Skip to main content

Comparison of embryological and clinical outcome in GnRH antagonist vs. GnRH agonist protocols for in vitro fertilization in PCOS non-obese patients. A prospective randomized study

Journal of Assisted Reproduction and Genetics volume 25, pages 365–374 (2008)Cite this article

Abstract

Purpose

Embryological and clinical efficacy of gonadotropin-releasing hormone (GnRH) antagonist and agonist stimulation protocols in non-obese women with polycystic ovarian syndrome (PCOS) were compared.

Methods

A prospective randomized study. Setting: Medical University Hospital. Patients: 70 infertile PCOS patients; 33 in GnRH antagonist and 37 in GnRH agonist group.

Results

Similar mature metaphase II oocyte rate (76% vs. 76%) was observed in both protocols. Optimal pronuclear morphology zygotes dominated in both groups (64% vs. 66%). Transferred embryo quality did not differ in both protocols. No significant differences between both protocols were found in delivery rate (p = 0.481), pregnancy rate (p = 0.810), multiple pregnancy rate (p = 0.501), miscarriage rate (p = 0.154), fertilization rate (p = 0.388) and implantation rate (p = 1.000). Duration of stimulation and total follicle-stimulating hormone (FSH) dose were significantly lower in GnRH antagonist protocol (p = 0.0005).

Conclusions

GnRH antagonist and agonist protocols in non-obese PCOS patients yield similar embryological and clinical outcomes. Shorter duration of treatment and lower FSH requirement in GnRH antagonist group may be financially beneficial and therefore attractive for patients.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Asuncion M, Calvo RM, San Millan JL. A prospective study of the prevalence of the polycystic ovary in unselected Caucasian women from Spain. J Clin Endocrinol Metab 2000;85:2434–8. doi:10.1210/jc.85.7.2434.

    PubMed  Article  CAS  Google Scholar 

  2. Knochenhauer ES, Key TJ, Kahsar-Miller M. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States; a prospective study. J Clin Endocrinol Metab 1998;83:3078–82. doi:10.1210/jc.83.9.3078.

    PubMed  Article  CAS  Google Scholar 

  3. Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod 2008;23:462–77. doi:10.1093/humrep/dem426.

    Article  Google Scholar 

  4. Homburg R. Management of infertility and prevention of ovarian hyperstimulation in women with polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol 2004;18:773–88. doi:10.1016/j.bpobgyn.2004.05.006.

    PubMed  Article  Google Scholar 

  5. Akagbosu FT. The use of GnRH agonists and antagonists in infertility. In: Brinsden PR, editor. A textbook of in vitro fertilization and assisted reproduction. New York, USA: Partheon; 1999. p. 83–9.

    Google Scholar 

  6. Moghissi KS. A clinician’s guide to use of gonadotropin-releasing hormone analogs in women. Medscape Womens Health 2000;5:5.

    PubMed  CAS  Google Scholar 

  7. Reissmann T, Felberbaum R, Diedrich K, Engel J, Comaru-Schally AM, Schally AV. Development and applications of luteinizing hormone-releasing hormone antagonists in the treatment of infertility. Hum Reprod 1995;10:1974–81.

    PubMed  CAS  Google Scholar 

  8. Kolibianakis EM, Collins J, Tarlatzis BC, Devroey P, Diedrich K, Griesinger G. Among patients treated for IVF with gonadotrophins and GnRH analogues, is the probability of live birth dependent on the type of analogue used? A systematic review and meta-analysis. Hum Reprod Update 2006;12:651–71. doi:10.1093/humupd/dml038.

    PubMed  Article  CAS  Google Scholar 

  9. Al-Inany HG, Abou-Setta AM, Aboulghar M. Gonadotrophin-releasing hormone antagonists for assisted conception. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD001750. doi:10.1002/14651858.CD001750.pub2

  10. Al-Inany HG, Abou-Setta AM, Aboulghar M. Gonadotrophin-releasing hormone antagonists for assisted conception: a Cochrane Review. Reprod Biomed Online 2007;14:640–9.

    PubMed  CAS  Article  Google Scholar 

  11. Griesinger G, Diedrich K, Tarlatzis BC, Kolibianakis EM. GnRH-antagonists in ovarian stimulation for IVF in patients with poor response to gonadotrophins, polycystic ovary syndrome, and risk of ovarian hyperstimulation: a meta-analysis. Reprod Biomed Online 2006;13:628–38.

    PubMed  CAS  Article  Google Scholar 

  12. Fedorcsák P, Dale PO, Storeng R, Tanbo T, Abyholm T. The impact of obesity and insulin resistance on the outcome of IVF or ICSI in women with polycystic ovarian syndrome. Hum Reprod 2001;16:1086–91. doi:10.1093/humrep/16.6.1086.

    PubMed  Article  Google Scholar 

  13. Fedorcsák P, Dale PO, Storeng R, Ertzeid G, Bjercke S, Oldereid N, et al. Impact of overweight and underweight on assisted reproduction treatment. Hum Reprod 2004;19:2523–8. doi:10.1093/humrep/deh485.

    PubMed  Article  Google Scholar 

  14. Wittemer C, Ohl J, Bailly M, Bettahar-Lebugle K, Nisand I. Does body mass index of infertile women have an impact on IVF procedure and outcome? J Assist Reprod Genet 2000;17:547–52. doi:10.1023/A:1026477628723.

    PubMed  Article  CAS  Google Scholar 

  15. Bellver J, Melo M, Bosch E, Serra V, Remohí J, Pellicer A. Obesity and poor reproductive outcome: the potential role of the endometrium. Fertil Steril 2007;88:446–51. doi:10.1016/j.fertnstert.2006.11.162.

    PubMed  Article  Google Scholar 

  16. Hillier SG. Gonadotropic control of ovarian follicular growth and development. Mol Cell Endocrinol 2001;179:36–46. doi:10.1016/S0303-7207(01)00469-5.

    Article  Google Scholar 

  17. Fauser BC, Van Heusdon AM. Manipulation of human ovarian function: physiological concepts and clinical consequences. Endocr Rev 1997;18:71–106. doi:10.1210/er.18.1.71.

    PubMed  Article  CAS  Google Scholar 

  18. Scheele F, Hompes PG, Van der Meer M, Schoute E, Schoemaker J. The relationship between follicle-stimulating hormone dose and level and its relevance for ovulation induction with adjuvant gonadotropin-releasing hormone-agonist treatment. Fertil Steril 1993;60:620–5.

    PubMed  CAS  Google Scholar 

  19. Laven JS, Imani B, Eijkemans MJ, Fauser BC. New approaches to PCOS and other forms of anovulation. Obstet Gynecol Surv 2002;57:755–67. doi:10.1097/00006254-200211000-00022.

    PubMed  Article  Google Scholar 

  20. Taylor AE, McCourt B, Martin K, Anderson EJ, Adams J, Schoebfeld D. Determinants of abnormal gonadotropin secretion in clinically defined women with PCOS. J Clin Endocrinol Metab 1997;82:2248–56. doi:10.1210/jc.82.7.2248.

    PubMed  Article  CAS  Google Scholar 

  21. Yoshimura Y, Wallach EE. Studies of the mechanism(s) of mammalian ovulation. Fertil Steril 1987;47:22–34.

    PubMed  CAS  Google Scholar 

  22. Balen AH, Tan SL, MacDougall J, Jacobs HS. Miscarriage rates following in-vitro fertilization are increased in women with polycystic ovaries and reduced by pituitary desensitization with buserelin. Hum Reprod 1993;8:959–64.

    PubMed  CAS  Google Scholar 

  23. Imani B, Eijkemans MJ, te Velde ER, Habbema JD, Fauser BC. Predictors of chances to conceive in ovulatory patients during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. J Clin Endocrinol Metab 1999;84:1617–22. doi:10.1210/jc.84.5.1617.

    PubMed  Article  CAS  Google Scholar 

  24. Nardo LG, Rai R, Backos M, El Gaddal S, Regan L. High serum luteinizing hormone and testosterone concentrations do not predict pregnancy outcome in women with recurrent miscarriage. Fertil Steril 2002;77:348–52. doi:10.1016/S0015-0282(01)02995-8.

    PubMed  Article  Google Scholar 

  25. Pagán YL, Srouji SS, Jimenez Y, Emerson A, Gill S, Hall JE. Inverse relationship between luteinizing hormone and body mass index in polycystic ovarian syndrome: investigation of hypothalamic and pituitary contributions. J Clin Endocrinol Metab 2006;91:1309–16. doi:10.1210/jc.2005-2099.

    PubMed  Article  CAS  Google Scholar 

  26. Arroyo A, Laughlin GA, Morales AJ, Yen SS. Inappropriate gonadotropin secretion in polycystic ovary syndrome: influence of adiposity. J Clin Endocrinol Metab 1997;82:3728–33. doi:10.1210/jc.82.11.3728.

    PubMed  Article  CAS  Google Scholar 

  27. World Health Organization. Manual for standardized investigation and diagnosis of the infertile couple. Melbourne: Cambridge University Press; 1993.

    Google Scholar 

  28. Kruger TF, Acosta AA, Simmons KF, Swanson RJ, Matta JF, Oehninger S. Predictive value of abnormal sperm morphology in in vitro fertilization. Fertil Steril 1988;49:112–7.

    PubMed  CAS  Google Scholar 

  29. Sakkas D, Shoukir Y, Chardonnens D, Bianchi PG, Campana A. Early cleavage of human embryos to the two-cell stage after intracytoplasmic sperm injection as an indicator of embryo viability. Hum Reprod 1998;13:182–7. doi:10.1093/humrep/13.1.182.

    PubMed  Article  CAS  Google Scholar 

  30. Tesarik J, Junca AM, Hazout A, Aubriot FX, Nathan C, Cohen-Bacrie P, et al. Embryos with high implantation potential after intracytoplasmic sperm injection can be recognized by a simple, non-invasive examination of pronuclear morphology. Hum Reprod 2000;15:1396–9. doi:10.1093/humrep/15.6.1396.

    PubMed  Article  CAS  Google Scholar 

  31. Scott L, Alvero R, Leondires M, Miller B. The morphology of human pronuclear embryos is positively related to blastocyst development and implantation. Hum Reprod 2000;15:2394–403. doi:10.1093/humrep/15.11.2394.

    PubMed  Article  CAS  Google Scholar 

  32. Baczkowski T, Kurzawa R, Glabowski W. Methods of embryo scoring in in vitro fertilization. Reprod Biol 2004;4:5–22.

    PubMed  Google Scholar 

  33. Practice Committee of the Society for Assisted Reproductive Technology, Practice Committee of the American Society for Reproductive Medicine. Guidelines on number of embryos transferred. Fertil Steril 2006;86:S51–2.

    Google Scholar 

  34. Balen AH, Tan SL, Jacobs HS. Hypersecretion of luteinizing hormone: a significant cause of infertility and miscarriage. Br J Obstet Gynaecol 1993;100:1082–9.

    PubMed  CAS  Google Scholar 

  35. Homburg R. In vitro fertilization and embryo transfer for the treatment of infertility associated with polycystic ovary syndrome. Fertil Steril 1993;5:858–63.

    Google Scholar 

  36. Ciepiela P, Baczkowski T, Brelik P, Antonowicz A, Safranow K, Kurzawa R. Biotechnological and clinical outcome of in vitro fertilization in non-obese patients with polycystic ovarian syndrome. Folia Histochem Cytobiol 2007;45:S65–71.

    PubMed  Google Scholar 

  37. Ashrafi M, Moini A, Mohammadzadeh A, Ezabadi Z, Zafarani F, Baghestani AR. Comparative study of GnRH antagonist and GnRH agonist in PCO patients undergoing IVF/ICSI cycles. Iranian J Reprod Med 2005;13:14–8.

    Google Scholar 

  38. Bahceci M, Ulug U, Ben-Shlomo I, Erden HF, Akman MA. Use of a GnRH antagonist in controlled ovarian hyperstimulation for assisted conception in women with polycystic ovary disease: a randomized, prospective, pilot study. J Reprod Med 2005;50:84–90.

    PubMed  CAS  Google Scholar 

  39. Hwang JL, Seow KM, Lin YH, Huang LW, Hsieh BC, Tsai YL, Wu Gj, Huang SC, Chen CY, Chen PH, Tzeng CR. Ovarian stimulation by concomitant administration of cetrorelix acetate and HMG following Diane-35 pre-treatment for patients with polycystic ovary syndrome: a prospective randomized study. Hum Reprod 2004;19:1993–2000. doi:10.1093/humrep/deh375.

    PubMed  Article  CAS  Google Scholar 

  40. Kim CH, Lee YJ, Hong SH. Efficiency of a GnRH antagonists during early and late ovarian hyperstimulation period in women with polycystic ovary syndrome undergoing IVF-ET. Hum Reprod 2004;19:105–9.

    Google Scholar 

  41. Martin KA, Hall JE, Adams J, Crowley WF. Comparison of exogenous gonadotropins and pulsatile GnRH for induction of ovulation hypogonadotropic amenorrhea. J Clin Endocrinol Metab 1993;77:125–9. doi:10.1210/jc.77.1.125.

    PubMed  Article  CAS  Google Scholar 

  42. Homburg R, Levy T, Ben-Rafael Z. A comparative prospective study of conventional regimen with chronic low-dose administration of follicle stimulating hormone for anovulation associated with polycystic ovary syndrome. Fertil Steril 1995;63:729–33.

    PubMed  CAS  Google Scholar 

  43. Nyboe A, Goossens V, Gianaroli L, Felberbaum R, de Mouzon J, Nygren KG. Assisted reproductive technology in Europe, 2003. Results generated from European registers by ESHRE. Hum Reprod 2007;22:1513–25. doi:10.1093/humrep/dem053.

    Article  Google Scholar 

  44. Wright VC, Chang J, Jeng G, Chen M, Macaluso M. Centers for Disease Control and Prevention. Assisted reproductive technology surveillance — United States, 2004. MMWR Surveill Summ 2007;56:1–22.

    PubMed  Google Scholar 

  45. Filicori M. The role of luteinizing hormone in folliculogenesis and ovulation induction. Fertil Steril 1999;71:405–14. doi:10.1016/S0015-0282(98)00482-8.

    PubMed  Article  CAS  Google Scholar 

  46. Schoot DC, Harlin J, Shoham Z, Mannaerts BM, Lahlou N, Bouchard P. Recombinant human follicle-stimulating hormone and ovarian response in gonadotropin-deficient women. Hum Reprod 1994;9:1237–42.

    PubMed  CAS  Google Scholar 

  47. Ludwig M, Finas DF, al-Hasani S. Oocyte quality and treatment outcome in intracytoplasmic sperm injection cycles of polycystic ovarian syndrome patients. Hum Reprod 1999;14:354–8. doi:10.1093/humrep/14.2.354.

    PubMed  Article  CAS  Google Scholar 

  48. Okon MA, Laird SM, Tuckerman EM, Li TC. Serum androgen levels in women who have recurrent miscarriages and their correlation with markers of endometrial function. Fertil Steril 1998;69:682–90. doi:10.1016/S0015-0282(98)00007-7.

    PubMed  Article  CAS  Google Scholar 

  49. Bjercke S, Fedorcsak P, Abyholm T, Storeng R, Ertzeid G, Oldereid N, et al. IVF/ICSI outcome and serum LH concentration on day 1 of ovarian stimulation with recombinant FSH under pituitary suppression. Hum Reprod 2005;20:2441–7. doi:10.1093/humrep/dei101.

    PubMed  Article  CAS  Google Scholar 

  50. Noci I, Maggi M, Fuzzi B, Biagiotti R, Ricci F, Marchionni M. Effects of low day 3 luteinizing hormone levels on in vitro fertilization treatment outcome. Gynecol Endocrinol 2000;14:321–6.

    PubMed  CAS  Article  Google Scholar 

  51. Cabrera RA, Stadtmauer L, Mayer JF, Gibbons WE, Oehninger S. Follicular phase serum levels of luteinizing hormone do not influence delivery rates in in vitro fertilization cycles down-regulated with a gonadotropin-releasing hormone agonist and stimulated with recombinant follicle-stimulating hormone. Fertil Steril 2005;83:42–8. doi:10.1016/j.fertnstert.2004.06.050.

    PubMed  Article  CAS  Google Scholar 

  52. Huirne JA, van Loenen AC, Schats R, McDonnell J, Hompes PG, Schoemaker J, et al. Dose-finding study of daily GnRH antagonist for the prevention of premature LH surges in IVF/ICSI patients: optimal changes in LH and progesterone for clinical pregnancy. Hum Reprod 2005;20:359–67. doi:10.1093/humrep/deh601.

    PubMed  Article  CAS  Google Scholar 

  53. Liu SY, Han JL, Peng XD, Dong X, Xu J, Yan JM. Effect of midfollicular luteinizing hormone levels on ovarian response and pregnancy outcome in patients undergoing in vitro fertilization in a short-term protocol. Fertil Steril 2005;83:1043–6. doi:10.1016/j.fertnstert.2004.12.015.

    PubMed  Article  CAS  Google Scholar 

  54. Penarrubia J, Fabregues F, Creus M, Manau D, Casamitjana R, Guimera M. LH serum levels during ovarian stimulation as predictors of ovarian response and assisted reproduction outcome in down-regulated women stimulated with recombinant FSH. Hum Reprod 2003;18:2689–97. doi:10.1093/humrep/deg506.

    PubMed  Article  CAS  Google Scholar 

  55. Lainas TG, Petsas GK, Zorzovilis IZ, Iliadis GS, Kolibianakis EM. Initiation of GnRH antagonist on Day 1 of stimulation as compared to the long agonist protocol in PCOS patients. A randomized controlled trial: effect on hormonal levels and follicular development. Hum Reprod 2007;22:1540–6. doi:10.1093/humrep/dem033.

    PubMed  Article  CAS  Google Scholar 

  56. Fauser CJM, Devroey P. Why is the clinical acceptance of gonadotropin-releasing hormone antagonist cotreatment during ovarian hyperstimulation for in vitro fertilization so slow? Fertil Steril 2005;83:1607–11. doi:10.1016/j.fertnstert.2005.02.011.

    PubMed  Article  Google Scholar 

Download references

Acknowledgement

Financial support—grant number KBN 2 P05E 034 28 from State Committee for Scientific Research

Author information

Affiliations

  1. Department of Reproductive Medicine and Gynecology, Pomeranian Medical University, 2 Siedlecka Street, Szczecin-Police, 72-010, Poland

    Rafal Kurzawa, Przemyslaw Ciepiela & Tomasz Baczkowski

  2. Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 72 al. Powstancow Wlkp. Street, Szczecin, 70-111, Poland

    Krzysztof Safranow

  3. Glan Clwyd Hospital, Conwy and Denbighshire NHS Trust, Rhyl, Benbighshire, LL18 5UJ, UK

    Pawel Brelik

Authors
  1. Rafal Kurzawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Przemyslaw Ciepiela
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tomasz Baczkowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Krzysztof Safranow
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pawel Brelik
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Przemyslaw Ciepiela.

Additional information

Capsule GnRH antagonist and agonist protocols in non-obese PCOS patients yield similar embryological and clinical outcomes. GnRH antagonist protocols may be financially and clinically attractive for patients undergoing IVF.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kurzawa, R., Ciepiela, P., Baczkowski, T. et al. Comparison of embryological and clinical outcome in GnRH antagonist vs. GnRH agonist protocols for in vitro fertilization in PCOS non-obese patients. A prospective randomized study. J Assist Reprod Genet 25, 365–374 (2008). https://doi.org/10.1007/s10815-008-9249-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-008-9249-7

Keywords

  • GnRH agonist
  • GnRH antagonist
  • IVF
  • Polycystic ovary syndrome
  • Prospective randomized trial