Browse > Article

The Efficacy of Letrozole in Women with a Poor Endometrial Response to Clomiphene Citrate  

Jang, Eun-Jeong (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital)
Jee, Byung-Chul (Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital)
Publication Information
Clinical and Experimental Reproductive Medicine / v.37, no.1, 2010 , pp. 73-81 More about this Journal
Abstract
Objective: To examine the efficacy of letrozole in infertile women showing a poor endometrial development at previous ovulation induction cycle by using clomiphene citrate. Methods: Eighteen infertile women were selected who showed a poor endometrial development (endometrial thickness$\leq$6.5 mm) after clomiphene treatment (50~100 mg) as ovulation induction for timed coitus. The mean age of the patients was $30.7{\pm}2.8$ years old and the mean duration of infertility was $33.1{\pm}26.6$ months. The infertility factors were identified as corrected endometriosis (n=1), polycystic ovary syndrome (n=5) and unexplained (n=12). Letrozole was given orally in a dose of 2.5 mg for 5 days starting 3~5 of menstrual cycle. Results: The number of follicles was significantly lower in the letrozole cycle when compared with previous clomiphene cycle ($1.1{\pm}0.3$ vs. $2.2{\pm}1.5$, p=0.011). The endometrial thickness (mm) at the time of triggering or LH surge was significantly greater in the letrozole cycle ($8.4{\pm}1.7$ vs. $5.8{\pm}0.5$, p<0.001). The endometrial pattern 'type C' was significantly higher in the letrozole cycle (94.4% vs. 50%, p=0.036). The pregnancy was achieved in 11.1% of the letrozole cycle. Conclusion: Use of letrozole was associated with more thick and improved endometrium than previous clomiphene cycles in which thin endometrium was identified. Use of letrozole appears to be an effective strategy for second-line treatment in women with inadequate endometrial response to clomiphene.
Keywords
Letrozole; Clomiphene; Ovulation induction; Endometrium;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Mitwally MF, Casper RF. Aromatase inhibition reduces gonadotrophin dose required for controlled ovarian stimulation in women with unexplained infertility. Hum Reprod 2003; 18: 1588-97.   DOI   ScienceOn
2 Badawy A, Metwally M, Fawzy M. Randomized controlled trial of three doses of letrozole for ovulation induction in patients with unexplained infertility. Reprod Biomed Online 2007; 14: 559-62.   DOI   ScienceOn
3 Al-Omari WR, Sulaiman WR, Al-Hadithi N. Comparison of two aromatase inhibitors in women with clomiphene-resistant polycystic ovary syndrome. Int J Gynaecol Obstet 2004; 85: 289-91.   DOI   ScienceOn
4 Requena A, Herrero J, Landeras J, Navarro E, Neyro JL, Salvador C, et al. Reproductive Endocrinology Interest Group of Spanish Society of Fertility. Use of letrozole in assisted reproduction: a systematic review and meta-analysis. Hum Reprod Update 2008; 14: 571-82.   DOI   ScienceOn
5 Biljan MM, Hemmings R, Brassard N. The outcome of 150 babies following the treatment with letrozole or letrozole and gonadotropins. Fertil Steril 2005; 84(suppl 1): S95.
6 Forman R, Gill S, Moretti M, Tulandi T, Koren G, Casper R. Fetal safety of letrozole and clomiphene citrate for ovulation induction. J Obstet Gynaecol Can 2007; 29: 668-71.   DOI
7 Ata B, Tulandi T. Reassurance of safety of letrozole and suggested approaches in controlled ovarian hyperstimulation. Fertil Steril 2009; 92: e6.   DOI   ScienceOn
8 Senturk LM, Erel CT. Thin endometrium in assisted reproductive technology. Curr Opin Obstet Gynecol 2008; 20: 221 -8.   DOI   ScienceOn
9 Badawy A, Abdel Aal I, Abulatta M. Clomiphene citrate or anastrozole for ovulation induction in women with polycystic ovary syndrome? A prospective controlled trial. Fertil Steril 2009; 92: 860-3.   DOI   ScienceOn
10 Badawy A, Mosbah A, Shady M. Anastrozole or letrozole for ovulation induction in clomiphene-resistant women with polycystic ovarian syndrome: a prospective randomized trial. Fertil Steril 2008; 89: 1209-12.   DOI   ScienceOn
11 Kupesic S, Bekavac I, Bjelos D, Kurjak A. Assessment of endometrial receptivity by transvaginal color Doppler and three-dimensional power Doppler ultrasonography in patients undergoing in vitro fertilization procedures. J Ultrasound Med 2001; 20: 125-34.   DOI
12 Elizur SE, Tulandi T. Drugs in infertility and fetal safety. Fertil Steril 2008; 89: 1595-602.   DOI   ScienceOn
13 Tulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari J, et al. Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril 2006; 85: 1761-5.   DOI   ScienceOn
14 Badawy A, Shokeir T, Allam AF, Abdelhady H. Pregnancy outcome after ovulation induction with aromatase inhibitors or clomiphene citrate in unexplained infertility. Acta Obstet Gynecol Scand 2009; 88: 187-91.   DOI   ScienceOn
15 Polyzos NP, Tzioras S, Mauri D, Tsappi M, Cortinovis I, Tsali L, et al. Treatment of unexplained infertility with aromatase inhibitors or clomiphene citrate: a systematic review and meta-analysis. Obstet Gynecol Surv 2008; 63: 472-9.   DOI   ScienceOn
16 Schild RL, Knobloch C, Dorn C, Fimmers R, van der Ven H, Hansmann M. Endometrial receptivity in an in vitro fertilization program as assessed by spiral artery blood flow, endometrial thickness, endometrial volume, and uterine artery blood flow. Fertil Steril 2001; 75: 361-6.   DOI   ScienceOn
17 Shapiro H, Cowell C, Casper RF. The use of vaginal ultrasound for monitoring endometrial preparation in a donor oocyte program. Fertil Steril 1993; 59: 1055-8.   DOI
18 Samani FG, Farzadi L, Nezami N, Tarzamni MK, Soleimani F. Endometrial and follicular development following letrozole intervention in unexplained infertile patients failed to get pregnant with clomiphene citrate. Arch Gynecol Obstet 2009; 280: 201-5.   DOI   ScienceOn
19 Badawy A, Mosbah A, Tharwat A, Eid M. Extended letrozole therapy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a novel protocol. Fertil Steril 2009; 92: 236-9.   DOI   ScienceOn
20 Gonen Y, Casper RF. Sonographic determination of a possible adverse effect of clomiphene citrate on endometrial growth. Hum Reprod 1990; 5: 670-4.   DOI
21 Oliveira JB, Baruffi RL, Mauri AL, Petersen CG, Borges MC, Franco JG Jr. Endometrial ultrasonography as a predictor of pregnancy in an in-vitro fertilization programme after ovarian stimulation and gonadotrophin-releasing hormone and gonadotrophins. Hum Reprod 1997; 12: 2515-8.   DOI   ScienceOn
22 Gonen Y, Casper RF. Prediction of implantation by the sonographic appearance of the endometrium during controlled ovarian stimulation for in vitro fertilization (IVF). J In Vitro Fertil Embryo Transf 1990; 7: 146-52.   DOI   ScienceOn
23 Casper RF. Letrozole versus clomiphene citrate: which is better for ovulation induction? Fertil Steril 2009; 92: 858-9   DOI   ScienceOn
24 Polyzos NP, Mauri D, Tzioras S. Letrozole in ovulation induction: time to make decisions. Hum Reprod Update 2009; 15: 263-4.
25 Begum MR, Quadir E, Begum A, Begum RA, Begum M. Role of aromatase inhibitor in ovulation induction in patients with poor response to clomiphene citrate. J Obstet Gynaecol Res 2006; 32: 502-6.   DOI   ScienceOn
26 Imani B, Eijkemans MJ, te Velde ER, Habbema JD, Fauser BC. A nomogram to predict the probability of live birth after clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. Fertil Steril 2002; 77: 91-7.   DOI   ScienceOn
27 Abu Hashim H, Shokeir T, Badawy A. Letrozole versus combined metformin and clomiphene citrate for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial. Fertil Steril. In press 2009.
28 Begum MR, Ferdous J, Begum A, Quadir E. Comparison of efficacy of aromatase inhibitor and clomiphene citrate in induction of ovulation in polycystic ovarian syndrome. Fertil Steril 2009; 92: 853-7.   DOI   ScienceOn
29 Eckmann KR, Kockler DR. Aromatase inhibitors for ovulation and pregnancy in polycystic ovary syndrome. Ann Pharmacother 2009; 43: 1338-46.   DOI   ScienceOn
30 Elnashar A, Fouad H, Eldosoky M, Saeid N. Letrozole induction of ovulation in women with clomiphene citrateresistant polycystic 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.   DOI   ScienceOn
31 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: 1432-5.   DOI   ScienceOn
32 Mitwally MF, Casper RF. Single-dose administration of an aromatase inhibitor for ovarian stimulation. Fertil Steril 2005; 83: 229-31.   DOI   ScienceOn
33 Atay V, Cam C, Muhcu M, Cam M, Karateke A. Comparison of letrozole and clomiphene citrate in women with polycystic ovaries undergoing ovarian stimulation. J Int Med Res 2006; 34: 73-6.   DOI   ScienceOn
34 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.   DOI   ScienceOn
35 Badawy A, Abdel Aal I, Abulatta M. Clomiphene citrate or letrozole for ovulation induction in women with polycystic ovarian syndrome: a prospective randomized trial. Fertil Steril 2009; 92: 849-52.   DOI   ScienceOn
36 Casper RF. Letrozole: ovulation or superovulation? Fertil Steril 2003; 80: 1335-9.   DOI   ScienceOn
37 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.
38 Sereepapong W, Suwajanakorn S, Triratanachat S, Sampatanukul P, Pruksananonda K, Boonkasemsanti W, et al. Effects of clomiphene citrate on the endometrium of regularly cycling women. Fertil Steril 2000; 73: 287-91.   DOI   ScienceOn
39 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.   DOI   ScienceOn
40 Casper RF, Mitwally MFM. Review: aromatase inhibitors for ovulation induction. J Clin Endocrinol Metab 2006; 91: 760 -71.   DOI