Fertility and Sterility
Volume 94, Issue 2 , Pages 662-665 , July 2010

What is the optimum maximal gonadotropin dosage used in microdose flare-up cycles in poor responders?

Partly presented at the 63rd Annual Meeting of the ASRM, Washington, DC, October 13 to 17, 2007.

  • Murat Berkkanoglu, M.D.

      Affiliations

    • Corresponding Author InformationReprint requests: Murat Berkkanoglu, M.D., Antalya Tup Bebek, Merkezi, 07080, Antalya, Turkey (FAX: +90 242 345 47 47).
    • ,
  • Kemal Ozgur, M.D.

Received 26 November 2008 ,Revised 27 February 2009 ,Accepted 9 March 2009.

References 

  1. Toner JP, Philput C, Jones GS, Muasher SJ. Basal follicle-stimulating hormone level is a better predictor of in vitro fertilization performance than age. Fertil Steril. 1991;55:784–791
  2. De Koning CH, Popp-Snijders C, Schoemaker J, Lambalk CB. Elevated FSH concentrations in imminent ovarian failure are associated with higher FSH and LH pulse amplitude and response to GnRH. Hum Reprod. 2000;15:1452–1456
  3. Smotrich DB, Widra EA, Gindoff PR, Levy MJ, Hall JL, Stillman RJ. Prognostic value of day 3 estradiol on in vitro fertilization outcome. Fertil Steril. 1995;64:1136–1140
  4. Seifer DB, Scott RT, Bergh PA, Abrogast LK, Friedman CI, Mack CK, et al. Women with declining ovarian reserve may demonstrate a decrease in day 3 serum inhibin B before a rise in day 3 follicle-stimulating hormone. Fertil Steril. 1999;72:63–65
  5. Van Rooij IA, Broekmans FJ, Te Velde ER, Fauser BC, Bancsi LF, de Jong FH, et al. Serum anti-Mullerian hormone levels: a novel measure of ovarian reserve. Hum Reprod. 2002;17:3065–3071
  6. Kwee J, Schats R, McDonnell J, Schoemaker J, Lambalk CB. The clomiphene citrate challenge test versus the exogenous follicle-stimulating hormone ovarian reserve test as a single test for identification of low responders and hyperresponders to in vitro fertilization. Fertil Steril. 2006;85:1714–1722
  7. Ravhon A, Aurell R, Lawrie H, Margara R, Winston RM. The significance of delayed suppression using buserelin acetate and recombinant follicle-stimulating hormone in a long protocol in vitro fertilization program. Fertil Steril. 2000;73:325–329
  8. Bancsi LF, Broekmans FJ, Eijkemans MJ, de Jong FH, Habbema JD, te Velde ER. Predictors of poor ovarian response in in vitro fertilization: a prospective study comparing basal markers of ovarian reserve. Fertil Steril. 2002;77:328–336
  9. Loverro G, Nappi L, Mei L, Giaccomoantonio L, Carriero C, Tartagni M. Evaluation of functional ovarian reserve in 60 patients. RBM Online. 2003;7:200–204
  10. Garcia J, Padilla S, Bayati J, Baramki T. Follicular phase gonadotropin-releasing hormone agonist and human menopausal gonadotropins: a better alternative for ovulation induction in in vitro fertilization. Fertil Steril. 1990;53:302–305
  11. Padilla SL, Dugan K, Maruschak V, Shalika S, Smith RD. Use of the flare-up protocol with high dose human follicle-stimulating hormone and human menopausal gonadotropins for in vitro fertilization in poor responders. Fertil Steril. 1996;65:796–799
  12. Leondires MP, Escalpes M, Segars JH, Scott RT, Miller BT. Microdose follicular phase gonadotropin-releasing hormone agonists (GnRH-a) compared with luteal phase GnRH-a for ovarian stimulation at in vitro fertilization. Fertil Steril. 1999;72:1018–1023
  13. Berkkanoglu M, Isikoglu M, Aydin D, Ozgur K. Clinical effects of ovulation induction with recombinant follicle-stimulating hormone supplemented with recombinant luteinizing hormone or low-dose recombinant human chorionic gonadotropin in the midfollicular phase in microdose cycles in poor responders. Fertil Steril. 2007;88:665–669
  14. Filicori M. Clinical review 81: gonadotropin-releasing hormone analogs in ovulation induction: current status and perspectives. J Clin Endocrinol Metab. 1996;81:2413–2416
  15. Ben Rafael Z, Benadiva C, Ausmanas M, Barber B, Blasco L, Flickinger G, et al. Dose of human menopausal gonadotropin influences the outcome of an in vitro fertilization program. Fertil Steril. 1987;48:964–968
  16. Hofmann G, Toner J, Muasher S, Jones G. High-dose follicle stimulating hormone (FSH) ovarian stimulation in low responder patients for in vitro fertilization. J In Vitro Fertil Embryo Transfer. 1993;6:285–289
  17. Surrey ES, Boer J, Hill DM, Ramsey J, Surey MW. Clinical and endocrine effects of a microdose GnRH agonist flare regimen administered to poor responders who are undergoing in vitro fertilization. Fertil Steril. 1998;69:419–424
  18. Out HJ, Braat DDM, Lintsen BME, Gurgan T, Bukulmez O, Gokmen O, et al. Increasing the daily dose of recombinant follicle stimulating hormone (Puregon) does not compensate for the age-related decline in retrievable oocytes after ovarian stimulation. Hum Reprod. 2000;15:29–35
  19. Klinkert ER, Broekmans FJ, Looman CW, Habbema JD, te Velde ER. Expected poor responders on the basis of an antral follicle count do not benefit from a higher starting dose of gonadotrophins in IVF treatment: a randomized controlled trial. Hum Reprod. 2005;20:611–615
  20. 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
  21. Hofmann GE, Toner JP, Muasher SJ, Jones GS. 1989. High-dose follicle-stimulating hormone (FSH) ovarian stimulation in low responder patients for in vitro fertilization. J In Vitro Fertil Embryo Transfer. 1989;6:285–289
  22. Raga F, Bonilla-Musoles F, Casan EM, Bonilla F. Recombinant follicle stimulating hormone stimulation in poor responders with normal basal concentrations of follicle stimulating hormone and oestradiol: improved reproductive outcome. Hum Reprod. 1999;14:1431–1434
  23. Faber BM, Mayer J, Cox B, Jones D, Toner JP, Oehninger S, et al. Cessation of gonadotropin-releasing hormone agonist therapy combined with high-dose gonadotropin stimulation yields favorable pregnancy results in low responders. Fertil Steril. 1998;69:826–830
  24. Wang PT, Lee RK, Su JT, Hou JW, Lin MH, Hu YM. Cessation of low-dose gonadotropin releasing hormone agonist therapy followed by high-dose gonadotropin stimulation yields a favorable ovarian response in poor responders. J Assist Reprod Genet. 2002;1:1–6
  25. Karande V, Morris R, Rinehart J, Miller C, Rao R, Gleicher N. Limited success using the “flare” protocol in poor responders in cycles with low basal follicle-stimulating hormone levels during in vitro fertilization. Fertil Steril. 1997;67:900–903
  26. Surrey ES, Bower JA, Hill DM, Ramsey J, Surrey MW. Clinical and endocrine effects of a microdose GnRH agonist flare regimen administered to poor responders who are undergoing in vitro fertilization. Fertil Steril. 1998;69:419–424
  27. Land JA, Yarmolinskaya MI, Dumoulin JC, Evers JLH. High-dose human menopausal gonadotropin stimulation in poor responders does not improve in vitro fertilization outcome. Fertil Steril. 1996;65:961–965
  28. Shulman A, Ghetler Y, Fejgin M, Kaneti H, Weinstein S, Byeth Y, et al. Relationship between the threshold of ovarian sensitivity to human menopausal gonadotropin stimulation and in-vitro fertilization treatment outcome. Hum Reprod. 1995;10:3198–3201
  29. Karande V, Jones G, Veeck L, Muasher S. 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;53:486–489
  30. Confino E, Zhang X, Kazer RR. GnRHa flare and IVF pregnancy rates. Int J Gynaecol Obstet. 2004;85:36–39
  31. Kailasam C, Keay SD, Wilson P, Ford WC, Jenkins JM. Defining poor ovarian response during IVF cycles, in women aged <40 years, and its relationship with treatment outcome. Hum Reprod. 2004;19:1544–1547
  32. Borini A, Dal Prato L. Tailoring FSH and LH administration to individual patients. Reprod Biomed Online. 2005;11:283–293
  33. Dorn C. FSH: what is the highest dose for ovarian stimulation that makes sense on an evidence-based level?. Reprod Biomed Online. 2005;11:555–561
  34. Karande V, Gleicher N. A rational approach to the management of low responders in IVF. Hum Reprod. 1999;14:1744–1749
  35. Karande V. Managing and predicting low response to standard in vitro fertilization therapy: a review of the options. Treat Endocrinol. 2003;2:257–272
  36. Centre for Clinical Effectiveness. In women labelled as poor responders to ovulation stimulation in an assisted reproduction program, is there evidence for the effectiveness of increasing the total dose of FSH above 3000 IU?. Cochrane Database. 2000;HTA:20030660

 M.B. has nothing to disclose. K.O. has nothing to disclose.

PII: S0015-0282(09)00592-5

doi: 10.1016/j.fertnstert.2009.03.027

Fertility and Sterility
Volume 94, Issue 2 , Pages 662-665 , July 2010

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