Clinical and Experimental Reproductive Medicine

  • 제36권1호
  • /
  • Pages.63-70
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  • 2009
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  • 2233-8233(pISSN)
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  • 2233-8241(eISSN)
대한생식의학회 (The Korean Society for Reproductive Medicine)
권호 표지

고령 불임여성의 체외수정술시 최소자극법의 효용성

Minimal Stimulation using rhFSH and GnRH Antagonist for IVF Treated Patients of Advanced Age

  • 김소라 (울산대학교 의과대학 서울아산병원 산부인과) ;
  • 김정훈 (울산대학교 의과대학 서울아산병원 산부인과) ;
  • 이진경 (울산대학교 의과대학 서울아산병원 산부인과) ;
  • 전균호 (울산대학교 의과대학 서울아산병원 산부인과) ;
  • 김성훈 (울산대학교 의과대학 서울아산병원 산부인과) ;
  • 채희동 (울산대학교 의과대학 서울아산병원 산부인과) ;
  • 강병문 (울산대학교 의과대학 서울아산병원 산부인과)
  • Kim, So-Ra (Department of Obstetrics and Gynecology, College of Medicine, University of Ulsan, Asan Medical Center) ;
  • Kim, Chung-Hoon (Department of Obstetrics and Gynecology, College of Medicine, University of Ulsan, Asan Medical Center) ;
  • Lee, Jin-Kyoung (Department of Obstetrics and Gynecology, College of Medicine, University of Ulsan, Asan Medical Center) ;
  • Jeon, Gyun-Ho (Department of Obstetrics and Gynecology, College of Medicine, University of Ulsan, Asan Medical Center) ;
  • Kim, Sung-Hoon (Department of Obstetrics and Gynecology, College of Medicine, University of Ulsan, Asan Medical Center) ;
  • Chae, Hee-Dong (Department of Obstetrics and Gynecology, College of Medicine, University of Ulsan, Asan Medical Center) ;
  • Kang, Byung-Moon (Department of Obstetrics and Gynecology, College of Medicine, University of Ulsan, Asan Medical Center)
  • 발행 : 2009.03.31
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초록

목 적: 본 연구는 전향적 무작위 배정법 연구로 40세 이상의 불임여성의 자연주기에서 소량의 재조합난포자극호르몬을 이용한 최소자극법의 효과를 성선자극호르몬분비호르몬길항제 다회투여법과 비교 분석하고자 한다. 연구방법: 불임크리닉을 방문하였던 환자들 중 나이가 40세 이상인 75명 환자들을 대상으로 시행하였다. 연구군은 최소자극법으로 37명, 대조군은 성선자극호르몬분비호르몬길항제 다회투여법으로 38명의 환자들로 구성되었으며 모두 체외수정시술을 시행 받았다. 주기 취소율, 난포자극호르몬 종 사용량과 일수, 성숙난자의 수, 이식된 배아의 수, 배아이식 주기당 임신율, 착상율 등을 비교하였으며, 통계학적인 방법은 평균값의 비교를 위하여 Student's t-test를 이용하였고 분율의 비교를 위하여 ${\chi}^2$ 검정, Fisher's exact test를 사용하였으며, p값이 0.05 미만인 경우에 통계학적으로 유의하다고 판정하였다. 결 과: 두 군간의 대상 환자들의 기본적인 특성은 차이가 없었다. rhFSH의 투여기간과 총용량에서 연구군의 경우 4.5${\pm}$1.2일, 632.2${\pm}$123.7 IU로 대조군에서의 11.3${\pm}$2.7일, 3124.6${\pm}$452.1 IU에 비하여 통계학적으로 유의하게 낮은 값을 보였고, 주기 취소율은 연구군에서 16.2%, 대조군에서 5.3%로 통계적으로 유의성은 없었다. 회수된 난자의 수, 성숙한 제 2감수분열 중기 상태의 난자의 수 및 수정된 난자의 수, 양질의 배아수, 배아이식된 배아의 수에 있어서 대조군에 비해서 연구군에서 통계적으로 유의하게 낮았다. 배란유도를 시작한 주기당 임상적 임신율과 배아이식 주기당 임상적임신율은 연구군의 경우 각각 10.8%와 13.4%로 대조군에서 13.2%와 13.9%에 비하여 다소 낮긴 하였으나 통계학적으로 유의성은 없었다. 착상율, 자연유산율에서는 두 군간의 차이가 없었다. 결 론: 40세 이상의 고령 여성에서 체외수정술을 시행하고자 할 때 배란유도의 방법으로 GnRH antagonist와 성선자극호르몬을 이용한 최소자극법은 성선자극호르몬분비호르몬길항제 다회투여법과 비교하여 임신율이 감소하지 않으며 비용면에서 효율적이고 효과적인 방법이다.

Objective: This study was performed to investigate the effectiveness of minimal stimulation using rhFSH and GnRH antagonist compared with GnRH antagonist multidose protocol (MDP) in IVF treated patients with aged 40 and above. Methods: Seventy-five patients with aged 40 and above were equally randomized to minimal stimulation group (n=37) or GnRH antagonist MDP group (n=38). For minimal stimulation group, ultrasound monitoring was started on cycle day 7 or 8. Daily injections of 0.25 mg cetrorelix together with 150 IU rhFSH were started from the day at 13${\sim}$14 mm of a leading follicle diameter. For GnRH antagonist MDP group, daily injections of 225 IU rhFSH were initiated from cycle day 2 and GnRH antagonist was started at a dose of 0.25 mg/day on rhFSH stimulation day 6 or the day at 13${\sim}$14 mm of leading follicle diameter. In both groups, transvaginal ultrasound-guided oocyte retrieval was performed. According to cleavage and morphologic characteristics of embryos, embryos were transferred 3 to 5 days after oocyte retrieval. Results: There were no differences in patients' characteristics and cycle cancellation rate between the two groups. Total dose and duration of rhFSH used were significantly fewer and shorter in minimal stimulation group than those in GnRH antagonist MDP group. The numbers of oocytes retrieved, mature oocytes and transferred embryos were also lower in minimal stimulation group. However, there were no significant differences in the clinical pregnancy rate and miscarriage rate between the two groups. Conclusions: This study demonstrates that minimal stimulation protocol provides comparable pregnancy rates to GnRH antagonist MDP with fewer dose and days of rhFSH used, and thus can be a cost-effective alternative in women aged 40 and above.

키워드

참고문헌

  1. Loutradis D, Drakakis P, Milingos S, et al. Alternative approaches in the management of poor response in controlled ovarian hyperstimulation. Ann N Y Acad Sci 2003; 997: 112-9 https://doi.org/10.1196/annals.1290.013
  2. Surrey E, Bower J, Hill D, Ramsey J, Surrey M. Clinical and endocrine effects of a microdose GnRH agonist flare regime administered to poor responders who are undergoing in vitro fertilization. Fetil Steril 1998; 69: 419-24 https://doi.org/10.1016/S0015-0282(97)00575-X
  3. Detti L, Williams D, Robins J, Maxwell R, Thomas M. A comparison of three down regulation approaches for poor responders undergoing in vitro fertilization. Fertil Steril 2005; 84: 1401-5 https://doi.org/10.1016/j.fertnstert.2005.04.053
  4. Homburg R, Ostergard H. Clinical application of growth hormone for ovarian stimulation. Hum Reprod Update 1995; 1: 264-75 https://doi.org/10.1093/humupd/1.3.264
  5. Battaglia C, Salvatori M, Maxia N, Petraglia F, Facchinetti F, Volpe A. Adjuvant L-arginine treatment for in-vitro fertilization in poor responder patients. Hum Repod 1999; 14: 1690-7 https://doi.org/10.1093/humrep/14.7.1690
  6. Kim CH, Chae HD, Chang YS. Pyridostigmine cotreatment for controlled ovarian stimulation in low responders undergoing in-vitro fertilization embryo transfer. Fertil Steril 1999; 71:652-7 https://doi.org/10.1016/S0015-0282(98)00527-5
  7. Keay SD, Lenton EA, Coole ID, Hull MGR, Jenkins JM. Low-dose dexamethasone augments the ovarian response to exogenous gonadotropins leading to a reduction in cycle cancellation rate in a standard IVF program. Hum Reprod 2001; 16: 1861-5 https://doi.org/10.1093/humrep/16.9.1861
  8. Casson PR, Lindsay EA, Pisarska MD, Carson SA, Buster JE. Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Hum Reprod 2000; 15: 2129-32 https://doi.org/10.1093/humrep/15.10.2129
  9. Check JH. In vitro fertilization is expensive: when should a couple be advised to stop trying with their own gamates and week other options? Review of three cases. Clin Exp Obstet Gynecol 2008; 35: 5-9
  10. Reyftmann L, Dechaud H, Loup V, Anahory T, Brunet-Joyeux C, Lacroix N, et al. Natural cycle in vitro fertilization cycle in poor responders. Gynecol Obstet Fertil 2007; 35: 352-8 https://doi.org/10.1016/j.gyobfe.2007.01.025
  11. Check JH, Chase J. Ovulation induction in hypergonadotropic amenorrhea with estrogen and human menopausal gonadotropin therapy. Fertile Steril 1984; 42: 919-22 https://doi.org/10.1016/S0015-0282(16)48266-X
  12. Check JH, Chase JS, Wu CH, Adelson HG. Ovulation induction and pregnancy with an estrogen-gonadotropin stimulation technique in a menopausal woman with marked hypoplasitc ovaries. Fertil Steril 1989; 160: 405-6
  13. Check JH, Katsoff B, Brasile D, Choe JK, Amui J. Pregnancy outcome following in vitro fertilization-embryo transfer (IVFET) in women of more advanced reproductive age with elevated serum follicle stimulating hormone (FSH) levels. Clin Exp Obstet Gynecol 2008; 35: 13-5
  14. Check JH, Peymer M, Lurie D. Effect of age on pregnancy outcome without assisted reproductive technology in women with elevated early follicular phase serum follicle-stimulating hormone levels. Gynecol Obstet Investig 1998; 45: 217-20 https://doi.org/10.1159/000009970
  15. Crosignani PG, Ragni G, Lombrosso GC, Scarduelli C, de Lauretis L, Caccamo A, et al. IVF: Induction of ovulation in poor responders. J Steroid Biochem 1989; 32: 171-3 https://doi.org/10.1016/0022-4731(89)90160-X
  16. Surrey ES, Schoolcraft WB. Evaluation strategies for improving ovarian response of the poor responder undergoing assisted reproductive techniques. Fertil Steril 2007; 73: 667-76 https://doi.org/10.1016/S0015-0282(99)00630-5
  17. Karacan M, Erkan H, Karabulut O, Sarikamis B, Camlibel T, Benhabib M. Clinical pregnancy rates in an IVF program:Use of the flare-up protocol after failure with long regimens of GnRH-a. J Reprod Med 2001; 46: 485-9
  18. Maroulis GB. Effect of aging on fertility and pregnancy. Seminars Reprod Endocrinol 1991; 9: 165 https://doi.org/10.1055/s-2007-1019407
  19. Gougeon A, Echochard R, Thalabard JC. Age-related changes of the population of human ovarian follicles: increase in the disappearance rate of non-growing and early-growing follicles in aging women. Biol Reprod 1994; 50: 653 https://doi.org/10.1095/biolreprod50.3.653
  20. Paulson RJ, Sauer MV, Lobo RA. Addition of a gonadotropin releasing hormone (GnRH) antagonist and exogenous gonadotropins to unstimulated in vitro fertilization (IVF) cycles:physiologic observation and preliminary experience. J Assist Reprod Genet 1994; 11: 28-32 https://doi.org/10.1007/BF02213694
  21. Ramsewak SS, Kumar A, Welsby R, Mowforth A, Lenton EA, Cooke ID. Is analgesia required for transvaginal single-follicle aspiration in in vitro fertilization? A double-blind study. J In Vitro Fert Embryo Transf 1990; 7: 103-6 https://doi.org/10.1007/BF01135583
  22. Biggers JD, Summers MC. When to avoid creating surplus human embryos. Hum Reprod 2004; 19: 2457-9 https://doi.org/10.1093/humrep/deh476
  23. Rongieres-Bertrand C, Olivennes F, Righini C, Fanchin R, Taieb J, Hamamah S. Revival of the natural cycles in in-vitro fertilization with the use of a new gonadotropin-releasing hormones antagonist (Cetrorelix): a pilot study with minimal stimulation. Hum Reprod 1999; 14: 683-8 https://doi.org/10.1093/humrep/14.3.683
  24. Weghofer A, Margreiter M, Bassim S, Sevelda U, Beilhack E, Feichtinger W. Minimal stimulation using recombinant folliclestimulation hormone and a gonadotropin-releasing hormone antagonist in women of advanced age. Fertil Steril 2004; 81:1002-6 https://doi.org/10.1016/j.fertnstert.2003.09.050
  25. Elizur SE, Aslan D, Shulman A, Weisz B, Bider D, Dor J. Modified natural cycle using GnRH antagonist can be an optional treatment in poor responders undergoing IVF. J Assist Reprod Genet 2005; 22: 75-9 https://doi.org/10.1007/s10815-005-1496-2
  26. Janssens RM, Lambalk CB, Vermeiden JP, Schats R, Schoemaker J. In-vitro fertilization in a spontaneous cycle:easy, cheap and realistic. Hum Reprod 2000; 15: 314-8 https://doi.org/10.1093/humrep/15.2.314