Hostname: page-component-89b8bd64d-5bvrz Total loading time: 0 Render date: 2026-05-06T13:39:14.671Z Has data issue: false hasContentIssue false
  • English
  • Français

Does high serum oestradiol during stimulation influence obstetrical outcomes and placental pathology in subsequent frozen embryo transfers?

Published online by Cambridge University Press:  29 September 2025

Inbal Navon Open the ORCID record for Inbal Navon [Opens in a new window] ,
Hadas Ganer ,
Alexander Volodarsky-Perel ,
Tuyet Nhung Ton Nu ,
Alexandre Machado-Gedeon ,
Yiming Cui ,
Jonathan Shaul  and
Michael H. Dahan
Inbal Navon*
Affiliation:
Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Hadas Ganer
Affiliation:
Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada Twig Fertility, Toronto, Ontario, Canada
Alexander Volodarsky-Perel
Affiliation:
Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Tuyet Nhung Ton Nu
Affiliation:
Department of Pathology, McGill University, Montreal, Quebec, Canada
Alexandre Machado-Gedeon
Affiliation:
Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada
Yiming Cui
Affiliation:
Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada
Jonathan Shaul
Affiliation:
Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada
Michael H. Dahan
Affiliation:
Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada
*
Corresponding author: Inbal Navon; Email: navon.inbal@gmail.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Aim:

High oestradiol levels during in vitro fertilization (IVF) fresh cycles have been linked to adverse obstetric outcomes, yet whether this is due to endometrial or oocyte effects remains unclear. Investigating subsequent frozen embryo transfer (FET) cycles can help clarify the origins of these effects. This study aimed to evaluate obstetric outcomes and placental histology in FET cycles for patients with elevated serum oestradiol levels during the ovarian stimulation cycle in which the embryos were created.

Methods:

A single centre retrospective cohort study of live singleton deliveries after IVF with programmed FET from 2009 to 2017. High oestradiol during ovarian stimulation was defined as ≥10,000 pmol/L. We compared obstetric outcomes and placental findings between pregnancies with high oestradiol levels in the preceding ovarian stimulation cycle and a control group.

Results:

We analyzed 114 deliveries in the high oestradiol group and 194 in the control group. Baseline demographics were comparable between groups. No significant differences were observed in obstetric outcomes, including low birth weight, preeclampsia and preterm delivery. The placental macroscopic and histopathological findings did not significantly differ between the groups as well.

Conclusion:

High oestradiol during the ovarian stimulation cycle used to create embryos is not associated with adverse obstetric outcomes or placental pathologies in pregnancies following FET. This is consistent with an endometrial effect of high oestradiol and thus support the practice of a freeze all approach in high oestradiol cycles.

Keywords

oestradiolfrozen embryo transferin vitro fertilizationplacenta

Information

Type
Research Article
Information
Zygote , Volume 33 , Issue 4 , August 2025 , pp. 230 - 235
Check for updates
Copyright
© The Author(s), 2025. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

Footnotes

*

The article has been updated since original publication. A notice detailing the change has also been published.

References

Aberdeen, G.W., Bonagura, T.W., Harman, C.R., Pepe, G.J. and Albrecht, E.D. (2012) Suppression of trophoblast uterine spiral artery remodeling by estrogen during baboon pregnancy: impact on uterine and fetal blood flow dynamics. American Journal of Physiology. Heart and Circulatory Physiology 302(10), H1936–H1944. https://doi.org/10.1152/ajpheart.00590.2011.CrossRefGoogle Scholar
Cai, J., Liu, L., Xu, Y., Liu, Z., Jiang, X., Li, P., Sha, A. and Ren, J. (2019) Supraphysiological estradiol level in ovarian stimulation cycles affects the birthweight of neonates conceived through subsequent frozen-thawed cycles: a retrospective study. BJOG : An International Journal of Obstetrics and Gynaecology 126(6), 711–718. https://doi.org/10.1111/1471-0528.15606.CrossRefGoogle ScholarPubMed
de Waal, E., Vrooman, L.A., Fischer, E., Ord, T., Mainigi, M.A., Coutifaris, C., Schultz, R.M. and Bartolomei, M.S. (2015) The cumulative effect of assisted reproduction procedures on placental development and epigenetic perturbations in a mouse model. Human Molecular Genetics 24(24), 6975–6985. https://doi.org/10.1093/hmg/ddv400.Google ScholarPubMed
Farhi, J., Ben-Haroush, A., Andrawus, N., Pinkas, H., Sapir, O., Fisch, B. and Ashkenazi, J. (2010) High serum oestradiol concentrations in IVF cycles increase the risk of pregnancy complications related to abnormal placentation. Reproductive Biomedicine Online 21(3), 331–337. https://doi.org/10.1016/j.rbmo.2010.04.022.CrossRefGoogle ScholarPubMed
Ganer Herman, H,, Volodarsky-Perel, A., Ton Nu, T.N., Machado-Gedeon, A., Cui, Y., Shaul, J. and Dahan, M.H. (2022) The effect of higher estradiol levels during stimulation on pregnancy complications and placental histology. Placenta 126, 114–118. https://doi.org/10.1016/J.PLACENTA.2022.06.013.CrossRefGoogle ScholarPubMed
Huang, J., Lu, X., Lin, J., Chen, Q., Gao, H., Lyu, Q., Cai, R. and Kuang, Y. (2020) Association between peak serum estradiol level during controlled ovarian stimulation and neonatal birthweight in freeze-all cycles: a retrospective study of 8501 singleton live births. Human Reproduction (Oxford, England) 35(2), 424–433. https://doi.org/10.1093/HUMREP/DEZ262.CrossRefGoogle ScholarPubMed
Imudia, A.N., Awonuga, A.O., Doyle, J.O., Kaimal, A.J., Wright, D.L., Toth, T.L. and Styer, A.K. (2012) 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. Fertility and Sterility 97(6), 1374–1379. https://doi.org/10.1016/j.fertnstert.2012.03.028.CrossRefGoogle ScholarPubMed
Irani, M., Canon, C., Robles, A., Maddy, B., Gunnala, V., Qin, X., Zhang, C., Xu, K. and Rosenwaks, Z. (2020) No effect of ovarian stimulation and oocyte yield on euploidy and live birth rates: an analysis of 12 298 trophectoderm biopsies. Human Reproduction (Oxford, England) 35(5), 1082–1089. https://doi.org/10.1093/HUMREP/DEAA028.CrossRefGoogle ScholarPubMed
Kohl Schwartz, A.S., Mitter, V.R., Amylidi-Mohr, S., Fasel, P., Minger, M.A., Limoni, C, Zwahlen, M. and von Wolff, M. (2019) The greater incidence of small-for-gestational-age newborns after gonadotropin-stimulated in vitro fertilization with a supraphysiological estradiol level on ovulation trigger day. Acta Obstetricia et Gynecologica Scandinavica 98(12), 1575–1584. https://doi.org/10.1111/aogs.13691.CrossRefGoogle Scholar
Kosmas, I.P., Kolibianakis, E.M. and Devroey, P. (2004) Association of estradiol levels on the day of hCG administration and pregnancy achievement in IVF: a systematic review. Human Reproduction (Oxford, England) 19(11), 2446–2453. https://doi.org/10.1093/HUMREP/DEH473.CrossRefGoogle ScholarPubMed
Li, Q., Ruan, L., Zhu, L., Yang, Z., Zhu, M. and Luo, Y. (2022) Elevated estradiol levels in frozen embryo transfer have different effects on pregnancy outcomes depending on the stage of transferred embryos. Scientific Reports 12(1), 5592. https://doi.org/10.1038/s41598-022-09545-7.CrossRefGoogle ScholarPubMed
Liu, S., Kuang, Y., Wu, Y., Feng, Y., Lyu, Q., Wang, L., Sun, Y. and Sun, X. (2017) High oestradiol concentration after ovarian stimulation is associated with lower maternal serum beta-HCG concentration and neonatal birth weight. Reproductive Biomedicine Online 35(2), 189–196. https://doi.org/10.1016/j.rbmo.2017.04.010.CrossRefGoogle ScholarPubMed
Maheshwari, A., Pandey, S., Amalraj Raja, E., Shetty, A., Hamilton, M. and Bhattacharya, S (2018) Is frozen embryo transfer better for mothers and babies? Can cumulative meta-analysis provide a definitive answer? Human Reproduction Update 24(1), 35–58. https://doi.org/10.1093/humupd/dmx031.CrossRefGoogle ScholarPubMed
Meczekalski, B., Szeliga, A., Podfigurna, A., Miechowicz, I. and Adashi, E.Y. (2020) Assisted reproductive technology outcome in United States of America and Australia with New Zealand: comparison of annual reports 2005–2016. Gynecological Endocrinology. https://doi.org/10.1080/09513590.2020.1737006.CrossRefGoogle ScholarPubMed
Mourad, S., Brown, J. and Farquhar, C. (n.d.) Interventions for the prevention of OHSS in ART cycles: an overview of Cochrane reviews. The Cochrane Database of Systematic Reviews 1, CD012103. https://doi.org/10.1002/14651858.CD012103.pub2.Google Scholar
Pereira, N., Elias, R.T., Christos, P.J., Petrini, A.C., Hancock, K., Lekovich, J.P. and Rosenwaks, Z. (2017) Supraphysiologic estradiol is an independent predictor of low birth weight in full-term singletons born after fresh embryo transfer. Human Reproduction (Oxford, England) 32(7), 1410–1417. https://doi.org/10.1093/humrep/dex095.CrossRefGoogle Scholar
Pereira, N., Reichman, D.E., Goldschlag, D.E., Lekovich, J.P. and Rosenwaks, Z. (2015) Impact of elevated peak serum estradiol levels during controlled ovarian hyperstimulation on the birth weight of term singletons from fresh IVF-ET cycles. Journal of Assisted Reproduction and Genetics 32(4), 527–532. https://doi.org/10.1007/s10815-015-0434-1.CrossRefGoogle ScholarPubMed
Senapati, S., Wang, F., Ord, T., Coutifaris, C., Feng, R. and Mainigi, M. (2018) Superovulation alters the expression of endometrial genes critical to tissue remodeling and placentation. Journal of Assisted Reproduction and Genetics 35(10), 1799–1808. https://doi.org/10.1007/s10815-018-1244-z.CrossRefGoogle ScholarPubMed
Tarlatzi, T., Venetis, C., Sassi, A., Devreker, F., Englert, Y. and Delbaere, A. (2021) Higher estradiol levels are associated with lower neonatal birthweight after fresh and frozen embryo transfers. A cohort study of 3631 singleton IVF pregnancies. Gynecological Endocrinology 37(7), 618–623. https://doi.org/10.1080/09513590.2020.1827383.CrossRefGoogle ScholarPubMed
Ying, Y., Lu, X., Zhang, H., Arhin, S.K., Hou, X., Wang, Z., Wu, H., Lu, J. and Tang, Y. (2021) Clinical and perinatal outcomes of fresh single-blastocyst-transfer cycles under an early follicular phase prolonged protocol according to day of trigger estradiol levels. PeerJ 9. https://doi.org/10.7717/PEERJ.11785.CrossRefGoogle Scholar
Yu Ng, E.H. (2000) High serum oestradiol concentrations in fresh IVF cycles do not impair implantation and pregnancy rates in subsequent frozen-thawed embryo transfer cycles. Human Reproduction 15(2), 250–255. https://doi.org/10.1093/humrep/15.2.250.CrossRefGoogle Scholar