Efficacy of letrozole versus clomiphene citrate for infertile women with polycystic ovary syndrome

Sinan S. Ay, Özer Birge, Mehmet S. Bakır, Ayşe E. Yumru


Background: The aim was to compare ovulation induction protocols in anovulatory patients, who make up a significant percentage of infertility patients, and to determine the most appropriate treatment for patients in the clinic based on the findings.

Methods: The effectiveness of clomiphene citrate (CC) and letrozole (aromatase inhibitor) in ovulation induction treatments were retrospectively compared in patients who applied for infertility in the last 5 years and were found to be anovulatory. 20 of these patients were being treated with clomiphene citrate, while the 18 were being treated with letrozole.

Results: The study included a total of 38 anovulatory infertile patients. The mean age of the patients was found to be 29.3. When the endometrial thicknesses (ET) after the treatment were compared, the first group's mean EC was 6.1, while that of the second group was 9.05. The endometrial thicknesses measured after the treatments were found to be significantly different, which were consistent with other studies in the literature. Post-treatment ovulation responses were similar with 55% in both groups. In the evaluation of pregnancy outcomes, 20% of pregnancy was achieved in the first group and 33% in the second group.

Conclusions: The use of letrozole, an aromatase inhibitor, may be suggested as an alternative to CC in the ovulation induction protocol in our clinical practice, particularly in obese patients.


Infertility, Polycystic ovary syndrome, Anovulation, Letrozole, Clomiphene citrate

Full Text:



Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81:19-25.

Legro RS, Barnhart HX, Schlaff WD. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007;356:551-66.

Kamphuis EI, Bhattacharya S, van der Veen F, Mol BW, Templeton A. Are we overusing IVF? BMJ. 2014;348:252.

Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Fertil Steril. 2008;89:505-22.

Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea, and subfertility. Cochrane Database Syst Rev. 2012;5:CD003053.

Casper RF, Mitwally MF. Review: aromatase inhibitors for ovulation induction. J Clin Endocrinol Metab. 2006;91:760-71.

Tulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari J, et al. Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril. 2006;85(6):1761-5.

Forman R, Gill S, Moretti M, Tulandi T, Koren G, Casper R. Fetal Safety of Letrozole and Clomiphene Citrate for Ovulation Induction. J Obstet Gynaecol Can. 2007;29(8):668-71.

Legro RS, Brzyski RG, Diamond MP. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014;371(2):119-29.

Bansal S, Goyal M, Sharma C, Shekhar S. Letrozole versus clomiphene citrate for ovulation induction in anovulatory women with polycystic ovarian syndrome: A randomized controlled trial. Int J Gynaecol Obstet. 2021;152(3):345-50.

ACOG Committee on Practice Bulletins-Gynecology. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists number 34, February 2002. Management of infertility caused by ovulatory dysfunction. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2002;99(2):347-58.

Joham AE, Teede HJ, Ranasinha S, Zoungas S, Boyle J. Prevalence of infertility and use of fertility treatment in women with polycystic ovary syndrome: data from a large community-based cohort study. J Women's Health (Larchmt). 2015;24(4):299-307.

Roy KK, Baruah J, Singla S, Sharma JB, Singh N, Jain SK, et al. A prospective randomized trial comparing the efficacy of Letrozole and Clomiphene citrate in induction of ovulation in polycystic ovarian syndrome. J Hum Reprod Sci. 2012;5(1):20-5.

Dewailly D. Diagnostic criteria for PCOS: Is there a need for a rethink? Best Pract Res Clin Obstet Gynaecol. 2016;37:5-11.

Kiddy DS, Hamilton-Fairley D, Bush A, Short F, Anyaoku V, Reed MJ, Franks S. Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Clin Endocrinol. 1992;36:105-11.

Dickey RP, Taylor SN, Curole DN, Rye PH, Lu PY, Pyrzak R. Relationship of clomiphene dose and patient weight to successful treatment. Hum Reprod. 1997;12:449-53.

Sturrock ND, Lannon B, Fay TN. Metformin does not enhance ovulation induction in clomiphene-resistant polycystic ovary syndrome in clinical practice. Br J Clin Pharmacol. 2002;53:469-73.

Sharief M, Nafee NR, Comparison of letrozole and clomiphene citrate in women with polycystic ovaries undergoing ovarian stimulation, J Pak Med Assoc. 2015;65(11):1149-52.

Fleming R, Hopkinson ZE, Wallace AM, Greer IA, Sattar N. Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial. J Clin Endocrinol Metab. 2002;87:569-74.

Liu C, Feng G, Huang W, Wang Q, Yang S, Tan J, Fu J, Liu D. Gynecol Endocrinol. 2017:1-5.

Dehbashi S, Kazerooni T, Robati M, Alborzi S, Parsanezhad ME, et al. Comparison of the effects of letrozole and clomiphene citrate on ovulation and pregnancy rate in patients with polycystic ovary syndrome. Iranian J Med Sci. 2009;34:23-8.

Najafi PZ, Noghabi SP, Afzali N, Mohammadzadeh S. Comparing the effect of clomiphene citrate and letrozole on ovulation induction in infertile women with polycystic ovary syndrome. J Pak Med Assoc. 2020;70(2):268-71.

Zadehmodares S, Niyakan M, Sharafy SA, Yazdi MH, Jahed F. Comparison of treatment outcomes of infertile women by clomiphene citrate and letrozole with gonadotropins underwent intrauterine insemination. Acta Med Iran. 2012;50(1):18-20.

Nanbakhsh F, Hagishafieha M, Tabatabe E, Mazloomi P, Oshnouei S. A Comparıson Of Effects Of Admınısterıng Letrezol And Chlomıphen Cıtrate On Infertılıty Treatment Outcomes In Patıents Wıth Polysıstıc Ovarıan Syndrome. J Urmia Univer Med Sci. 2013;24:543-9.

El Bigawy AF, Fouda UM, Wahab HA. A randomized trial of letrozole versus clomiphene citrate in induction of ovulation in patients with polycystic ovary syndrome (PCOS). Middle East fertility society J. 2008;13:52-6.

Abu Hashim H. Aromatase Inhibitors for Endometriosis-Associated Infertility; Do We Have Sufficient Evidence? İnt J Fertil Steril. 2016;10(3):270-7.

Sakar MN, Oglak SC. Letrozole is superior to clomiphene citrate in ovulation induction in patients with polycystic ovary syndrome. Pak J Med Sci. 2020;36(7):1460-5.