A Study for Clinical Efficacy of GnRH Antagonist (Cetrorelix) Minimal Stimulation Protocol in Assisted Reproductive Techniques for Polycystic Ovaian Syndrome

다낭성 난소증후군의 과배란유도시 GnRH Antagonist (Cetrorelix)를 병합한 Minimal Stimulation Protocol의 임상적 유용성에 관한 연구

  • Park, Sung-Dae (Department of Obstetrics and Gynecology, College of Medicine, Chung-Ang University) ;
  • Lee, Sang-Hoon (Department of Obstetrics and Gynecology, College of Medicine, Chung-Ang University)
  • 박성대 (중앙대학교 의과대학 산부인과학교실) ;
  • 이상훈 (중앙대학교 의과대학 산부인과학교실)
  • Published : 2002.12.30

Abstract

Objective : The aim of this study was to evaluate the outcomes of the GnRH antagonist (Cetrotide) minimal stimulation protocol comparing with GnRH agonist combined long step down stimulation protocol in PCOS patients. Materials and Method: From Apr 2001 to May 2002, 22 patients (22 cycles) were performed in controlled ovarian hyperstimulation using by GnRH antagonist and GnRH agonist for PCOS patients. GnRH antagonist (Cetrotide) combined minimal stimulation protocol was administered in 10 patients (10 cycles, Study Group) and GnRH agonist long step down stimulation protocol was administered in 12 patients (12 cycles, Control Group). We compared the pregnancy rate/cycle, total FSH (A)/cycle, Retrieved oocyte/cycle, the incidence of ovarian hyperstimulation syndrome, multiple pregnancy rate between the two groups. Student-t test were used to determine statistical significance. Statistical significance was defined as p<0.05. Results: Group of GnRH antagonist (Cetrorelix) minimal stimulation protocol produced fewer oocytes (6.4 versus 16.3 oocytes/cycle) using a lower dose of FSH (22.2 versus 36.1 Ample/cycle) and none developed OHSS and multiple pregnancy. Although the trends were in favour of the GnRH antagonist (Cetrorelix) protocol, the differences did not reach statistical significance. This was probably due to small sample size. Conclusion: The use of GnRH antagonist reduce the risk of ovarian hyperstimulation and multiple pregnancy. We suggest that GnRH antagonist might be alternative controlled ovarian hyperstimulation method, especially in PCOS patients who will be ovarian high response.

Keywords

References

  1. Tummon IS, Daniel SAJ, Kaplan BR, Nisker JA, Yuzpe AA. Randomized, prospective comparison of luteal leuprolide acetate and gonadotropins versus clomiphene citrate and gonadotropins in 408 first cycles of in vitro fertilizatin. Fertil Steril 1992; 58:563-8 https://doi.org/10.1016/S0015-0282(16)55264-9
  2. Poter RN, Smith W, Craft IL. Induction of ovulation for in vitro fertilization using buserelin and gonadotropins. Lancet II 1984; 1284-5
  3. Albrecht JL, Tomich PG. The maternal and neonatal outcome of triple gestations. American Journal of Obstetrics and Gynecology 1996; 174: 1551-6 https://doi.org/10.1016/S0002-9378(96)70605-1
  4. Judith AF Huirne, Cornelis B Lambalk. Gonadotropin-releasing-hormone-receptor antagonists. The Lancet 2001; 358: 1793-803 https://doi.org/10.1016/S0140-6736(01)06797-6
  5. Olivennes F, Fanchin R, Bouchard P, et al. The single or dual administration of the gonadotrophin-releasing hormone antagonist Cetrorelix is an in vitro fertilization-embryo transfer programme. Fertil Steril 1994; 62: 468-76 https://doi.org/10.1016/S0015-0282(16)56933-7
  6. Albano C, Riethmuller-Winzen H, Smitz J, Van Steirteghem A, Camus M, Devroey P. Comparison of different doses of gonadotropin-releasing hormone antagonist Cetrorelix during controlled ovarian hyperstimulation. Fertil Steril 1997;67;5:917-22
  7. Smitz J, Camus M, Devroey P. Incidence of severe ovarian hyperstimulation syndrome after GnRH agonist/HMG superovulation for in vitro fertilization. Hum Reprod 1990; 5: 933-40 https://doi.org/10.1093/oxfordjournals.humrep.a137223
  8. Graft I, Gorgy A, Jennifer H, Menon D, Podsiadly B. Will GnRH antagonists provide new hope for patients considered 'difficult responders' to GnRH agonist protocols? 1999; 12(22): 2959-62
  9. Andreyko JL, Marshall LA, Dumesic DA, Jaffe RB. Therapeutic uses of gonadotropin-releasing hormone analogs. Obstet Gynecol Surv 1987; 42: 1-21 https://doi.org/10.1097/00006254-198701000-00001
  10. Albano C, Platteau P, Devroey P. Gonadotropin releasing hormone antagonist: how good is the new hope? Curr Opin Obstet Gynecol 2001; 13: 257-62
  11. Albano C, Felberbaum R, Smitz J, et al. On behalf of the European Cetrorelix Study Group. Ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the luteinizing hormone-releasing hormone (LHRH)antagonist cetrorelix and the LHRH-agonist buserelin. Hum Reprod 2000; 3: 526-31
  12. Elchalal U, Schenken JG. The pathophysiology of ovarian hyperstimulation syndrome - views and ideas. Hum Reprod 1997; 12: 1129-37 https://doi.org/10.1093/humrep/12.6.1129
  13. Egbase PE, Sharhan M, Grudzinskas J. 'Early coasting' in patients with polycystic ovarian syndrome is consistent with good clinical outcome. Hum Reprod 2002; 17: 1212-6 https://doi.org/10.1093/humrep/17.5.1212
  14. Ulug U, Bahceci M, Erden H, Shalev E, Ben-Shlomo I. The significance of coasting duration during ovarian stimulation for conception in assisted fertilization cycles. Hum Reprod 2002; 17(2):310-3 https://doi.org/10.1093/humrep/17.2.310
  15. Demetrios M, Michael MA, Selwyn PO, Susan ML, Joseph FM, Spyros NP. Gonadotropin-releasing hormone antagonist versus agonist administration in women undergoing controlled ovarian hyperstimulation: Cycle performance and in vitro steroidogenesis of granulosa-lutein cells. American Journal of Obstetrics and Gynecology 1995; 172(5): 1518-25 https://doi.org/10.1016/0002-9378(95)90490-5
  16. Hoff JD, Lasley BL, Yen SSC. The functional relationship between priming and releasing actions of luteinizing hormone-releasing hormone. J Clin Endocrinol Metab 1979; 49: 8-15 https://doi.org/10.1210/jcem-49-1-8
  17. Yen SSC. The polycystic ovarian disease. Clin Endocrinol (Oxford) 1980; 12: 177-207 https://doi.org/10.1111/j.1365-2265.1980.tb02132.x
  18. Yen SSC, Jaffe RB. Reproduction. Endocrinology 3rd Ed, Philadelpia, WB Saunders 1991; 593-7
  19. Falcone T, Bourque J, Granger L, Hemmings R, Miron P. Polycystic ovary syndrome. Current Roblems Obset Gynecol Fertil 1993; 16: 72-89
  20. Gysler MG, March CM, Mishell DR, Gailey EJ. A decade's experience with an individualized clomiphene treatment regimen including its effect on the postcoital test. Fertil Steril 1982;37: 161-7 https://doi.org/10.1016/S0015-0282(16)46033-4
  21. Chung-hoon Kim, Hee-done C, Eun-hee K, Hyung-sik C, Byund-moon K, Yoon-seok C. The effects of somatostatin analogue on ovarian response to ovulation induction in patients with polycystic ovarian syndrome. 대한산부회지 1999; 42(3): 496-503
  22. Ben-Rafael Z, Strauss JF Ill, Mastroianni L Jr, Flickinger GL. Differences in ovarian stimulation in human menopausal gonadotropin treated woman may be related to follicle-stimulating hormone accumulation. Fertil Steril 1986; 46: 586-92 https://doi.org/10.1016/S0015-0282(16)49632-9
  23. Navot D, Margalioth EJ, Laufer N, Birkenfeld A, Relou A, Rosler A, et al. Direct correlation between plasma renin activity and severity of the ovarian hyperstimulation syndrome. Fertil Steril 1987;48:57-61
  24. Wu TCJ, Gelety TH, Jih MH, Fournet N, Buyalos RP. Successful management of predicted severe ovarian hyperstimulation syndrome with gonadotropin-releasing hormone agonist. J Assist Reprod Genet 1992; 622-4
  25. Itskovitz J, Boldes R, Levron J, Erlik Y, Kahana L, Brandes JM. Induction of preovulatory luteinizing hormone surge and prevention of ovarian hyperstimulation syndrome by gonadotropin-releasing hormone agonist. Fertil Steril 1991; 56:213-20 https://doi.org/10.1016/S0015-0282(16)54474-4
  26. Urman B, Pride SM, Yuen BH. Management of overstimulated gonadotrophin cycles with a controlled drift period. Hum Reprod 1992; 7: 918-22 https://doi.org/10.1093/oxfordjournals.humrep.a137770
  27. Hall JE. Gonadotropin-releasing hormone antagonists: Effects on the ovarian follicle and corpus luteum. Clin Obstet Gynecol 1993; 36:744-52 https://doi.org/10.1097/00003081-199309000-00031
  28. Borm G, Mannaerts B. The European Orgalutran Study Group. Treatment with the gonadotrophin releasing hormone antagonist ganirelix in women undergoing ovarian stimulation with recombinant follicle stimulating hormone is effective, safe and convenient: results of a controlled, randomized, multicentre trial. Hum Reprod 2000; 15: 1490-8 https://doi.org/10.1093/humrep/15.7.1490