Lomiphene citrate versus letrozole as first line ovulation induction drug in infertile anovulatory polycystic ovarian syndrome women: a prospective randomized controlled trial


  • Monica Soni Department of Obstetrics and Gynecology, SPMC, Bikaner, Rajasthan, India
  • Jeevika Gupta Department of Obstetrics and Gynecology, SPMC, Bikaner, Rajasthan, India
  • Arti Meena Department of Obstetrics and Gynecology, SPMC, Bikaner, Rajasthan, India




Anovulatory infertility, Clomiphene citrate, Letrozole, Polycystic ovarian syndrome


Background: The present study was design to compare letrozole (5 mg) and clomiphene citrate (100 mg) as first line ovulation induction drug in infertile anovulatory polycystic ovarian syndrome (PCOS) women.

Methods: This prospective randomized clinical trial included 60 cases of PCOS with anovulatory infertility. The first group comprised of 30 patients who received 5 mg letrozole daily and the second group received 100 mg clomiphene citrate daily for 5 days starting on day 2-5 of menses. Both the groups were followed by ultrasound for follicle monitoring, ovulation and endometrial thickness. When dominant follicle reaches a diameter of more than or equal to 18mm and endometrial thickness ≥7.5 mm, human chorionic gonadotrophin (hCG) 5,000 IU was given intramuscularly and timed intercourse was advised. Main outcome measures were occurrence of ovulation, endometrial thickness and pregnancy rates.

Results: The mean age, body mass index, and number of cases of primary and secondary infertility in both the groups showed no statistically significant difference. Multi-follicular development during induction was statistically significantly greater in the clomiphene group (1.27±1.11 versus 2.03±1.65; p=0.041). Ovulation occurred in 24 subjects (80%) in letrozole group and 18 subjects (60%) in the clomiphene group, with a statistically significant difference between the two groups (p=0.024). Pregnancy occurred in 16 subjects (53.33%) in letrozole group and 7 subjects (23.33%) in clomiphene group, which shows statistically significant difference between the two groups (p=0.048).

Conclusions: Though number of developing follicles was found statistically significant with clomiphene citrate but ovulation rate and pregnancy rate were higher with letrozole group. Therefore, letrozole is a safe and better alternative for ovulation induction in patients of anovulatory PCOS, and it may be considered as a first line treatment for ovulation induction in these patients.



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;87:5.

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

Saxena P, Prakash A, Ngam 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 Endomcrinol Metab. 2012;16:996-9.

Dor J, Lerner-Geva L, Rabinovici J, Chetrit A, Levran D, Lunenfeld B, et al. Cancer incidence in a cohort of infertile women who underwent in vitro fertilization. Fertil Steril. 2002;77:324-7.

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

Holzer H, Casper R, Tulandi T. A new era in ovulation induction. Fertil Steril. 2006;85:277-84.

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

Yagel S, Ben-Chetrit A, Anteby E, Zacut D, Hochner-Celnikter D, Ron M. The effect of ethinyl estradiol on endometrial thickness and uterine volume during ovulation induction by clomiphene citrate. Fertil Streil. 1992;57:33-6.

Dicke RP, Olar TT, Taylor SN, Curole DN, Matulich EM. Relationship of endometrial thickness and pattern to fecundity in ovulation induction cycles: effect of clomiphene citrate alone and with human menopausal gonadotrophin. Fertil Steril. 1993;59:756-60.

Opsahl MS, Robins ED, O’Conner DM, Scott RT, Fritz MA. Characteristics of gonadotropin response, follicular development, and endometrial growth and maturation across consecutive cycles of clomiphene citrate treatment. Fertil Steril. 1996;66:533-9.

Eden JA, Place J, Carter GD, Jones J, Alaghband-Zadeh J, Pawson ME. The effect of clomiphene citrate on follicular phase increase endometrial thickness and uterine volume. Obstet Gynecol. 1989;73:187-90.

Kettel LM, Roseff SJ, Berga SL. Hypthalamus-pituitary-ovarian response tp clomiphene citrate in women with polycystic ovary syndrome. Fertil Steril. 1993;59:532-8.

Franks S. Polycystic ovary syndrome. N Eng J Med. 1995;333:853-61.

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.

Nakamura Y, Ono M, Yoshida Y. Effect of clomiphene citatre on endometrial thickness and echogenic pattern of the endometrium. Fertil Steril. 1997;67:256-60.

Randall JM, Templeto A. Cervical mucus score and in vitro sperm mucus interaction in spontaneous and clomiphene citrate cycles. Fertil Steril. 1991;56:465-8.

Sammour A, Biljan MM, Tan SL, Tulandi T. Prospective randomised trial comparing the effects of letrozole and clomiphene citrate (CC) on follicular development, endometrial thickness and pregnancy rate in patients undergoing superovulation prior to intrauterine insemination. 57th Annual Meeting of the American Society for Reproductive Medicine. Fertil Steril. 2001;76(suppl 1):S110.






Original Research Articles