Skip to main content
SpringerLink
Log in

Depot GnRH Agonists in COH for ART

  • Chapter
Ovarian Stimulation Protocols

Abstract

The ability of gonadotropin-releasing hormone (GnRH) agonists (GnRH-a), particularly when used in a long protocol, to fine-tune and conveniently program ovarian stimulation cycles with significant advantages in the prevention of premature luteinization and satisfactory clinical outcomes, has made them a preferred inclusion in stimulation protocols for assisted reproduction. GnRH-a may be administered as short-acting daily low-dose injections or as a single long-acting high-dose injection (depot). A remarkable improvement in clinical pregnancy rates has been reported following downregulation with GnRH-a depot formulation and gonadotropin stimulation compared to gonadotropins alone, particularly in hyperandrogenic patients. The higher duration of gonadotropin stimulation and gonadotropin requirement with the long-acting depot, owing to the suggested profound pituitary suppression, is controversial, and no significant differences in clinical outcomes, the levels of endogenous hormones, or time to pituitary desensitization have been reported in a majority of the studies compared with the short-acting daily preparations. Despite comparable pregnancy outcomes, the use of depot GnRH-a in controlled ovarian hyperstimulation (COH) protocols for assisted reproductive technology (ART) is controversial, with some favoring its use in terms of patient compliance and ease of administration, and results, especially with the reduced dose, while others favoring the short-acting daily GnRH-a in terms of cost-effectiveness, and ovarian response in poor responders. However, the GnRH antagonist single-dose protocol has proved to be superior to the depot GnRH-a for COH with advantages of a significantly reduced duration of gonadotropin stimulation and requirement, higher flexibility in treatment, economy, convenience, and safety despite comparable pregnancy outcomes. Poor responders, in contrast, are reported to benefit from a flare-up GnRH-a protocol with a depot formulation compared to the GnRH antagonist, with higher total pregnancy and implantation rates, possibly due to improved oocyte/embryo competence.

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 49.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 64.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 99.99
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

References

  1. Marcus SF, Ledger WL. Efficacy and safety of long-acting GnRH agonists in in vitro fertilization and embryo transfer. Hum Fertil (Camb). 2001;4(2):85–93.

    Article  CAS  Google Scholar 

  2. Meldrum DR. Ovulation induction protocols. Arch Pathol Lab Med. 1992;116(4):406–9.

    CAS  PubMed  Google Scholar 

  3. Yim SF, Lok IH, Cheung LP, Briton-Jones CM, Chiu TT, Haines CJ, Yim SF, Lok IH, Cheung LP, Briton-Jones CM, Chiu TT, Haines CJ. Dose-finding study for the use of long-acting gonadotrophin-releasing hormone analogues prior to ovarian stimulation for IVF. Hum Reprod. 2001;16(3):492–4.

    Article  CAS  PubMed  Google Scholar 

  4. Dada T, Salha O, Baillie HS, Sharma V. A comparison of three gonadotrophin-releasing hormone analogues in an in-vitro fertilization programme: a prospective randomized study. Hum Reprod. 1999;14(2):288–93.

    Article  CAS  PubMed  Google Scholar 

  5. 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(2):157–67.

    Article  CAS  PubMed  Google Scholar 

  6. Dal Prato L, Borini A, Cattoli M, Bonu MA, Sereni E, Flamigni C. GnRH analogs: depot versus short formulations. Eur J Obstet Gynecol Reprod Biol. 2004;115 Suppl 1:S40–3.

    Article  CAS  PubMed  Google Scholar 

  7. Engel JB, Schally AV. Drug Insight: clinical use of agonists and antagonists of luteinizing-hormone-releasing hormone. Nat Clin Pract Endocrinol Metab. 2007;3(2):157–67.

    Article  CAS  PubMed  Google Scholar 

  8. Albuquerque LE, Tso LO, Saconato H, Albuquerque MC, Macedo CR. Depot versus daily administration of gonadotrophin-releasing hormone agonist protocols for pituitary down regulation in assisted reproduction cycles. Cochrane Database Syst Rev. 2013;(1):CD002808.

    Google Scholar 

  9. Fraser HM, Baird DT. Clinical applications of LHRH analogues. Baillieres Clin Endocrinol Metab. 1987;1(1):43–70.

    Article  CAS  PubMed  Google Scholar 

  10. Fujisaki A, Kondo Y, Goto K, Morita T. Life-threatening anaphylaxis to leuprorelin acetate depot: case report and review of the literature. Int J Urol. 2012;19(1):81–4.

    Article  CAS  PubMed  Google Scholar 

  11. Gelbaya TA, Gordts S, D’Hooghe TM, Gergolet M, Nardo LG. Management of endometrioma prior to IVF: compliance with ESHRE guidelines. Reprod Biomed Online. 2010;21(3):325–30.

    Article  PubMed  Google Scholar 

  12. Broekmans FJ, Bernardus RE, Broeders A, Berkhout G, Schoemaker J. Pituitary responsiveness after administration of a GnRH agonist depot formulation: decapeptyl CR. Clin Endocrinol (Oxf). 1993;38(6):579–87.

    Article  CAS  Google Scholar 

  13. Geber S, Sampaio M. Effect of duration of the GnRH agonists in the luteal phase in the outcome of assisted reproduction cycles. Gynecol Endocrinol. 2013;29(6):608–10.

    Article  CAS  PubMed  Google Scholar 

  14. Schmutzler RK, Germer U, Diedrich K, Krebs D. [GnRH agonist treatment for in vitro fertilization in hyperandrogenemia]. [Article in German]. Geburtshilfe Frauenheilkd. 1994;54(9):510–4.

    Article  CAS  PubMed  Google Scholar 

  15. Orvieto R, Kerner R, Krissi H, Ashkenazi J, Ben Rafael Z, Bar-Hava I. Comparison of leuprolide acetate and triptorelin in assisted reproductive technology cycles: a prospective, randomized study. Fertil Steril. 2002;78(6):1268–71.

    Article  PubMed  Google Scholar 

  16. Dal Prato L, Borini A, Trevisi MR, Bonu MA, Sereni E, Flamigni C. Effect of reduced dose of triptorelin at the start of ovarian stimulation on the outcome of IVF: a randomized study. Hum Reprod. 2001;16(7):1409–14.

    Article  CAS  PubMed  Google Scholar 

  17. Vlaisavljević V, Kovacic B, Gavrić-Lovrec V, Reljic M. Simplification of the clinical phase of IVF and ICSI treatment in programmed cycles. Int J Gynaecol Obstet. 2000;69(2):135–42.

    Article  PubMed  Google Scholar 

  18. Tsai HD, Chen CM, Lo HY, Chang CC. Subcutaneous low dose leuprolide acetate depot versus leuprolide acetate for women undergoing ovarian stimulation for in-vitro fertilization. Hum Reprod. 1995;10(11):2909–12.

    CAS  PubMed  Google Scholar 

  19. Gonen Y, Dirnfeld M, Goldman S, Koifman M, Abramovici H. The use of long-acting gonadotropin-releasing hormone agonist (GnRH-a; decapeptyl) and gonadotropins versus short-acting GnRH-a (buserelin) and gonadotropins before and during ovarian stimulation for in vitro fertilization (IVF). J In Vitro Fert Embryo Transf. 1991;8(5):254–9.

    Article  CAS  PubMed  Google Scholar 

  20. Safdarian L, Mohammadi FS, Alleyassin A, Aghahosseini M, Meysamie A, Rahimi E. Clinical outcome with half-dose depot triptorelin is the same as reduced-dose daily buserelin in a long protocol of controlled ovarian stimulation for ICSI/embryo transfer: a randomized double-blind clinical trial (NCT00461916). Hum Reprod. 2007;22(9):2449–54.

    Article  CAS  PubMed  Google Scholar 

  21. Isikoglu M, Ozdem S, Berkkanoglu M, Jamal H, Senturk Z, Ozgur K. Single-dose depot leuprolide is as efficient as daily short-acting leuprolide in ICSI cycles. Hum Reprod. 2007;22(6):1657–61.

    Article  CAS  PubMed  Google Scholar 

  22. Geber S, Sales L, Sampaio MA. Comparison between a single dose of goserelin (depot) and multiple daily doses of leuprolide acetate for pituitary suppression in IVF treatment: a clinical endocrinological study of the ovarian response. J Assist Reprod Genet. 2002;19(7):313–8.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Hsieh Y, Tsai H, Chang C, Lo H. Comparison of a single half-dose, long-acting form of gonadotropin-releasing hormone analog (GnRH-a) and a short-acting form of GnRH-a for pituitary suppression in a controlled ovarian hyperstimulation program. Fertil Steril. 2000;73(4):817–20.

    Article  CAS  PubMed  Google Scholar 

  24. Fábregues F, Balasch J, Creus M, Cívico S, Carmona F, Puerto B, Vanrell JA. Long-term down-regulation does not improve pregnancy rates in an in vitro fertilization program. Fertil Steril. 1998;70(1):46–51.

    Article  PubMed  Google Scholar 

  25. Porcu E, Filicori M, Dal Prato L, Fabbri R, Seracchioli R, Colombi C, Flamigni C. Comparison between depot leuprorelin and daily buserelin in IVF. J Assist Reprod Genet. 1995;12(1):15–9.

    Article  CAS  PubMed  Google Scholar 

  26. Porcu E, Dal Prato L, Seracchioli R, Fabbri R, Longhi M, Flamigni C. Comparison between depot and standard release triptorelin in in vitro fertilization: pituitary sensitivity, luteal function, pregnancy outcome, and perinatal results. Fertil Steril. 1994;62(1):126–32.

    CAS  PubMed  Google Scholar 

  27. Sonntag B, Kiesel L, Nieschlag E, Behre HM. Differences in serum LH and FSH levels using depot or daily GnRH agonists in controlled ovarian stimulation: influence on ovarian response and outcome of ART. J Assist Reprod Genet. 2005;22(7–8):277–83.

    Article  PubMed  Google Scholar 

  28. Lorusso F, Depalo R, Selvaggi L. Relationship between gonadotropin releasing hormone agonist dosage and in vitro fertilization outcome. Gynecol Endocrinol. 2004;18(2):69–73.

    Article  CAS  PubMed  Google Scholar 

  29. Lindner C, Braendle W, Lichtenberg V, Bettendorf G. Induction of pharmacological hypogonadotropism using gonadotropin-releasing hormone agonists in patients undergoing controlled ovarian stimulation. Gynecol Obstet Invest. 1990;29(2):132–9.

    Article  CAS  PubMed  Google Scholar 

  30. Dal Prato L, Borini A, Coticchio G, Cattoli M, Flamigni C. Half-dose depot triptorelin in pituitary suppression for multiple ovarian stimulation in assisted reproduction technology: a randomized study. Hum Reprod. 2004;19(10):2200–5.

    Article  CAS  PubMed  Google Scholar 

  31. Li Y, Yang D, Zhang Q. Clinical outcome of one-third-dose depot triptorelin is the same as half-dose depot triptorelin in the long protocol of controlled ovarian stimulation. J Hum Reprod Sci. 2012;5(1):14–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Olivennes F, Righini C, Fanchin R, Torrisi C, Hazout A, Glissant M, Fernandez H, Frydman R. [Ovarian stimulation using a protocol of low dose agonist in patients with an elevated basal FSH].[Article in French]. Contracept Fertil Sex. 1996;24(12):912–6.

    CAS  PubMed  Google Scholar 

  33. Gerli S, Villani C. Endocrine changes and follicular development in patients during ovulation induction using Goserelin and different gonadotropin treatments. Clin Exp Obstet Gynecol. 1993;20(4):245–50.

    CAS  PubMed  Google Scholar 

  34. Balasch J, Peñarrubia J, Fábregues F, Vidal E, Casamitjana R, Manau D, Carmona F, Creus M, Vanrell JA. Ovarian responses to recombinant FSH or hMG in normogonadotrophic women following pituitary desensitization by a depot GnRH agonist for assisted reproduction. Reprod Biomed Online. 2003;7(1):35–42.

    Article  CAS  PubMed  Google Scholar 

  35. Olivennes F, Belaisch-Allart J, Emperaire JC, Dechaud H, Alvarez S, Moreau L, Nicollet B, Zorn JR, Bouchard P, Frydman R. 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(2):314–20.

    Article  CAS  PubMed  Google Scholar 

  36. Del Gadillo JC, Siebzehnrübl E, Dittrich R, Wildt L, Lang N. Comparison of GnRH agonists and antagonists in unselected IVF/ICSI patients treated with different controlled ovarian hyperstimulation protocols: a matched study. Eur J Obstet Gynecol Reprod Biol. 2002;102(2):179–83.

    Article  PubMed  Google Scholar 

  37. Roulier R, Chabert-Orsini V, Sitri MC, Barry B, Terriou P. Depot GnRH agonist versus the single dose GnRH antagonist regimen (cetrorelix, 3 mg) in patients undergoing assisted reproduction treatment. Reprod Biomed Online. 2003;7(2):185–9.

    Article  CAS  PubMed  Google Scholar 

  38. Vlaisavljevic V, Reljic M, Lovrec VG, Kovacic B. Comparable effectiveness using flexible single-dose GnRH antagonist (cetrorelix) and single-dose long GnRH agonist (goserelin) protocol for IVF cycles--a prospective, randomized study. Reprod Biomed Online. 2003;7(3):301–8.

    Article  CAS  PubMed  Google Scholar 

  39. Yang S, Chen XN, Qiao J, Liu P, Li R, Chen GA, Ma CH. Comparison of GnRH antagonist fixed protocol and GnRH agonists long protocol in infertile patients with normal ovarian reserve function in their first in vitro fertilization-embryo transfer cycle]. [Article in Chinese]. Zhonghua Fu Chan Ke Za Zhi. 2012;47(4):245–9.

    CAS  PubMed  Google Scholar 

  40. Manno M, Tomei F, Cervi M, Favretti C, Adamo V. Comparison of protocols efficacy in poor responders: differences in oocytes/embryos competence with different protocols, a retrospective study. Fertil Steril. 2009;91(4 Suppl):1431–3.

    Article  CAS  PubMed  Google Scholar 

  41. Eldar-Geva T, Zylber-Haran E, Babayof R, Halevy-Shalem T, Ben-Chetrit A, Tsafrir A, Varshaver I, Brooks B, Margalioth EJ. Similar outcome for cryopreserved embryo transfer following GnRH-antagonist/GnRH-agonist, GnRH-antagonist/HCG or long protocol ovarian stimulation. Reprod Biomed Online. 2007;14(2):148–54.

    Article  PubMed  Google Scholar 

  42. Weissman A, Barash A, Shapiro H, Casper RF. Ovarian hyperstimulation following the sole administration of agonistic analogues of gonadotrophin releasing hormone. Hum Reprod. 1998;13(12):3421–4.

    Article  CAS  PubMed  Google Scholar 

  43. Park HT, Bae HS, Kim T, Kim SH. Ovarian hyper-response to administration of an GnRH-agonist without gonadotropins. J Korean Med Sci. 2011;26(10):1394–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Assisted Reproduction,, Rotunda – The Center for Human Reproduction, Rotunda-Blue Fertility Clinic and Keyhole Surgery Center, 36 Turner Road, #304-05, 3rd Floor, B-Wing, Bandra (W), Mumbai, Maharashtra, 40050, India

    Gautam N. Allahbadia MD, DGO, DFP, FCPS, DNB, FNAMS

  2. Department of Assisted Reproduction, The Center for Human Reproduction, 36 Turner Road, #304-05, 3rd Floor, B-Wing, Bandra (W), Mumbai, Maharashtra, 40050, India

    Rubina Merchant PhD

Authors
  1. Gautam N. Allahbadia MD, DGO, DFP, FCPS, DNB, FNAMS
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rubina Merchant PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gautam N. Allahbadia MD, DGO, DFP, FCPS, DNB, FNAMS .

Editor information

Editors and Affiliations

  1. 1st floor, Rotunda-CHR 36, Mumbai, India

    Gautam N. Allahbadia

  2. IVF Namba Clinic, Osaka, Japan

    Yoshiharu Morimoto

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer India

About this chapter

Cite this chapter

Allahbadia, G.N., Merchant, R. (2016). Depot GnRH Agonists in COH for ART. In: Allahbadia, G., Morimoto, Y. (eds) Ovarian Stimulation Protocols. Springer, New Delhi. https://doi.org/10.1007/978-81-322-1121-1_10

Download citation

  • DOI: https://doi.org/10.1007/978-81-322-1121-1_10

  • Publisher Name: Springer, New Delhi

  • Print ISBN: 978-81-322-1120-4

  • Online ISBN: 978-81-322-1121-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation