Use of letrozole versus clomiphene citrate combined with gonadotropins for ovulation induction in infertile women with polycystic ovary syndrome: a pilot study

Amitoj Athwal, Ratnabali Chakravorty, Dipanshu Sur, Rupam Saha


Background: The aim of the study was to evaluate the efficacy of letrozole and clomiphene citrate (CC) in gonadotropin-combined for ovulation stimulation in women with polycystic ovary syndrome (PCOS). It was a prospective pilot study.

Methods: This prospective trial included 124 patients of infertile women with PCOS. Letrozole dose of 5 mg/day (n = 65) or a CC dose of 100 mg/day (n = 59) was given on day 3 to day 7 of the menstrual cycle, combined with gonadotropin i.e. follicle stimulating hormone (FSH) at a dose 75 IU every day starting on day 7 and continued to day 9. Main outcome measures were occurrence of ovulation, number of mature follicles, serum estradiol (E2) and endometrial thicknesses on the day of human chorionic gonadotropin (hCG), and pregnancy rates.

Results: The clinical profile including mean age, duration of infertility, BMI, baseline FSH, LH and E2 of patients belonging to both groups were comparable. The numbers of mature follicles (4.3±0.3 vs. 2.9±0.7) were significantly higher in letrozole+FSH group. Serum E2 levels on the day of hCG (301.78±85.7 vs. 464.7±72.9 pg/mL) were significantly lower in the letrozole+FSH group. Significant differences were found in endometrial thickness measured on the day of hCG in letrozole+FSH group (p=<0.0001). The rate of ovulation was higher in letrozole+FSH group and it was marginally statistically significant (p=0.040). The rate of pregnancy was slightly greater in the letrozole+FSH group (17.85% versus 13.33%), although not statistically significant.

Conclusions: Letrozole in combination with FSH appears to be a suitable ovulation inducing agent versus CC with FSH in PCOS. This combination may be more appropriate in patients who are particularly sensitive to gonadotropin.


Clomiphene citrate, Gonadotropin, Letrozole, Ovulation induction

Full Text:



Norman RJ, Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. Lancet. 2007;370:685-97.

Dankert T, Kremer JAM, Cohlen BJ, Hamilton CJCM, Pasker-de Jong PCM, Straatman H, et al. A randomized clinical trial of clomiphene citrate versus low dose recombinant FSH for ovarian hyperstimulation in intrauterine insemination cycles for unexplained and male subfertility. Hum Reprod. 2007;22:792-7.

Elnashar A, Fouad H, Eldosoky M, Saeid N. Letrozole induction of ovulation in women with clomiphene citrate-resistant polycys-tic ovary syndrome may not depend on the period of infertility, the body mass index, or the luteinizing hormone/follicle-stimulating hormone ratio. Fertil Steril. 2006;85:511-3.

Eijkemans MJ, Polinder S, Mulders AG, Laven JS. Habbema JDF, Fauser BC: Individualized cost-effective conventional ovulation induction treatment in normogonadotrophic anovulatoryinfertility (WHO group 2). Hum Reprod. 2005;20:2830-7.

MFM M, Casper RF. Aromatase inhibition reduces gonadotrophin dose required for controlled ovarian stimulation in women with unexplained infertility. Hum Reprod. 2003;8:1588-97.

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.

Casper RF. Letrozole: ovulation or superovulation? Fertil Steril. 2003;80:1335-7.

Mitwally MF, Casper RF. Aromatase inhibitors in ovulation induction. Semin Reprod Med. 2004;22:61-78.

The Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Work- shop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod. 2008;23:462-77.

Wang CF, Gemzell C. The use of human gonadotropins for the induction of ovulation in women with polycystic ovarian disease. Fertil Steril. 1980;33:479-86.

Mattenberg C, Fondop JJ, Romoscanu I, Luyet C, Bianchi-Demicheli F, de Ziegler D. Use of aromatase inhibitors in infertile women. Gynecol Obstet Fertil. 2005;33:348-55.

Bedaiwy MA, Forman R, Mousa NA, Al Inany HG, Casper RF. Cost-effectiveness of aromatase inhibitor co-treatment for con-trolled ovarian stimulation. Hum Reprod. 2006;21:2838-44.

Jee BC, Ku SY, Suh CS, Kim KC, Lee WD, Kim SH. Use of letrozole versus clomiphene citrate combined with gonadotropins in intrauterine insemination cycles: a pilot study. Fertil Steril. 2006;85:1774-7.

Homburg R. Oral agents for ovulation-induction-clomiphene citrate versus aromatase inhibitors. Hum Fertil (Camb). 2008;11:17-22.

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

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. Fertil Steril. 2006;86:1447-51.

Bayar U, Tanriverdi HA, Barut A, Ayoğlu F, Ozcan O, Kaya E. Letrozole vs. clomiphene citrate in ovulatory infertility. Fertil Steril 2006;85:1045-9.

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.