Journal of Assisted Reproduction and Genetics

, Volume 26, Issue 1, pp 19–24 | Cite as

Comparison of letrozole with continuous gonadotropins and clomiphene-gonadotropin combination for ovulation induction in 1387 PCOS women after clomiphene citrate failure: a randomized prospective clinical trial

  • Ashalatha Ganesh
  • Sourendra Kant Goswami
  • Ratna Chattopadhyay
  • Koel Chaudhury
  • Baidyanath Chakravarty
GENERAL INFERTILITY

Abstract

Purpose

Letrozole, though reported to be an effective ovulation inducing agent, warrants larger randomized trials. The purpose of this study is to compare the efficacy of letrozole with that of rFSH and clomiphene citrate(CC)/rFSH for ovarian stimulation in IUI cycles.

Methods

Randomized, prospective, single-blinded clinical trial. 1387 PCOS women after CC failure were randomized into three groups: Group A received letrozole, Group B received CC with two doses rFSH and Group C received continuous rFSH day 2 onwards until hCG injection.

Results

Group A, B and C had an ovulation rate of 79.30%, 56.95% and 89.89% and cycle cancellation rate of 20.70%, 43.05% and 10.11%, respectively. Pregnancy rates in Group A, B and C were 23.39%, 14.35% and 17.92%, while the miscarriage rates were 13.80%, 16.67% and 14.52%, respectively.

Conclusion

Letrozole appears to be a suitable ovulation inducing agent in PCOS women with CC failure and is found to be most effective when baseline estradiol level >60 pg/ml.

Keywords

Baseline estradiol Clomiphene citrate failure Letrozole Ovulation induction rFSH 

References

  1. 1.
    Dankert T, Kremer JAM, Cohlen BJ, Hamilton CJCM, Pasker-de Jong PCM, Straatman H, van Dop PA. A randomized clinical trial of clomiphene citrate versus low dose recombinant FSH for ovarian hyperstimulation in intrauterine insemination cycles for unexplained and male subfertility. Hum Reprod. 2007;22:792–7. doi:10.1093/humrep/del441.PubMedCrossRefGoogle Scholar
  2. 2.
    Elnashar A, Fouad H, Eldosoky M, Saeid N. Letrozole induction of ovulation in women with clomiphene citrate-resistant polycystic ovary syndrome may not depend on the period of infertility, the body mass index, or the luteinizing hormone/follicle-stimulating hormone ratio. Fertil Steril. 2006;85:511–3. doi:10.1016/j.fertnstert.2005.08.016.PubMedCrossRefGoogle Scholar
  3. 3.
    Eijkemans MJ, Polinder S, Mulders AG, Laven JS. Habbema JDF, Fauser BC: Individualized cost-effective conventional ovulation induction treatment in normogonadotrophic anovulatoryinfertility (WHO group 2). Hum Reprod. 2005;20:2830–7. doi:10.1093/humrep/dei164.PubMedCrossRefGoogle Scholar
  4. 4.
    Matorras R, Diaz T, Corcostegui B, Ramon O, Pijoan JI, Rodriguez-Escudero FJ. Ovarian stimulation in intrauterine insemination with donor sperm: a randomized study comparing clomiphene citrate in fixed protocol versus highly purified FSH. Hum Reprod. 2002;17:2107–11. doi:10.1093/humrep/17.8.2107.PubMedCrossRefGoogle Scholar
  5. 5.
    Gregoriou O, Vlahos NF, Konidaris S, Papadias K, Botsis D, Creatsas GK. Randomized controlled trial comparing superovulation with letrozole versus recombinant follicle-stimulating hormone combined to intrauterine insemination for couples with unexplained infertility who had failed clomiphene citrate stimulation and intrauterine insemination. Fertil Steril. 2007;(Oct):23. PMID: 17961561.Google Scholar
  6. 6.
    Quintero RB, Urban R, Lathi RB, Westphal LM, Dahan MH. A comparison of letrozole to gonadotropins for ovulation induction, in subjects who failed to conceive with clomiphene citrate. Fertil Steril. 2007;88:879–85. doi:10.1016/j.fertnstert.2006.11.166.PubMedCrossRefGoogle Scholar
  7. 7.
    Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Fertil Steril 2008;89:505–22. doi:10.1016/j.fertnstert.2007.09.041.CrossRefGoogle Scholar
  8. 8.
    Mitwally MFM, Casper RF. Aromatase inhibition reduces gonadotrophin dose required for controlled ovarian stimulation in women with unexplained infertility. Hum Reprod. 2003;8:1588–97. doi:10.1093/humrep/deg311.CrossRefGoogle Scholar
  9. 9.
    Brzechffa P, Daneshmand S, Buyalos R. Sequential clomiphene citrate and human menopausal gonadotrophin with intrauterine insemination: the effect of patient age on clinical outcome. Hum Reprod. 1998;13:2110–4. doi:10.1093/humrep/13.8.2110.PubMedCrossRefGoogle Scholar
  10. 10.
    Goswami SK, Das T, Chattopadhyay R, Sawhney V, Kumar J, Chaudhury K, Chakravarty BN, Kabir SN. 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. doi:10.1093/humrep/deh359.PubMedCrossRefGoogle Scholar
  11. 11.
    Casper RF, Mitwally MFM. Review: Aromatase Inhibitors for Ovulation Induction. J Clin Endocrinol Metab. 2006;91:760–71. doi:10.1210/jc.2005-1923.PubMedCrossRefGoogle Scholar
  12. 12.
    Barroso G, Menocal G, Felix H, Rojas-Ruiz JC, Arslan M, Oehninger S. Comparison of the efficacy of the aromatase inhibitor letrozole and clomiphene citrate as adjuvants to recombinant follicle-stimulating hormone in controlled ovarian hyperstimulation: a prospective, randomized, blinded clinical trial. Fertil Steril. 2006;86:1428–31. doi:10.1016/j.fertnstert.2006.03.044.PubMedCrossRefGoogle Scholar
  13. 13.
    Baysoy A, Serdaroglu H, Jamal H, Karatekeli E, Ozornek H, Attar E. Letrozole versus human menopausal gonadotrophin in women undergoing intrauterine insemination. Reprod Biomed Online. 2006;13:208–12.PubMedCrossRefGoogle Scholar
  14. 14.
    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. doi:10.1016/S0015-0282(00)01705-2.PubMedCrossRefGoogle Scholar
  15. 15.
    Badawy A, Mosbah A, Shady M. Anastrozole or letrozole for ovulation induction in clomiphene-resistant women with polycystic ovarian syndrome: a prospective randomized trial. Fertil Steril. 2008;89:1209–12. doi:10.1016/j.fertnstert.2007.05.010.PubMedCrossRefGoogle Scholar
  16. 16.
    Mattenberg C, Fondop JJ, Romoscanu I, Luyet C, Bianchi-Demicheli F, de Ziegler D. Use of aromatase inhibitors in infertile women. Gynecol Obstet Fertil. 2005;33:348–55. doi:10.1016/j.gyobfe.2005.03.026.PubMedCrossRefGoogle Scholar
  17. 17.
    Bedaiwy MA, Forman R, Mousa NA, Al Inany HG, Casper RF. Cost-effectiveness of aromatase inhibitor co-treatment for controlled ovarian stimulation. Hum Reprod. 2006;21:2838–44. doi:10.1093/humrep/del273.PubMedCrossRefGoogle Scholar
  18. 18.
    Jee BC, Ku SY, Suh CS, Kim KC, Lee WD, Kim SH. Use of letrozole versus clomiphene citrate combined with gonadotropins in intrauterine insemination cycles: a pilot study. Fertil Steril. 2006;85:1774–7. doi:10.1016/j.fertnstert.2006.02.070.PubMedCrossRefGoogle Scholar
  19. 19.
    Homburg R. Oral agents for ovulation-induction-clomiphene citrate versus aromatase inhibitors. Hum Fertil (Camb). 2008;11:17–22. doi:10.1080/14647270701689670.CrossRefGoogle Scholar
  20. 20.
    The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group Revised 2003 consensus on diagnostic criteria and long-term risks related to polycystic ovarian syndrome. Fertil Steril. 2004;81:19–25.Google Scholar
  21. 21.
    WHO. Laboratory manual for examination of human semen and sperm-cervical mucus interaction. 4th ed. Cambridge, UK: Cambridge University Press; 1999.Google Scholar
  22. 22.
    Begum MR, Ferdous J, Begum A, Quadir E. Comparison of efficacy of aromatase inhibitor and clomiphene citrate in induction of ovulation in polycystic ovarian syndrome. Fertil Steril. 2008;(Jan):3. PMID: 18177867.Google Scholar
  23. 23.
    Sh Tehrani Nejad E, Abediasl Z, Rashidi BH, Azimi Nekoo E, Shariat M. Amirchaghmaghi: Comparison of the efficacy of the aromatase inhibitor letrozole and clomiphen citrate gonadotropins in controlled ovarian hyperstimulation: a prospective, simply randomized, clinical trial. J Assist Reprod Genet. 2008;25:187–90. doi:10.1007/s10815-008-9209-2.PubMedCrossRefGoogle Scholar
  24. 24.
    Bayar U, Basaran M, Kiran S, Coskun A, Gezer S. Use of an aromatase inhibitor in patients with polycystic ovary syndrome: a prospective randomized trial. Fertil Steril. 2006;86:1447–51. doi:10.1016/j.fertnstert.2006.04.026.PubMedCrossRefGoogle Scholar
  25. 25.
    Bayar U, Tanriverdi HA, Barut A, Ayoğlu F, Ozcan O, Kaya E. Letrozole vs. clomiphene citrate in ovulatory infertility. Fertil Steril 2006;85:1045–9. doi:10.1016/j.fertnstert.2005.09.045.PubMedCrossRefGoogle Scholar
  26. 26.
    Al-Fozan H, Al-Khadouri M, Tan SL, Tulandi T. A randomized trial of letrozole versus clomiphene citrate in women undergoing superovulation. Fertil Steril. 2004;82:1561–3. doi:10.1016/j.fertnstert.2004.04.070.PubMedCrossRefGoogle Scholar
  27. 27.
    Homburg R. Clomiphene citrate—end of an era? a mini-review. Hum Reprod. 2005;20:2043–51. doi:10.1093/humrep/dei042.PubMedCrossRefGoogle Scholar
  28. 28.
    Dahan MH, Quintero RB, Urban R. A comparison of letrozole to gonadotropins for ovulation induction in subjects with advanced maternal age: a retrospective pilot study. Fertil Steril. 2007;(Nov):30. PMID: 18061174.Google Scholar
  29. 29.
    Tarlatzis BC, Grimbizis G. Future use of clomiphene in ovarian stimulation. Will clomiphene persist in the 21st century? Hum Reprod. 1998;13:2356–8. doi:10.1093/humrep/13.9.2356.Google Scholar
  30. 30.
    van Santbrink EJ, Eijkemans MJ, Laven JS, Fauser BC. Patient-tailored conventional ovulation induction algorithms in anovulatory infertility. Trends Endocrinol Metab. 2005;16:381–9. doi:10.1016/j.tem.2005.08.006.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Ashalatha Ganesh
    • 1
  • Sourendra Kant Goswami
    • 2
  • Ratna Chattopadhyay
    • 2
  • Koel Chaudhury
    • 1
  • Baidyanath Chakravarty
    • 2
  1. 1.School of Medical Science and TechnologyIndian Institute of TechnologyKharagpurIndia
  2. 2.Institute of Reproductive MedicineKolkataIndia

Personalised recommendations