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Aromatase inhibitors for subfertile women with polycystic ovary syndrome

  1. Sebastian Franik1,*,
  2. Jan AM Kremer2,
  3. Willianne LDM Nelen3,
  4. Cindy Farquhar4

Editorial Group: Cochrane Gynaecology and Fertility Group

Published Online: 24 FEB 2014

DOI: 10.1002/14651858.CD010287.pub2


How to Cite

Franik S, Kremer JAM, Nelen WLDM, Farquhar C. Aromatase inhibitors for subfertile women with polycystic ovary syndrome. Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No.: CD010287. DOI: 10.1002/14651858.CD010287.pub2.

Author Information

  1. 1

    Radboud University Nijmegen, Faculty of Medical School, Nijmegen, Netherlands

  2. 2

    Radboud University Nijmegen Medical Center, Department of Obstetrics and Gynaecology, Nijmegen, Netherlands

  3. 3

    Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

  4. 4

    University of Auckland, Department of Obstetrics and Gynaecology, Auckland, New Zealand

*Sebastian Franik, Faculty of Medical School, Radboud University Nijmegen, Geert Grooteplein 9, PO Box 9101, Nijmegen, 6500HB, Netherlands. S.Franik@gmx.de.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 24 FEB 2014

SEARCH

References

References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
Abdellah 2011 {published data only}
  • Abdellah MS. Reproductive outcome after letrozole versus laparoscopic ovarian drilling for clomiphene-resistant polycystic ovary syndrome. International Journal of Gynecology and Obstetrics 2011;113:218-21.
Abu Hashim June 2010 {published data only}
  • Abu Hashim H, Mashaly AM, Badawy A. Letrozole versus laparoscopic ovarian diathermy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial. Archives of Gynecology and Obstetrics 2010;282:567-71.
Abu Hashim Sept 2010 {published data only}
  • Abu Hashim H, Shokeir T, Badawy A. Letrozole versus combined metformin and clomiphene citrate for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial. Fertility and Sterility 2010;94:1405-9.
Al-Omari 2004 {published data only}
  • Al-Omari WR, Sulaiman WR, Al-Hadithi N. Comparison of two aromatase inhibitors in women with clomiphene-resistant polycystic ovary syndrome. International Journal of Gynecology & Obstetrics 2004;85:289-91.
Atay 2006 {published data only}
  • Atay V, Cam C, Muhcu M, Cam M, Karateke A. Comparison of letrozole and clomiphene citrate in women with polycystic ovaries undergoing ovarian stimulation. Journal of International Medical Research 2006;34:73-6.
Badawy 2008 {published data only}
  • Badawy A, Mosbah A, Shady M. Anastrozole or letrozole for ovulation induction in clomiphene-resistant women with polycystic ovarian syndrome: a prospective randomized trial. Fertility and Sterility 2008;89:1209-12.
Badawy July 2009 {published data only}
  • Badawy A, Mosbah A, Tharwat A, Eid M. Extended letrozole therapy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a novel protocol. Fertility and Sterility 2009;92:236-9.
Badawy Sept 2009 {published and unpublished data}
  • Badawy A, Abdel Aal I, Abulatta M. Clomiphene citrate or letrozole for ovulation induction in women with polycystic ovarian syndrome: a prospective randomized trial. Fertility and Sterility 2009;92:849-52.
Bayar 2006 {published data only}
  • 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. Fertility and Sterility 2006;86:1447-51.
Begum 2009 {published and unpublished data}
  • 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. Fertility and Sterility 2009;92:853-7.
Davar 2011 {published data only}
  • Davar R, Javedani M, Fallahzadeh MH. Metformin-letrozole in comparison with Metformin-clomiphene citrate in clomiphene-resistance PCOS patients undergoing IUI. Iranian Journal of Reproductive Medicine 2011;9:31-6.
Dehbashi 2009 {published data only}
  • Dehbashi S, Kazerooni T, Robati M, Alborzi S, Parsanezhad ME, Shadman A. Comparison of the effects of letrozole and clomiphene citrate on ovulation and pregnancy rate in patients with polycystic ovary syndrome. Iranian Journal of Medical Sciences 2009;34:23-8.
Elgafor 2013 {published data only}
Foroozanfard 2011 {published data only}
  • Foroozanfard F, Mahdian M, Mousavi Gl, Pejmanmanesh M, Soleimani A. Use of letrozole versus clomiphene citrate combined with gonadotropins in patients with clomiphene resistant polycystic ovarian syndrome: A comparative study. Pakistan Journal of Medical Sciences 2011;27:967-70.
Ganesh 2009 {published data only}
  • Ganesh A, Goswami SK, Chattopadhyay R, Chaudhury K, Chakravarty B. 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. Journal of assisted reproduction and genetics 2009. Journal of assisted reproduction and genetics 2009;26(1):19-24.
Kamath 2010 {published and unpublished data}
  • Kamath MS, Aleyamma TK, Chandy A, George K. Aromatase inhibitors in women with clomiphene citrate resistance: a randomized, double-blind, placebo-controlled trial. Fertility and Sterility 2010;94:2857-9.
Kar 2012 {published data only}
  • Kar S. Clomiphene citrate or letrozole as first-line ovulation induction drug in infertile PCOS women: A prospective randomized trial. Journal of Human Reproductive Sciences 2012;5(3):262-265. [DOI: 10.4103/0974-1208.106338]
Legro 2014 {published and unpublished data}
  • Legro RS, Brzyski RG, Diamond MP, Coutifaris C, Schlaff WD et al for the NICHD Reproductive Medicine Network. Letrozole versus clomiphene for infertility in the polycycstic ovary syndrome. NEJM 2014;371(2):119-29.
  • Legro RS, Kunselman AR, Brzyski RG, Casson PR, Diamond MP, Schlaff WD, Christman GM, Coutifaris C, Taylor HS, Eisenberg E, Santoro N, Zhang H. Effect of Letrozole versus Clomiphene on live birth in women with anovulatory infertility due to Polycystic Ovary Syndrome (PCOS): A randomized double-blind multi-center trial. ASRM 2013 conference abstract 2013:S51.
Nazik 2012 {published data only}
  • Nazik H, Kumtepe Y. Comparison of efficacy of letrozole and clomiphene citrate in ovulation induction for women with polycystic ovarian syndrome. HealthMED 2012;6:879-83.
Ramezanzadeh 2011 {published data only}
  • Ramezanzadeh F, Nasiri R, Yazdi MS, Baghrei M. A randomized trial of ovulation induction with two different doses of Letrozole in women with PCOS. Archives of Gynecology and Obstetrics 2011;284(4):1029-34.
Ray 2012 {published data only}
  • Ray PB, Ray A, Chakraborti PS. Comparison of efficacy of letrozole and clomiphene citrate in ovulation induction in Indian women with polycystic ovarian syndrome. Archives of Gynecology and Obstetrics 2012;285(3):873-7.
Roy 2012 {published data only}
  • Roy K, Baruah J, Singla S, Sharma JB, Singh N, Jain SK, Goyal M. A prospective randomized trial comparing the efficacy of Letrozole and Clomiphene citrate in induction of ovulation in polycystic ovarian syndrome. Journal of Human Reproductive Sciences 2012;5:20-5.
Selim 2012 {published data only}
  • Selim MF, Borg TF. Letrozole and Clomiphene Citrate Effect on Endometrialand Subendometrial Vascularity in Treating Infertilityin Women with Polycystic Ovary Syndrome. Journal of Gynaecologic Surgery 2012;28(6):405-410. [DOI: 10.1089/gyn.2012.0033]
Sh-El-Arab Elsedeek 2011 {published data only}
  • Sheikh-El-Arab Elsedeek M, Elmaghraby HAH. Predictors and characteristics of letrozole induced ovulation in comparison with clomiphene induced ovulation in anovulatory PCOS women. Middle East Fertility Society Journal 2011;16:125-30.
Sohrabvand 2006 {published data only}
  • Sohrabvand F, Ansari SH, Bagheri M. Efficacy of combined metformin-letrozole in comparison with metformin-clomiphene citrate in clomiphene-resistant infertile women with polycystic ovarian disease. Human Reproduction 2006;21:1432-5.
Zeinalzadeh 2010 {published data only}
  • Zeinalzadeh M, Basirat Z, Esmailpour M. Efficacy of letrozole in ovulation induction compared to that of clomiphene citrate in patients with polycystic ovarian syndrome. The Journal of reproductive medicine 2010;55:36-40.

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
Angel 2014 {published data only}
  • Angel M, Ghose S, Gowda M. A randomized trial comparing the ovulation induction efficacy of clomiphene citrate and letrozole. Journal of Natural Science Biology & Medicine 2014;5(2):450-452.
Anwary 2012 {published data only}
  • Anwary SA, Alfazzaman M, Bar, N, Islam MR. Outcome of Metformin Treatment in Polycystic Ovary Syndrome. Mymensingh Medical Journal 2012;21(1):60-65.
Azargoon 2012 {published data only}
  • Azargoon A, Toussy JA, Darbanan FF. Pregnancies following the use of sequential treatment of metformin and incremental doses of letrozole in clomiphene-resistant women with polycystic ovary syndrome. Iranian Journal of Reproductive Medicine 2012;10(1):33-40.
Badawy 2009 {published data only}
  • Badawy A, Abdel Aal I, Abulatta M. Clomiphene citrate or anastrozole for ovulation induction in women with polycystic ovary syndrome? A prospective controlled trial. Fertility and Sterility 2009;92:860-3.
Baruah 2009 {published data only}
  • Baruah J, Roy KK, Rahman SM, Kumar S, Sharma JB, Karmakar D. Endometrial effects of letrozole and clomiphene citrate in women with polycystic ovary syndrome using spiral artery Doppler. Archives of Gynecology & Obstetrics 2009;279:311-4.
Bigawy 2008 {published data only}
  • El Bigawy AF, Fouda UMF, Wahab HAE. A randomized trial of letrozole versus clomiphene citrate in induction of ovulation in patients with polycystic ovary syndrome (PCOS). Middle East Fertility Society Journal 2008;13:52-6.
Foroozanfard 2013 {published data only}
  • Foroozanfard F, Saberi H, Moravvegi A, Kazemi M. Pregnancy rate following luteal phase support in polycystic ovarian syndrome using combination therapies for ovulation induction: A randomized clinical trial.. Conference abstracts: 29th Annual Meeting of the European Society of Human Reproduction and Embryology. June 2013.
Mittal 2004 {published data only}
  • Mittal S, Kamthane VP, Goswami SK, Ghosh S, Chakravarty BN. Comparative evaluation of different stimulation protocols in CC resistant P.C.O women undergoing IUI. Abstracts of the 20th Annual Meeting of the ESHRE, Berlin, Germany, 27-30 June 2004. 2004:i122.
Nahid 2012 {published data only}
  • Nahid L, Sirous K. Comparison of the effects of letrozole and clomiphene citrate for ovulation induction in infertile women with polycystic ovary syndrome. Minerva Ginecologica 2012;64:253-8.
Ozdemir 2013 {published data only}
  • Ozdemir U, Ozaksit G, Cakir Gungor AN, Aydogan M. Letrozole usage adjuvant to gonadotropins for ovulation induction for patients with clomiphene citrate failure. Archives of Gynecology and Obstetrics 2013;288(2):445-448.
Yang 2008 {published data only}
  • Yang M, Quan S, Li H, Song Y, Xing F. Effect of two different doses of letrozole in promoting ovulation in infertile women with polycystic ovarian syndrome. Journal of Southern Medical University 2008;28(11):2060-2062.

References to studies awaiting assessment

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
Aygen 2007 {published data only}
  • Aygen EM, Guzel Z, Ozgun T, Atakul T, Sahin Y. [The use of letrozole for ovulation induction in infertile women with polycystic ovarian syndrome]. Erciyes Tip Dergisi 2007;29:195-200.
Hazlina 2012 {published data only}
  • Study On The Effects of Letrozole And Clomiphene Citrate For Induction of Ovulation In Polycystic Ovarian Syndrome(PCOS). https://clinicaltrials.gov/ct2/show/NCT01577017?term=ovulation+induction+and+aromatase&rank=1.
Lorzadeh 2011 {published data only}
  • Lorzadeh N, Kazemirad S, Mohammadi Z. Comparison of effects letrozole and clomiphene citrate for ovulation induction in women with polycystic ovary syndrome. Iranian Journal of Obstetrics, Gynecology and Infertility 2011;14.(3):13-19.
Parihar 2008 {published data only}
  • Parihar. An Open, Randomized, Parallel-Group, Multicentric, Comparative Study of Letrozole With Clomiphene Citrate for Induction of Ovulation in Anovulatory Infertility.. https://clinicaltrials.gov/ct2/show/NCT00610077?term=ovulation+induction+and+aromatase&rank=8. [NCT00610077]
Safdarian 2012 {published data only}
  • Safdarian L, Dibazar NS, Ahmadzadeh A, Yekta BG. Comparing two ovulation induction methods by brachial artery ultrasonography in infertile women with polycystic ovary syndrome. Tehran University Medical Journal 2012;70:242-9.
Sharma 2010 {published data only}
  • Sharma S, Goswami SK, Rajani S, et al. Effcacy of letrozole-gonadotropin, clomiphene-gonadotropin and only gonadotropin in clomiphene and letrozole resistant PCOS women undergoing IUI. Human Reproduction 2010;25 suppl 1:i46.
Shirin 2009 {published data only}
  • Shirin G, Mehran A, Maryam B, Maryam G, Masoumeh M. Comparing the effects of clomiphene-HMG and letrozole-HMG on ovulation Induction in infertile women. Journal of Reproduction and Infertility 2009;10:156.

References to ongoing studies

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
Ali 2012 {published data only}
  • Letrozole or combined clomiphene citrate metformin as a first line treatment in women with polycystic ovary syndrome (PCO). Ongoing study January 2009.
Amer 2007 {published data only}
  • Letrozole versus clomiphene citrate for Ovulation induction. Ongoing study 2007.
Feng 2011 {published data only}
  • the ovulation-induced therapy for polycystic ovary syndrome. Ongoing study 2011.
Ghanem 2013 {published data only}
  • Clomiphene Citrate Plus HPuFSH Versus Letrozole Plus HPuFSH in Clomid Resistant Infertile PCOS Women. Ongoing study March 2013.
Hou 2011 {published data only}
  • Letrozole Versus Chinese Herbal Compound on Polycystic Ovary Syndrome. Ongoing study September 2011.
Li 2013 {published data only}
  • Letrozole and Berberine in Infertile PCOS Patients. Ongoing study October 2009.
Philihawadana 2008 {published data only}
  • A study on anti-eostrogen clomifene citrate and aromatase inhibitor letrozole in induction of ovulation, in WHO group II anovulatory subjects, and in augmentation of ovulation in ovulatory infertility. Ongoing study 2008.
Sarvi 2010 {published data only}
  • The effect of metformin in different phenotypes of poly cystic ovary syndrome according to Rotterdam criteria criteria. Ongoing study 2010.

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to studies awaiting assessment
  4. References to ongoing studies
  5. Additional references
Abu 2012
  • Abu Hashim H. Clomiphene citrate alternatives for the initial management of polycystic ovary syndrome: an evidence-based approach. Archives of Gynecology and Obstetrics 2012;285:1737-45.
Azziz 2009
  • Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF, Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen Excess and PCOS Society. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertility and Sterility 2009;91(2):456. [PUBMED: 18950759]
Biljan 2005
  • Biljan, MM, Hemmings, R, Brassard, N. The Outcome of 150 Babies Following the Treatment With Letrozole or Letrozole and Gonadotropins. Fertility and Sterility 2005;84:95.
Brown 2009
Casper 2006
Casper 2011
Cole 1990
Farquhar 2002
  • Farquhar, CM, Williamson, K, Gudex, G, Johnson, NP, Garland, J, Sadler, L. A randomized controlled trial of laparoscopic ovarian diathermy versus gonadotropin therapy for women with clomiphene citrate-resistant polycystic ovary syndrome. Fertility and Sterility 2002;78(2):404.
Farquhar 2012
Forman 2007
  • Forman R, Gill S, Moretti M, Tulandi T, Koren G, Casper R. Fetal safety of letrozole and clomiphene citrate for ovulation induction.. Journal of obstetrics and gynaecology Canada 2007;29(8):668.
Higgins 2011
  • Julian PT Higgins, Sally Green. Cochrane Handbook for Systematic Reviews of Interventions. Vol. 5.1.0, The Cochrane Collaboration, March 2011.
Jirge 2010
  • Jirge PR, Patil RS. Comparison of endocrine and ultrasound profiles during ovulation induction with clomiphene citrate and letrozole in ovulatory volunteer women. Fertility and Sterility 2010;93:174-83.
Lee 2011
Lunenfeld 2004
Misso 2012
  • Misso ML, Wong JLA, Teede HJ, Hart R, Rombauts L, Melder AM Norman RJ, Costello MF. Aromatase inhibitors for PCOS: a systematic review and meta-analysis. Human Reproduction Update 2012;18(3):301-312.
Mitwally 2001
Reproductive Medicine Network 2013
  • Letrozole versus clomiphene citrate in anovulatory PCOS women: A cost-effectiveness analysis.. Conference Abstract: International Federation of Fertility Societies 21st World Congress on Fertility and Sterility and the 69th Annual Meeting of the American Society for Reproductive Medicine, IFFS-ASRM 2013 Boston, MA United States.
Rotterdam 2003
  • Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Human Reproduction 2004;19(1):41.
Samani 2009
  • Samani FG, Farzadi L, Nezami N, Tarzamni MK, Soleimani F. Endometrial and follicular development following letrozole intervention in unexplained infertile patients failed to get pregnant with clomiphene citrate. Archives of Gynecology and Obstetrics 2009;280:201-5.
Tulandi 2006
  • Tulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari J, Librach C, Greenblatt E, Casper RF. Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertility and Sterility 2006;85(6):1761.
Velázquez 1997
White 1996
  • White DM, Polson DW, Kiddy D, Sagle P, Watson H, Gilling-Smith C, Hamilton-Fairley D, Franks S. Induction of ovulation with low-dose gonadotropins in polycystic ovary syndrome: an analysis of 109 pregnancies in 225 women. Journal of Clinical Endocrinology and Metabolism 1996;81(11):3821.
Zawadski 1992
  • Zawadski JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: Towards a rational approach. Polycystic Ovary Syndrome (Current Issues in Endocrinology and Metabolism), Dunaif A, Givens JR, Haseltine FP, Merriam GE (Eds), Blackwell Scientific Inc., Boston 1992:377.