A comparative study of letrozole and clomiphene citrate for ovulation induction in women with polycystic ovarian syndrome: a randomized controlled trial

Subashree Ilangovan

doi:10.18203/2320-1770.ijrcog20241954

Authors

Subashree Ilangovan Department of Obstetrics and Gynaecology, Sri Venkateshwara Medical College Hospital and Research Institute, Red Hills, Thiruvallur, Tamil Nadu, India

DOI:

https://doi.org/10.18203/2320-1770.ijrcog20241954

Keywords:

Polycystic ovary syndrome, Letrozole, CC, Ovulation induction, Infertility

Abstract

Background: Effective ovulation induction is crucial in management of polycystic ovarian syndrome (PCOS) related infertility. Clomiphene citrate (CC) has long been the first line of treatment for inducing ovulation in women with PCOS. Letrozole, an aromatase inhibitor, has emerged as a promising alternative to CC for ovulation induction. The present study was aimed to compare efficacy and safety of letrozole versus CC for ovulation induction in women with PCOS.

Methods: This study consists of 384 PCOS women, randomized into two groups: Letrozole (2.5 mg/day) and CC (50 mg/day), both administered from day 3 to day 7 of the menstrual cycle. The primary outcome was the ovulation rate, confirmed by serum progesterone levels >10 ng/ml. Secondary outcomes included clinical pregnancy rate, live birth rate, endometrial thickness, adverse effects, cost-effectiveness, and patient satisfaction. Participants were monitored through transvaginal ultrasound and serum progesterone measurements.

Results: Ovulation was achieved in 76.0% of participants in the letrozole group compared to 55.2% in the CC group (p<0.001). Clinical pregnancy rates were significantly higher in the letrozole group (44.8%) compared to the CC group (28.1%) (p<0.001). Similarly, live birth rates were higher with letrozole (36.5% vs. 22.4%; p=0.002). Endometrial thickness was greater in the letrozole group (8.7 mm vs. 7.5 mm; p<0.001). Adverse effects, were significantly lower in the letrozole group.

Conclusions: Letrozole is more effective than CC in inducing ovulation and achieving higher pregnancy and live birth rates in women with PCOS.

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References

Fauser BC, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, et al. Consensus on women's health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril. 2012;97(1):28-38.

Azziz R, Carmina E, Chen Z, Dunaif A, Laven JS, Legro RS, et al. Polycystic ovary syndrome. Nat Rev Dis Primers. 2016;2:16057.

Yland JJ, Chiu YH, Rinaudo P, Hsu J, Hernán MA, Hernández-Díaz S. Emulating a target trial of the comparative effectiveness of clomiphene citrate and letrozole for ovulation induction. Hum Reprod. 2022;37(4):793-805.

Brown J, Farquhar C, Beck J, Boothroyd C, Hughes E. Clomiphene and anti-oestrogens for ovulation induction in PCOS. Cochrane Database Syst Rev. 2009;(4):CD002249.

Beck JI, Boothroyd C, Proctor M, Farquhar C, Hughes E. Oral anti-oestrogens and medical adjuncts for subfertility associated with anovulation. Cochrane Database Syst Rev. 2005;(1):CD002249.

Franks S, Stark J, Hardy K. Follicle dynamics and anovulation in polycystic ovary syndrome. Hum Reprod Update. 2008;14(4):367-78.

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.

Franik S, Eltrop SM, Kremer JA, Kiesel L, Farquhar C. Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2018;5(5):CD010287.

Dewailly D, Robin G, Peigne M, Decanter C, Pigny P, Catteau-Jonard S. Interactions between androgens, FSH, anti-Müllerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary. Hum Reprod Update. 2016;22(6):709-24.

Abu-Zaid A, Gari A, Sabban H, Alshahrani MS, Khadawardi K, Badghish E, et al. Comparison of Letrozole and Clomiphene Citrate in Pregnancy Outcomes in Patients with Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis. Reprod Sci. 2024;31(4):883-905.

Franik S, Le QK, Kremer JA, Kiesel L, Farquhar C. Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2022;9(9):CD010287.

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.

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(2):119-29.

Weiss NS, Kostova E, Nahuis M, Mol BWJ, van der Veen F, van Wely M. Gonadotrophins for ovulation induction in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2019;1(1):CD010290.