Aromatase Inhibitors in Ovulation Induction for Women with Unexplained Infertility: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

LIU Zhen ^1,2 , TANG Huilin ² ,  ZHAI Suodi ²

1. Beijing Obstetrics and Gynecology Hospital, Beijing 100026, China; 2. Peking University Third Hospital, Beijing 100191, China;

Corresponding author：

ZHAI Suodi, Email: zhaisuodi@163.com

Keywords：

Aromatase inhibitors; Unexplained infertility; Ovulation induction; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20110222

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Objective 　To evaluate the effectiveness and safety of aromatase inhibitors in ovulation induction for women with unexplained infertility.
Methods　 The databases such as CNKI (1994 to June 2011), WanFang Data (1982 to June 2011), PubMed (1966 to June 2011) and The Cochrane Library (Issue 6, 2011) were searched to collect randomized controlled trials (RCTs) and quasi-randomized controlled trials (quasi-RCTs) for the comparison between aromatase inhibitors (AIs) and clomiphene citrate (CC). The quality of the retrieved trials was critically appraised and meta-analyses were conducted using RevMan 5.0.1 software.
Results　 Nine studies were included; all of them were published in English. The results of meta-analyses showed there were no significant differences between AIs and CC in the pregnancy rate (RR=1.02, 95%CI 0.71 to 1.47), miscarriage rate (RR=1.00 95%CI 0.61 to 1.63), multiple pregnancy rate (RD= –0.02, 95%CI –0.07 to 0.03), and incidence rate of adverse events (RD=0.00, 95%CI –0.01 to 0.01); there were still no significant differences between the AIs+gonadotropin (Gn) group and the CC+Gn group in the pregnancy rate (RR=0.98, 95%CI 0.68 to 1.42), miscarriage rate (RR=1.23, 95%CI 0.70 to 2.15), multiple pregnancy rate (RD=0.00, 95%CI –0.10 to 0.10), and incidence rate of adverse events (RD=0.00, 95%CI –0.10 to 0.01).
Conclusion　 Whether aromatase inhibitors can replace clomiphene citrate in ovulation induction for women with unexplained infertility is still an issue that has to be identified by performing well-designed large scale RCTs with longer follow-up duration.

Citation： LIU Zhen,TANG Huilin,ZHAI Suodi. Aromatase Inhibitors in Ovulation Induction for Women with Unexplained Infertility: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2011, 11(11): 1327-1334. doi: 10.7507/1672-2531.20110222 Copy

1.	2 El-Toukhy T, Khalaf Y. Treatment of unexplained infertility. BMJ , 2008, 337(a772): 362-363.
2.	3 Bhattachrya S, Harrild K, Mollison S, et al . Clomifene citrate or intrauterine insemination compared with expectant management for unexplained infertility: pragmatic randomised controlled trial. BMJ , 2008, 337: a716.
3.	4 Holzer H, Casper R, Tulandi T. A new era in ovulation induction. Fertil and Steril , 2006, 85(2): 277-784.
4.	7 Sammour A, Biljan MM, Tan SL, et al . Prospective randomized trial comparing the effects of letrazole (LE) and clomiphene citrate (CC) on follicular development, endometrial thickness and pregnancy rate in patients undergoing super-ovulation prior to intrauterine insemination (IUI). Fertil and Steril , 2001, 76: (3 suppl 1): S110.
5.	8 Bayar Ü, Tanriverdi HA, Barut A, et al. Letrozole vs clomiphene citrate in patients with ovulatory infertility. Fertil and Steril , 2006, 85(4): 1045-1048.
6.	9 Wu HH, Wang AM, Cheng ML, et al . A randomized comparison of ovulation induction and hormone profile between the aromatase inhibitor anastrozole and clomiphene citrate in women with infertility. Gynecol Endocrinol , 2007, 23: 76-81.
7.	10 Badawy A, Elnashar A, Totongy M, et al . Clomiphene citrate or aromatase inhibitors for superovulation in women with unexplained infertility undergoing intrauterine insemination: a prospective randomized trial. Fertil and Steril , 2009, 92(4): 1355-1359.
8.	11 Badawy A, Skokeir T, Allam AF, et al . Pregnancy outcome after ovulation induction with aromatase inhibitors or clomiphene citrate in unexplained infertility. Octa Obstet et Gynecol , 2009, 88: 187-191.
9.	12 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, blindedclinicaltrial. Fertil and Steril , 2006, 86(5): 1428-1431.
10.	13 Davar R, Asgharnia M, Tayebi M. Comparison of the success rate of letrozole and clomiphene citrate in women undergoing intrauterine insemination. J of Res in Med Sci , 2006, 11(6): 382-387.
11.	14 Badawy A, Elnashar A, Totongy M. Clomiphene citrate or aromatase inhibitors combined with gonadotropins for super ovulation in women undergoing intrauterine insemination: A prospective randomised trial. J Obstet and Gynaecol , 2010, 30(6): 617-621.
12.	15 Fouda UM, Sayed AM. Extended letrozole regimen versus clomiphene citrate for superovulation in patients with unexplained infertility undergoing intrauterine insemination: a randomized controlled trial. Reprod Biol Endocrinol , 2011, 9(1): 84.
13.	16 Dankert T, Kremer JA, Cohlen BJ, 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: 792-797.
14.	17 Casper RF, Mitwally MF. Review: Aromatase inhibitors for ovulation induction. J Clin Endocrinol Metab , March 2006, 91(3): 760-771.
15.	18 Casper RF, Mitwally MF. Aromatase inhibitors improves ovarian response to follicle-stimulating hormone in poor responders. Fertil and Steril , 2002, 77(4): 776-779.
16.	19 Baruah J, Roy KK, Rahman SM, et al . Endometrial effects of letrozole and clomiphene citrate in women with polycystic ovary syndrome using spiral artery Doppler. Arch Gynecol Obstet , 2009, 279(3): 311-314.
17.	20 Polyzos NP, Tzioras S, Mauri D, et al . Treatment of unexplained infertility with aromatase inhibitors or clomiphene citrate: a systematic review and meta-analysis. Obstet Gynecol Surv , 2008, 63(7): 472-479.
18.	21 Polyzos NP, Tzioras S, Badawy AM, et al . Aromatase inhibitors for female infertility: a systematic review of the literature. Reprod Biomed Online , 2009, 19(4): 456-471.
19.	刘嘉茵. 不明原因不孕症的诊治. 实用妇产科杂志, 2005, 21(8): 457-459.
20.	郭鹊晖, 郑志群. 来曲唑的促排卵及胚胎毒性的研究进展. 生殖与避孕, 2009, 29(2): 120-127.
21.	Cochrane Handbook for Systematic Reviews of Interventions Ver-sion 5. 0. 1[updated September 2008]. e Cochrane Collaboration, 2008. [www. cochrane-handbook. org/]. Accessed 10 March 2009.

1. 2 El-Toukhy T, Khalaf Y. Treatment of unexplained infertility. BMJ , 2008, 337(a772): 362-363.
2. 3 Bhattachrya S, Harrild K, Mollison S, et al . Clomifene citrate or intrauterine insemination compared with expectant management for unexplained infertility: pragmatic randomised controlled trial. BMJ , 2008, 337: a716.
3. 4 Holzer H, Casper R, Tulandi T. A new era in ovulation induction. Fertil and Steril , 2006, 85(2): 277-784.
4. 7 Sammour A, Biljan MM, Tan SL, et al . Prospective randomized trial comparing the effects of letrazole (LE) and clomiphene citrate (CC) on follicular development, endometrial thickness and pregnancy rate in patients undergoing super-ovulation prior to intrauterine insemination (IUI). Fertil and Steril , 2001, 76: (3 suppl 1): S110.
5. 8 Bayar Ü, Tanriverdi HA, Barut A, et al. Letrozole vs clomiphene citrate in patients with ovulatory infertility. Fertil and Steril , 2006, 85(4): 1045-1048.
6. 9 Wu HH, Wang AM, Cheng ML, et al . A randomized comparison of ovulation induction and hormone profile between the aromatase inhibitor anastrozole and clomiphene citrate in women with infertility. Gynecol Endocrinol , 2007, 23: 76-81.
7. 10 Badawy A, Elnashar A, Totongy M, et al . Clomiphene citrate or aromatase inhibitors for superovulation in women with unexplained infertility undergoing intrauterine insemination: a prospective randomized trial. Fertil and Steril , 2009, 92(4): 1355-1359.
8. 11 Badawy A, Skokeir T, Allam AF, et al . Pregnancy outcome after ovulation induction with aromatase inhibitors or clomiphene citrate in unexplained infertility. Octa Obstet et Gynecol , 2009, 88: 187-191.
9. 12 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, blindedclinicaltrial. Fertil and Steril , 2006, 86(5): 1428-1431.
10. 13 Davar R, Asgharnia M, Tayebi M. Comparison of the success rate of letrozole and clomiphene citrate in women undergoing intrauterine insemination. J of Res in Med Sci , 2006, 11(6): 382-387.
11. 14 Badawy A, Elnashar A, Totongy M. Clomiphene citrate or aromatase inhibitors combined with gonadotropins for super ovulation in women undergoing intrauterine insemination: A prospective randomised trial. J Obstet and Gynaecol , 2010, 30(6): 617-621.
12. 15 Fouda UM, Sayed AM. Extended letrozole regimen versus clomiphene citrate for superovulation in patients with unexplained infertility undergoing intrauterine insemination: a randomized controlled trial. Reprod Biol Endocrinol , 2011, 9(1): 84.
13. 16 Dankert T, Kremer JA, Cohlen BJ, 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: 792-797.
14. 17 Casper RF, Mitwally MF. Review: Aromatase inhibitors for ovulation induction. J Clin Endocrinol Metab , March 2006, 91(3): 760-771.
15. 18 Casper RF, Mitwally MF. Aromatase inhibitors improves ovarian response to follicle-stimulating hormone in poor responders. Fertil and Steril , 2002, 77(4): 776-779.
16. 19 Baruah J, Roy KK, Rahman SM, et al . Endometrial effects of letrozole and clomiphene citrate in women with polycystic ovary syndrome using spiral artery Doppler. Arch Gynecol Obstet , 2009, 279(3): 311-314.
17. 20 Polyzos NP, Tzioras S, Mauri D, et al . Treatment of unexplained infertility with aromatase inhibitors or clomiphene citrate: a systematic review and meta-analysis. Obstet Gynecol Surv , 2008, 63(7): 472-479.
18. 21 Polyzos NP, Tzioras S, Badawy AM, et al . Aromatase inhibitors for female infertility: a systematic review of the literature. Reprod Biomed Online , 2009, 19(4): 456-471.
19. 刘嘉茵. 不明原因不孕症的诊治. 实用妇产科杂志, 2005, 21(8): 457-459.
20. 郭鹊晖, 郑志群. 来曲唑的促排卵及胚胎毒性的研究进展. 生殖与避孕, 2009, 29(2): 120-127.
21. Cochrane Handbook for Systematic Reviews of Interventions Ver-sion 5. 0. 1[updated September 2008]. e Cochrane Collaboration, 2008. [www. cochrane-handbook. org/]. Accessed 10 March 2009.

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