Skip to main content
SpringerLink
Log in

Mild Stimulation Protocol for Poor Ovarian Responders Undergoing IVF

  • Chapter
  • First Online:
Development of In Vitro Maturation for Human Oocytes

  • 781 Accesses

Abstract

The incidence of poor ovarian responders (PooResp) among infertile women undergoing controlled ovarian stimulation (COS) for in vitro fertilization (IVF) has been estimated at 9–24%, but according to recent reviews, it seems to have slightly increased in the last years [1]. Despite the huge number of trials that have been performed and published in the last two decades with the aim to find more efficient stimulation protocols for the management of PooResp, systematic reviews suggest that we still have insufficient evidence to recommend a specific treatment, the poor ovarian response remaining one of the most challenging tasks in reproductive medicine [2].

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Polyzos NP, Nwoye M, Corona R, et al. Live birth rates in Bologna poor responders treated with ovarian stimulation for IVF/ICSI. Reprod Biomed Online. 2014;28:469–74.

    Article  PubMed  Google Scholar 

  2. Ubaldi F, Vaiarelli A, D’nna R, et al. Management of poor responders in IVF: is there anything new? Biomed Res Int. 2014;352098.

    Google Scholar 

  3. Ferraretti AP, La Marca A, Fauser BC, et al. ESHRE consensus on the definition of poor response to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011;26:1616–24.

    Article  CAS  PubMed  Google Scholar 

  4. Haas J, Zilberberg E, Machtinger R, et al. Do poor responder patients benefit from increasing the daily gonadotropin dose during controlled ovarian hyperstimulation for IVF? Gynecol Endocrinol. 2015;31:79–82.

    Article  CAS  PubMed  Google Scholar 

  5. Karande VC, Jones GS, Veeck LL, et al. Highdose 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.

    Article  CAS  PubMed  Google Scholar 

  6. van Hooff MHA, Alberda AT, Huisman GJ, et al. Doubling the human menopausal gonadotrophin dose in the course of an in-vitro fertilization treatment cycle in low responders: a randomised study. Hum Reprod. 1993;8:369–73.

    Article  PubMed  Google Scholar 

  7. Land JA, Yarmolinskaya MI, Dumoulin JCM, et al. High-dose human menopausal gonadotropin stimulation in poor responders does not improve in vitro fertilization outcome. Fertil Steril. 1996;65:961–5.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  9. Berkkanoglu M, Ozgur K. What is the optimum maximal gonadotropin dosage used in microdose flare-up cycles in poor responders? Fertil Steril. 2010;94:662–5.

    Article  CAS  PubMed  Google Scholar 

  10. Fauser BC, Nargund G, Andersen AN, et al. Mild ovarian stimulation for IVF: 10 years later. Hum Reprod. 2010;25:2678–84.

    Article  PubMed  Google Scholar 

  11. Revelli A, Casano S, Salvagno F, et al. Mild is better? Advantages and disadvantages of “mild” ovarian stimulation for human in vitro fertilization. Reprod Biol Endocrinol. 2011;16:9–25.

    Google Scholar 

  12. Adashi EY. Clomiphene Citrate: mechanisms and sites of action- a hypothesis revisited. Fertil Steril. 1984;42:331–43.

    Article  CAS  PubMed  Google Scholar 

  13. Yanaihara A, Yorimitsu T, Motoyama H, et al. The decrease of serum luteinizing hormone level by a gonadotropin releasing hormone antagonist following the mild IVF stimulation protocol for IVF and its clinical outcome. J Assist Reprod Genet. 2008;25:115–8.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Craft I, Gorgy A, Hill J, et al. Will GnRH antagonists provide new hope for patients considered “difficult responders” to GnRH protocols? Hum Reprod. 1999;14:2959–62.

    Article  CAS  PubMed  Google Scholar 

  15. Takahashi K, Mukaida T, Tomiyana T, et al. GnRH antagonist improved blastocyst quality and pregnancy outcome after multiple failures of IVF/ICSI-ET with a GnRH agonist protocol. J Assist Reprod Genet. 2004;21:317–22.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Revelli A, Chiadò A, Dalmasso P, et al. “Mild” vs. “long” protocol for controlled ovarian hyperstimulation in patients with expected poor ovarian responsiveness undergoing in vitro fertilization (IVF): a large prospective randomized trial. J Assist Reprod Genet. 2014;31:809–15.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Mochtar MH, Van der Veen A, Ziech M et al. Recombinant Luteinizing Hormone (rLH) for controlled ovarian hyperstimulation in assisted reproductive cycles. Cochrane Database Syst Rev. 2007;18:CD005070.

    Google Scholar 

  18. Yoo JH, Cha SH, Park CW, et al. Comparison of mild ovarian stimulation with conventional ovarian stimulation in poor responders. Clin Exp Reprod Med. 2011;38:159–63.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Oride A, Kanasaki H, Miyazaki K. Comparison of human menopausal gonadotropin stimulation with and without clomiphene for in vitro fertilization in poor responders. J Obstet Gynaecol. 2015;35:163–7.

    Article  CAS  PubMed  Google Scholar 

  20. Mitwally MF, Casper RF. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril. 2001;75:305–9.

    Article  CAS  PubMed  Google Scholar 

  21. Mitwally MFM, Casper RF. Aromatase inhibitors for the treatment of infertily. Expert Opin Investig Drugs. 2003;12:353–71.

    Article  CAS  PubMed  Google Scholar 

  22. Fisher SA, Reid RL, Van Vugt DA, et al. A randomized double-blind comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on ovulatory function in normal women. Fertil Steril. 2002;78:280–5.

    Article  PubMed  Google Scholar 

  23. Weil S, Vendola K, Zhou J, et al. Androgen and follicle-stimulating hormone interactions in primate ovarian follicle development. J Clin Endocrinol Metab. 1999;84:2951–6.

    Article  CAS  PubMed  Google Scholar 

  24. Yarali H, Esinler I, Polat M, et al. Antagonist/letrozole protocol in poor ovarian responders for intracytoplasmic sperm injection: a comparative study with the microdose flare-up protocol. Fertil Steril. 2009;92:231–5.

    Article  CAS  PubMed  Google Scholar 

  25. Biljan MM, Hcmmings R, Brassard N. The outcome of 150 babies following the treatment with letrozole or lerozole and gonadotrophins. Fertil Steril. 2005;84(Suppl.):1033.

    Google Scholar 

  26. Gill SK, Moretti M, Koren G. Is the use of letrozole to induce ovulation teratogenic? Cana Fam Phys. 2008;54:353–4.

    Google Scholar 

  27. Rockville MD. FDA oncology tools product label details for administration of letrozole.http://www.accessdata.fda.gov/scripts/cder/onctools/administer.cfm?GN=letrozole/. Retrieved 15.03.08 2003.

  28. Tulandi T, Martin J, Al-Fadhli R, et al. Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril. 2006;85:1761–5.

    Article  CAS  PubMed  Google Scholar 

  29. Requena A, Herrero J, Landeras J, et al. Use of letrozole in assisted reproduction: a systematic review and meta-analysis. Hum Reprod Update. 2008;14:571–82.

    Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  32. Healey S, Tan SL, Tulandi T, et al. Effects of letrozole on superovulation with gonadotropins in women undergoing intrauterine insemination. Fertil Steril. 2003;80:1325–9.

    Article  PubMed  Google Scholar 

  33. Song Y, Li Z, Wu X, et al. Effectiveness of the antagonist/letrozole protocol for treating poor responders undergoing in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis. Ginecol Endocrinol. 2014;30:330–4.

    Article  CAS  Google Scholar 

  34. Davar R, Oskouian H, Armadi S, et al. GnRH antagonist/letrozole versus microdose GnRH agonist flare protocol in poor responders undergoing in vitro fertilization. J Obstet Gynecol. 2010;49:297–301.

    Google Scholar 

  35. Garcia-Velasco JA, Moreno L, Pacheco A, et al. The aromatase inhibitor letrozole increases the concentration of intraovarian androgens and improves in vitro fertilization outcome in low responder patients: a pilot study. Fertil Steril. 2005;84:82–7.

    Article  CAS  PubMed  Google Scholar 

  36. Ozmen B, Sonmezer M, Atabekoglu CS, et al. Use of aromatase inhibitors in poor-responder patients receiving GnRH antagonist protocols. Reprod Biomed Online. 2009;19:478–85.

    Article  CAS  PubMed  Google Scholar 

  37. Schoolcraft WB, Surrey ES, Minjarez DA, et al. Management of poor responders: can outcomes be improved with a novel gonadotropin-releasing hormone antagonist/letrozole protocol? Fertil Steril. 2008;89:151–6.

    Article  CAS  PubMed  Google Scholar 

  38. Verpoest WMJA, Kolibianakis E, Papanikolaou E, et al. Aromatase inhibitors in ovarian stimulation for IVF/ICSI: a pilot study. Reprod Biomed Online. 2006;13:166–72.

    Article  CAS  PubMed  Google Scholar 

  39. Goswami SK, Das T, Chattopadhyay R, et al. A randomized single-blind controlled trial of letrozole as a low-cost IVF protocol in women with poor ovarian response: a preliminary report. Hum Reprod. 2004;19:2031–5.

    Article  CAS  PubMed  Google Scholar 

  40. Lee VCY, Chan CC, Ng EH, et al. Sequential use of letrozole and gonadotrophin in women with poor ovarian reserve: a randomised controlled trial. Reprod Biomed Online. 2011;23:380–8.

    Article  CAS  PubMed  Google Scholar 

  41. Merci R, Caserta D, Dolo V, et al. GnRH antagonist in IVF poor- responder patients: results of a randomied trial. Reprod Biomed Online. 2005;11:189–1993.

    Article  Google Scholar 

  42. Kenigsberg D, Littman BA, Hodgen GD. Medical hypophysectomy: I. Dose-response using a gonadotropin releasing hormone antagonist. Fertil Steril. 1984;42:112–5.

    Article  CAS  PubMed  Google Scholar 

  43. Mohsen IA, El Din RE. Minimal stimulation protocol using letrozole versus microdose flare up GnRH agonist protocol in women with poor ovarian response undergoing ICSI. Gynecol Endocrinol. 2013;29:105–8.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gynecology and Obstetrics 1, Physiopathology of Reproduction and IVF Unit, S. Anna Hospital, University of Torino, Via Ventimiglia 3, 10126, Turin, Italy

    Alberto Revelli MD, PhD, Simona Casano MD, PhD & Chiara Benedetto MD, PhD

Authors
  1. Alberto Revelli MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Simona Casano MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chiara Benedetto MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alberto Revelli MD, PhD .

Editor information

Editors and Affiliations

  1. McGill University, Longueuil, Québec, Canada

    Ri-Cheng Chian

  2. St. George's Hospital, London, United Kingdom

    Geeta Nargund

  3. Stanford University, Palo Alto, California, USA

    Jack Y. J. Huang

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Revelli, A., Casano, S., Benedetto, C. (2017). Mild Stimulation Protocol for Poor Ovarian Responders Undergoing IVF. In: Chian, RC., Nargund, G., Huang, J. (eds) Development of In Vitro Maturation for Human Oocytes. Springer, Cham. https://doi.org/10.1007/978-3-319-53454-1_16

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-53454-1_16

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-53452-7

  • Online ISBN: 978-3-319-53454-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation