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Early gonadotropin-releasing hormone antagonist protocol in women with polycystic ovary syndrome: A preliminary randomized trial

  • Shin, Jae Jun (Department of Obstetrics and Gynecology, Seoul National University College of Medicine) ;
  • Park, Kyung Eui (Department of Obstetrics and Gynecology, Seoul National University College of Medicine) ;
  • Choi, Young Min (Department of Obstetrics and Gynecology, Seoul National University College of Medicine) ;
  • Kim, Hye-Ok (Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine) ;
  • Choi, Dong-Hee (Department of Obstetrics and Gynecology, CHA Bundang Fertility Center, CHA University School of Medicine) ;
  • Lee, Woo Sik (Department of Obstetrics and Gynecology, CHA Gangnam Fertility Center, CHA University School of Medicine) ;
  • Cho, Jung-Hyun (Department of Obstetrics and Gynecology, CHA Gangnam Fertility Center, CHA University School of Medicine)
  • Received : 2018.04.13
  • Accepted : 2018.06.23
  • Published : 2018.09.30

Abstract

Objective: To prospectively evaluate the efficacy and safety of a fixed early gonadotropin-releasing hormone (GnRH) antagonist protocol compared to a conventional midfollicular GnRH antagonist protocol and a long GnRH agonist protocol for in vitro fertilization (IVF) in patients with polycystic ovary syndrome (PCOS). Methods: Randomized patients in all three groups (early antagonist, n = 14; conventional antagonist, n = 11; long agonist, n = 11) received 21 days of oral contraceptive pill treatment prior to stimulation. The GnRH antagonist was initiated on the 1st day of stimulation in the early antagonist group and on the 6th day in the conventional antagonist group. The GnRH agonist was initiated on the 18th day of the preceding cycle. The primary endpoint was the number of oocytes retrieved, and the secondary endpoints included the rate of moderate-to-severe ovarian hyperstimulation syndrome (OHSS) and the clinical pregnancy rate. Results: The median total number of oocytes was similar among the three groups (early, 16; conventional, 12; agonist, 19; p= 0.111). The early GnRH antagonist protocol showed statistically non-significant associations with a higher clinical pregnancy rate (early, 50.0%; conventional, 11.1%; agonist, 22.2%; p= 0.180) and lower incidence of moderate-to-severe OHSS (early, 7.7%; conventional, 18.2%; agonist, 27.3%; p= 0.463), especially among subjects at high risk for OHSS (early, 12.5%; conventional, 40.0%; agonist, 50.0%; p= 0.324). Conclusion: In PCOS patients undergoing IVF, early administration of a GnRH antagonist may possibly lead to benefits due to a reduced incidence of moderate-to-severe OHSS in high-risk subjects with a better clinical pregnancy rate per embryo transfer. Further studies with more subjects are required.

Keywords

References

  1. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 2004;89:2745-9. https://doi.org/10.1210/jc.2003-032046
  2. Diamanti-Kandarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC, Spina GG, et al. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab 1999;84:4006-11. https://doi.org/10.1210/jcem.84.11.6148
  3. Knochenhauer ES, Key TJ, Kahsar-Miller M, Waggoner W, Boots LR, Azziz R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol Metab 1998;83:3078-82.
  4. Hull MG. Epidemiology of infertility and polycystic ovarian disease: endocrinological and demographic studies. Gynecol Endocrinol 1987;1:235-45. https://doi.org/10.3109/09513598709023610
  5. Delvigne A, Demoulin A, Smitz J, Donnez J, Koninckx P, Dhont M, et al. The ovarian hyperstimulation syndrome in in-vitro fertilization: a Belgian multicentric study. I. Clinical and biological features. Hum Reprod 1993;8:1353-60. https://doi.org/10.1093/oxfordjournals.humrep.a138260
  6. Al-Inany H, Aboulghar M. GnRH antagonist in assisted reproduction: a Cochrane review. Hum Reprod 2002;17:874-85. https://doi.org/10.1093/humrep/17.4.874
  7. Pundir J, Sunkara SK, El-Toukhy T, Khalaf Y. Meta-analysis of GnRH antagonist protocols: do they reduce the risk of OHSS in PCOS? Reprod Biomed Online 2012;24:6-22. https://doi.org/10.1016/j.rbmo.2011.09.017
  8. Kolibianakis EM, Albano C, Kahn J, Camus M, Tournaye H, Van Steirteghem AC, et al. Exposure to high levels of luteinizing hormone and estradiol in the early follicular phase of gonadotropin- releasing hormone antagonist cycles is associated with a reduced chance of pregnancy. Fertil Steril 2003;79:873-80. https://doi.org/10.1016/S0015-0282(02)04920-8
  9. Park CW, Hwang YI, Koo HS, Kang IS, Yang KM, Song IO. Early gonadotropin-releasing hormone antagonist start improves follicular synchronization and pregnancy outcome as compared to the conventional antagonist protocol. Clin Exp Reprod Med 2014;41:158-64. https://doi.org/10.5653/cerm.2014.41.4.158
  10. Hwang JL, Seow KM, Lin YH, Huang LW, Hsieh BC, Tsai YL, et al. Ovarian stimulation by concomitant administration of cetrorelix acetate and HMG following Diane-35 pre-treatment for patients with polycystic ovary syndrome: a prospective randomized study. Hum Reprod 2004;19:1993-2000. https://doi.org/10.1093/humrep/deh375
  11. Lainas TG, Petsas GK, Zorzovilis IZ, Iliadis GS, Lainas GT, Cazlaris HE, et al. Initiation of GnRH antagonist on day 1 of stimulation as compared to the long agonist protocol in PCOS patients: a randomized controlled trial: effect on hormonal levels and follicular development. Hum Reprod 2007;22:1540-6. https://doi.org/10.1093/humrep/dem033
  12. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and longterm health risks related to polycystic ovary syndrome. Fertil Steril 2004;81:19-25.
  13. Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and longterm health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004;19:41-7. https://doi.org/10.1093/humrep/deh098
  14. Golan A, Weissman A. Symposium: update on prediction and management of OHSS. A modern classification of OHSS. Reprod Biomed Online 2009;19:28-32. https://doi.org/10.1016/S1472-6483(10)60042-9
  15. Bahceci M, Ulug U, Ben-Shlomo I, Erden HF, Akman MA. Use of a GnRH antagonist in controlled ovarian hyperstimulation for assisted conception in women with polycystic ovary disease: a randomized, prospective, pilot study. J Reprod Med 2005;50:84-90.
  16. Asch RH, Li HP, Balmaceda JP, Weckstein LN, Stone SC. Severe ovarian hyperstimulation syndrome in assisted reproductive technology: definition of high risk groups. Hum Reprod 1991;6:1395-9. https://doi.org/10.1093/oxfordjournals.humrep.a137276
  17. Forman RG, Frydman R, Egan D, Ross C, Barlow DH. Severe ovarian hyperstimulation syndrome using agonists of gonadotropinreleasing hormone for in vitro fertilization: a European series and a proposal for prevention. Fertil Steril 1990;53:502-9. https://doi.org/10.1016/S0015-0282(16)53348-2
  18. Lainas TG, Sfontouris IA, Zorzovilis IZ, Petsas GK, Lainas GT, Alexopoulou E, et al. Flexible GnRH antagonist protocol versus GnRH agonist long protocol in patients with polycystic ovary syndrome treated for IVF: a prospective randomised controlled trial (RCT). Hum Reprod 2010;25:683-9. https://doi.org/10.1093/humrep/dep436
  19. Al-Inany HG, Youssef MA, Ayeleke RO, Brown J, Lam WS, Broekmans FJ. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev 2016;4:CD001750.
  20. Griesinger G, Diedrich K, Tarlatzis BC, Kolibianakis EM. GnRH-antagonists in ovarian stimulation for IVF in patients with poor response to gonadotrophins, polycystic ovary syndrome, and risk of ovarian hyperstimulation: a meta-analysis. Reprod Biomed Online 2006;13:628-38. https://doi.org/10.1016/S1472-6483(10)60652-9
  21. Kolibianakis EM, Albano C, Camus M, Tournaye H, Van Steirteghem AC, Devroey P. Initiation of gonadotropin-releasing hormone antagonist on day 1 as compared to day 6 of stimulation: effect on hormonal levels and follicular development in in vitro fertilization cycles. J Clin Endocrinol Metab 2003;88:5632-7. https://doi.org/10.1210/jc.2003-030805