The Effectiveness of Letrozole in Ovulation Induction Treatment: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

 XIAO Jinsong , CHEN Shuangyun , ZHANG Chunlian

The Department of Obstetrics and Gynecology, Affiliated Taihe Hospital of Shiyan Yunyang Medical College, Shiyan 442000, China;

Corresponding author：

XIAO Jinsong, Email: xjs660@sohu.com

Keywords：

Letrozole; Ovulation induction; Effectiveness; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20100482

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective 　To assess the effectiveness of letrozole in ovulation induction treatment.
Methods 　We searched CBMdisc (1979 to 2009), Wanfang (1994 to 2009), CNKI (1994 to 2009), VIP(1989 to 2009), PubMed (1997 to 2009), PML (1997 to 2009), FMJS(2000 to 2009) and 9 relevant journals to identify randomized controlled trails (RCTs) comparing letrozole with clomiphene citrate in ovulation induction treatment. The quality of the included trials was critically appraised. RevMan 4.2.7 software was used for statistical analyses.
Results 　Ten RCTs involving 3100 patients were included, among which 5 RCTs were graded A, 4 were graded B, and 1 was graded C. Five RCTs showed that endometrial thickness at the time of human chorionic gonadotrophin (HCG) administration in the letrozole group was significantly higher than that in the clomiphene group. One RCT showed that endometrial thickness at the time of HCG administration in the letrozole group was significantly lower than that in the clomiphene group. Three RCTs showed no significant differences between the two groups. Four RCTs showed that the number of dominant follicle at the time of HCG administration in the letrozole group was signficantly lower than that in the clomiphene group. One RCT showed that the number of dominant follicle at the time of HCG administration in the letrozole group was significantly higher than that in the clomiphene group. Two RCTs showed no significant differences between the two groups. Compared with clomiphene citrate, the pregnancy rate in the letrozole monotherapy group was slightly lower at the RR 1.03 and 95%CI 0.82 to 1.29, pregnancy rate in the combination group was higher at RR 1.73 and 95%CI 1.37 to 2.18. The ovulation rate in the letrozole group was higher and no significant differences were found between the two groups at RR 1.23 and 95%CI 0.97 to 1.57.
Conclusions 　There may be differences between letrozole and clomiphene citrate in ovulation induction treatment in terms of endometrial thickness, number of dominant follicle, ovulation rate, and pregnancy rate, but no significant differences. Letrozole can make up for the shortcomings of clinical clomiphene in ovulation induction and serve as an alternative. This conclusion needs to be further confirmed through more well-designed, multi-centered, large-sample RCTs.

Citation： XIAO Jinsong,CHEN Shuangyun,ZHANG Chunlian. The Effectiveness of Letrozole in Ovulation Induction Treatment: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2010, 10(6): 718-723. doi: 10.7507/1672-2531.20100482 Copy

1.	Al-Fozan H, Al-Khadouri M, Tan SL, et al. A randomized trial of letrozole versus clomiphene citrate in women undergoing superovulation. Fertil Steril, 2004, 82(6): 1561-1563.
2.	Mitwally MFM, Casper RF. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril, 2001, 75(2): 305-309.
3.	Mitwally M, Biljan M, Casper R. Pregnancy outcome after the use of an aromatase inhibitor for ovarian stimulation. Am J Obstet Gynecol, 2005, 192(2): 381-386.
4.	Juni P, Altman DG, Egger M. Assessing the quality of controlled clinical trials. BMJ, 2001, 323(7303): 42-46.
5.	Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies epidemiology: a proposal for reporting. JAMA, 2000, 283(15): 2008-2012.
6.	Cochrane Reviewer’ Handbook 4.1. The Cochrane Collaboration, 2000.
7.	Schulz KF, Chalmers I, Hayes RJ, et al. Empirical evidence of bias.JAMA, 1995, 273(5): 408-421.
8.	Jee BC, Ku SY, Suh CS, et al. Use of letrozole versus clomiphene citrate combined with gonadotropins in intrauterine insemination cycles: a pilot study. Fertil Steril, 2006, 85(6): 1774-1777.
9.	Sh E, Nejad T, Abediasl Z, et al. Comparison of the efficacy of the aromatase inhibitor letrozole and clomiphen citrate gonadotropins in controlled ovarian hyperstimulation: a prospective, simply randomized, clinical trial. J Assist Reprod Genet, 2008, 25(5): 187-190.
10.	Badawy A, Abdel Aal I, Abulatta M. Clomiphene citrate or letrozole for ovulation inductionin women with polycystic ovarian syndrome:a prospective randomized trial. Fertil Steril, 2009, 92(3): 849-852.
11.	Ganesh A, Goswami SK, Chattopadhyay R, et al. Comparison of letrozole with continuous gonadotropins and clomiphene-gonadotrop in combination for ovulation induction in 1387 PCOS women after clomiphene citrate failure: a randomized prospective clinical trial. J Assist Reprod Genet, 2009, 26(1): 19-24.
12.	Atay V, Cam C, Muhcu M, et al. Comparison of Letrozole and Clomiphene Citrate in women with polycystic ovaries undergoing ovarian stimulation. J Int Med Res, 2006, 34(1): 73-76.
13.	Barroso G, Menocal G, Felix H, et al. Comparison of the efficacy of the aromatase inhibitor letrozole and clomiphene citrate as adjuvants to recombinant follicle-stimulating hormone in controlled ovarian hyperstimulation: a prospective, randomized, blinded clinical trial. Fertil Steril, 2006, 85(5): 1428-1431.
14.	Bayar ü, Basaran M, Kiran S, et al. Use of an aromatase inhibitor in patients with polycystic ovary syndrome: a prospective randomized trial. Fertil Steril, 2006, 82(5): 1447-1451.
15.	Begum M, Ferdous J, Begum A, et al. Comparison of efficacy of aromatase inhibitor andclomiphene citrate in induction of ovulation in polycystic ovarian syndrome. Fertil Steril, 2009, 92(3): 853-856.
16.	Sohrabvand F, Ansari Sh, Bagheri M. Efficacy of combined Metformin-Letrozole in comparison with Metformin-Clomiphene citrate in clomiphene-resistant infertile women with polycystic ovarian disease. Hum Reprod, 2006, 21(6): 1432- 1435.
17.	Cortinez I, De Carvalho D, Vantman F, et al. Hormonal profile and endometrial morphology in letrozole-controlled ovarian hyperstimulation in ovulatory infertile patients. Fertil Steril, 2005, 83(1): 110-115.
18.	Fisher SA, Reid RL, Van Vugt DA, et al. A randomized double-blind comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on ovulatory function in normal women. Fertil Steril, 2002, 78(2): 280-285.
19.	Kistner RW. Induction of ovulation with clomiphene citrate (clomid). Obstet Gynecol Survey, 1965, 20(6): 873-900.
20.	Heard MJ, Pierce A, Carson SA, et al. Pregnancies following use of metformin for ovulation induction in patients with polycystic ovary syndrome. Fertil Steril, 2002, 77(4): 669-673.
21.	Nestler JE, Jakubowicz DJ, Evans WS, et al. Effects of metformin on spontaneous and clomiphene – induced ovulation in the polycystic ovary syndrome. N Engl J Med, 1998, 338(26): 1876-1880.
22.	FG Samani, L Farzadi, N Nezami, et al. Endometrial and follicular development following letrozole intervention in unexplained infertile patients failed to get pregnant with clomiphene citrate. Arch Gynecol Obstet, 2009, 280(2): 201-205.
23.	RF Casper. letrozole ovulation or superovulation? Fertil Steril, 2003, 80(2): 1335-1337.

1. Al-Fozan H, Al-Khadouri M, Tan SL, et al. A randomized trial of letrozole versus clomiphene citrate in women undergoing superovulation. Fertil Steril, 2004, 82(6): 1561-1563.
2. Mitwally MFM, Casper RF. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril, 2001, 75(2): 305-309.
3. Mitwally M, Biljan M, Casper R. Pregnancy outcome after the use of an aromatase inhibitor for ovarian stimulation. Am J Obstet Gynecol, 2005, 192(2): 381-386.
4. Juni P, Altman DG, Egger M. Assessing the quality of controlled clinical trials. BMJ, 2001, 323(7303): 42-46.
5. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies epidemiology: a proposal for reporting. JAMA, 2000, 283(15): 2008-2012.
6. Cochrane Reviewer’ Handbook 4.1. The Cochrane Collaboration, 2000.
7. Schulz KF, Chalmers I, Hayes RJ, et al. Empirical evidence of bias.JAMA, 1995, 273(5): 408-421.
8. Jee BC, Ku SY, Suh CS, et al. Use of letrozole versus clomiphene citrate combined with gonadotropins in intrauterine insemination cycles: a pilot study. Fertil Steril, 2006, 85(6): 1774-1777.
9. Sh E, Nejad T, Abediasl Z, et al. Comparison of the efficacy of the aromatase inhibitor letrozole and clomiphen citrate gonadotropins in controlled ovarian hyperstimulation: a prospective, simply randomized, clinical trial. J Assist Reprod Genet, 2008, 25(5): 187-190.
10. Badawy A, Abdel Aal I, Abulatta M. Clomiphene citrate or letrozole for ovulation inductionin women with polycystic ovarian syndrome:a prospective randomized trial. Fertil Steril, 2009, 92(3): 849-852.
11. Ganesh A, Goswami SK, Chattopadhyay R, et al. Comparison of letrozole with continuous gonadotropins and clomiphene-gonadotrop in combination for ovulation induction in 1387 PCOS women after clomiphene citrate failure: a randomized prospective clinical trial. J Assist Reprod Genet, 2009, 26(1): 19-24.
12. Atay V, Cam C, Muhcu M, et al. Comparison of Letrozole and Clomiphene Citrate in women with polycystic ovaries undergoing ovarian stimulation. J Int Med Res, 2006, 34(1): 73-76.
13. Barroso G, Menocal G, Felix H, et al. Comparison of the efficacy of the aromatase inhibitor letrozole and clomiphene citrate as adjuvants to recombinant follicle-stimulating hormone in controlled ovarian hyperstimulation: a prospective, randomized, blinded clinical trial. Fertil Steril, 2006, 85(5): 1428-1431.
14. Bayar ü, Basaran M, Kiran S, et al. Use of an aromatase inhibitor in patients with polycystic ovary syndrome: a prospective randomized trial. Fertil Steril, 2006, 82(5): 1447-1451.
15. Begum M, Ferdous J, Begum A, et al. Comparison of efficacy of aromatase inhibitor andclomiphene citrate in induction of ovulation in polycystic ovarian syndrome. Fertil Steril, 2009, 92(3): 853-856.
16. Sohrabvand F, Ansari Sh, Bagheri M. Efficacy of combined Metformin-Letrozole in comparison with Metformin-Clomiphene citrate in clomiphene-resistant infertile women with polycystic ovarian disease. Hum Reprod, 2006, 21(6): 1432- 1435.
17. Cortinez I, De Carvalho D, Vantman F, et al. Hormonal profile and endometrial morphology in letrozole-controlled ovarian hyperstimulation in ovulatory infertile patients. Fertil Steril, 2005, 83(1): 110-115.
18. Fisher SA, Reid RL, Van Vugt DA, et al. A randomized double-blind comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on ovulatory function in normal women. Fertil Steril, 2002, 78(2): 280-285.
19. Kistner RW. Induction of ovulation with clomiphene citrate (clomid). Obstet Gynecol Survey, 1965, 20(6): 873-900.
20. Heard MJ, Pierce A, Carson SA, et al. Pregnancies following use of metformin for ovulation induction in patients with polycystic ovary syndrome. Fertil Steril, 2002, 77(4): 669-673.
21. Nestler JE, Jakubowicz DJ, Evans WS, et al. Effects of metformin on spontaneous and clomiphene – induced ovulation in the polycystic ovary syndrome. N Engl J Med, 1998, 338(26): 1876-1880.
22. FG Samani, L Farzadi, N Nezami, et al. Endometrial and follicular development following letrozole intervention in unexplained infertile patients failed to get pregnant with clomiphene citrate. Arch Gynecol Obstet, 2009, 280(2): 201-205.
23. RF Casper. letrozole ovulation or superovulation? Fertil Steril, 2003, 80(2): 1335-1337.

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