock K, Lekovich JP, et al. Supraphysiologic estradiol is an independent predictor of low birth weight in full-term singletons born after fresh embryo transfer. Hum Reprod Oxf Engl. 2017;32(7):1410–7.

    Article  CAS  Google Scholar 

  16. 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 Genet. 2015;32(4):527–32.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Sunkara SK, La Marca A, Seed PT, Khalaf Y. Increased risk of preterm birth and low birthweight with very high number of oocytes following IVF: an analysis of 65 868 singleton live birth outcomes. Hum Reprod Oxf Engl. 2015;30(6):1473–80.

    Article  CAS  Google Scholar 

  18. Pereira N, Petrini AC, Lekovich JP, Schattman GL, Rosenwaks Z. Comparison of perinatal outcomes following fresh and frozen-thawed blastocyst transfer. Int J Gynaecol Obstet Off Organ Int Fed Gynaecol Obstet. 2016;135(1):96–100.

    Article  Google Scholar 

  19. Bourdon M, Santulli P, Gayet V, et al. Assisted reproduction technique outcomes for fresh versus deferred cryopreserved day-2 embryo transfer: a retrospective matched cohort study. Reprod Biomed Online. 2016. https://doi.org/10.1016/j.rbmo.2016.11.015.

  20. Papanikolaou EG, Humaidan P, Polyzos N, et al. New algorithm for OHSS prevention. Reprod Biol Endocrinol. 2011;9(1):147. https://doi.org/10.1186/1477-7827-9-147

  21. Papanikolaou EG, Pozzobon C, Kolibianakis EM, et al. Incidence and prediction of ovarian hyperstimulation syndrome in women undergoing gonadotropin-releasing hormone antagonist in vitro fertilization cycles. Fertil Steril. 2006;85(1):112-120. https://doi.org/10.1016/j.fertnstert.2005.07.1292

  22. Ego A, Prunet C, Lebreton E, Blondel B, Kaminski M, Goffinet F, et al. Customized and non-customized French intrauterine growth curves. I - Methodology. J Gynecol Obstet Biol Reprod (Paris). 2016;45(2):155–64.

    Article  CAS  Google Scholar 

  23. Blondel B, Kermarrec M. French national perinatal survey 2010. Situation in 2010 and trends since 2003; 2011 http://www.europeristat.com/reports/national-perinatal-health-reports.html Accessed Jan 20, 2016.

  24. ACOG Committee on Obstetric Practice. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet Off Organ Int Fed Gynaecol Obstet. 2002;77(1):67–75.

    Article  Google Scholar 

  25. American College of Obstetricians and Gynecologists, Committee on Practice Bulletins—Obstetrics. ACOG practice bulletin no. 127: Management of preterm labor. Obstet Gynecol. 2012;119(6):1308–17.

    Article  Google Scholar 

  26. Association AD. Gestational Diabetes Mellitus. Diabetes Care. 2003;26(suppl 1):s103–5.

    Google Scholar 

  27. Salomon LJ, Bernard JP, Duyme M, Buvat I, Ville Y. The impact of choice of reference charts and equations on the assessment of fetal biometry. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol. 2005;25(6):559–65.

    Article  CAS  Google Scholar 

  28. Vayssière C, Sentilhes L, Ego A, et al. Fetal growth restriction and intra-uterine growth restriction: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians. Eur J Obstet Gynecol Reprod Biol. 2015;193:10-18. https://doi.org/10.1016/j.ejogrb.2015.06.021

  29. Humaidan P, Nelson SM, Devroey P, et al. Ovarian hyperstimulation syndrome: review and new classification criteria for reporting in clinical trials. Hum Reprod Oxf Engl. 2016;31(9):1997-2004. https://doi.org/10.1093/humrep/dew149

  30. Ertzeid G, Storeng R. The impact of ovarian stimulation on implantation and fetal development in mice. Hum Reprod Oxf Engl. 2001;16(2):221–5.

    Article  CAS  Google Scholar 

  31. Weinerman R, Ord T, Bartolomei MS, Coutifaris C, Mainigi M. The superovulated environment, independent of embryo vitrification, results in low birthweight in a mouse model. Biol Reprod. 2017;97(1):133–42.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Mainigi MA, Olalere D, Burd I, Sapienza C, Bartolomei M, Coutifaris C. Peri-implantation hormonal milieu: elucidating mechanisms of abnormal placentation and fetal growth. Biol Reprod. 2014;90(2):26.

    Article  PubMed  Google Scholar 

  33. Royster GD, Krishnamoorthy K, Csokmay JM, Yauger BJ, Chason RJ, DeCherney AH, et al. Are intracytoplasmic sperm injection and high serum estradiol compounding risk factors for adverse obstetric outcomes in assisted reproductive technology? Fertil Steril. 2016;106(2):363–370.e3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Manzanares MA, Gómez-Palomares JL, Ricciarelli E, Hernández ER. Triggering ovulation with gonadotropin-releasing hormone agonist in in vitro fertilization patients with polycystic ovaries does not cause ovarian hyperstimulation syndrome despite very high estradiol levels. Fertil Steril. 2010;93(4):1215-1219. https://doi.org/10.1016/j.fertnstert.2008.12.019

  35. Roque M, Haahr T, Geber S, Esteves SC, Humaidan P. Fresh versus elective frozen embryo transfer in IVF/ICSI cycles: a systematic review and meta-analysis of reproductive outcomes. Hum Reprod Update. 2019;25(1):2-14. https://doi.org/10.1093/humupd/dmy033

  36. Vuong LN, Dang VQ, Ho TM, Huynh BG, Ha DT, Pham TD, et al. IVF Transfer of Fresh or Frozen Embryos in Women without Polycystic Ovaries. N Engl J Med. 2018;378(2):137–47.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors wish to thank the staff members from our department for their expert assistance with data collection, and Valerie Blanchet, Julia Gonnot, and Celie Cervantes in particular.

Author information

Author notes

  1. Mathilde Bourdon, Marion Ouazana, Charles Chapron and Pietro Santulli contributed equally to this work.

Authors and Affiliations

  1. Département de Gynécologie Obsétrique II et Médecine de la Reproduction, Université de Paris, Faculté de Médecine, AP-HP-Centre Université de Paris, Hôpital Cochin, 123 boulevard de Port-Royal, 75014, Paris, France

    Mathilde Bourdon, Marion Ouazana, Chloé Maignien, Louis Marcellin, Charles Chapron & Pietro Santulli

  2. Département 3I « Infection, Immunité et inflammation, Institut Cochin, INSERM U1016, Université de Paris, Paris, France

    Mathilde Bourdon, Khaled Pocate-Cheriet, Louis Marcellin, Charles Chapron & Pietro Santulli

  3. Departement d’histologie, embryologie et biologie de la reproduction, Université de Paris, Faculté de Médecine, AP-HP-Centre Université de Paris, Hôpital Cochin, Paris, France

    Khaled Pocate-Cheriet & Catherine Patrat

  4. Department “Development, Reproduction and Cancer”, Institut Cochin, INSERM U1016 (Doctor Vaiman), Université de Paris, Paris, France

    Louis Marcellin, Charles Chapron & Pietro Santulli

Authors
  1. Mathilde Bourdon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marion Ouazana
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chloé Maignien
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Khaled Pocate-Cheriet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Catherine Patrat
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Louis Marcellin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Charles Chapron
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Pietro Santulli
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

PS, OM, MB designed the study, perform data analysis, wrote the first draft and corrected the final version of the manuscript. MC, PK, PC, ML, and CC helped draft the manuscript, critically review and corrected the final version of the manuscript of the study. All participants were members of the gynecology and reproductive medicine team and approved the final version to be submitted.

Corresponding author

Correspondence to Pietro Santulli.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

Supplementary Fig. 1

Birth weight according to estradiol level the day of trigger: g, grams; r, Pearson coefficient of correlation, p, p value. (PNG 164 kb)

High resolution image (TIFF 170 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bourdon, M., Ouazana, M., Maignien, C. et al. Impact of Supraphysiological Estradiol Serum Levels on Birth Weight in Singletons Born After Fresh Embryo Transfer. Reprod. Sci. 27, 1770–1777 (2020). https://doi.org/10.1007/s43032-020-00174-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-020-00174-x

Keywords

Search

Navigation