Serum estradiol level on the day of ovulation trigger and pregnancy outcomes in in-vitro fertilisation-intracytoplasmic sperm injection cycles


  • Avani Pillai Department of Reproductive Medicine and Surgery, Amrita Institute of Medical Sciences, Kochi, Kerala, India
  • Fessylouis T. Department of Reproductive Medicine and Surgery, Amrita Institute of Medical Sciences, Kochi, Kerala, India
  • Ramesh P. Department of Reproductive Medicine and Surgery, Amrita Institute of Medical Sciences, Kochi, Kerala, India
  • Parvathy T. Department of Reproductive Medicine and Surgery, Amrita Institute of Medical Sciences, Kochi, Kerala, India
  • Aparna N. Department of Reproductive Medicine and Surgery, Amrita Institute of Medical Sciences, Kochi, Kerala, India



Embryo transfer Embryo quality, Implantation, Oocyte


Background: There is conflicting evidence with regards to the impact of supraphysiologic estradiol levels in in-vitro fertilisation-intracytoplasmic sperm injection (IVF-ICSI) cycles on pregnancy outcomes such as oocyte quality, implantation, and clinical pregnancy. The objective of our study was to evaluate the effect of serum estradiol levels on the day of ovulation trigger on pregnancy outcomes in IVF-ICSI cycles.

Methods: We performed a retrospective cohort study, which included eighty-three women who underwent IVF-ICSI and experienced fresh embryo transfer (ET) over one year period. The women included in the study were divided into four groups according to the serum estradiol level on the day of ovulation trigger; Group I: <2000pg/ml, Group II: 2000-3000pg/ml, Group III: 3000-4000pg/ml and Group IV: >4000pg/ml. The outcome measures including number of oocytes retrieved, MII (metaphase II) oocytes, fertilization rate, embryo quality, overall pregnancy rate, implantation rate and clinical pregnancy rate were compared among these four groups.

Results: The total number of oocytes, MII oocytes as well as good quality embryos significantly increased from group 1 to group 4. The implantation rate was lowest in group 4 compared to all other groups, although not statistically significant. There was no significant difference in overall and clinical pregnancy rate between the groups.

Conclusions: Serum estradiol level shows a positive correlation with the number of oocytes retrieved and good quality embryos. A higher estradiol level does not have a significant negative impact on the implantation rate, overall or clinical pregnancy rate.


Malhotra N, Shah D, Pai R, Pai HD, Bankar M. Assisted reproductive technology in India: A 3 year retrospective data analysis. J Hum Reprod Sci. 2013;6(4):235-40.

Pittaway DE, Wentz AC. Evaluation of the exponential rise of serum estradiol concentrations in human menopausal gonadotropin induced cycles. Fertil Steril. 1983;40:763-7.

Liu SM, Zheng YZ, Wang HB, Sun ZY, Zhen JR, Shen K, et al. Factors associated with effectiveness of treatment and reproductive outcomes in patients with thin endometrium undergoing estrogen treatment. Chin Med J. 2015;128:3173-7.

Wang XM, Jiang H, Zhang WX, Li Y. The effects of growth hormone on clinical outcomes after frozen-thawed embryo transfer. Int J Gynaecol Obstet. 2016;133:347-50.

Pelinck MJ, Hoek A, Simons AH, Heineman MJ. Efficacy of natural cycle IVF: a review of the literature. Hum Reprod Update. 2002;8:129-39.

Chen CD, Chen SU, Chou CH, Chen MJ, Wen WF, Wu SY, et al. High estradiol concentrations induce heat shock protein 70 expression and suppress nuclear factor kappa B activation in human endometrial epithelial cells. Biol Reprod. 2016;95:87.

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;10:2432-7.

Yu Ng EH, Yeung WS, Yee Lan Lau E, So WW, Ho PC. High serum oestradiol concentrations in fresh IVF cycles do not impair implantation and pregnancy rates in subsequent frozen-thawed embryo transfer cycles. Hum Reprod. 2000;15:250-5.

Levi AJ, Drews MR, Bergh PA, Miller BT, Scott RT. Controlled ovarian hyperstimulation does not adversely affect endometrial receptivity in in vitro fertilization cycles. Fertil Steril. 2001;76:670-4.

Sharara FI, McClamrock HD. High estradiol levels and high oocyte yield are not detrimental to in vitro fertilization outcome. Fertil Steril. 1999;72:401-5.

Testart J, Belaisch-Allart J, Forman R, Gazengel A, Strubb N, Hazout A, et al. Influence of different stimulation treatments on oocyte characteristics and in-vitro fertilizing ability. Hum Reprod. 1989;4:92-7.

Rosen MP, Shen S, Shen S, Rinaudo PF, Huddleston HG, McCulloch CE, et al. Fertilization rate is an independent predictor of implantation rate. Fertil Steril. 2010;94(4):1328-33.

Balaban B, Brison D, Calderón G, Catt J, Conaghan J, Cowan L, et al. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011;26:1270-83.

Pasternak MC, Christos P, Spandorfer SD. The relationship between body mass index and anti-mullerian hormone levels in reproductive-age women; is there a negative correlation? Fertil Steril. 2018;109(3):53.

Rehman R, Hussain Z, Faraz N. Effect of estradiol levels on pregnancy outcome in obese women. J Ayub Med Coll Abbottabad. 2012;24:3-5.

Kligman I, Rosenwaks Z. Differentiating clinical profiles: predicting good responders, poor responders, and hyperresponders. Fertil Steril. 2001;76:6.

Lee TH. Serum anti-mullerian hormone and estradiol levels as predictors of ovarian hyperstimulation syndrome in assisted reproduction technology cycles. Human Repro. 2008;23(1):160-7.

Cem Fiçiciogˇlu, Kutlu T, Baglam E, Bakacak Z. Early follicular antimüllerian hormone as an indicator of ovarian reserve. Fertil Steril. 2006;85:3.

Kara M, Kutlu T, Sofuoglu K, Devranoglu B, Cetinkaya T. Association between serum estradiol level on the hCG administration day and IVF-ICSI outcome. Iran J Reprod Med. 2012;10:53-8.

Blazar AS, Hogan JW, Frankfurter D, Hackett R, Keefe DL. Serum estradiol positively predicts outcomes in patients undergoing in vitro fertilization. Fertil Steril. 2004;81(6):1707-9.

Joo BS, Park SH, An BM, Kim KS, Moon SE, Moon HS. Serum estradiol levels during controlled ovarian hyperstimulation influence the pregnancy outcome of in vitro fertilization in a concentration-dependent manner. Fertil Steril. 2010;93:442-6.

Arslan M, Bocca S, Arslan EO, Duran HE, Stadtmauer L, Oehninger S. Cumulative exposure to high estradiol levels during the follicular phase of IVF cycles negatively affects implantation. J Assist Reprod Genet. 2007;24(4):111-7.

Wu CH, Kuo TC, Wu HH, Yeh GP, Tsai HD. High serum estradiol levels are not detrimental to in vitrofertilization outcome. Taiwan J Obstet Gynecol. 2007;46:54-9.

Mittal S, Gupta P, Malhotra N, Singh N. Serum estradiol as a predictor of success of in vitrofertilization. J Obstet Gynaecol India. 2014;64:124-9.

Valbuena D, Jasper M, Remohí J, Pellicer A, Simón C. Ovarian stimulation and endometrial receptivity. Hum Reprod. 1999;14(Suppl 2):107-11.

Peña JE, Chang PL, Chan LK, Zeitoun K, Thornton MH, Sauer MV. Supraphysiological estradiol levels do not affect oocyte and embryo quality in oocyte donation cycles. Hum Reprod. 2002;17(1):83-7.

Ng EH, Lau EY, Yeung WS, Ho PC. Oocyte and embryo quality in patients with excessive ovarian response during in vitro fertilization treatment. J Assist Reprod Genet. 2003;20(5):186-91.

Papageorgiou T, Guibert J, Goffinet F, Patrat C, Fulla Y, Janssens Y, et al. Percentile curves of serum estradiol levels during controlled ovarian stimulation in 905 cycles stimulated with recombinant FSH show that high estradiol is not detrimental to IVF outcome. Hum Reprod. 2002;17:2846-50.

Paulson RJ, Sauer MV, Lobo RA. Embryo implantation after human in vitro fertilization: importance of endometrial receptivity. Fertil Steril. 1990;53:870-4.

Kosmas IP, Kolibianakis EM, Devroey P. Association of estradiol levels on the day of hCG administration and pregnancy achievement in IVF: a systematic review. Hum Reprod. 2004;19:2446-53.






Original Research Articles