Evaluation of the relationship between serum estradiol levels on human chorionic gonadotropin administration day and intracytoplasmic sperm injection outcomes: A retrospective population-based study


Background: The correlation between high estradiol (E2) levels induced by controlled ovarian hyperstimulation (COH) and pregnancy is controversial.

Objective: To assess the effect of serum E2 levels on the day of human chorionic gonadotropin administration on the intracytoplasmic sperm injection (ICSI) outcome.

Materials and Methods: The current study included 551 participants who had undergone ICSI between May 2014 and May 2016. Based on E2 levels, the individuals aged < 37 yr (n = 502) and 37-42 yr (n = 49) were categorized into six and three groups, respectively. ICSI outcomes including the number of retrieved oocytes (NRO), number of embryos (NE), pregnancy rate, and abortion rate were analyzed in both groups.

Results: Among participants aged < 37 yr, the NRO and NE were 8.69 ± 3.82 and 5.24 ± 2.32, respectively and they had a significant correlation with the E2 level on human chorionic gonadotropin administration day (p < 0.001 for both). Among participants aged > 37 yr, NRO and NE were 5.18 ± 3.17 and 3.40 ± 2.23, respectively, and the NRO (p < 0.001), NE (p < 0.001), pregnancy rate (p < 0.001), abortion rate (p = 0.007), and the number of grade A and B embryos (p = 0.003) had a significant association with the E2 level.

Conclusion: COH is a costly procedure that may have negative effects on endometrial receptivity. Thus, in order to prevent these effects and also to reduce the costs of COH, we recommend gaining optimum number of oocytes rather than maximum number during the procedure.

Key words: Intracytoplasmic sperm injection, In vitro fertilization, Estradiol, Pregnancy.

[1] Polat M, Bozdag G, Yarali H. Best protocol for controlled ovarian hyperstimulation in assisted reproductive technologies: Fact or opinion? Semin Reprod Med 2014; 32: 262–271.

[2] 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: 2446–2453.

[3] 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 concentrationdependent manner. Fertil Steril 2010; 93: 442–446.

[4] Valbuena D, Martin J, De Pablo JL, Remohi J, Pellicer A, Simón C. Increasing levels of estradiol are deleterious to embryonic implantation because they directly affect the embryo. Fertil Steril 2001; 76: 962–968.

[5] Wang M, Hao C, Bao H, Huang X, Liu Zh, Zhang W, 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 2017; 295: 407–414.

[6] 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: 1707–1709.

[7] Ng EHY, Yeung WS, Lau EYL, 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: 250–255.

[8] Chen CH, Zhang X, Barnes R, Confino E, Milad M, Puscheck E, et al. Relationship between peak serum estradiol levels and treatment outcome in in vitro fertilization cycles after embryo transfer on day 3 or day 5. Fertil Steril 2003; 80: 75–79.

[9] Papageorgiou Th, 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: 2846–2850.

[10] Hu XL, Feng Ch, Lin XH, Zhong ZX, Zhu YM, Lv PP, et al. High maternal serum estradiol environment in the first trimester is associated with the increased risk of small-for-gestationalage birth. J Clin Endocrinol Metab 2014; 99: 2217– 2224.

[11] 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 2015; 30: 1473–1480.

[12] 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: 527–532.

[13] Serna J, Cholquevilque JL, Cela V, Martínez- Salazar J, Requena A, Garcia-Velasco JA. Estradiol supplementation during the luteal phase of IVF-ICSI patients: A randomized, controlled trial. Fertil Steril 2008; 90: 2190–2195.

[14] Peña JE, Chang PL, Chan LK, Zeitoun Kh, Thornton MH, Sauer MV. Supraphysiological estradiol levels do not affect oocyte and embryo quality in oocyte donation cycles. Hum Reprod 2002; 17: 83–87.

[15] Mitwally MF, Bhakoo HS, Crickard K, Sullivan MW, Batt RE, Yeh J. Estradiol production during controlled ovarian hyperstimulation correlates with treatment outcome in women undergoing in vitro fertilization-embryo transfer. Fertil Steril 2006; 86: 588–596.

[16] Kyrou D, Popovic-Todorovic B, Fatemi HM, Bourgain C, Haentjens P, Van Landuyt L, 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 2009; 24: 2902–2909.

[17] Basir GhS, Wai-Sum O, Yu Ng EH, Ho PCh. Morphometric analysis of peri-implantation endometrium in patients having excessively high oestradiol concentrations after ovarian stimulation. Hum Reprod 2001; 16: 435–440.

[18] Cai Q, Wan F, Huang K, Zhang H. Does the number of oocytes retrieved influence pregnancy after fresh embryo transfer? PLoS One 2013; 8: e56189. 1–7.

[19] Mittal S, Gupta P, Malhotra N, Singh N. Serum estradiol as a predictor of success of in vitro fertilization. J Obstet Gynaecol India 2014; 64: 124–129.

[20] 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: 53–58.

[21] Simon A, Laufer N. Assessment and treatment of repeated implantation failure (RIF). J Assist Reprod Genet 2012; 29: 1227–1239.