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Effect of estrogen priming through luteal phase and stimulation phase in poor responders in in-vitro fertilization

  • ASSISTED REPRODUCTION TECHNOLOGIES
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Abstract

Purpose

To verify whether a novel protocol administering E2 during the luteal phase of the preceding cycle and during ovarian stimulation in GnRH antagonist cycle could enhance follicular response and hence improve outcomes in poor responders.

Methods

In this retrospective analysis, a total of 155 poor responder patients subjected to IVF/ICSI were analyzed. All the patients had history of more than one prior IVF cycle failure with poor response (less than 5 oocytes retrieved and/or maximal E2 level less than 500 pg/mL) by using conventional long agonist or antagonist protocol. In luteal E2 treatment protocol (n = 86), oral estradiol valerate 4 mg/day was initiated on luteal day 21 and either stopped at menstrual cycle day 3 (Protocol A, n = 28) or continued during the period of ovarian stimulation until the day of hCG injection (Protocol B, n = 58). IVF parameters and pregnancy outcome of luteal E2 treatments group were compared with a standard GnRH antagonist protocol (n = 69) which the patients received no hormonal pretreatment.

Results

Compared to standard GnRH antagonist protocol, cancellation rate was lower with luteal E2 group (15.1% vs 37.7%, p < 0.01). Moreover, patients treated with luteal estrogen resulted in an increased number of oocytes retrieved (4.5 ± 2.9 vs 3.2 ± 1.9; p < 0.01). A trend toward increase in number of normally fertilized embryos (2.9 ± 2.1vs 2.3 ± 1.9; p = 0.043), and increased prevalence of good quality embryos (51.2% vs 25%; p = 0.047) were noted. Comparing protocol A and B, there were no significant difference between embryologic data, however there were slight increase in ongoing pregnancy rate in protocol B compared to A (27.1% vs 20%, p = 0.357), although statistical significance was not achieved.

Conclusion

Estrogen priming through luteal phase and stimulation phase improved ovarian responsiveness and this may lead to an increase in pregnancy rate in poor responders with failed cycle.

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References

  1. Keay SD, Liversedge NH, Mathur RS, Jenkins JM. Assisted conception following poor ovarian response to gonadotrophin stimulation. Br J Obstet Gynaecol. 1997;104:521–27.

    Article  PubMed  CAS  Google Scholar 

  2. Hugues JN, Cedrin Durnerin IC. Revisiting gonadotrophin-releasing hormone agonist protocols and management of poor ovarian responses to gonadotrophins. Hum Reprod Update. 1998;4:83–101.

    Article  PubMed  CAS  Google Scholar 

  3. Battaglia C, Salvatori M, Maxia N, Petraglia F, Facchinetti F, Volpe A. Adjuvant L-arginine treatment for in-vitro fertilization in poor responder patients. Hum Reprod. 1999;14:1690–97.

    Article  PubMed  CAS  Google Scholar 

  4. Tarlatzis BC, Zepiridis L, Grimbizis G, Bontis J. Clinical management of low ovarian response to stimulation for IVF: a systematic review. Hum Reprod Update. 2003;9:61–76.

    Article  PubMed  CAS  Google Scholar 

  5. Dor J, Seidman DS, Ben-Shlomo I, Levran D, Karasik A, Mashiach S. The prognostic importance of the number of oocytes retrieved and estradiol levels in poor and normal responders in in vitro fertilization (IVF) treatment. J Assist Reprod Genet. 1992;9:228–32.

    Article  PubMed  CAS  Google Scholar 

  6. Land JA, Yarmolinskaya MI, Dumoulin JC, Evers JL. High-dose human menopausal gonadotropin stimulation in poor responders does not improve in vitro fertilization outcome. Fertil Steril. 1996;65:961–65.

    PubMed  CAS  Google Scholar 

  7. Spandorfer S, Navarro J, Kump LM, Liu HC, Davis OK, Rosenwaks Z. “Co-Flare” stimulation in the poor responder patient: predictive value of the flare response. J Assist Reprod Genet. 2001;18:629–33.

    Article  PubMed  CAS  Google Scholar 

  8. Ulug U, Ben-Shlomo I, Turan E, Erden HF, Akman MA, Bahceci M. Conception rates following assisted reproduction in poor responder patients: a retrospective study in 300 consecutive cycles. Reprod Biomed Online. 2003;6:439–43.

    Article  PubMed  Google Scholar 

  9. Kyrou D, Kolibianakis EM, Venetis CA, Papanikolaou EG, Bontis J, Tarlatzis BC. How to improve the probability of pregnancy in poor responders undergoing in vitro fertilization: a systematic review and meta-analysis. Fertil Steril. 2009;91:749–66.

    Article  PubMed  CAS  Google Scholar 

  10. Loutradis D, Drakakis P, Milingos S, Stefanidis K, Michalas S. Alternative approaches in the management of poor response in controlled ovarian hyperstimulation (COH). Ann N Y Acad Sci. 2003;997:112–9.

    Article  PubMed  Google Scholar 

  11. Karande VC, Jones GS, Veeck LL, Muasher SJ. High-dose follicle-stimulating hormone stimulation at the onset of the menstrual cycle does not improve the in vitro fertilization outcome in low-responder patients. Fertil Steril. 1990;53:486–9.

    PubMed  CAS  Google Scholar 

  12. Surrey ES, Schoolcraft WB. Evaluating strategies for improving ovarian response of the poor responder undergoing assisted reproductive techniques. Fertil Steril. 2000;73:667–76.

    Article  PubMed  CAS  Google Scholar 

  13. Frankfurter D, Dayal M, Dubey A, Peak D, Gindoff P. Novel follicular-phase gonadotropin-releasing hormone antagonist stimulation protocol for in vitro fertilization in the poor responder. Fertil Steril. 2007;88:1442–5.

    Article  PubMed  CAS  Google Scholar 

  14. Horvath PM, Styler M, Hammond JM, Shelden RM, Kemmann E. Exogenous gonadotropin requirements are increased in leuprolide suppressed women undergoing ovarian stimulation. Fertil Steril. 1988;49:159–62.

    PubMed  CAS  Google Scholar 

  15. Kolibianakis EM, Papanikolaou EG, Camus M, Tournaye H, Van Steirteghem AC, Devroey P. Effect of oral contraceptive pill pretreatment on ongoing pregnancy rates in patients stimulated with GnRH antagonists and recombinant FSH for IVF. A randomized controlled trial. Hum Reprod. 2006;21:352–7.

    Article  PubMed  CAS  Google Scholar 

  16. Schachter M, Friedler S, Raziel A, Strassburger D, Bern O, Ron-el R. Improvement of IVF outcome in poor responders by discontinuation of GnRH analogue during the gonadotropin stimulation phase-a function of improved embryo quality. J Assist Reprod Genet. 2001;18:197–204.

    Article  PubMed  CAS  Google Scholar 

  17. Leipheimer RE, Bona-Gallo A, Gallo RV. Influence of estradiol and progesterone on pulsatile LH secretion in 8-day ovariectomized rats. Neuroendocrinology. 1986;43:300–7.

    Article  PubMed  CAS  Google Scholar 

  18. Fanchin R, Cunha-Filho JS, Schonauer LM, Kadoch IJ, Cohen-Bacri P, Frydman R. Coordination of early antral follicles by luteal estradiol administration provides a basis for alternative controlled ovarian hyperstimulation regimens. Fertil Steril. 2003;79:316–21.

    Article  PubMed  Google Scholar 

  19. Fanchin R, Salomon L, Castelo-Branco A, Olivennes F, Frydman N, Frydman R. Luteal estradiol pre-treatment coordinates follicular growth during controlled ovarian hyperstimulation with GnRH antagonists. Hum Reprod. 2003;18:2698–703.

    Article  PubMed  CAS  Google Scholar 

  20. Takekida S, Matsuo H, Maruo T. GnRH agonist action on granulosa cells at varying follicular stages. Mol Cel Endocrinol. 2003;202:155–64.

    Article  CAS  Google Scholar 

  21. Yang BC, Uemura T, Minaguchi H. Effects of a gonadotropin releasing hormone agonist on oocyte maturation, fertilization, and embryonal development of mice. J Assist Reprod Genet. 1995;12:728–32.

    Article  PubMed  CAS  Google Scholar 

  22. Yoshimura Y, Nakamura Y, Ando M, Shiokawa S, Koyama N, Nanno T. Direct effect of gonadotropin-releasing hormone agonists on the rabbit ovarian follicle. Fertil Steril. 1992;57:1091–7.

    PubMed  CAS  Google Scholar 

  23. Hill MJ, McWilliams GD, Miller KA, Scott Jr RT, Frattarelli JL. A luteal estradiol protocol for anticipated poor-responder patients may improve delivery rates. Fertil Steril. 2009;91:739–43.

    Article  PubMed  CAS  Google Scholar 

  24. Weitzman VN, Engmann L, DiLuigi A, Maier D, Nulsen J, Benadiva C. Comparison of luteal estradiol patch and gonadotropin-releasing hormone antagonist suppression protocol before gonadotropin stimulation versus microdose gonadotropin-releasing hormone agonist protocol for patients with a history of poor in vitro fertilization outcomes. Fertil Steril. 2009;92:226–30.

    Article  PubMed  CAS  Google Scholar 

  25. Frattarelli JL, Hill MJ, McWilliams GD, Miller KA, Bergh PA, Scott RT. A luteal estradiol protocol for expected poor-responders improves embryo number and quality. Fertil Steril. 2008;89:1118–22.

    Article  PubMed  CAS  Google Scholar 

  26. Tartagni M, Cicinelli E, De Pergola G, De Salvia MA, Lavopa C, Loverro G. Effects of pretreatment with estrogens on ovarian stimulation with gonadotropins in women with premature ovarian failure: a randomized, placebo-controlled trial. Fertil Steril. 2007;87:858–61.

    Article  PubMed  CAS  Google Scholar 

  27. Cedrin-Durnerin I, Bstandig B, Parneix I, Bied-Damon V, Avril C, Decanter C. Effects of oral contraceptive, synthetic progestogen or natural estrogen pre-treatments on the hormonal profile and the antral follicle cohort before GnRH antagonist protocol. Hum Reprod. 2007;22:109–16.

    Article  PubMed  CAS  Google Scholar 

  28. Ireland JJ, Richards JS. Acute effects of estradiol and follicle-stimulating hormone on specific binding of human [125I] iodofollicle-stimulating hormone to rat ovarian granulosa cells in vivo and in vitro. Endocrinol. 1978;102:876–83.

    Article  CAS  Google Scholar 

  29. Wang XN, Greenwald GS. Synergistic effects of steroids with FSH on folliculogenesis, steroidogenesis and FSH- and hCG-receptors in hypophysectomized mice. J Reprod Fertil. 1993;99:403–13.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This study was supported by a grant (no. A084923) from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea.

These findings are presented at the 27th Annual Meeting of the European Society of Human Reproduction and Embryology, Stockholm, Sweden on 3–6 July, 2011.

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Authors and Affiliations

  1. Fertility Center of CHA Gangnam Medical Center, Department of Obstetrics and Gynecology, College of Medicine, CHA University, 650-9 Yeoksam, Kangnamgu, Seoul, 135-081, Korea

    Eun Mi Chang, Ji Eun Han, Hyung Jae Won, You Shin Kim, Tae Ki Yoon & Woo Sik Lee

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  1. Eun Mi Chang
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  2. Ji Eun Han
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  3. Hyung Jae Won
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Correspondence to Woo Sik Lee.

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Capsule Estrogen priming through luteal phase and stimulation phase improved ovarian responsiveness and this may lead to an increase in pregnancy rate in poor responders.

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Chang, E.M., Han, J.E., Won, H.J. et al. Effect of estrogen priming through luteal phase and stimulation phase in poor responders in in-vitro fertilization. J Assist Reprod Genet 29, 225–230 (2012). https://doi.org/10.1007/s10815-011-9685-7

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  • DOI: https://doi.org/10.1007/s10815-011-9685-7

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