Clinical and Experimental Reproductive Medicine

The Korean Society for Reproductive Medicine (대한생식의학회)
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GnRH Antagonist Versus Agonist Flare-up Protocol in Ovarian Stimulation of Poor Responder Patients

저 반응군의 체외수정시술을 위한 과배란유도에 있어 GnRH Antagonist 요법과 GnRH Agonist Flare Up 요법의 효용성에 관한 연구

  • Ahn, Young-Sun (Department of Obstetrics & Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Yeun, Myung-Jin (Department of Obstetrics & Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Cho, Yun-Jin (Department of Obstetrics & Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Kim, Min-Ji (Department of Obstetrics & Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Kang, Inn-Soo (Department of Obstetrics & Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Koong, Mi-Kyoung (Department of Obstetrics & Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Kim, Jin-Yeong (Department of Obstetrics & Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Yang, Kwang-Moon (Department of Obstetrics & Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Park, Chan-Woo (Department of Obstetrics & Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Kim, Hye-Ok (Department of Obstetrics & Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Cha, Sun-Hwa (Department of Obstetrics & Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University, College of Medicine) ;
  • Song, In-Ok (Department of Obstetrics & Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University, College of Medicine)
  • 안영선 (관동대학교 의과대학 제일병원 산부인과) ;
  • 연명진 (관동대학교 의과대학 제일병원 산부인과) ;
  • 조연진 (관동대학교 의과대학 제일병원 산부인과) ;
  • 김민지 (관동대학교 의과대학 제일병원 산부인과) ;
  • 강인수 (관동대학교 의과대학 제일병원 산부인과) ;
  • 궁미경 (관동대학교 의과대학 제일병원 산부인과) ;
  • 김진영 (관동대학교 의과대학 제일병원 산부인과) ;
  • 양광문 (관동대학교 의과대학 제일병원 산부인과) ;
  • 박찬우 (관동대학교 의과대학 제일병원 산부인과) ;
  • 김혜옥 (관동대학교 의과대학 제일병원 산부인과) ;
  • 차선화 (관동대학교 의과대학 제일병원 산부인과) ;
  • 송인옥 (관동대학교 의과대학 제일병원 산부인과)
  • Published : 2007.06.30
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Abstract

Objective: The aim of this study was to compare GnRH antagonist and agonist flare-up treatment in the management of poor responder patients. Methods: One hundred forty-four patients from Jan. 1, 2002 to Aug. 31, 2005 undergoing IVF/ICSI treatment who responded poorly to the previous cycle (No. of oocyte retrieved$\leq$5) and had high early follicular phase follicle stimulating hormone (FSH>12 mIU/ml were selected. Seventy-five patients received agonist flare-up protocol and 71 patients received antagonist protocol. We analyzed the number of oocytes retrieved, number of good embryos (GI, GI-1), total dose of hMG administered, implantation rate, cycle cancellation rate, pregnancy rate, live birth rate. Results: The cancellation rate was high in antagonist protocol (53.5% vs. 30.1%). The number of oocyte retrieved, the number of good embyos were high in agonist flare-up group. There was no statistical difference between GnRH agonist flare up protocol and GnRH antagonist protocol in implantation rate (14.5%, 10.1%), clinical pregnancy rate per transfer (29.4%, 21.2%) and live birth rate per transfer (21.6%, 18.2%). Although the result was not statistically significant, GnRH agonist flare up group showed a nearly doubled pregnancy rate and live birth rate per initial cycle than GnRH antagonist group. Conclusions: The agonist flare-up protocol appears to be slightly more effective than the GnRH antagonist protocol in implantation rate, pregnancy rate, live birth rate but shows statistically no significance. Agonist flare-up protocol improved the ovarian response in poor responders. However, based of the result of the study, we can expect improved ovarian response in poor responders by GnRH agonist flare up protocol.

목 적: 난소 반응이 저하된 환자에서 GnRH agonist flare up protocol과 GnRH antagonist protocol의 효용성을 비교하고자 하였다. 연구방법: 2003년 1월부터 2005년 8월까지 체외수정시술을 받은 환자들 가운데 이전의 체외수정시술 주기에서 5개 이하의 난자가 채취되고 기저 FSH 농도가 12 mIU/ml 이상인 총 144명 가운데 73명은 GnRH agonist flare up요법을 사용하였고 71명은 GnRH antagonist 요법을 사용하였다. 양군간에 주기의 취소율, 채취된 난자수, 양질의 수정란의 수, 착상율, 임신율, 출산율을 비교하였다. 결 과: 각 군간에 나이는 평균 37.4세와 38.1세로 antagonist group에서 높았으나 통계학적 유의성은 없었다. 그 외에 기저 FSH 농도와 이전 주기의 취소율도 통계학적 유의성은 없었다. GnRH agonist flare up 주기와 GnRH antagonist 주기에서 취소율은 각각 30.1%, 53.5%로 GnRH antagonist protocol에서 유의 있게 높게 나타났다. 채취된 난자수도 각각 4.18개와 2.16개로 차이를 보였으며 난소 과자극 기간은 각각 10.5일과 9.2일로 antagonist protocol에서 약간 낮은 모습을 보였다. 최고 혈중 E$_2$의 농도와 good embryo 개수도 GnRH agonist flare up요법에서 유의 있게 높게 나타났다. 각 군에서의 착상율, 이식 주기당 임신율, 이식 주기당 출생율은 GnRH agonist flare up요법에서 약간 높은 경향을 보이기는 하였으나 통계학적인 유의성은 없었다. 결 론: 두 군간의 비교에서 GnRH agonist flare up 요법이 시작 주기당 임신율, 출산율에서 높은 경향을 보였으나 통계학적 의의는 없었다. 하지만 난소기능이 저하된 환자에서 난자의 채취 개수는 GnRH agonist flare up 요법이 GnRH antagonist를 사용한 주기보다 의의있게 높게 나타났다. 이러한 연구 결과로 볼 때 저 반응군에 있어서 GnRH antagonist flare up요법이 저 반응군에 있어 향상된 난소 반응을 기대할 가능성이 높을 것으로 생각된다.

Keywords

References

  1. Pellicer A, Ardiles G, Neuspiller F, Remohi J, Simon C, Bonilla-Musoles F. Evaluation of the ovarian reserve in young low responders with normal basal FSH levels using 3-D ultrasound. Fertil Sterile 1998; 70: 671-5. https://doi.org/10.1016/S0015-0282(98)00268-4
  2. Keay SD, Liversedge NH, Mathur RS, Jenkins JM. Assisted conception following poor ovarian response to gonadotrophin stimulation. Br J Obstet Gynaecol 1997; 104: 521-7 https://doi.org/10.1111/j.1471-0528.1997.tb11525.x
  3. Land JA, Yarmolinskaya MI, Dumoulin JCM, Evers JLH. High-dose human menopausal gonadotrophin stimulation in poor responders does not improve in vitro fertilisation outcome. Fertil Steril 1996; 65: 961-5 https://doi.org/10.1016/S0015-0282(16)58269-7
  4. Garcia-Velasco JA, Isaza V, Requena A, Martinez-Salazar FJ, Land-azabal A, Remohi J, et al. high doses of gonadotropins combined with stop versus non-stop protocol of GnRH analogue administration in low responder IVF patients: a prospective, randomized, controlled trial. Human Reprod 2000; 15: 2292-6 https://doi.org/10.1093/humrep/15.11.2292
  5. Howles CM, Loumaye E, Germond M, Yates R, Brinsden P, Healy D, et al. Does growth hormone-releasing factor assist follicular development in poor responder patients undergoing ovarian stimulation for in-vitro fertilization? Hum Reprod 1999; 14: 1939-43 https://doi.org/10.1093/humrep/14.8.1939
  6. Lok IH, Yip SK, Cheung LP, Leung PHY, Haines CJ Adjuvant low-dose aspirin therapy in poor responders undergoing in vitro fertilization: a prospective, randomised, double-blind, placebo-controlled trial. Fertil Steril 2004; 81: 556-61 https://doi.org/10.1016/j.fertnstert.2003.07.033
  7. Surrey ES, Bower J, Hill DM. Clinical and endocrine effects of a microdose GnRH agonist flare regimen administered to poor responders who are undergoing in vitro fertilization. Fertil Steril 1998; 69: 419-24 https://doi.org/10.1016/S0015-0282(97)00575-X
  8. Schoolcraft W, Schlenker T, Gee M, Stevens J, Wagley L. Improved controlled ovarian hyperstimulation in poor responders in vitro fertilization patients with a microdose follicle stimulating hormone flare, growth hormone protocole. Fertil Steril 1997; 67: 93-7 https://doi.org/10.1016/S0015-0282(97)81862-6
  9. Sozos JF, Neri L, Shelley SE, Aby L, Arye H, Alex S. GnRH antagonist versus GnRH agonist in ovarian stimulation of poor responders undergoing IVF. J assist Reprod Genet 2003; 20: 455-60 https://doi.org/10.1023/B:JARG.0000006707.88826.e7
  10. Akman M, Erden H, Tosun S, Bayazit N, Akosy E, Bahceci M. Addition of GnRH antagonist in cycles of poor responders undergoing IVF. Hum Reprod 2000; 15: 2145-7 https://doi.org/10.1093/humrep/15.10.2145
  11. 박찬우, 차선화, 김해숙, 김혜옥, 양광문, 김진영 등. 37세 이상의 환자에서 체외수정시술 시 GnRH agonist주기와 GnRH antagonist 주기의 비교 연구. 대한불임학회지 2005; 32: 261-8
  12. Crosignani PG, Ragni G, Lombroso 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
  13. Garcia-Velasco JA, Isaza V, Requena A, Martinez-Salazar FJ, Landazabal A, Remohi J, et al. High doses of gonadotrophins combined with stop versus non-stop protocol of GnRH analogue administration in low responder IVF patients: a prospective, randomized, controlled trial. Hum Reprod 2000; 15: 2292-6 https://doi.org/10.1093/humrep/15.11.2292
  14. Kamel A. Mohamed, W.A.R. Davies, Julian Allsopp, Hany, Lashen. Agonist 'flare-up' versus antagonist in the management of poor responders undergoing in vitro fertilization treatment. Fertil Steril 2005; 83: 331-5 https://doi.org/10.1016/j.fertnstert.2004.07.963
  15. Stanley GP, Judith LB, Milton WM, John KT, Heather G, Renee M. Effect of GnRH antagonist on cancellation rates in IVF cycles. Fertil Steril 2003; 80: S182
  16. Malmusi S, La Marca A, Giulini S, Xella S, Tagliasacchi D, Marsella T, et al. Comparison of a gonadotropin-releasing hormone antagonist and GnRH agonist flare-up regimen in poor responders undergoing ovarian stimulation. Fertil Steril 2005; 84: 402-6 https://doi.org/10.1016/j.fertnstert.2005.01.139