Skip to main content

Advertisement

SpringerLink
Log in

Letrozole versus clomiphene citrate in polycystic ovary syndrome: a meta-analysis of randomized controlled trials

  • Review
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Polycystic ovary syndrome (PCOS) is a common endocrine disturbance affecting women in the reproductive age group. The present study aimed to compare the effects of letrozole (LE) and clomiphene citrate (CC) for ovulation induction in women with PCOS.

Methods

The PUBMED, Web of Science, and EMBASE databases were screened systematically for randomized controlled trials (RCTs) published from database inception to July 2017.

Results

Eleven RCTs involving 2255 patients were included, and data were independently extracted and analyzed using 95% risk ratios (RRs) and confidence intervals (CIs) based on a random- or fixed-effect model (as appropriate). Meta-analyses of nine RCTs comparing LE and CC ovulation induction, followed by timed intercourse, indicated that the former significantly increased the ovulation rate (RR = 1.18; 95% CI 1.03–1.36, P = 0.01), pregnancy rate (RR = 1.34; 95% CI 1.09–1.64, P = 0.006), and live birth rate (RR = 1.55; 95% CI 1.28–1.88, P < 0.00001). However, LE and CC did not differ significantly in terms of the multiple pregnancy and abortion rates. Furthermore, LE for ovulation induction significantly improved the pregnancy rate after IUI.

Conclusion

LE is superior to CC for ovulation induction in patients with PCOS.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Solomon CG (1999) The epidemiology of polycystic ovary syndrome. Prevalence and associated disease risks. Endocrinol Metab Clin N Am 28:247–263

    Article  CAS  Google Scholar 

  2. Nestler JE (2016) Polycystic ovary syndrome. N Engl J Med 375:1398. https://doi.org/10.1056/NEJMc1610000.10.1056/NEJMc1610000#SA2

    PubMed  Google Scholar 

  3. Fauser BC, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, Carmina E, Chang J, Yildiz BO, Laven JS, Boivin J, Petraglia F, Wijeyeratne CN, Norman RJ, Dunaif A, Franks S, Wild RA, Dumesic D, Barnhart K (2012) Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril 97(28–38):e25. https://doi.org/10.1016/j.fertnstert.2011.09.024

    Google Scholar 

  4. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO (2004) The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 89:2745–2749. https://doi.org/10.1210/jc.2003-032046

    Article  CAS  PubMed  Google Scholar 

  5. Young SL, Opsahl MS, Fritz MA (1999) Serum concentrations of enclomiphene and zuclomiphene across consecutive cycles of clomiphene citrate therapy in anovulatory infertile women. Fertil Steril 71:639–644

    Article  CAS  PubMed  Google Scholar 

  6. Randall JM, Templeton A (1991) Cervical mucus score and in vitro sperm mucus interaction in spontaneous and clomiphene citrate cycles. Fertil Steril 56:465–468

    Article  CAS  PubMed  Google Scholar 

  7. Gonen Y, Casper RF (1990) Sonographic determination of a possible adverse effect of clomiphene citrate on endometrial growth. Hum Reprod 5:670–674

    Article  CAS  PubMed  Google Scholar 

  8. Al-Fozan H, Al-Khadouri M, Tan SL, Tulandi T (2004) A randomized trial of letrozole versus clomiphene citrate in women undergoing superovulation. Fertil Steril 82:1561–1563. https://doi.org/10.1016/j.fertnstert.2004.04.070

    Article  CAS  PubMed  Google Scholar 

  9. Nakamura Y, Ono M, Yoshida Y, Sugino N, Ueda K, Kato H (1997) Effects of clomiphene citrate on the endometrial thickness and echogenic pattern of the endometrium. Fertil Steril 67:256–260. https://doi.org/10.1016/s0015-0282(97)81907-3

    Article  CAS  PubMed  Google Scholar 

  10. Franks S, Adams J, Mason H, Polson D (1985) Ovulatory disorders in women with polycystic ovary syndrome. Clin Obstet Gynaecol 12:605–632

    CAS  PubMed  Google Scholar 

  11. Pfister CU, Martoni A, Zamagni C, Lelli G, De Braud F, Souppart C, Duval M, Hornberger U (2001) Effect of age and single versus multiple dose pharmacokinetics of letrozole (Femara) in breast cancer patients. Biopharm Drug Dispos 22:191–197

    Article  CAS  PubMed  Google Scholar 

  12. Kar S (2012) Clomiphene citrate or letrozole as first-line ovulation induction drug in infertile PCOS women: a prospective randomized trial. J Hum Reprod Sci 5:262–265. https://doi.org/10.4103/0974-1208.106338

    Article  PubMed  PubMed Central  Google Scholar 

  13. Atay V, Cam C, Muhcu M, Cam M, Karateke A (2006) Comparison of letrozole and clomiphene citrate in women with polycystic ovaries undergoing ovarian stimulation. J Int Med Res 34:73–76. https://doi.org/10.1177/147323000603400109

    Article  CAS  PubMed  Google Scholar 

  14. Mitwally MF, Casper RF (2001) Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril 75:305–309

    Article  CAS  PubMed  Google Scholar 

  15. Roy KK, Baruah J, Singla S, Sharma JB, Singh N, Jain SK, Goyal M (2012) A prospective randomized trial comparing the efficacy of letrozole and clomiphene citrate in induction of ovulation in polycystic ovarian syndrome. J Hum Reprod Sci 5:20–25. https://doi.org/10.4103/0974-1208.97789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sharief M, Nafee NR (2015) Comparison of letrozole and clomiphene citrate in women with polycystic ovaries undergoing ovarian stimulation. J Pak Med Assoc 65:1149–1152

    PubMed  Google Scholar 

  17. Misso ML, Wong JL, Teede HJ, Hart R, Rombauts L, Melder AM, Norman RJ, Costello MF (2012) Aromatase inhibitors for PCOS: a systematic review and meta-analysis. Hum Reprod Update 18:301–312. https://doi.org/10.1093/humupd/dms003

    Article  CAS  PubMed  Google Scholar 

  18. Ganesh A, Goswami SK, Chattopadhyay R, Chaudhury K, Chakravarty B (2009) 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. J Assist Reprod Genet 26:19–24. https://doi.org/10.1007/s10815-008-9284-4

    Article  PubMed  PubMed Central  Google Scholar 

  19. Badawy A, Abdel Aal I, Abulatta M (2009) Clomiphene citrate or letrozole for ovulation induction in women with polycystic ovarian syndrome: a prospective randomized trial. Fertil Steril 92:849–852. https://doi.org/10.1016/j.fertnstert.2007.02.062

    Article  CAS  PubMed  Google Scholar 

  20. Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928. https://doi.org/10.1136/bmj.d5928

    Article  PubMed  PubMed Central  Google Scholar 

  21. Bayar U, Basaran M, Kiran S, Coskun A, Gezer S (2006) Use of an aromatase inhibitor in patients with polycystic ovary syndrome: a prospective randomized trial. Fertil Steril 86:1447–1451. https://doi.org/10.1016/j.fertnstert.2006.04.026

    Article  CAS  PubMed  Google Scholar 

  22. Legro RS, Brzyski RG, Diamond MP, Coutifaris C, Schlaff WD, Casson P, Christman GM, Huang H, Yan Q, Alvero R, Haisenleder DJ, Barnhart KT, Bates GW, Usadi R, Lucidi S, Baker V, Trussell JC, Krawetz SA, Snyder P, Ohl D, Santoro N, Eisenberg E, Zhang H (2014) Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med 371:119–129. https://doi.org/10.1056/NEJMoa1313517

    Article  PubMed  PubMed Central  Google Scholar 

  23. Liu C, Feng G, Huang W, Wang Q, Yang S, Tan J, Fu J, Liu D (2017) Comparison of clomiphene citrate and letrozole for ovulation induction in women with polycystic ovary syndrome: a prospective randomized trial. Gynecol Endocrinol. https://doi.org/10.1080/09513590.2017.1332174

    Google Scholar 

  24. Banerjee Ray P, Ray A, Chakraborti PS (2012) Comparison of efficacy of letrozole and clomiphene citrate in ovulation induction in Indian women with polycystic ovarian syndrome. Arch Gynecol Obstet 285:873–877. https://doi.org/10.1007/s00404-011-2091-7

    Article  CAS  PubMed  Google Scholar 

  25. Ghahiri A, Mogharehabed N, Mamourian M (2010) Letrozole as the first-line treatment of infertile women with poly cystic ovarian syndrome (PCOS) compared with clomiphene citrate: a clinical trial. Adv Biomed Res 5:6. https://doi.org/10.4103/2277-9175.175237

    Google Scholar 

  26. Zeinalzadeh M, Basirat Z, Esmailpour M (2010) Efficacy of letrozole in ovulation induction compared to that of clomiphene citrate in patients with polycystic ovarian syndrome. J Reprod Med 55:36–40

    CAS  PubMed  Google Scholar 

  27. Dehbashi S, Dehbashi S, Kazerooni T, Robati M, Alborzi S, Parsanezhad ME, Shadman A (2009) Comparison of the effects of letrozole and clomiphene citrate on ovulation and pregnancy rate in patients with polycystic ovary syndrome. Iran J Med Sci 34:23–28

    Google Scholar 

  28. Roque M, Tostes AC, Valle M, Sampaio M, Geber S (2015) Letrozole versus clomiphene citrate in polycystic ovary syndrome: systematic review and meta-analysis. Gynecol Endocrinol 31:917–921. https://doi.org/10.3109/09513590.2015.1096337

    Article  CAS  PubMed  Google Scholar 

  29. Franik S, Kremer JA, Nelen WL, Farquhar C, Marjoribanks J (2015) Aromatase inhibitors for subfertile women with polycystic ovary syndrome: summary of a Cochrane review. Fertil Steril 103:353–355. https://doi.org/10.1016/j.fertnstert.2014.10.016

    Article  CAS  PubMed  Google Scholar 

  30. Begum MR, Ferdous J, Begum A, Quadir E (2009) Comparison of efficacy of aromatase inhibitor and clomiphene citrate in induction of ovulation in polycystic ovarian syndrome. Fertil Steril 92:853–857. https://doi.org/10.1016/j.fertnstert.2007.08.044

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant no. 81671507), Fundamental Research Funds for the Central Universities (HUST; Grant no. 2015ZDTD050), and National Key Research and Development Program (Grant no. 2016YFC1000903).

Author information

Author notes

  1. Shifu Hu and Qiong Yu contributed equally to this work.

Authors and Affiliations

  1. Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan, 430030, Hubei, China

    Shifu Hu, Yingying Wang, Mei Wang, Wei Xia & Changhong Zhu

  2. Reproductive Medicine Center, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China

    Qiong Yu

  3. Reproductive Medicine Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China

    Wei Xia & Changhong Zhu

Authors
  1. Shifu Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qiong Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yingying Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wei Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Changhong Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SH, first author: project development, data collection, data analysis, and manuscript writing. QY, co-first author: project development, data collection, statistical analysis. YW and MW: data collection. WX, corresponding author: manuscript editing. CZ, co-corresponding author: manuscript editing.

Corresponding authors

Correspondence to Wei Xia or Changhong Zhu.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hu, S., Yu, Q., Wang, Y. et al. Letrozole versus clomiphene citrate in polycystic ovary syndrome: a meta-analysis of randomized controlled trials. Arch Gynecol Obstet 297, 1081–1088 (2018). https://doi.org/10.1007/s00404-018-4688-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-018-4688-6

Keywords

Search

Navigation