Comparative study of clomiphene citrate versus letrozole as first-line ovulation induction drug in infertile polycystic ovary syndrome women


  • Mahija Sahu Department of Obstetrics and Gynecology, Sriram Chandra Bhanj Medical College and Hospital, Cuttack, Odisha, India
  • Nihar Ranjan Rout Department of Obstetrics and Gynecology, Institute of Medical Sciences and SUM Hospital, Bhubaneswar, Odisha, India



Clomifene citrate, Letrozole, Ovulation induction, Polycystic ovary syndrome


Background: Polycystic ovary syndrome is the commonest endocrinopathy resulting in anovulatory infertile young women. Clomifene citrate (clomiphene) is a long-standing standard drug for ovulation induction, and is still considered as first line option in PCOS women. However, clomiphene has certain disadvantage letrozole an aromatase inhibitor acts by reducing estrogen production and has no adverse effects on endometrium and cervical mucous. Indian PCOS women have high prevalence of insulin resistance and thus are likely to have high clomiphene resistance. So letrozole could prove to be a good alternative for ovulation induction in such women.

Methods: This was a prospective randomized, parallel, comparative clinical trial of two ovulation induction drugs letrozole 5 mg versus clomiphene citrate 100 mg as first-line ovulation induction drug in infertile polycystic ovarian syndrome women. The target population of the study was one hundred infertile women with PCO (taking at least 2 Rotterdam’s parameters). 50 women were allocated to clomifene citrate and 50 were allocated to Letrozole for ovulation induction. Parameters like age, duration of infertility, B MI, ovulation rate, number of follicles, pregnancy rate, endometrial thickness were noted and analyzed.

Results: In letrozole group, the ovulation rate, mono-follicular development, mean endometrial thickness and pregnancy rate was better in comparison to clomifene citrate group.

Conclusions: The result of this study suggests that letrozole may replace clomiphene as the first line drug for ovulation induction in infertile PCOS women.


Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol. 1935;29:181-91.

The Australian Longitudinal Study on Women's Health (ALSWH), 2017. Available at: - and-reports/published - papers. Accessed on 19th July 2017.

Greenblatt RB, Barfield WE, Jungck EC, Ray AW. Induction of ovulation with MRL/41. JAMA. 1961;178:101-5.

Biljan MM, Mahutte NG, Tulandi T, Tan SL. Prospective randomized double-blind trial of the correlation between time of administration and antiestrogenic effects of clomiphene citrate on reproductive end organs. Fertil Steril. 1999;71(4):633-8.

The Rotterdam ESHRE/ASRM sponsored PCOS con-sensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Human Reprod. 2004;19:41-7.

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

Kar S. Clomiphene citrate or letrozole as first-line ovulation induction drug in infertile PCOS women: a prospective randomized trial. J Hum Reprod Sci. 2012;5(3):262-5.

Sioufi A, Gauducheau N, Pineau V, Marfil F, Jaouen A, Cardot JM, et al. Absolute bioavailability of letrozole in healthy postmenopausal women. Biopharmac Drug Dispos. 1997;18(9):779-89.

Kerin JF, Liu JH, Phillipou G, Yen SSS. Evidence for a hypothalamic site of action of clomiphene citrate in women. J Clin Endocrinol Metab. 1985;61:265-8.

Mitwally MFM, Casper RF. Aromatase Inhibitors: a novel method of ovulation induction in women with polycystic ovarian syndrome. Reprod Technol. 2000;10:244-7.

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.

Gonen Y, Casper RF. Sonographic determination of an adverse effect of clomiphene citrate on endometrial growth. Hum Reprod. 1990;5:670-4.

Badawy A, Mosbah A, Shady M. Anastrozole or letrozole for ovulatin induction in clomiphene-resistant women with polycystic ovarian syndrome: a prospective randomize trial. Fertil Steril. 2008;89:1209-12.

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. Fertile Steril. 2010;94:1405-9.






Original Research Articles