Skip to main content

Advertisement

Log in

Different ovarian stimulation protocols for women with diminished ovarian reserve

  • Symposium of the aging ovary
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To review the available treatments for women with significantly diminished ovarian reserve and assess the efficacy of different ovarian stimulation protocols.

Methods

Literature research performed among studies that have been published in the Pubmed, in the Scopus Search Machine and in Cohrane database of systematic reviews.

Results

A lack of clear, uniform definition of the poor responders and a lack of large-scale randomized studies make data interpretation very difficult for precise conclusions. Optimistic data have been presented by the use of high doses of gonadotropins, flare up Gn RH-a protocol (standard or microdose), stop protocols, luteal onset of Gn RH-a and the short protocol. Natural cycle or a modified natural cycle seems to be an appropriate strategy. Low dose hCG in the first days of ovarian stimulation has promising results. Molecular biology tools (mutations, single nucleotide polymorphisms (SNPs)) have been also considered to assist the management of this group of patients.

Conclusions

The ideal stimulation for these patients with diminished ovarian reserve remains a great challenge for the clinician, within the limits of our pharmaceutical quiver.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Shanbhag S, Aucott L, Bhattacharya S, Hamilton MA, McTavish AR. Intervensions for “poor responders” to controlled ovarian hyperstimulation (COH) in in vitro fertilization (IVF). Cochrane Database Syst Rev 2007;(1):CD004379.

  2. Keay SD, Liversedge NH, Mathur RS, Jenkins JM. Assisted conception following poor ovarian response to gonadotrophin stimulation. Br J Obstet Gynaecol 1997;104:521–7.

    PubMed  CAS  Google Scholar 

  3. Surrey ES, Schoolcraft WB. Evaluating strategies of improving ovarian response of the poor responder undergoing assisted reproductive techniques. Fertil Steril 2000;73(4):667–74.

    PubMed  CAS  Google Scholar 

  4. Ubaldi FM, Rienzi L, Ferrero S, Baroni E, Sapienza F, Cobellis L, et al. Management of poor responders in IVF. Reprod Biomed Online 2005;10(2):235–46.

    PubMed  CAS  Google Scholar 

  5. Pellicer A, Ardiles G, Neuspiller F, Remohi J, Simon C, Bonilla-Musoles F. Evaluation of the ovarian reserve in young low responders with normal basal FSH levels using 3-D ultrasound. Fertil Steril 1998;70:671–5.

    PubMed  CAS  Google Scholar 

  6. Mahutte NG, Arici A. Poor responders: does the protocol make a difference? Curr Opin Obstet Gynecol 2002;14:275–81.

    PubMed  Google Scholar 

  7. Beckers NGM, Macklon NS, Eijkemans MJC, Fauser BCJM. Women with regular menstrual cycles and a poor response to ovarian hyperstimulation for in vitro fertilization exhibit follicular phase characteristics suggestive of ovarian aging. Fertil Steril 2002;78:291–7.

    PubMed  Google Scholar 

  8. De Boer EJ, Tonkelaar I, te Velde ER, Burger, Klip H, van Leeuwen FE. A low number of retrieved oocytes at in vitro fertilization treatment is predictive of early menopause. Fertil Steril 2002;77:978–85.

    PubMed  Google Scholar 

  9. Nikolaou D, Lavery S, Turner C, Margara R, Trew G. Is there a link between an extremely poor response to ovarian hyperstimulation and an early ovarian failure? Hum Reprod 2002;17:1106–11.

    PubMed  CAS  Google Scholar 

  10. Jenkins JM, Davies DW, Devonport H, Anthony FW, Gadd SC, Watson RH, et al. Comparison of “poor” responders with “good” responders using a standard bucerelin/human menopausal gonadotrophin regimen for in vitro fertilization. Hum Reprod 1991;6:918–21.

    PubMed  CAS  Google Scholar 

  11. Kligman I, Rosenwaks Z. Differentiating clinical profiles: predicting good responders, poor responders, and hyperresponders. Fertil Steril 2001;76(6):1185–90.

    PubMed  CAS  Google Scholar 

  12. Zeleznik AJ, Shuler HM, Reichter LE. Gonadotrophin binding sites in the rhesus monkey ovary; role of the vasculature in the selective distribution of HCG to preovulatory follicle. Endocrinology 1981;109:356–62.

    PubMed  CAS  Google Scholar 

  13. Hernandez ER, Hurwitz A, Vera A, Pellicer A, Adashi EY, Le Roith D, et al. Expression of the genes encoding the IGFs and their receptors in the human ovary. J Clin Endocrinol Metab 1992;74:419–25.

    PubMed  CAS  Google Scholar 

  14. Pellicer A, Ballester MJ, Serrano MD, Mir A, Serra-Serra V, Remohi J, et al. Aetiological factors involved in the low response to gonadotrophins in infertile women with normal basal FSH levels. Hum Reprod 1994;9:906–11.

    Google Scholar 

  15. Neulen J, Wenzel D, Hornig C, Wünsch E, Weissenborn U, Grunwald K, et al. Poor responder-high responder: the importance of soluble vascular endothelial growth factor receptor 1 in ovarian stimulation protocols. Hum Reprod 2001;16(4):621–6.

    PubMed  CAS  Google Scholar 

  16. Martinez F, Barri PN, Coroleu B, Tur R, Sorsa-Leslie T, Harris WJ, et al. Women with poor response to IVF have lowered circulating gonadotrophin surge-attenuating factor (GnSAF) bioactivity during spontaneous and stimulated cycles. Hum Reprod 2002;17:634–40.

    PubMed  CAS  Google Scholar 

  17. Land J, Yarmolinskaya M, Dumoulin J, Evers J. High-dose human menopausal gonadotropin stimulation in poor responders does not improve in vitro fertilization outcome. Fertil Steril 1996;65:961–5.

    PubMed  CAS  Google Scholar 

  18. Fridstrom M, Akerlof E, Sjoblom P, Hillensjo T. Serum levels of luteinizing and follicle-stimulating hormones in normal and poorresponding patients undergoing ovarian stimulation with urofollitropin after pituitary down regulation. Gynecol Endocrinol 1997;11:25–8.

    PubMed  CAS  Google Scholar 

  19. 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;14:1431–4.

    PubMed  CAS  Google Scholar 

  20. Rombauts L, Suikkari A, MacLachlan V, Trounson A, Healy D. Recruitment of follicles by recombinant human follicle-stimulating hormone commencing in the luteal phase of the ovarian cycle. Fertil Steril 1998;69:665–9.

    PubMed  CAS  Google Scholar 

  21. 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;69:419–24.

    PubMed  CAS  Google Scholar 

  22. Schoolcraft W, Schlenker T, Gee M, Stevens J, Wagley L. Improved controlled ovarian hyperstimulation in poor responder in vitro fertilization patients with a microdose follicle-stimulating hormone flare, growth hormone protocol. Fertil Steril 1997;67:93–7.

    PubMed  CAS  Google Scholar 

  23. Droesch K, Muasher SJ, Brzyski RG, Jones GS, Simonetti S, Liu H, et al. Value of suppression with a gonadotropin releasing hormone agonist prior to gonadotropin stimulation for in vitro fertilization. Fertil Steril 1989;51:292–7.

    PubMed  CAS  Google Scholar 

  24. Feldberg D, Farhi J, Ashkenazi J, Dicker D, Shalev J, Ben-Rafael Z. Minidose gonadotropin releasing hormone agonist is the treatment of choice in poor responders with high FSH levels. Fertil Steril 1994;62:343–6.

    PubMed  CAS  Google Scholar 

  25. Olivennes F, Righini C, Fanchin R, Torrisi C, Hazout A, Glissant M, et al. A protocol using a low dose of gonadotrophin-releasing hormone agonist might be the best protocol for patients with high FSH concentrations on day-3. Hum Reprod 1996;11:1169–72.

    PubMed  CAS  Google Scholar 

  26. 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;67:900–3.

    PubMed  CAS  Google Scholar 

  27. Van Rooij IAJ, Bancsi LF, Broekmans FJ, Looman CW, Habbema JD, Te Velde ER. Women older than 40 years of age and those with elevated follicle-stimulating hormone levels differ in poor response rate and embryo quality in in vitro fertilization. Fertil Steril 2003;79(3):482–8.

    PubMed  Google Scholar 

  28. 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.

    PubMed  CAS  Google Scholar 

  29. Shaker A, Yates R, Flemming R, Coutts J, Jamieson M. Absence of effect of adjuvant growth hormone therapy on follicular responses to exogenous gonadotrophins in women: normal and poor responders. Fertil Steril 1992;58:919–23.

    PubMed  CAS  Google Scholar 

  30. 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;69:826–30.

    PubMed  CAS  Google Scholar 

  31. Toth T, Awwad J, Veeck L, Jones H, Muasher S. Suppression and flare regimens of gonadotropin-releasing hormone agonist: use in women with different basal gonadotropin values in an in vitro fertilization program. J Reprod Med 1996;41:321–6.

    PubMed  CAS  Google Scholar 

  32. Gorgy A, Taramissi M. Defining and predicting the poor responder! Fertil Steril 2001;75:226–7.

    PubMed  CAS  Google Scholar 

  33. Barri PN, Martinez F, Coroleu B, Parera N, Veiga A. Managing non-responders. Fertility and reproductive medicine. In: Proceedings of XVI World Congress on Fertility and Sterility, 1998, p. 127–137.

  34. 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;19(1):1–6.

    PubMed  Google Scholar 

  35. 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.

    PubMed  Google Scholar 

  36. Navot, D, Rosenwaks Z, Margalioth EJ. Prognostic assessment of female fecundity. Lancet 1987;19(2):645–7.

    Google Scholar 

  37. Padilla S, Smith R, Garcia J. The lupron screening test: tailoring the use of leuprolide acetate in ovarian stimulation for in vitro fertilization. Fertil Steril 1991;56:79–83.

    PubMed  CAS  Google Scholar 

  38. Fanchin R, de Ziegler D, Oliveness F, Taiels J, Dzik A, Frydman R. Exogenous follicle stimulating hormone ovarian reserve test (EFORT): a simple and reliable screening test for detecting “poor responders” in in-vitro fertilization. Hum Reprod 1994;9:1607–11.

    PubMed  CAS  Google Scholar 

  39. Mukherjee T, Copperman AB, Lapinski R, Sandler B, Bustillo M, Grunfeld L. An elevated Day-3 FSH:LH ratio in the presence on normal day-3 FSH predicts a poor response to COH. Fertil Steril 1996;65:588–93.

    PubMed  CAS  Google Scholar 

  40. Karande V, Gleicher N. A rational approach to the management of low responders in in-vitro fertilization. Hum Reprod 1999;14:1744–8.

    PubMed  CAS  Google Scholar 

  41. Cameron IT, O’Shea FC, Rolland JM, Hughes EG, de Krester DM, Jealy DL. Occult ovarian failure: a syndrome of infertility regular menses, and elevated follicle-stimulating hormone concentrations. J Clin Endocrinol Metab 1988;67:1190–4.

    PubMed  CAS  Google Scholar 

  42. Scott RT, Toner JP, Muasher SJ, Oehninger S, Robinson S, Rosenwaks Z. Follicle-stimulating hormone levels on cycle day 3,are predictive of in vitro fertilization outcome. Fertil Steril 1989;51:651–4.

    PubMed  CAS  Google Scholar 

  43. Toner J, Philput C, Jones G, Muasher S. Basal folliclestimulating hormone level is a better predictor of in vitro fertilization performance than age. Fertil Steril 1991;55:784–91.

    PubMed  CAS  Google Scholar 

  44. Licciardi F, Liu H, Rosenwaks Z. Day 3 estradiol serum concentrations as prognosticators of ovarian stimulation response and pregnancy outcome in patients undergoing in vitro fertilization. Fertil Steril 1995;64:991–4.

    PubMed  CAS  Google Scholar 

  45. Seifer DB, Lambert-Masserlian B, Hogan JW, Gardiner AC, Blazar AS, Berk CA. Day 3 serum inhibin-B is predictive ofassisted reproductive technologies outcome. Fertil Steril 1997;67:110–4.

    PubMed  CAS  Google Scholar 

  46. Oosterhuis GJE, Vermes I, Lambalk CB, Michgelsen HW, Schoemaker J. Insulin like growth factor (IGF)-I and IGF binding protein-3 concentrations in fluid from human stimulated follicles. Hum Reprod 1998;13:285–9.

    PubMed  CAS  Google Scholar 

  47. De Vet A, Laven JS, de Jong FH, Themmen AP, Fauser BC. Anti-mullerian hormone serum levels: a putative marker for ovarian aging. Fertil Steril 2002;77:357–62.

    PubMed  Google Scholar 

  48. Lass A, Skull J, McVeigh E, Margara R, Winston R. Measurement of ovarian volume by transvaginal sonography before ovulation induction with human menopausal gonadotropin for in vitro fertilization can predict poor response. Hum Reprod 1997;12:294–7.

    PubMed  CAS  Google Scholar 

  49. Chang M, Chiang C, Hsieh T, Soong Y, Hsu K. Use of the antral follicle count to predict the outcome of assisted reproductive technologies. Fertil Steril 1998;69:505–10.

    PubMed  CAS  Google Scholar 

  50. 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;77:328–36.

    PubMed  Google Scholar 

  51. Engmann L, Sladkevicius P, Agrawal R, Bekir JS, Campbell S, Tan SL. Value of ovarian stromal blood flow velocity measurement after pituitary suppression in the prediction of ovarian responsiveness and outcome of in vitro fertilization treatment. Fertil Steril 1999;71:22–9.

    PubMed  CAS  Google Scholar 

  52. Tarlatzis BC, Zepiridis L, Grimbizis G, Bontis J. Clinical management of low ovarian response to stimulation for IVF: a systematic review. Hum Reprod 2003;9(1):61–76.

    CAS  Google Scholar 

  53. Zafeiriou S, Loutradis D, Michalas S. The role of gonadotropins in follicular development and their use in ovulation induction protocols for assisted reproduction. Eur J Contracept Reprod Health Care 2000;5:157–67.

    PubMed  CAS  Google Scholar 

  54. Loutradis D, Patsoula E, Minas V, Koussidis G, Antsaklis A, Michalas S, et al. FSH receptor gene polymorphisms have a role for different ovarian reponse to stimulation in patients entering IVF/ICSI-ET programs. J Assist Reprod Genet 2006;23:177–84.

    PubMed  Google Scholar 

  55. Crosignani PG, Ragni G, Lombroso GC, Scarduelli C, de Lauretis L, Caccamo A, et al. IVF: induction of ovulation in poor responders. J Steroid Biochem 1989;32:171–3.

    PubMed  CAS  Google Scholar 

  56. Hofmann GE, Toner JP, Muasher SJ, Jones GS. High-dose follicle-stimulating hormone (FSH) ovarian stimulation in low-responder patients for in vitro fertilization. J In Vitro Fert Embryo Transf 1989;6:285–9.

    PubMed  CAS  Google Scholar 

  57. 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 

  58. Manzi DL, Thornton KL, Scott LB, Nulsen JC. The value of increasing the dose of human menopausal gonadotropins in women who initially demonstrate a poor response. Fertil Steril 1994;62:251–6.

    PubMed  CAS  Google Scholar 

  59. Ben-Rafael Z, Benadiva CA, Ausmanas M, Barber B, Blasco L, Flickinger GL, et al. Dose of human menopausal gonadotropin influences the outcome of an in vitro fertilization program. Fertil Steril 1987;48:964–8.

    PubMed  CAS  Google Scholar 

  60. Garcia-Velasco JA, Isaza V, Requena A, Martinez-Salazar FJ, Landazabal A, Remohi J, et al. High doses of gonadotrophins combined with stop versus non-stop protocol of GnRH analogue administration in low responder IVF patients: a prospective, randomized, controlled trial. Hum Reprod 2000;15:2292–6.

    PubMed  CAS  Google Scholar 

  61. 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 Syst Rev 2000;HTA-20030660.

  62. Siristatidis CS, Hamilton MP. What should be the maximum FSH dose in IVF/ICSI in poor responders? J Obstet Gynecol 2007;27(4):401–5.

    CAS  Google Scholar 

  63. De Placido G, Alviggi C, Mollo A, Strina I, Varricchio MT, Molis M. Recombinant follicle stimulating hormone is effective in poor responders to highly purified follicle stimulating hormone. Hum Reprod 2000;15:17–20.

    PubMed  Google Scholar 

  64. Out HJ, Mannaerts BM, Driessen SG, Coelingh Bennink HJ. Recombinant follicle stimulating hormone (rFSH: Puregon) in assisted reproduction: more oocytes, more pregnancies. Results from five comparative studies. Hum Reprod Update 1996;2(2):162–71.

    PubMed  CAS  Google Scholar 

  65. Ng EH, Lau EY, Yeung WS, Ho PC. HMG is as good as recombinant human FSH in terms of oocyte and embryo quality: a prospective randomized trial. Hum Reprod 2001;16:319–25.

    PubMed  CAS  Google Scholar 

  66. Westergaard LG, Erb K, Laursen SB, Rex S, Rasmussen PE. Human menopausal gonadotropin versus recombinant follicle-stimulating hormone in normogonadotropic women down-regulated with a gonadotropin-releasing hormone agonist who were undergoing in vitro fertilization and intracytoplasmic sperm injection: a prospective randomized study. Fertil Steril 2001;76:543–9.

    PubMed  CAS  Google Scholar 

  67. Gordon UD, Harrison RF, Fawzy M, Hennelly B, Gordon AC. A randomized prospective assessor-blind evaluation of luteinizing hormone dosage and in vitro fertilization outcome. Fertil Steril 2001;75:324–31.

    PubMed  CAS  Google Scholar 

  68. De Placido G, Mollo A, Alviggi C, Strina I, Varricchio MT, Ranieri A, et al. Rescue of IVF cycles by HMG in pituitary down-regulated normogonadotrophic young women characterized by a poor initial response to recombinant FSH. Hum Reprod 2001;16:1875–9.

    PubMed  Google Scholar 

  69. Eskandar M, Jaroudi K, Jambi A, Archibong EI, Coscun S, Sobande AA. Is recombinant follicle-stimulating hormone more effective in IVF poor responders than human menopausal gonadotrophins? Med Sci Monit 2004;10:16–9.

    Google Scholar 

  70. Drakakis P, Loutradis D, Kallianidis K, Bletsa R, Milingos S, Dionyssiou-Asteriou A, et al. A comparative study of the effect of ovarian stimulation protocols with different gonadotropin preparations on the biological and clinical parameters of the outcome of introcytoplasmic sperm injection. Clin Exp Obstet Gynecol 2002;29(4):286–9.

    PubMed  CAS  Google Scholar 

  71. Al-Inany H, Aboulghar M, Mansour R, Serour G. Ovulation induction in the millennium: Recombinant follicle-stimulating hormone versus human menopausal gonadotropin. Gynecol Endocrinol 2005;20(3):161–9.

    PubMed  CAS  Google Scholar 

  72. Gougeon A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr Rev 1996;17:121–55.

    PubMed  CAS  Google Scholar 

  73. Sullivan MW, Stewart-Akers A, Krasnow JS, Berga SL, Zeleznic AJ. Ovarian responses in women to recombinant follicle-stimulating hormone and luteinizing hormone (LH) a role for LH in the final stages of follicular maturation. J Clin Endocrinol Metab 1999;84:228–32.

    PubMed  CAS  Google Scholar 

  74. Esposito MA, Barnhart KT, Coutifaris C, Patrizio P. Role of periovulatory luteinizing hormone concentrations during assisted reproductive technology cycles stimulated exclusively with recombinant follicle-stimulating hormone. Fertil Steril 2001;75:519–24.

    PubMed  CAS  Google Scholar 

  75. Westergaard LG, Laursen SB, Andersen CY. Increased risk of early pregnancy loss by profound suppression of luteinizing hormone during ovarian stimulation in normogonadotrophic women undergoing assisted reproduction. Hum Reprod 2000;15:1003–8.

    PubMed  CAS  Google Scholar 

  76. Drakakis P, Loutradis D, Kallianidis K, Liapi A, Milingos S, Makrigiannakis A, et al. Small doses of LH activity are needed early in ovarian stimulation for better quality oocytes in IVF-ET. Eur J Obstet Gynecol Reprod Biol 2005;121:77–80.

    PubMed  CAS  Google Scholar 

  77. Porter RN, Smith W, Craft IL, Abdulwahid NA, Jacobs HS. Induction of ovulation for in vitro fertilization using buserelin and gonadotropins. Lancet 1984;2:1284–5.

    PubMed  CAS  Google Scholar 

  78. Mochtar MH, Van der Veen, Ziech M, van Wely M. Recombinant luteinizing hormone (rLH) for controlled ovarian hyperstimulation in assisted reproductive cycles. Cochrane Database Syst Rev 2007;18(2):CD005070.

    Google Scholar 

  79. Jia X, Kalmijn J, Hsueh A. Growth hormone enhances follicle-stimulating hormone-induced differentiation of cultured rat granulosa cells. Endocrinology 1986;118:1401–6.

    PubMed  CAS  Google Scholar 

  80. Hsu C, Hammond J. Concomitant effects of growth hormone on secretion of insulin-like growth factor I and progesterone by cultured porcine granulosa cells in vitro. Endocrinology 1988;120:198–207.

    Google Scholar 

  81. Davoren J, Hsueh A. Growth hormone increases ovarian levels of immunoreactive somatomedin-C/insulin-like growth factor I in vivo. Endocrinology 1986;118:888–90.

    PubMed  CAS  Google Scholar 

  82. Barreca A, Artini PG, Del Monte P, Ponzani P, Pasquini P, Cariola G, et al. In vivo and in vitro effect of growth hormone on estradiol secretion by granulosa cells. J Clin Endocrinol Metab 1993;77:61–7.

    PubMed  CAS  Google Scholar 

  83. Adashi E, Resnick C, D’Erole J, Svoboda M, Van Nyk J. Insulin-like growth factors as intraovarian regulators of granulosa cell growth and function. Endocr Rev 1985;6:400–20.

    PubMed  CAS  Google Scholar 

  84. Ibrahim ZH, Matson PL, Buck P, Lieberman BA. The use of biosynthetic human growth hormone to augment ovulation induction with buserelin acetate/human menopausal gonadotropin in women with a poor ovarian response. Fertil Steril 1991;55(1):202–4.

    PubMed  CAS  Google Scholar 

  85. Hugues JN, Torresani T, Herve F, Martin-Pont B, Tamboise A, Santarelli J. Interest of growth hormone-releasing administration for improvement of ovarian responsiveness to gonadotropins in poor responder women. Fertil Steril 1991;55:945–51.

    PubMed  CAS  Google Scholar 

  86. Wu MY, Chen HF, Ho HN, Chen SU, Chao KH, Huang SC, et al. The value of human grown hormone as an adjuvant for ovarian stimulation in a human in vitro fertilization program. J Obstet Gynecol Res 1996;22:443–50.

    CAS  Google Scholar 

  87. Chung-Hoon K, Hee-Dong C, Yoon-Seok C. Pyridostigmine cotreatment for controlled ovarian hyperstimulation in low responders undergoing in vitro fertilization± embryo transfer. Fertil Steril 1999;71:652–7.

    Google Scholar 

  88. Levy T, Limor R, Villa Y, Eshel A, Eckstein N, Vagman I, et al. Another look at co-treatment with growth hormone and human menopausal gonadotrophins in poor ovarian responders. Hum Reprod 1993;8:834–9.

    PubMed  CAS  Google Scholar 

  89. Hughes SM, Huang ZH, Morris ID, Matson PL, Buck P, Lieberman BA. A double-blind cross-over controlled study to evaluate the effect of human bio-synthetic growth hormone on ovarian stimulation in previous poor responders to in-vitro fertilization. Hum Reprod 1994;9:13–8.

    PubMed  CAS  Google Scholar 

  90. Dor J, Seidman DS, Amudai E, Bider D, Levran D, Mashiach S. Adjuvant growth hormone therapy in poor responders to in-vitro fertilization: a prospective randomized placebo-controlled double-blind study. Hum Reprod 1995;10:40–3.

    Article  PubMed  CAS  Google Scholar 

  91. Suikkari AM, Seppala M, McLachlan V, Healey D, Koistinen R. Double blind placebo controlled study: human biosynthetic growth hormone for assisted reproductive technology. Fertil Steril 1996;65:800–5.

    PubMed  CAS  Google Scholar 

  92. Howles CM, Loumaye E, Germond M, Yates R, Brinsden P, Healey D, et al. Does growth hormone releasing factor assist follicular development in poor responder patients undergoing ovarian stimulation for IVF? Hum Reprod 1999;14:1939–43.

    PubMed  CAS  Google Scholar 

  93. Kotarba D, Kotarba J, Hughes E. Growth hormone for in vitro fertilization (Cochrane Review). In: The Cochrane Library, 1: Update Software. Oxford: The Cochrane Collaboration; 2002.

  94. Loutradis D, Drakakis P, Kallianidis K, Milingos S, Dendrinos S, Michalas S. Oocyte morphology correlates with embryo quality and pregnancy rate after intracytoplasmic sperm injection. Fertil Steril 1999;72:240–4.

    PubMed  CAS  Google Scholar 

  95. Loutradis D, Kallianidis K, Siskos K, Bletsa R, Creatsas G, Michalas S, Aravatinos D. Combined Gn RH-agonist and HMG therapy in patients with stimulation failure. Int J Gynecol Obstet 1991;36:317–21.

    CAS  Google Scholar 

  96. Loutradis D, Drakakis P, Kallianidis K, Bletsa R, Milingos S, Makris N, et al. The effect of the duration of GnRH-agonist down regulation before ovarian stimulation on the biological and clinical outcome after intracytoplasmic sperm injection. Eur J Obstet Gynecol Reprod Biol 1998;80:251–5.

    PubMed  CAS  Google Scholar 

  97. Loutradis D, Stefanidis K, Drakakis P, El Sheikh A, Milingos S, Antsaklis A, et al. Comparison between “short” and “long” protocols in an ICSI programme. Eur J Obstet Gynecol Reprod Biol 2005;120:69–72.

    PubMed  CAS  Google Scholar 

  98. Loutradis D, Kallianidis K, Sakellaropoulos G, Dokos J, Siskos K, Creatsas G, et al. Outcome of ovarian response after suppression with a gonadotropin releasing hormone agonist in different chronological periods prior to gonadotropin stimulation for in vitro fertilization. Gynecol Obstet Invest 1991;32:68–71.

    Article  PubMed  CAS  Google Scholar 

  99. Latouche J, Crumeyrolle-Arias M, Jordan D, Kopp N, Augendre-Ferrante B, Cedard L, et al. GnRH receptors in human granulosa cells. Anatomical localization and characterization by autoradiographic study. Endocrinology 1989;125:1739–41.

    Article  PubMed  CAS  Google Scholar 

  100. Kowalik A, Barmat L, Damario M, Liu HC, Davis O, Rosenwaks Z. Ovarian estradiol production in vivo. Inhibitory effect of leuprolide acetate. J Reprod Med 1998;43:413–7.

    PubMed  CAS  Google Scholar 

  101. De Ziegler, Cedars M, Randle D, Lu J, Judd H, Meldrum D. Suppression of the ovary using a gonadotropin releasing hormone agonist prior to stimulation for oocyte retrieval. Fertil Steril 1987;48:807–10.

    PubMed  Google Scholar 

  102. Cummins J, Yovich J, Edirisinghe W, Yovich J. Pituitary down-regulation using leuprolide for the intensive ovulation management of poor prognosis patients having in vitro fertilization treatments. J In Vitro Fert Embryo Transf 1989;6:345–52.

    PubMed  CAS  Google Scholar 

  103. Droesch K, Muasher SJ, Brzyski RG, Jones GS, Simonetti S, Liu HC, et al. Value of suppression with a gonadotropinreleasing hormone agonist prior to gonadotropin stimulation for in vitro fertilization. Fertil Steril 1989;51:292–7.

    PubMed  CAS  Google Scholar 

  104. Serafini P, Stone B, Kerin J, Batzofin J, Quinn P, Marrs R. An alternate approach to controlled ovarian hyperstimulation in “poor responders”: pretreatment with a gonadotropin-releasing hormone analog. Fertil Steril 1988;49:90–5.

    PubMed  CAS  Google Scholar 

  105. McKenna K, Foster P, McBain J, Martin M, Johnston W. Combined treatment with gonadotropin-releasing hormone agonist and gonadotropins in poor responders to hyperstimulation for in vitro fertilization (IVF): clinical and endocrine results. Aust N Z J Obstet Gynaecol 1989;29:428–32.

    PubMed  CAS  Google Scholar 

  106. Horvath P, Styler M, Hammond J, Shelden R, Kemmann E. Exogenous gonadotropin requirements are increased in leuprolide suppressed women undergoing ovarian stimulation. Fertil Steril 1988;49:159–62.

    PubMed  CAS  Google Scholar 

  107. Ashrafi M, Ashtiani SK, Zafarani F, Samani RO, Eshrati B. Evaluation of ovulation induction protocols for poor responders undergoing assisted reproduction techniques. Saudi Med J 2005;26(4):593–6.

    PubMed  Google Scholar 

  108. Dirnfeld M, Fruchter O, Yshai D, Lissak A, Ahdut A, Abramovici H. Cessation of gonadotropin-releasing hormone analogue (GnRHa) upon down-regulation versus conventional long GnRH-a protocol in poor responders undergoing in vitro fertilization. Fertil Steril 1999;72:406–11.

    PubMed  CAS  Google Scholar 

  109. 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.

    PubMed  CAS  Google Scholar 

  110. Pinkas H, Orvieto R, Avrech OM, Rufas O, Ferber A, Ben-Rafael Z, et al. Gonadotropin stimulation following GnRH-a priming for poor responders in in vitro fertilization-embryo transfer programs. Gynecol Endocrinol 2000;14:11–4.

    Article  PubMed  CAS  Google Scholar 

  111. Pu-Tsui W, Kuo-Kuang LR, Jin-Tsung S, Jen-Wan H, Ming-Huei L, Yu-Ming H. Cessation of low dose gonadotropin-releasing hormone agonist therapy combined followed by high-dose gonadotropin stimulation yields a favorable ovarian response in poor responders. J Assist Reprod Genet 2002;19:1–6.

    Google Scholar 

  112. Katayama K, Roesler M, Gunnarson G, Stehlik E, Jagusch S. Short-term use of gonadotropin-releasing hormone agonist (leuprolide) for in vitro fertilization. J In Vitro Fert Embryo Transfer 1988;5:332–7.

    PubMed  CAS  Google Scholar 

  113. Garcia J, Padilla S, Bargati J, Baramki T. Follicular phase gonadotropin-releasing hormone agonist and human gonadotropins: a better alternative for in vitro fertilization. Fertil Steril 1990;53:302–5.

    PubMed  CAS  Google Scholar 

  114. Padilla S, Dugan K, Shalika S, Smith R. Use of the flare-up protocol with high dose follicle stimulating hormone and human menopausal gonadotropins for in vitro fertilization in poor responders. Fertil Steril 1996;65:796–9.

    PubMed  CAS  Google Scholar 

  115. Cramer DW, Powers DR, Oskowitz SP, Liberman RF, Hornstein MD, McShane PM, et al. Gonadotropin-releasing hormone agonist use in assisted reproduction cycles: the influence of long and short regimens on pregnancy rates. Fertil Steril 1999;72:83–9.

    PubMed  CAS  Google Scholar 

  116. Kondaveeti-Gordon U, Harrison R, Barry-Kinsella C, Gordon A, Drudy L, Cottell E. A randomized prospective study of early follicular or midluteal initiation of long protocol gonadotropin-releasing hormone in an in vitro fertilization program. Fertil Steril 1996;66:582–6.

    PubMed  CAS  Google Scholar 

  117. 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;67:900–3.

    PubMed  CAS  Google Scholar 

  118. Loumaye E, Van Krieken L, Depreester S, Psalti I, de Cooman S, Thomas K. Hormonal changes induced by short-term administration of a gonadotropin-releasing hormone agonist during ovarian hyperstimulation for in vitro fertilization and their consequences for embryo development. Fertil Steril 1989;51:105–11.

    PubMed  CAS  Google Scholar 

  119. Ron-El R, Herman A, Golan A, van der Ven H, Caspi E, Diedrich K. The comparison of early follicular and midluteal administration of long-acting gonadotropin-releasing hormone. Fertil Steril 1990;54:233–7.

    PubMed  CAS  Google Scholar 

  120. Gindoff P, Hall J, Stillman R. Ovarian suppression with leuprolide acetate: comparison of luteal, follicular, and flare-up administration in controlled ovarian hyperstimulation for oocyte retrieval. J In Vitro Fert Embryo Transf 1990;7:94–7.

    PubMed  CAS  Google Scholar 

  121. Anserini P, Magnasco A, Remorgida V, Gaggero G, Testa D, Capitanio G. Comparison of a blocking vs. a flare-up protocol in poor responders with a normal and abnormal clomiphene citrate challenge test. Gynecol Endocrinol 1997;11:321–6.

    Article  PubMed  CAS  Google Scholar 

  122. San Roman G, Surrey E, Judd H, Kerin J. A prospective randomized comparison of luteal phase versus concurrent follicular phase initiation of gonadotropin-releasing hormone agonist for in vitro fertilization. Fertil Steril 1992;58:744–9.

    PubMed  CAS  Google Scholar 

  123. Scott R, Navot D. Enhancement of ovarian responsiveness with microdoses of gonadotropin-releasing hormone agonists during ovulation induction for in vitro fertilization. Fertil Steril 1994;61:880–5.

    PubMed  CAS  Google Scholar 

  124. Deaton J, Baugness P, Huffman C, Miller K. Pituitary response to early follicular phase minidose gonadotropin releasing hormone agonist (GnRH-a) therapy: evidence for a second flare. J Assist Reprod Genet 1996;13:390–4.

    PubMed  CAS  Google Scholar 

  125. Loutradis D, Stefanidis K, Drakakis P, Kallianidis K, El Sheikh A, Milingos S, et al. Does pre-treatment with micronized progesterone affect the ovarian response to a gonadotropin releasing hormone agonist flare-up protocol? Gynecol Endocrinol 2003;17:101–6.

    PubMed  CAS  Google Scholar 

  126. 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;69:419–24.

    PubMed  CAS  Google Scholar 

  127. Biljan M, Mahutte N, Dean N, Hemmings R, Bissonnette F, Tan S. Effects of pretreatment with an oral contraceptive on the time required to achieve pituitary suppression with gonadotropin-releasing hormone analogues and on subsequent pregnancy rates. Fertil Steril 1998;70:1063–9.

    PubMed  CAS  Google Scholar 

  128. Shaller A, Pittrof R, Zaidi J, Bekir J, Kyei-Mensah A, Tan S. Administration of progestogens to hasten pituitary desensitization after the use of gonadotropin-releasing hormone agonist in in vitro fertilization in a prospective randomized study. Fertil Steril 1995;64:791–5.

    Google Scholar 

  129. Gonen Y, Jacobsen W, Casper R. Gonadotropin suppression with oral contraceptives before in vitro fertilization. Fertil Steril 1990;53:282–7.

    PubMed  CAS  Google Scholar 

  130. Cédrin-Durnerin I, Bulwa S, Herve F, Martin-Pont B, Uzan M, Hugues J. The hormonal flare-up following gonadotropin-releasing hormone agonist administration is influenced by a progestogen pretreatment. Hum Reprod 1996;11:1859–63.

    PubMed  Google Scholar 

  131. Lindheim S, Barad D, Witt B, Ditkoff E, Sauer M. Short-term gonadotrophin suppression with oral contraceptives benefits poor responders prior to controlled ovarian hyperstimulation. J Assist Reprod Genet 1996;16:745–7.

    Google Scholar 

  132. Klein TA, Mishell DR. Gonadotropin, prolactin, and steroid hormone levels after discontinuation of oral contraceptives. Am J Obstet Gynecol 1977;127:585–9.

    PubMed  CAS  Google Scholar 

  133. Benadiva CA, Ben-Rafael Z, Blasco L, Tureck R, Mastroianni Jr L, Flickinger GL. Ovarian response to human menopausal gonadotropin following suppression with oral contraceptives. Fertil Steril 1988;50:516–8.

    PubMed  CAS  Google Scholar 

  134. Al-Mizyen E, Sabatini L, Lower AM, Wilson CMY, Al-Shawaf T, Grudzinskas JG. Does pretreatment with progestogen or oral contraceptive pills in low responders followed by the GnRHa flare protocol improve the outcome of IVF-ET? J Assist Reprod Genet 2000;17:140–6.

    PubMed  CAS  Google Scholar 

  135. 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;72:1018–23.

    PubMed  CAS  Google Scholar 

  136. Keltz MD, Ger RS, Skorupski J, Stein E. Comparison of FSH flare with and without pretreatment with oral contraceptive pills in poor responders undergoing in vitro fertilization. Fertil Steril 2007;88(2):350–3.

    PubMed  CAS  Google Scholar 

  137. Loutradis D, Stefanidis K, Drakakis P, Kallianidis K, Kallipolitis G, El Sheih A, et al. Does the addition of menopausal gonadotropin to recombinant FSH in pituitary suppressed women improve clinical pregnancy in an intracytoplasmic sperm injection program? MEFSJ 2003;8:30–5.

    Google Scholar 

  138. Levy DP, Navarro JM, Schattman GL, Davis OK, Rosenwaks Z. The role of LH in ovarian stimulation. Exogenous LH: Let’s design the future. Hum Reprod 2002;15:2258–65.

    Google Scholar 

  139. Tasdemir M, Tasdemir I, Kodama H, Fukuda J, Tanaka T. Short protocol of gonadotropin-releasing hormone agonist administration gave better results in long protocol poor responders in IVF/ET. J Obstet Gynecol Res 1996;22:73–7.

    CAS  Google Scholar 

  140. Weissman A, Farhi J, Royburt M, Nahum H, Glezerman M, Levran D. Prospective evaluation of two stimulation protocols for low responders who were undergoing in vitro fertilization-embryo transfer. Fertil Steril 2003;79(4):886–92.

    PubMed  Google Scholar 

  141. Detti L, Williams D, Robins JC, Maxwell RA, Thomas MA. Acomparison of three down-regulation approaches for poor responders undergoing in vitro fertilization. Fertil Steril 2005;84(5):1401–5.

    PubMed  CAS  Google Scholar 

  142. Kenigsberg D, Littman BA, Williams RF, Hodgen GD. Medical hypophysectomy II: Variability of ovarian response to gonadotrophin therapy. Fertil Steril 1984;42:116–26.

    PubMed  CAS  Google Scholar 

  143. Messinis IE, Loutradis D, Domali E, Kotsovassilis CP, Papastergiopoulou L, Kallitsaris A, et al. Alternate day and daily administration of GnRH antagonist may prevent premature luteinization to a similar extent during FSH treatment. Hum Reprod 2005;20(11):3192–7.

    PubMed  CAS  Google Scholar 

  144. Diedrich K, Diedrich C, Santos E, Zoll C, al-Hasani S, Reissmann T, et al. Suppression of the endogenous luteinizing hormone surge by the gonadotrophin-releasing hormone antagonist cetrorelix during ovarian stimulation. Hum Reprod 1994;9:788–91.

    PubMed  CAS  Google Scholar 

  145. Albano C, Felberbaum RE, Smitz J, Riethmuller-Winzen H, Diedrich K, Devroey P, et al. Ovarian stimulation with HMG: Results of a prospective randomized phase III European study comparing the luteinizing-hormone-releasing hormone (LHRH)-antagonist cetrorelix and the LHRH-agonist buserelin. Hum Reprod 2000:15(3):526–31.

    PubMed  CAS  Google Scholar 

  146. Olivennes F, Belaisch-Allart J, Emperaire JC, Dechaud H, Alvarez S, Moreau L, et al. Prospective, randomized, controlled study of in vitro fertilization-embryo transfer with a single dose of a luteinizing hormone-releasing hormone (LH-RH) antagonist (cetrorelix) or a depot formula of an LH-RH agonist (triptorelin). Fertil Steril 2000;73:314–20.

    PubMed  CAS  Google Scholar 

  147. The European Middle East Orgalutran Study Group. Comparable clinical outcome using the GnRH antagonist ganirelix or a long protocol of the GnRH agonist triptorelin for the prevention of premature LH surges in women undergoing ovarian stimulation. Hum Reprod 2001;16:644–51.

    Google Scholar 

  148. Loutradis D, Stefanidis K, Drakakis P, Milingos S, Antsaklis A, Michalas S. A modified gonadotropin-releasing hormone (GnRH) antagonist protocol failed to increase clinical pregnancy rates in comparison with the long GnRH protocol. Fertil Steril 2004;82:1446–8.

    PubMed  Google Scholar 

  149. Craft I, Gorgy A, Hill J, Menon D, Podsiadly B. Will GnRH antagonists provide new hope for patients considered ‘difficult responders’ to GnRH agonist protocols? Hum Reprod 1999;14:2959–62.

    PubMed  CAS  Google Scholar 

  150. Nikolettos N, Al-Hasani S, Felberbaum R, Demirel LC, Kupker W, Montzka P, et al. Gonadotropin-releasing hormone antagonist protocol: a novel method of ovarian stimulation in poor responders. Eur J Obstet Gynecol Reprod Biol 2001;97:202–7.

    PubMed  CAS  Google Scholar 

  151. Mohamed KA, Davies WAR, Allsopp J, Lashen H. Agonist “flare-up” versus antagonist in the management of poor responders undergoing in vitro fertilization treatment. Fertil Steril 2005;83(2):331–5.

    PubMed  Google Scholar 

  152. Schmidt DW, Bremner T, Orris JJ, Maier DB, Benadiva CA, Nulsen JC. A randomized prospective study of microdose leuprolide versus ganirelix in in vitro fertilization cycles for poor responders. Fertil Steril 2005;83(5):1568–71.

    PubMed  CAS  Google Scholar 

  153. Cheung LP, Lam PM, Lok IH, Chiu TT, Yeung SY, Tjer CC, et al. GnRH antagonist versus long GnRH agonist protocol in poor responders undergoing IVF: a randomized controlled trial. Hum Reprod 2005;20(3):616–21.

    PubMed  CAS  Google Scholar 

  154. Akman MA, Erden HF, Tosun SB, Bayazit N, Aksoy E, Bahceci M. Comparison of agonistic flare-up-protocol and antagonistic multiple dose protocol in ovarian stimulation of poor responders: results of a prospective randomized trial. Hum Reprod 2001;16:868–70.

    PubMed  CAS  Google Scholar 

  155. Akman MA, Erden HF, Tosun SB, Bayazit N, Aksoy E, Bahceci M. Addition of GnRH antagonist in cycles of poor responders undergoing IVF. Hum Reprod 2000;15(10):2145–7.

    PubMed  CAS  Google Scholar 

  156. Marci R, Caserta D, Dolo V, Tatone C, Pavan A, Moscarini M. GnRH antagonist in IVF poor-responder patients: results of a randomized trial. Reprod Biomed Online 2005;11:189–93.

    PubMed  CAS  Google Scholar 

  157. Griesinger G, Diedrich K, Tarlatzis BC, Kolimbianakis EM. Gn RH-antagonists in ovarian stimulation for IVF in patients with poor response to gonadotrophins, polysystic ovary syndrome, and risk of ovarian hyperstimulation: a meta-analysis. Reprod Biomed Online 2006;13(5):628–38.

    PubMed  CAS  Google Scholar 

  158. Amato G, Caroppo E, Pasqadibisceglie A, Carone D, Vitti A, Vizziello GM. A novel protocol of ovulation induction with delated gonadotropin-releasing hormone antagonist administration combined with high dose recombinant follicle stimulating hotmone and clomiphene citrate for poor responders and women over 35 years. Fertil Steril 2004;81(6):1572–7.

    PubMed  Google Scholar 

  159. Humaidan P, Bungum L, Bungum M, Hald F, Agerholm I, Bllaabjerg J, et al. Reproductive outcome using a Gn RH antagonist (cetrorelix) for luteolysis and follicular synchronization in poor responder IVF/ICSI patients treated with a flexible Gn RH antagonist protocol. Reprod Biomed Online 2005;11(6):679–84.

    PubMed  CAS  Google Scholar 

  160. Acevedo B, Sanchez M, Gomez JL, Cuadros J, Ricciarelli E, Hernandez ER. Luteinizing hormone supplementation increases pregnancy rates in gonadotropin-releasing hormone antagonist donor cycle. Fertil Steril 2004;82:343–7.

    PubMed  CAS  Google Scholar 

  161. De Placid G, Mollo A, Clarizia R, Strina I, Conforti S, Alviggi C. Gonadotropin-releasing hormone (Gn RH) antagonist plus recombinant luteinizizng hormone vs a standard Gn RH agonist short protocol in patients at risk for poor ovarian response. Fertil Steril 2006;85(1):247–50.

    Google Scholar 

  162. Griesinger G, Schultze-Mosgau A, Dafopoulos K, Schroeder A, Schroer A, von Otte S, et al. Recombinant luteinizing hormone supplementation to recombinant follicle-stimulating hormone induced ovarian hyperstimulation in the GnRH-antagonist multiple-dose protocol. Hum Reprod 2005;83:452–4.

    Google Scholar 

  163. Cédrin-Durnerin I, Grange-Dujardin D, Laffy A, Parneix I, Massin N, Galey J, et al. Recombinant human LH supplementation during GnRH antagonist administration in IVF/ICSI cycles: a prospective randomized study. Hum Reprod 2004;19:1979–84.

    PubMed  Google Scholar 

  164. Chung K, Krey L, Katz J, Noyes N. Evaluating the role of exogenous luteinizing hormone in poor responders undergoing in vitro fertilization with gonadotropin-releasing hormone antagonists. Fertil Steril 2005;84:313–8.

    PubMed  CAS  Google Scholar 

  165. Kolibianakis EM, Tarlatzis B, Devroey P. GnRH antagonists in IVF. Reprod Biomed Online 2005;10:705–12.

    PubMed  CAS  Google Scholar 

  166. Bendikson K, Milki AA, Speck-Zulak A, Westpha LM. Comparison of Gn RH antagonist cycles with and without oral contraceptive pre-treatment in potential poor prognosis patients. Clin Exp Obstet Gynecol 2006;33(3):145–7.

    PubMed  CAS  Google Scholar 

  167. Franco JR, Baruffi RLR, Mauri AL, Petersen CG, Felipe V, Cornicelli J, et al. Gn RH agonist versus Gn RH antagonist in poor ovarian responders: A meta-analysis. Reprod Biomed Online 2006;13(50):618–27.

    Article  PubMed  Google Scholar 

  168. Mahutte NG, Arici A. Role of gonadotropin-releasing hormone antagonists in poor responders. Fertil Steril 2007;87(2):241–9.

    PubMed  CAS  Google Scholar 

  169. Steptoe PC, Edwards RG. Birth after the reimplantation of a human embryo. Lancet 1978;12:366.

    Google Scholar 

  170. 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.

    PubMed  CAS  Google Scholar 

  171. Bassil A, Godin PA, Donnez J. Outcome of in-vitro fertilization through natural cycles in poor responders. Hum Reprod 1999;14(5):1262–5.

    PubMed  CAS  Google Scholar 

  172. Lindheim SR, Vidali A, Ditkoff E, Sauer MV, Zinger M. Poor responders to ovarian hyperstimulation may benefit from an attempt at natural-cycle oocyte retrieval. J Assist Reprod Genet 1997;14:174–6.

    PubMed  CAS  Google Scholar 

  173. Janssens RM, Lambalk CB, Schats R, Schoemaker J. Successful in-vitro fertilization in a natural cycle after four previously failed attempts in stimulated cycles. Hum Reprod 1999;14:2497–8.

    PubMed  CAS  Google Scholar 

  174. Jenkins JM, Davies DW, Devonport H, Anthony FW, Gadd SC, Watson RH, et al. Comparison of ‘poor’ responders with ‘good’ responders using a standard buserelin/human menopausal gonadotrophin regime for in-vitro fertilization. Hum Reprod 1991;6:918–21.

    PubMed  CAS  Google Scholar 

  175. Fauser BC, Devroey P, Yen SS, Gosden R, Crowley WF Jr, Baird DT, et al. Minimal ovarian stimulation for IVF: appraisal of potential benefits and drawbacks. Hum Reprod 1999;14:2681–6.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  177. Olivennes F, Frydman R. Friendly IVF: the way of the future? Hum Reprod 1998;13:1121–4.

    PubMed  CAS  Google Scholar 

  178. Feldman B, Seidman DS, Levron J, Bider D, Shulman A, Shine S, et al. In vitro fertilization following natural cycles in poor responders. Gynecol Endocrinol 2001;15:328–34.

    PubMed  CAS  Google Scholar 

  179. Elizur SE, Aslan D, Shulman A, Weisz B, Bider D, Dor J. Modified natural cycle using Gn RH antagonist can be optional treatment in poor responders undergoing IVF. J Assist Reprod Genet 2005;22(2):75–9.

    PubMed  Google Scholar 

  180. Reyftmann L, Dechaud H, Loup V, Anahory T, Brunet-Joyeux C, Lacroix N, et al. Natural cycle in vitro fertilization cycle in poor responders. Gynecol Obstet Fertil 2007;35(4):352–8.

    PubMed  CAS  Google Scholar 

  181. Casson PR, Lindasay MS, Pisarka MD, Carson SA, Buster JE. Dehydroepiandrosterone supplementation augmrnts ovarian stimulation in poor responders: A case series. Hum Reprod 2000;15(10):2129–32.

    PubMed  CAS  Google Scholar 

  182. Van Weering HGI, Gutnecht DR, Schats R. Augmentation of ovarian response by dehydroepiandrosterone. Hum Reprod 2001;16(7):1537–9.

    Google Scholar 

  183. Balasch J, Fabreques F, Penarruba J, Carmona F, Casamitjana R, Creus M, et al. Pretreatment with transdermal testosterone may improve ovarian response to gonadotrophins in poor-responder IVF patients with normal basal concentrations of FSH. Hum Reprod 2006;21(7):1884–93.

    PubMed  CAS  Google Scholar 

  184. Massin N, Cedrin-Durnerin I, Coussieu C, Galey-Fontaine J, Wolf JP, Hugues JN. Effects of transdermal testosterone application on the ovarian response to FSH in poor responders undergoing assisted reproduction technique-A prospective, randomized, double-blind study. Hum Reprod 2006;21(5):1204–11.

    PubMed  CAS  Google Scholar 

  185. Farouk MM, Mitwally MD, Casper RF. Aromatase inhibition improves ovarian response to follicle-stimulating hormone in poor responders. Fertil Steril 2002;77(4):776–80.

    Google Scholar 

  186. Mitwally MFM, Casper RF. Aromatase inhibition improves ovarian response to follicle-stimulating hormone in poor responders. Fertil Steril 2002;77(4):776–80.

    PubMed  Google Scholar 

  187. Mitwally MFM, Casper RF. Aromatase inhibition reduces gonadotrophin dose required for controlled ovarian stimulation in women with unexplained infertility. Hum Reprod 2003;18:1588–97.

    PubMed  CAS  Google Scholar 

  188. Mitwally MF, Casper RF. Aromatase inhibition: a novel method of ovulation induction in women with polycystic ovary syndrome. Reprod Technol 2000;10:244–47.

    CAS  Google Scholar 

  189. Healy S, Tan SL, Tulandi T, Biljan MM. Effects of letrozole on superovulation with gonadotropins in women undergoing intrauterine insemination. Fertil Steril 2003;80:1325–9.

    Google Scholar 

  190. Vendola K, Zhou J, Wang J, Bondy CA. Androgens promote insuline-like growth factor-I and insuline-like growth factor-I receptor gene expression in the primate ovary. Hum Reprod 1999;14:2328–32.

    PubMed  CAS  Google Scholar 

  191. Palter SF, Tavares A, Hourvitz A, Veldhuis JD, Adashi EY. Are estrogen of importance to primate/human ovarian folliculogenesis? Endocr Rev 2001;22:389–424.

    PubMed  CAS  Google Scholar 

  192. Goswami SK, Das T, Chattopadhyay R, Sawhney V, Kumar J, Chaudhury K, et al. A randomized single-blind controlled trial of letroze as a low cost IVF protocol in women with poor ovarian response: a preliminary report. Hum Reprod 2004;19(9):2031–5.

    PubMed  CAS  Google Scholar 

  193. Lok IH, Yip SK, Chung LP, Haines CJ. Adjuvant low-dose aspirin therapy in poor responders undergoing in vitro fertilization: A prospsective, randomized, double-blind, placebo-controlled trial. Fertil Steril 2004;81(3):556–61.

    PubMed  Google Scholar 

  194. Loutradis D, Patsoula E, Stefanidis K, Drakakis P, Antonakis G, Bletsa R, et al. Follicle-stimulating hormone receptor gene mutations are not evident in Greek women with premature ovarian failure and poor responders. Gynecol Obstet Invest 2006;61(1):56–60.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D. Loutradis.

Additional information

Stimulation protocols commonly used for women with significantly diminished ovarian reserve.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Loutradis, D., Drakakis, P., Vomvolaki, E. et al. Different ovarian stimulation protocols for women with diminished ovarian reserve. J Assist Reprod Genet 24, 597–611 (2007). https://doi.org/10.1007/s10815-007-9181-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-007-9181-2

Keywords

Navigation