GnRH antagonist rescue protocol combined with cabergoline versus cabergoline alone in the prevention of ovarian hyperstimulation syndrome: a randomized controlled trial

Usama M Fouda, Ahmed M Sayed, Hesham S Elshaer, Bahaa Eldin M Hammad, Mona M Shaban, Khaled A Elsetohy, Mohamed A Youssef, Usama M Fouda, Ahmed M Sayed, Hesham S Elshaer, Bahaa Eldin M Hammad, Mona M Shaban, Khaled A Elsetohy, Mohamed A Youssef

Abstract

Background: The aim of this study was to compare the efficacy of antagonist rescue protocol (replacing GnRH agonist with GnRH antagonist and reducing the dose of gonadotropins) combined with cabergoline versus cabergoline alone in the prevention of ovarian hyperstimulation syndrome (OHSS) in patients pretreated with GnRH agonist long protocol who were at high risk for OHSS.

Methods: Two hundred and thirty six patients were randomized in a 1:1 ratio to the cabergoline group or the antagonist rescue combined with cabergoline group. Both groups received oral cabergoline (0.5 mg/day) for eight days beginning on the day of HCG administration. In the antagonist rescue combined with cabergoline group, when the leading follicle reached 16 mm, GnRH agonist (triptorelin) was replaced with GnRH antagonist (cetrorelix acetate) and the dose of HP-uFSH was reduced to 75 IU/day. HCG (5,000 IU/I.M) was administered when the serum estradiol level dropped below 3500 pg/ml. The study was open label and the outcome assessors (laboratory staff and the doctor who performed oocyte retrieval) were blind to treatment allocation.

Results: The incidence of moderate/severe OHSS was significantly lower in the antagonist rescue combined with cabergoline group [5.08 % Vs 13.56 %, P value =0.025, OR = 0.342, 95 % CI, 0.129-0.906]. Four cycles were cancelled in the cabergoline group. There were no significant differences between the groups with respect to the number of retrieved oocytes, metaphase II oocytes, high quality embryos and fertilization rate. Moreover, the implantation and pregnancy rates were comparable between both groups.

Conclusion: GnRH antagonist rescue protocol combined with cabergoline is more effective than cabergoline alone in the prevention of OHSS.

Trial registration: Clinical trial.gov ( NCT02461875 ).

Keywords: Cabergoline; GnRH antagonist; IVF-ET; Ovarian hyperstimulation syndrome.

Figures

Fig. 1
Fig. 1
The flow of the patients in the study

References

    1. Kumar P, Sait SF, Sharma A, Kumar M. Ovarian hyperstimulation syndrome. J Hum Reprod Sci. 2011;4:70–5. doi: 10.4103/0974-1208.86080.
    1. Tang H, Hunter T, Hu Y, Zhai SD, Sheng X, Hart RJ. Cabergoline for preventing ovarian hyperstimulation syndrome. Cochrane Database Syst Rev. 2012;15:CD008605.
    1. Kosaka K, Fujiwara H, Tatsumi K, Yoshioka S, Sato Y, Egawa H, et al. Human chorionic gonadotropin (HCG) activates monocytes to produce IL-8 via a different pathway from luteinizing hormone (LH)/HCG receptor system. J Clin Endocrinol Metab. 2002;87:5199–208. doi: 10.1210/jc.2002-020341.
    1. Kosaka K, Fujiwara H, Yoshioka S, Fujii S. Vascular endothelial growth factor production by circulating immune cells is elevated in ovarian hyperstimulation syndrome. Hum Reprod. 2007;22:1647–51. doi: 10.1093/humrep/dem042.
    1. Busso CE, Garcia-Velasco J, Gomez R, Alvarez C, Simón C, Pellicer A. Symposium: update on prediction and management of OHSS. Prevention of OHSS--dopamine agonists. Reprod Biomed Online. 2009;19:43–51. doi: 10.1016/S1472-6483(10)60044-2.
    1. Leitao VM, Moroni RM, Seko LM, Nastri CO, Martins WP. Cabergoline for the prevention of ovarian hyperstimulation syndrome: systematic review and meta-analysis of randomized controlled trials. Fertil Steril. 2014;101:664–75. doi: 10.1016/j.fertnstert.2013.11.005.
    1. Baumgarten M, Polanski L, Campbell B, Raine-Fenning N. Do dopamine agonists prevent or reduce the severity of ovarian hyperstimulation syndrome in women undergoing assisted reproduction? A systematic review and meta-analysis. Hum Fertil (Camb) 2013;16:168–74. doi: 10.3109/14647273.2013.833348.
    1. Gustofson RL, Segars JH, Larsen FW. Ganirelix acetate causes a rapid reduction in estradiol levels without adversely affecting oocyte maturation in women pretreated with leuprolide acetate who are at risk of ovarian hyperstimulation syndrome. Hum Reprod. 2006;21:2830–7. doi: 10.1093/humrep/del059.
    1. Aboulghar MA, Mansour RT, Amin YM, Al-Inany HG, Aboulghar MM, Serour GI. A prospective randomized study comparing coasting with GnRH antagonist administration in patients at risk for severe OHSS. Reprod Biomed Online. 2007;15:271–9. doi: 10.1016/S1472-6483(10)60339-2.
    1. Rollene NL, Amols MH, Hudson SB, Coddington CC. Treatment of ovarian hyperstimulation syndrome using a dopamine agonist and gonadotropin releasing hormone antagonist: a case series. Fertil Steril. 2009;92:1169.e15–7. doi: 10.1016/j.fertnstert.2009.05.062.
    1. Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel group randomized trials. Ann Intern Med. 2001;134:657–62. doi: 10.7326/0003-4819-134-8-200104170-00011.
    1. Fouda UM, Sayed AM, Abdelmoty HI, Elsetohy KA. Ultrasound guided aspiration of hydrosalpinx fluid versus salpingectomy in the management of patients with ultrasound visible hydrosalpinx undergoing IVF-ET: a randomized controlled trial. BMC Womens Health. 2015;15:177. doi: 10.1186/s12905-015-0177-2.
    1. Golan A, Ron-el R, Herman A, Soffer Y, Weinraub Z, Caspi E. Ovarian hyperstimulation syndrome: an update review. Obstet. Gynecol. Surv. 1989;44:430–40. doi: 10.1097/00006254-198906000-00004.
    1. Agrawal R, Tan SL, Wild S, Sladkevicius P, Engnrann L, Payne N, et al. Serum vascular endothelium growth factor concentrations in in vitro fertilization cycles predict the risk of ovarian hyperstimulation syndrome. Fertil Steril. 1999;71:287–93. doi: 10.1016/S0015-0282(98)00447-6.
    1. D’Angelo A, Brown J, Amso NN. Coasting (withholding gonadotrophins) for preventing ovarian hyperstimulation syndrome. Cochrane Database Syst Rev. 2011;15:CD002811.
    1. Sher G, Salem R, Feinman M, Dodge S, Zouves C, Knutzen V. Eliminating the risk of life-endangering complications following overstimulation with menotropin fertility agents: a report on women undergoing in vitro fertilization and embryo transfer. Obstet Gynecol. 1993;81:1009–11.
    1. Mansour R, Aboulghar M, Serour G, Amin Y, Abou-Setta AM. Criteria of a successful coasting protocol for the prevention of severe ovarian hyperstimulation syndrome. Hum Reprod. 2005;20:3167–72. doi: 10.1093/humrep/dei180.
    1. Nardo LG, Cheema P, Gelbaya TA, Horne G, Fitzgerald CT, Pease EH, et al. The optimal length of ‘coasting protocol’ in women at risk of ovarian hyperstimulation syndrome undergoing in vitro fertilization. Hum Fertil (Camb) 2006;9:175–80. doi: 10.1080/14647270600787575.
    1. Leung PC, Cheng CK, Zhu XM. Multi-factorial role of GnRH-I and GnRH-II in the human ovary. Mol Cell Endocrinol. 2003;202:145–53. doi: 10.1016/S0303-7207(03)00076-5.
    1. Khosravi S, Leung PC. Differential regulation of gonadotropin releasing hormone (GnRH)I and GnRHII messenger ribonucleic acid by gonadal steroids in human granulosa luteal cells. J Clin Endocrinol Metab. 2003;88:663–72. doi: 10.1210/jc.2002-020866.
    1. Asimakopoulos B, Nikolettos N, Nehls B, Diedrich K, Al-Hasani S, Metzen E. Gonadotropin-releasing hormone antagonists do not influence the secretion of steroid hormones but affect the secretion of vascular endothelial growth factor from human granulosa luteinized cell cultures. Fertil Steril. 2006;86:636–41. doi: 10.1016/j.fertnstert.2006.01.046.
    1. Martínez F, Mancini F, Solé M, José Gomez M, Beatriz Rodríguez D, Buxaderas R, et al. Antagonist rescue of agonist IVF cycle at risk of OHSS: a case series. Gynecol Endocrinol. 2014;30:145–8. doi: 10.3109/09513590.2013.860128.
    1. Hill MJ, Chason RJ, Payson MD, Segars JH, Csokmay JM. GnRH antagonist rescue in high responders at risk for OHSS results in excellent assisted reproduction outcomes. Reprod Biomed Online. 2012;25:284–91. doi: 10.1016/j.rbmo.2012.05.004.
    1. Hejinen EMEW, Eijkemans MJC, De Klerk C, Polinder S, Beckers NGM, Klinkert ER, et al. A mild treatment strategy for in vitro fertilization: a randomised non inferiority trial. Lancet. 2007;369:743–9. doi: 10.1016/S0140-6736(07)60360-2.
    1. Karimzadeh MA, Ahmadi S, Oskouian H, Rahmani E. Comparison of mild stimulation and conventional stimulation in ART outcome. Arch Gynecol Obstet. 2010;281:741–6. doi: 10.1007/s00404-009-1252-4.
    1. Sher G, Zouves C, Feinman M, Maassarani G. “Prolonged coasting”: an effective method for preventing severe ovarian hyperstimulation syndrome in patients undergoing in-vitro fertilization. Human Reproduction. 1995;10:3107–9.
    1. Fluker MR, Hooper WM, Yuzpe A. Withholding gonadotropins (“coasting”) to minimize the risk of ovarian hyperstimulation during superovulation and in vitro fertilization-embryo transfer cycles. Fertil Steril. 1999;71:294–301. doi: 10.1016/S0015-0282(98)00438-5.
    1. Tsoumpou I, Muglu J, Gelbaya TA, Nardo LG. Symposium: update on prediction and management of OHSS. Optimal dose of HCG for final oocyte maturation in IVF cycles: absence of evidence? Reprod Biomed Online. 2009;19(1):52–8. doi: 10.1016/S1472-6483(10)60045-4.
    1. Whelan JG, 3rd, Vlahos NF. The ovarian hyperstimulation syndrome. Fertil Steril. 2000;73:883–96. doi: 10.1016/S0015-0282(00)00491-X.
    1. Schmidt DW, Maier DB, Nulsen JC, Benadiva CA. Reducing the dose of human chorionic gonadotropin in high responders does not affect the outcomes of in vitro fertilization. Fertil Steril. 2004;82:841–6. doi: 10.1016/j.fertnstert.2004.03.055.
    1. Kolibianakis EM, Papanikolaou EG, Tournaye H, Camus M, Van Steirteghem AC, Devroey P. Triggering final oocyte maturation using different doses of human chorionic gonadotrophin: a randomized pilot study in patients with polycystic ovary syndrome treated with gonadotropin-releasing hormone antagonists and recombinant follicle-stimulating hormone. Fertil Steril. 2007;88:1382–8. doi: 10.1016/j.fertnstert.2006.12.058.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel