Clinical and Experimental Reproductive Medicine

  • 제37권1호
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  • Pages.73-81
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  • 2010
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  • 2233-8233(pISSN)
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  • 2233-8241(eISSN)
대한생식의학회 (The Korean Society for Reproductive Medicine)
권호 표지

클로미펜에 불량한 자궁내막 발달을 보이는 여성에서 레트로졸의 유용성

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

  • 장은정 (분당서울대학교병원 산부인과) ;
  • 지병철 (분당서울대학교병원 산부인과)
  • 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)
  • 발행 : 2010.03.31
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초록

목 적: 클로미펜을 이용한 배란유도 주기에서 불량한 자궁내막 발달을 보이는 불임 여성에서 레트로졸의 효용성을 알아보고자 하였다. 연구방법: 2004년 3월부터 2009년 8월까지 분당서울대학교병원에서 클로미펜을 이용한 배란유도 주기에서 자궁내막 두께가 6.5 mm 이하여서 다음 주기에 레트로졸을 사용하였던 18명의 불임 여성을 선정하였다. 환자들의 평균 연령은 $30.7{\pm}2.8$세, 불임 기간은 $33.1{\pm}26.6$개월이었다. 불임의 인자는 자궁내막증이 1명, 다낭성난소증후군이 5명, 원인불명의 불임증이 12명이었다. 레트로졸은 2.5 mg의 용량으로 월경 3~5일 사이에 시작하여 5일간 투여하였다. 결 과: 이전 클로미펜 사용시와 비교하였을 때 레트로졸 주기에서 우성난포의 개수는 더 적었으나 ($1.1{\pm}0.3$ vs. $2.2{\pm}1.5$, p=0.011) 자궁내막 두께는 유의하게 증가하였으며 ($8.4{\pm}1.7$ mm vs. $5.8{\pm}0.5$ mm, p<0.001) 자궁내막 패턴 중 type C의 빈도는 이전 클로미펜 주기에서 50%이었던 것이 레트로졸 사용시 94.4%로 유의한 증가를 보였다 (p=0.036). 레트로졸을 이용한 배란 유도 주기에서 임신율은 11.1%였다. 결 론: 얇은 자궁내막 발달을 보였던 클로미펜 주기에 비해 레트로졸 사용시 자궁내막이 좀 더 두꺼워지고 패턴이 호전되는 것으로 보아 클로미펜에 불량한 자궁내막을 보이는 여성에서 이차 선택약제로 레트로졸의 사용은 유용한 방법으로 사료된다.

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.

키워드

참고문헌

  1. 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.
  2. 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. https://doi.org/10.1016/S0015-0282(99)00509-9
  3. 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. https://doi.org/10.1016/S0015-0282(00)01705-2
  4. Casper RF. Letrozole: ovulation or superovulation? Fertil Steril 2003; 80: 1335-9. https://doi.org/10.1016/j.fertnstert.2003.05.004
  5. Casper RF, Mitwally MFM. Review: aromatase inhibitors for ovulation induction. J Clin Endocrinol Metab 2006; 91: 760 -71. https://doi.org/10.1210/jc.2005-1923
  6. 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. https://doi.org/10.1016/j.fertnstert.2005.08.016
  7. Mitwally MF, Casper RF. Single-dose administration of an aromatase inhibitor for ovarian stimulation. Fertil Steril 2005; 83: 229-31. https://doi.org/10.1016/j.fertnstert.2004.07.952
  8. 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. https://doi.org/10.1177/147323000603400109
  9. 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. https://doi.org/10.1016/j.fertnstert.2006.04.026
  10. 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. https://doi.org/10.1093/humrep/del020
  11. 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. https://doi.org/10.1016/j.fertnstert.2007.02.062
  12. 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. https://doi.org/10.1093/humupd/dmn033
  13. 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.
  14. 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. https://doi.org/10.1016/j.fertnstert.2007.08.044
  15. Casper RF. Letrozole versus clomiphene citrate: which is better for ovulation induction? Fertil Steril 2009; 92: 858-9 https://doi.org/10.1016/j.fertnstert.2007.03.094
  16. Eckmann KR, Kockler DR. Aromatase inhibitors for ovulation and pregnancy in polycystic ovary syndrome. Ann Pharmacother 2009; 43: 1338-46. https://doi.org/10.1345/aph.1M096
  17. 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. https://doi.org/10.1007/BF01135678
  18. Polyzos NP, Mauri D, Tzioras S. Letrozole in ovulation induction: time to make decisions. Hum Reprod Update 2009; 15: 263-4.
  19. 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. https://doi.org/10.1111/j.1447-0756.2006.00434.x
  20. 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. https://doi.org/10.1016/S0015-0282(01)02929-6
  21. 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. https://doi.org/10.1016/j.fertnstert.2008.04.065
  22. Gonen Y, Casper RF. Sonographic determination of a possible adverse effect of clomiphene citrate on endometrial growth. Hum Reprod 1990; 5: 670-4. https://doi.org/10.1093/oxfordjournals.humrep.a137165
  23. 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. https://doi.org/10.1016/S0015-0282(16)55927-5
  24. 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. https://doi.org/10.1093/humrep/12.11.2515
  25. 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. https://doi.org/10.1016/S0015-0282(00)01695-2
  26. 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. https://doi.org/10.7863/jum.2001.20.2.125
  27. 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. https://doi.org/10.1007/s00404-008-0888-9
  28. 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. https://doi.org/10.1093/humrep/deg311
  29. 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. https://doi.org/10.1080/00016340802638199
  30. 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. https://doi.org/10.1097/OGX.0b013e31817d4e8d
  31. 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. https://doi.org/10.1016/S1472-6483(10)61046-2
  32. 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. https://doi.org/10.1016/j.fertnstert.2007.08.034
  33. 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. https://doi.org/10.1016/j.ijgo.2003.11.010
  34. 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. https://doi.org/10.1016/j.fertnstert.2007.05.010
  35. 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.
  36. Elizur SE, Tulandi T. Drugs in infertility and fetal safety. Fertil Steril 2008; 89: 1595-602. https://doi.org/10.1016/j.fertnstert.2008.02.092
  37. 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. https://doi.org/10.1016/j.fertnstert.2006.03.014
  38. 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. https://doi.org/10.1016/S1701-2163(16)32551-8
  39. Ata B, Tulandi T. Reassurance of safety of letrozole and suggested approaches in controlled ovarian hyperstimulation. Fertil Steril 2009; 92: e6. https://doi.org/10.1016/j.fertnstert.2009.03.103
  40. Senturk LM, Erel CT. Thin endometrium in assisted reproductive technology. Curr Opin Obstet Gynecol 2008; 20: 221 -8. https://doi.org/10.1097/GCO.0b013e328302143c