Clomiphene versus letrozole: a better agent for ovulation induction

Aritra Maji, Manisha V. Ramani, Kajal Kiran


Background: Anovulatory dysfunction is a commonly encountered problem which is responsible for about 40% of female infertility. One of the leading causes of female infertility is polycystic ovarian syndrome (PCOS). Clomiphene citrate has been the drug of choice in treating women with anovulatory infertility. However, in recent years, letrozole, an aromatase inhibitor, has emerged as alternative ovulation induction agent. Aim of this study was to compare efficacy of clomiphene citrate and letrozole as first line therapy for ovulation induction in polycystic ovarian syndrome.

Methods: This study was a hospital based prospective comparative study done in MVJ MC and RH involving 100 females suffering from infertility due to anovulation. They were divided into 2 groups of 50 each. One group was given clomiphene citrate 50 mg while another group was given letrozole 2.5 mg from day 3 to day 7 of menstrual cycle. Ultrasonographic follicular monitoring was done and injection beta HCG 5000 IU was given once follicle reached optimum size (≥18 mm) and endometrial thickness was adequate (≥7 mm). Patients were advised for timed intercourse after 24-36 hours of HCG administration. Ovulation was detected by sonographic findings of follicular rupture done after 48 hours. Primary outcomes measured were number of growing follicles (≥18 mm), endometrial thickness, ovulation rate and pregnancy rate.

Results: In our study there was significant difference in the outcomes of ovulation induction between letrozole group and clomiphene group.  Women who received letrozole showed improved endometrial growth (8.44 mm versus 7.86 mm), ovulation rate (72% versus 56%) and pregnancy rate (22.2% versus 14.3%) than those who received clomiphene. However, variation in follicular growth was negligible between the two groups (1.28 versus 1.36).

Conclusions: Letrozole is a superior alternative to clomiphene citrate for ovulation induction in cases of PCOS with anovulatory menstrual cycle, and can be considered as first-line therapy for ovulation induction in such women.


Clomiphene citrate, Letrozole, Ovulation induction

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The 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.

Saxena P, Prakash A, Nigam A, Mishra A. Polycystic ovary syndrome: Is obesity a sine qua non? A clinical, hormonal, and metabolic assessment in relation to body mass index. Indian J Endocrinol Metab. 2012;16:996-9.

Gorlitsky GA, Kase NG, Speroff L. Ovulation and pregnancy rates with clomiphene citrate. Obstet Gynecol. 1978;51:265-9.

Dickey RP, Taylor SN, Curole DN, Rey PH, Pyrzak R. Incidence of spontaneous abortion in clomiphene pregnancies. Hum Reprod. 1996;11:2623-8.

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.

Homburg R. Clomiphene citrate- end of an era? A mini review. Hum Reprod. 2005;20:2043-51.

Young SL, Opashi MS, Fritz MA. Serum concentration of euclomiphene and zuclomiphene across consecutive cycles of clomiphene citrate therapy in anovulatory infertile women. Fertil Steril. 1999;71:639-44.

Ghomian N, Khosravi A, Mousavifar N. A randomized clinical trial on comparing the cycle characteristics of two different initiation days of letrozole treatment in clomiphene citrate resistant PCOS patients in IUI cycles. Int J Fertil Steril. 2015;9(1):17-26.

Atay V, Cam C, Muhcu M, Cam M, Karateke A. Comparision of letrozole and clomiphene citrate in women with polycystic ovaries undergoing ovarian stimulation. J Int Med Res. 2006;34:73-6.

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 Human Reprod Sci. 2012;5(1):20-5.

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.

Hegde R, Maitra C. Comparison of the role of letrozole and clomiphene citrate as a first line ovulation induction drug in infertile women with polycystic ovary syndrome. Indian J Obstet Gynecol Res. 2020;7(1):12-5.

Harira M. Use of Letrozole versus clomiphene-estradiol for treating infertile women with unexplained infertility not responding well to clomiphene alone, comparative study. Middle East Fertil Soc J. 2018;23:384-7.

Badawy A, Abdel Aal I, Abulatta M. Clomiphene citrate or Letrozole in women polycystic ovarian syndrome: a prospective randomized trial. Fertil Steril. 2009;92:849-52.

Legro RS, Brzyski RG, Diamond MP, Coutifaris C, Schlaff WD, Casson P, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014;371:119-29

Nahid L, Sirous K. Comparison of the effects of letrozole and clomiphene citrate for ovulation induction in infertile women with polycystic ovary syndrome. Minerva Ginecol. 2012;64(3):253-8.

Al-Shaikh S, Al-Mukhatar E, Al-Zubaidy A, Al-Rubaie B, Al-Khuzaee L. Use of clomiphene or letrozole for treating women with polycystic ovary syndrome related subfertility in Hilla city. Middle East Fertil Soc J. 2017;22(2):105-10.

Kamath MS, George K. Letrozole or clomiphene citrate as first line for anovulatory infertility: a debate. Reprod Biol Endocrinol. 2011;9:86.

Casper RF. Letrozole versus clomiphene citrare: which is better for ovulation induction? Fertil Steril. 2009;92:858-9.

Amer SA, Smith J, Mahran A, Fox P, Fakis A. Double-blind randomized controlled trial of letrozole versus clomiphene citrate in subfertile women with polycystic ovarian syndrome. Hum Reprod. 2017;32(8):1631‐8.