In high responding patients undergoing an initial IVF cycle, elevated estradiol on the day of hCG has no effect on live birth rate

Reproductive Biology and Endocrinology

Karl R Hansen²  Dena O’Leary¹  Sana N Kahn²  Robert A Wild²  LaTasha B Craig²  Michael T Zavy² 

[1] Section of Uro-gynecology, Department of Obstetrics and Gynecology, Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma, USA;Section of Reproductive Endocrinology and Infertility Department of Obstetrics and Gynecology, Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma, USA

关键词: Day of embryo transfer;    Embryo quality;    Age;    Live birth rate;    High responder;    Estradiol level;    IVF;   

Others  :  1132325
DOI  :  10.1186/1477-7827-12-119

 received in 2014-09-10, accepted in 2014-11-20,  发布年份 2014

【 摘 要 】

Background

The impact of elevated estradiol on the day of human chorionic gonadotropin (hCG) administration on in vitro fertilization (IVF) outcomes has been debated for over 25 years. Some investigators have shown a positive effect, others a negative effect; while most have shown no effect. Few studies have expressed their findings based on live birth. This study examined the relationship between estradiol level and other IVF cycle response parameters in relation to pregnancy, with a focus on live births after controlling for embryo quality.

Methods

We performed a retrospective cohort study on 489 patients <40 years old that underwent an initial IVF cycle. Estradiol concentration on the day of hCG was categorized as; low <2000 pg/ml), mid (2001-4000 pg/ml) and high (>4000 pg/ml) to determine how estradiol level on the day of hCG affected response variables during the IVF cycle. We performed a subgroup analysis restricted to patients with good/fair quality embryos transferred (n = 428), to control for embryo quality and assessed pregnancy outcome. The association between estradiol and live birth (LB) was then evaluated after identifying and controlling for confounding factors. Multivariate analysis was used to identify significant main effects and interactions in the model. Estradiol levels were also compared in patients having a LB or not (NLB) in both populations.

Results

We found that estradiol was significantly related to + hCG, clinical pregnancy rate, age, and most other IVF cycle response variables. After performing the subgroup analysis controlling for embryo quality, we found that LB rates were not different. Only the main effects of average embryo quality at transfer (AEQS), age and transferring two embryos influenced LB. Estradiol levels were also compared in patients having a LB or NLB in both populations and was found to be higher/not different in LB patients. LB rates and AEQS were also not different in a subgroup of patients having an elevated level of estradiol (>4200 pg/ml) on the day of hCG in patients having embryo transfer on day 3 or day 5.

Conclusions

After controlling for embryo quality, elevated estradiol on the day of hCG had no effect on LB.

【 授权许可】

   
2014 Zavy et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Chenette PE, Sauer MV, Paulson RJ: Very high serum E2 levels are not detrimental to clinical outcome of in vitro fertilization. Fertil Steril 1990, 54:858-863.
• [2]Gelety TJ, Buyalos RP: The influence of supraphysiologic E2 levels on human nidation. J Assist Reprod Genet 1995, 12:406-412.
• [3]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.
• [4]Kummer N, Benadiva C, Feinn R, Mann J, Nulsen J, Engmann : Factors that predict the probability of a successful clinical outcome after induction of oocyte maturation with a gonadotropin-releasing hormone agonist. Fertil Steril 2011, 96:63-68.
• [5]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, 10:2432-2437.
• [6]Ng EHY, Yeung WSB, Lau EYL, So WWK, Ho PC: High serum estradiol 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.
• [7]Chen QJ, Sun XX, Li L, Gao XH, Wu Y, Gemzell-Danielsson K, Chen LN: Effects of ovarian high response on implantation and pregnancy outcome during controlled ovarian hyperstimulation (with GnRH agonist and rFSH). Acta Obstet Gynecol Scand 2007, 86:849-854.
• [8]Arslan M, Bocca S, Ozturk E, Hakan A, Duran E, 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, 24:111-117.
• [9]Sharara FI, McClamrock HD: High estradiol levels and high oocyte yield are not detrimental to in vitro fertilization outcome. Fertil Steril 1999, 72:401-405.
• [10]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, 76:670-674.
• [11]Pena 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, 17:83-87.
• [12]Papageorgiou T, Guibert J, Goffinet F, Patrat C, Fulla Y, Janssens Y, Zorn JR: 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.
• [13]Ulug U, Tosun S, Jozwiak EA, Mesut A, Sismanohlu A, Bahceci M: Subclinical pregnancy losses among women undergoing in-vitro fertilization with ICSI. J Assist Reprod Genet 2006, 23:261-267.
• [14]Wu CH, Kuo TC, Wu HH, Yeh GP, Tsai HD: High serum estradiol levels are not detrimental to in vitro fertilization outcome. Taiwan J Obstet Gynecol 2007, 46:54-59.
• [15]Kong GWS, Cheung LP, Haines CJ: Comprehensive assessment of serum estradiol impact on selected physiologic markers observed during in-vitro fertilization and embryo transfer cycles. J Exp Clin Assist Reprod 2009, 6:5-13.
• [16]Yoldemir T, Fraser IS: The effect of elevated serum estradiol levels on the day of human chorionic gonadotropin injection on pregnancy outcomes in an assisted reproduction program. Aust N Z J Obstet Gynecol 2009, 49:545-550.
• [17]Kyrou D, Popovic-Todorovic B, Fatemi HM, Bourgain C, Haentjens P, Van Landuyt L, Devroey P: 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.
• [18]Wu Z, Li R, Ma Y, Deng B, Zhang X, Meng Y, Chen X, Liu P, Qiao J: Effect of HCG-day serum progesterone and oestradiol concentrations on pregnancy outcomes in GnRH agonist cycles. Reprod BioMed Online 2012, 24:511-520.
• [19]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.
• [20]Elgindy EA, Abou-Setta AM, Mostafa MI: Blastocyst-stage versus cleavage-stage embryo transfer in women with high oestradiol concentrations; randomized controlled trial. Reprod BioMed Online 2011, 23:789-798.
• [21]Moraloglu O, Tongue EA, Ozel M, Ozaksit G, Var T, Sarikaya E: The effect of peak and mid-luteal estradiol levels on in vitro fertilization outcome. Arch Gynecol Obstet 2012, 285:857-862.
• [22]Chen CH, Zhang X, Barnes R, Confino E, Milad M, Puscheck P, Kazer RR: Relationship between peak serum estradiol and treatment outcome in in vitro fertilization cycles after embryo transfer on day 3 or day 5. Fertil Steril 2003, 80:75-79.
• [23]Racowsky C, Vernon MV, Mayer J, Ball GD, Behr B, Pomeroy KO, Wininger D, Gibbons W, Conaghan J, Stern JE: Standardization of grading embryo morphology. Fertil Steril 2010, 94:1152-1153.
• [24]Fr DD, Tarlatzis R: Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovarian syndrome. Fertil Steril 2004, 81:19-25.
• [25]Kyrou D, AlAzemi M, Papanikolaou EG, Donoso P, Tziomalos K, Devroey P, Fatemi HM: The relationship between premature progesterone rise with serum estradiol levels and number of follicles in GnRH antagonist/recombinant FSH-stimulated cycles. Eur J Obstet Gynecol Reprod Biol 2012, 162:165-168.
• [26]Fatemi HM, Doody K, Griesinger G, Witjes H, Mannaerts B: High ovarian response does not jeopardize ongoing pregnancy rates and increases cumulative pregnancy rates in GnRH-antagonist protocol. Hum Reprod 2013, 28:442-452.
• [27]Requena A, Cruz M, Bosch E, Meseguer M, Garcia-Velasco JA: High progesterone levels in women with high ovarian response do not affect clinical outcomes: a retrospective cohort study. Reprod Biol and Endocrinol 2014, 12:69-75. BioMed Central Full Text
• [28]Griesinger G, Mannaerts B, Andersen CY, Witjes H, Kolibianakis EM, Gordon K: Progesterone elevation does not compromise pregnancy rates in high responders: a pooled analysis of in vitro fertilization patients treated with recombinant follicle-stimulating hormone/gonadotropin-releasing hormone antagonist in six trials. Fertil Steril 2013, 100:1622-1628.
• [29]Farhi J, Haroush AB, Andrawus N, Pinkas H, Sapir O, Fisch B, Ashkenazi J: High serum oestradiol concentrations in IVF cycles increase the risk of pregnancy complications related to abnormal placentation. Reprod BioMed Online 2010, 21:331-337.
• [30]Imudia AN, Awonuga AO, Doyle JO, Kaimal AJ, Wright DL, Toth TL, Styer AK: 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, 97:1374-1379.
• [31]Hu XL, Feng C, Lin XH, Zhong ZX, Zhu YM, Lv PP, Lv M, Meng Y, Zhang D, Lu XE, Jin F, Sheng JZ, Xu J, Huang HF: 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, 99:2217-2224.