Clinical and Experimental Reproductive Medicine

  • 제33권3호
  • /
  • Pages.149-157
  • /
  • 2006
  • /
  • 2233-8233(pISSN)
  • /
  • 2233-8241(eISSN)
대한생식의학회 (The Korean Society for Reproductive Medicine)
권호 표지

정상 배란주기의 불임 여성에서 Clomiphene Citrate 단독 사용과 GnRH Antagonist 병합 요법의 임상적 효용성에 관한 연구

The Clinical Efficiency of Clomiphene Citrate vs Clomiphene Citrate/GnRH Antagonist on Infertile Women with Normal Ovulatory Cycles

  • 이우석 (중앙대학교 부속병원 산부인과학교실) ;
  • 상재홍 (중앙대학교 부속병원 산부인과학교실) ;
  • 김재준 (중앙대학교 부속병원 산부인과학교실) ;
  • 김광준 (중앙대학교 부속병원 산부인과학교실) ;
  • 김동호 (중앙대학교 부속병원 산부인과학교실) ;
  • 이상훈 (중앙대학교 부속병원 산부인과학교실)
  • Lee, Woo Seok (Department of Obstetrics and Gynecology, College of Medicine, Chung-Ang University) ;
  • Sang, Jae Hong (Department of Obstetrics and Gynecology, College of Medicine, Chung-Ang University) ;
  • Kim, Jae Joon (Department of Obstetrics and Gynecology, College of Medicine, Chung-Ang University) ;
  • Kim, Gwang June (Department of Obstetrics and Gynecology, College of Medicine, Chung-Ang University) ;
  • Kim, Dong Ho (Department of Obstetrics and Gynecology, College of Medicine, Chung-Ang University) ;
  • Lee, Sang Hun (Department of Obstetrics and Gynecology, College of Medicine, Chung-Ang University)
  • 발행 : 2006.09.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

목 적: 본 연구는 인공 수정 시술에 있어서 정상 배란주기의 여성에서 clomiphene citrate와 GnRH antagonist를 병합하여 임선을 시도한 방법을 기존의 clomiphene citrate 단독으로 사용한 방법과 비교하여 그 임상적 유용성을 알아보고자 하였다. 연구방법: 116명의 환자들 중 43명에게는 자연 배란주기를 이용하여 인공 수정 시술을 시행하였고, 38명과 35명에게 각각 clomiphene citrate 단독 요법과 clomiphene citrate와 GnRH antagonist 병합 요법으로 인공 수정 시술을 시행하여 그 임상 결과를 비교 분석하였다. 결 과: 각각의 군에서 기저 LH, FSH, $E_2$와 배란 유도를 위해 hCG를 투여하는 날의 FSH, $E_2$는 차이를 보이지 않았으나 clomiphene citrate/GnRH antagonist 병합 요법군에서 hCG를 투여한 날의 LH와 자궁 내막 두께는 의미 있게 감소하였으며 유의한 임신율의 증가가 관찰되었다. 결 론: 자연 배란주기법군, clomiphene citrate 단독 요법 사용군에 비해 clomiphene citrate/GnRH antagonist 병합 요법 사용군에서 유의하게 임신율의 향상을 나타냈다.

Objective: This study was to investigate the clinical efficiency of clomiphene citrate/GnRH antagonist protocol comparing with the clomiphene citrate only protocol in infertile women with normal ovulatory cycles. Method: Among 116 patients, 43 were received assisted reproductive technologies using natural ovulatory cycle, 38 and 35 were received clomiphene citrate only protocol and clomiphene citrate/GnRH antagonist combined protocol, respectively, and the clinical results were compared and analyzed Results: In each group, basal levels of LH, FSH, $E_2$ and FSH, $E_2$ on hCG day injected were not different, but LH level and endometrial thickness on hCG injected day were decreased significantly and the pregnancy rate was increased significantly in clomiphene citrate/GnRH antagonist group. Conclusion: The pregnancy rate was increased significantly in clomiphene citrate/GnRH antagonist group compared with natural ovulatory cycle and clomiphene citrate only group.

키워드

참고문헌

  1. Jonathan SB, Rebecca DR, Paula J, Eli Y. 13th ed. Novak's gynecology. Lipppincott Williams & Wilkins, 2002; 974-1018
  2. Speroff L, Glass RH, Kase NG. 6th ed. Clinical gynecologic endocrinology and infertility. Blatimore: Lippincott Williams & Wilkins, 1999; 1013-35
  3. Robert B, John K, Daniel RM, Richard JP. A prospective randomized trial comparing clomiphene citrate with tamoxifen citrate for ovulation induction. Fertil Steril 2001; 75: 1024-6 https://doi.org/10.1016/S0015-0282(01)01749-6
  4. Shaun CW, William EG, Suhell JM, Sergio O. Minimal ovarian hyperstimulation for in vitro fertilization using sequential clomiphene citrate and gonadotropin with or without the addition of a gonadotropin releasing hormone antagonist. Fertil Steril 2002; 78: 1068-72 https://doi.org/10.1016/S0015-0282(02)03374-5
  5. Diamond MP, Hill GA, Webster BW, Herbert CM, Rogers BJ, Osteen KG, et al. Comparison of human menopausal gonadotropin, clomiphene citrate and combined human menopausal gonadotropin-clomiphene citrate stimulation protocols for in vitro fertilization. Fertil Steril 1986; 46: 1108-12 https://doi.org/10.1016/S0015-0282(16)49889-4
  6. Adashi EY. Clomiphene citrate: mechanism(s) and site(s) of action - a hypothesis revisited. Fertil Steril 1984; 42: 331-44 https://doi.org/10.1016/S0015-0282(16)48069-6
  7. Kerin JF, Liu JH, Phillipou G, Yen SS. Evidence for a hypothalamic site of action of clomiphene citrate in women. J Clin Endocrinol Metab 1985; 61: 265-8 https://doi.org/10.1210/jcem-61-2-265
  8. Haritha S, Rajagopalan G. Folicular growth, endometrial thickness, and serum estradiol levels in spontaneous and clomiphene citrate-induced cycle. Int J Gyneco Obst 2003; 81: 287-92 https://doi.org/10.1016/S0020-7292(02)00404-6
  9. Tavaniotou A, Albano C, Smitz J, Devroey P. Effect of clomiphene citrate on follicular and luteal phase luteinizing hormone concentrations in in-vitro fertilization cycles stimulated with gonadotropins and gonadotropin-releasing hormone antagonist. Fertil Steril 2002; 77: 733-7 https://doi.org/10.1016/S0015-0282(01)03265-4
  10. Casper RF, Yen SS. Induction of luteolysis in the human with a ling-acting analog of luteinizing hormone-releasing factor. Science 1979; 205: 408-10 https://doi.org/10.1126/science.377491
  11. McLachlan RI, Cohen NL, Vale WW, Rivier JE, Burer HG, Brenner WJ, et al. The importance of luteinizing hormone in the control of inhibin and progesterone secretion by the human corpus luteum. J Clin Endocrionl Metab 1989; 68: 1078-85 https://doi.org/10.1210/jcem-68-6-1078
  12. Fujii S, Fukui A, Fukushi Y, Kagiya A, Sato S, Saito Y, et al. The effects of clomiphene citrate on normally ovulatory women. Fertil Steril 1997; 68: 997-9 https://doi.org/10.1016/S0015-0282(97)00394-4
  13. Martinez AR, Bernardus RE, Voorhorst FJ, Vermeiden JP, Schoemaker J. Intrauterine insemination does and clomiphene citrate does not improve fecundity in couples with infertility due to male or idiopathic factor: a prospective, randomized, controlled study. Fertil Steril 1990; 53: 847-53 https://doi.org/10.1016/S0015-0282(16)53520-1
  14. Sakae G, Kenji T, Keiko N, Takako Y, Yoichi N. Efficacy of clomiphene citrate and cyclofenil for infertile women with normal ovulatory cycles 2001; 76: 409-411 https://doi.org/10.1016/S0015-0282(01)01906-9
  15. Randall JM, Templeton A. The effects of clomiphene citrate upon ovulation and endocrinology when administered to patients with unexplained infertility. Hum Reprod 1991; 6: 256-60
  16. Stanger JD, Yovich JL. Reduced in-vitro fertilization of human oocytes from patients with raised basal luteinizing hormone levels during the follicular phase. Br J Obstet Gynecol 1985; 92: 385-93 https://doi.org/10.1111/j.1471-0528.1985.tb01113.x
  17. Howeles CM, Macnamee MC, Edward RG, Goswamy R, Speptoe PC. Effect of high tonic levels of luteinizing hormone on outcome of in-vitro fertilization. Lancet 1986; 2: 521-2
  18. Shoham Z, Borenstein R, Lunenfeld B, Parente C. Hormonal profiles following clomiphene citrate therapy in conception and nonconception cycles. Clin Endocrinol (Oxf) 1990; 33: 271-8 https://doi.org/10.1111/j.1365-2265.1990.tb00491.x
  19. Fisch P, Casper RF, Brown SE, Wrixon W, Collins JA, Reid RF, et al. Unexplained infertility: evaluation of treatment with clomiphene citrate and human chorionic gonadotropin. Fertil Steril 1989; 51: 828-33 https://doi.org/10.1016/S0015-0282(16)60674-X
  20. 이방현, 김정훈, 오영미, 김성훈, 채희동, 강병문. 체외수정 시술을 위한 과배란 유도에 있어 GnRH Antagonist 다회투여법과 GnRH Agonist 장기 요법의 비교 연구. 대한산부회지 2003; 46(6): 1202-8
  21. Frydman R, Belaisch-Allart J, Parneix I, Forman R, Hazout A, Testart J. Comparison between flare-up and down regulatio effect of luteinizing hormone-releasing hormone agonists in an in vitro fertilization program. Fertil Steril 1998; 50: 471-5
  22. 정진호, 김동호, 이상훈. 보조생식 시술의 과배란 유도에서 GnRH antagonist를 사용한 minimal stimulation protocol의 임상적 효용성에 관한 연구. 대한산부회지 2004; 47(1):38-44
  23. Leung, P.C.K. GnRH receptor and potential action in human ovary. Gynecol Endocrinol 1999; 13: 10
  24. Tummon IS, Daniel SAJ, Kaplan BR, Nisker JA, Yuzpe AA. Randomized prostpective comparison of luteal leuprolide acetate and gonadotropins versus CLomiphene citrate and gonadotropins in 408 first cycles of in vitro fertilization. Fertil Steril 1992; 58: 563-8 https://doi.org/10.1016/S0015-0282(16)55264-9
  25. Erb K, Klippping C, Duijkers K, Pechsterin B, Schulerler A, Hermann R. Pharmacodynamic effects and plasma pharmacokinetics of single doses of cetrorelix acetate in healthy premenopausal women. Fertil Steril 2001; 75: 316-23 https://doi.org/10.1016/S0015-0282(00)01702-7
  26. Dickey RP, Lotkamp DE. Development, pharmacology and clinical experience with clomiphene citrate. Hum Reprod Update 1996; 2: 483-506 https://doi.org/10.1093/humupd/2.6.483
  27. Yagel S, Ben-Chetrit A, Anteby E, Zacut D, HochnerCelnikier D, Ron M. The effect of ethinyl estradiol on endometrial thickness and uterine volume during ovulation induction by clomiphene citrate. Fertil Steril 1992; 57(1): 33-6 https://doi.org/10.1016/S0015-0282(16)54772-4
  28. Dickey RP, Taylor SN, Lu PY, Sartor BM, Pyrzak R. Clomiphene citrate intrauterine insemination before gonadotropin IUI affects the pregnancy rate and the rate of high-order multiple pregnancy. Fertil Steril 2004; 81(3): 545-9 https://doi.org/10.1016/j.fertnstert.2003.07.031
  29. Gelty TJ, Buyalos RP. The effect of clomiphene citrate and menopausal gonadotropins on cervical mucus in ovulatory cycles. Fertil Steril 1993; 60: 471-6 https://doi.org/10.1016/S0015-0282(16)56163-9
  30. Massai MR, Ziegler DD, LEsobre V, Cergeron C, Frydman R, Bouchard P. Clomiphene citrate affects cervical mucus and endometrial morphology independently of the changes in plasma hormonal levels induced by multiple follicular recruitment. Fertil Steril 1993; 59: 1179-86 https://doi.org/10.1016/S0015-0282(16)55973-1
  31. Thompson LA, Barratt CL, Thornton SJ, Bolton AE, Cooke ID. The effects of clomiphene citrate and cyclofenil on cervical mucus volume and receptivity over the periovulatory period. Fertil Steril 1993; 59: 125-9 https://doi.org/10.1016/S0015-0282(16)55627-1
  32. Cohen BM, Berry L, Roethemeyer V, Smith D. Sonographic assessment of late proliferative phase endometrium during ovulation induction. J Reprod MEd 1992; 37: 685-90
  33. Yagel S, Ben-chetrit A, Anteby E, ZAcut D, Hochmer-Celnikier D, Ron B. The effect of ethinyl estradiol on endometrial thickness and uterine volume during ovulation induction by clomiphene citrate. Fertil Steril 1992; 57: 33-6 https://doi.org/10.1016/S0015-0282(16)54772-4
  34. Dickey RP, Olar TT, Taylor SN, Curole DN, Matulich EM. Relationship of endometrial thickness and pattern to fecundity in ovulation induction cycles: effect of clomiphene citrate alone and with human menopausal gonadotropin. Fertil Steril 1993; 59: 756-60 https://doi.org/10.1016/S0015-0282(16)55855-5
  35. 이은실, 김동호, 배도환, 이상훈. 저반응군 환자에서 GnRH Antagonist를 이용한 과배란 유도의 효용성에 관한 연구. 대한산부회지 2003; 46(10): 1999-2004
  36. River JE, Perter J, Rivier CL. New effective GnRH antagonists with minimal potency for histamine release in vitro. J Med Chem 1986; 29: 1846-51 https://doi.org/10.1021/jm00160a008