Skip to main content
SpringerLink
Log in

Efficacy of Low-Dose Human Chorionic Gonadotropin (hCG) in a GnRH Antagonist Protocol

  • Assisted Reproduction
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Purpose: To examine the efficacy of low-dose hCG using a GnRH antagonist protocol.

Methods: Prospective randomized study was performed at the Kyono Ladies Clinic. One hundred ninety-two women (<40 –years old, <3 previous cycles) were randomly assigned to GnRH agonist (buserelin) long protocol (LP, n = 66), GnRH antagonist (cetrorelix) with no low-dose hCG protocol (NhCGP, n = 63), or GnRH antagonist with low-dose hCG protocol (hCGP, n = 63).

Results: The hCGP was associated with reduced total amounts of FSH, increased oocyte maturation rate, high-quality day 3 embryos rate, and number of frozen embryos. Ovarian hyperstimulation syndrome (OHSS) tended to be lower in the GnRH antagonist protocol. Pregnancy and implantation rates did not differ significantly between study groups.

Conclusions: Daily low-dose hCG supplementation in the late follicular phase could improve the outcome in FSH based-GnRH antagonist protocol. This protocol, however, does require further modifications, including determination of the optimal doses for hCG and gonadotropin pretreatment.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Alvano C, Felberbaum RE, Smitz J, Riethmuller-Winzen H, Engel J, Diedrich K, Devroey P: 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. European Cetrorelix Study Group. Hum Reprod 2000;15:526–531

    Article  Google Scholar 

  2. Ludwig M, Katalinic A, Diedrich K: Use of GnRH antagonists in ovarian stimulation for assisted reproductive technologies compared to the long protocol. Meta analysis. Arch Gynecol Obstet 2001;265:175–182

    Article  PubMed  CAS  Google Scholar 

  3. Al-Inary H, Aboulghar H: GnRH antagonist in assisted reproduction: A Cochran review. Hum Reprod 2002;17:874–885

    Article  Google Scholar 

  4. Zeleznik AJ, Hillier SG: The role of gonadotropins in the selection of the preovulatory follicle. Clin Obstet Gynecol 1984;27:927–940

    Article  PubMed  CAS  Google Scholar 

  5. Filicori M, Cognigni GE, Taraborrelli D, Spettoli D, Ciampaglia W, de Fatis CT, Pocognoli P: Luteinizing Hormone Activity Supplementation Enhances Follicle-Stimulating Hormone Efficacy and Improves Ovulation Induction Outcome. J Clin Endocrinol Metab 1999;84:2659–2663

    Article  PubMed  CAS  Google Scholar 

  6. Filicori M, Cognigni GE, Tabarelli C, Pocognoli P, Taraborrelli S, Spettoli D, Ciampaglia W: Stimulation and growth of antral ovarian follicles by selective LH activity administration in women. J Clin Endocrinol Metab 2002;87:1156–1161

    Article  PubMed  CAS  Google Scholar 

  7. Filicori M, Cognigni GE, Pocognoli P, Tabarelli C, Ferlini F, Perri T, Parmegiani L: Comparison of controlled ovarian stimulation with human menopausal gonadotropin or recombinant follicle stimulating hormone. Fertil Steril 2003;80:390–397

    Article  PubMed  Google Scholar 

  8. Filicori M, Cognigni GE, Gamberini E, Parmegiani L, Troilo E, Roset B: Efficacy of low-dose human chorionic gonadotropin alone to complete controlled ovarian stimulation. Fertil Steril 2005;84:394–401

    Article  PubMed  CAS  Google Scholar 

  9. Filicori M, Fazleabas AT, Huhtaniemi I, Licht P, Rao ChV, Tesarik J, Zygmunt M: Novel concepts of human chorionic gonadotropin: Reproductive system interactions and potential in the management of infertility. Fertil Steril 2005;84:275–284

    Article  PubMed  CAS  Google Scholar 

  10. Golan A, Ron-EI R, Herman A, Weinraub Z, Soffer Y, Capsi E: Ovarian hyperstimulation syndrome: An update review. Obstet Gynecol Surv 1989;44:430–440

    Article  PubMed  CAS  Google Scholar 

  11. Hillier SG: Current concepts of the roles of follicle stimulating hormone and luteinizing hormone in folliculogenesis. Hum Reprod 1994;9:188–191

    PubMed  CAS  Google Scholar 

  12. Chappel S, Howles C: Re-evaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process. Hum Reprod 1991;6:1206–1212

    PubMed  CAS  Google Scholar 

  13. Fleming R, Chung CC, Yates RWS, Coutts JRT: Purified urinary follicle stimulating hormone induces different hormone profiles compared with menotrophins, dependent upon the route of administration and endogenous luteinizing hormone activity. Hum Reprod 1996;11:1854–1858

    PubMed  CAS  Google Scholar 

  14. 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;75:324–331

    Article  PubMed  CAS  Google Scholar 

  15. Ferraretti AP, Gianaroli L, Magli MC, D’angelo A, Farfali V, Montanaro N: Exogenous luteinzing hormone in controlled ovarian hyperstimulation for assisted reproduction techniques. Fertil Steril 2004;82:1521–1526

    Article  PubMed  CAS  Google Scholar 

  16. Rao CV: Multiple novel roles of luteinizing hormone. Fertil Steril 2001;76:1097–1100

    Article  PubMed  CAS  Google Scholar 

  17. Semesh M: Actions of gonadotrophins on the uterus. Reproduction 2001;121:835–842

    Article  Google Scholar 

  18. Tesarik J, Mendoza JK: Effects of exogenous LH administration during ovarian stimulation of pituitary down-regulated young oocyte donors on oocyte yield and developmental competence. Hum Reprod 2002;17:3129–3137

    Article  PubMed  CAS  Google Scholar 

  19. Tesaric J, Hazout A, Mendoza C: Luteinizing hormone affects uterine receptivity independently of ovarian function. Reprod Biomed Online 2003;7:59–64

    Google Scholar 

  20. Garirelix ose Finding Study Group: A double-blind, randomized, dose-finding study to assess the efficacy of the gonadotrophin-releasing hormone antagonist ganirelix (Org 37462) to prevent premature luteinizing hormone surges in women undergoing ovarian stimulation with recombinant follicle stimulating hormone (Puregon®). Hum Reprod 1998;13:3023–3031

    Article  Google Scholar 

  21. Kolibianakis EM, Albano C, Kahn J, Camus M, Touraye H, Van Steirteghem AC, Devroey P: Exposure to high levels of luteinizing hormone and estradiol in the early follicular phase of gonadotropin-releasing hormone antagonist cycles is associated with a reduced chance of pregnancy. Fertil Steril 2003;79:873–880

    Article  PubMed  Google Scholar 

  22. Stanger JD, Yovich JL: Reduced in-vitro fertilization of human oocytes from patients with raised basal luteinizing hormone levels during the follicular phase. Br J Obstet Gynecol 1985;92:385–393

    CAS  Google Scholar 

  23. Howles CM, Macnamee MC, Edwards RG, Goswamy R, Steptoe PC: Effect of high tonic levels of luteinizing hormone on outcome of in-vitro fertilization. Lancet 1986;2:521–522

    Article  PubMed  CAS  Google Scholar 

  24. Homburg R, Armar NA, Eshel A, Adams J, Jacobs HS: Influence of serum luteinizing hormone concentrations on ovulation, conception, and early pregnancy loss in polycystic ovary syndrome. Br Med J 1988;297:1024–1026

    Article  CAS  Google Scholar 

  25. Serono Study No. 7313: Data on file, 1998, Geneva, Switzerland.

  26. The European Recombinant Human LH Study Group: Recombinant human luteinizing hormone (LH) to support recombinant follicle stimulating hormone (FSH) -induced follicular development in LH-and FSH-deficient anovulatory women: A dose-finding study. J Clin Endocrinol Metab 1998;83:1507–1514

    Article  Google Scholar 

  27. Marrs R, Meldrum D, Muasher S, Schoolkraft W, Werlin L, Kelly E: Randomized trial to compare the effect of recombinant human FSH (follitropin alfa) with or without recombinant human LH in women undergoing assisted reproduction treatment. Reprod BioMed Online 2003;8:175–182

    Google Scholar 

  28. Humaidan P, Bungum M, Bungum L, Anderson CY: Effect of recombinant LH supplementation in women undergoing assisted reproduction with GnRH agonist down-regulation and stimulation with recombinant FSH: An opening study. Reprod BioMed Online 2004;8:635–643

    Article  PubMed  CAS  Google Scholar 

  29. Stokman PG, de Leeuw R, van den Wijngaard HA, Kloosterboer HJ,Vemer HM, Sanders AL: Human chorionic gonadotropin in commercial human menopausal gonado-tropin preparations. Fertil Steril 1993;60:176–178

    Google Scholar 

  30. The European Recombinant LH study Group: Human recombinant luteinizing hormone is as effective as, but safer than, urinary human chorionic gonadotropin in inducing final follicular maturation and ovulation in in vitro fertilization procedures: Results of a multicenter double-blind study. J Clin Endocrinol Metab 2001;86:2607–2618

    Article  Google Scholar 

  31. Sullivan M, Stewart-Akers A, Krasnow JS, Berga SL, Zeleznik 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;84:228–232

    Article  PubMed  CAS  Google Scholar 

  32. Loumaye E, Engrand P, Shoham Z, Hillier SG, Baird DT on behalf of the recombinant LH study group. Clinical evidence of an LH ceiling effect induced by administration of recombinant human LH during the late follicular phase of stimulated cycles in World Health Organization type I ans type II anovulation. Hum Reprod 2003;18:314–322.

    Article  PubMed  CAS  Google Scholar 

  33. Takahashi K, Kurioka H, Ozaki T, Kanasaki H, Kohsaka M, Miyasaki K, Karino K: Increased prevalence of luteinizing hormone β-subunit variant in Japanese infertility patients. Hum Reprod 1998;13:3338–3344

    Article  PubMed  CAS  Google Scholar 

  34. Fanchin R, Salomon L, Castero-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;18:2698–2703

    Article  PubMed  CAS  Google Scholar 

  35. Fanchin R, Castelo A, Kadoch IJ, Hosny G, Bagirova M, Frydman R: Premenstrual administration of gonadotropin-releasing hormone antagonist coordinates early antral follicle sizes and sets up the basis for an innovative concept of controlled ovarian hyperstimulation. Fertil Steril 2004;81:1554–1559

    Article  PubMed  CAS  Google Scholar 

Download references

ACKNOWLEDGMENT

The authors thank Mr. Nobuhide Ebina for the analysis of the data and statistical advice

Author information

Authors and Affiliations

  1. Kyono Ladies Clinic, Furukawa, Miyagi, Japan

    Kyono Koichi, Nakajo Yukiko, Kumagai Shima & Sasaki Sachiko

  2. Kyono Reproduction Research Center, Furukawa, Miyagi, Japan

    Kyono Koichi, Nakajo Yukiko, Kumagai Shima & Sasaki Sachiko

  3. Kyono Reproduction Research Center, 3-8-6, Omiya, Furukawa, Miyagi Prefecture, 989-6221, Japan

    Kyono Koichi

Authors
  1. Kyono Koichi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nakajo Yukiko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kumagai Shima
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sasaki Sachiko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kyono Koichi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koichi, K., Yukiko, N., Shima, K. et al. Efficacy of Low-Dose Human Chorionic Gonadotropin (hCG) in a GnRH Antagonist Protocol. J Assist Reprod Genet 23, 223–228 (2006). https://doi.org/10.1007/s10815-006-9036-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-006-9036-2

KEY WORDS:

Search

Navigation