GnRH agonist protokolü IVFsikluslarında GnRH antagonist protokol kadar etkin midir?

Yıl 2021, Cilt: 7 Sayı: 3, 415 - 423, 01.09.2021

Seda Şahin Aker Ruşen Aytaç

https://doi.org/10.53394/akd.981419

Öz

Giriş/Amaç:IVF-ET uygulanan 1000 siklusun GnRH antagonist ve agonist protokollerinin etkinliğinin karşılaştırılması amaçlanmıştır.
Gereç ve Yöntemler:1000 siklus çalışmaya dahil edilmiştir,bu siklusların 283?üne agonist protokol,717?sine antagonist protokol uygulanmıştır. Her iki protokol grubu demografik özellikleri, tedavi karakteristikleri, gebelik oranları açısından karşılaştırılmıştır.
Bulgular:Agonist protokol grubunda ?coasting? uygulaması ve OHSS gelişimi istatistiksel olarak yüksekti (p<0,001).Siklus iptal oranlarına bakıldığında antagonist protokol grubunda istatistiksel olarak anlamlı derecede yüksekti (p<0,001). Agonist protokol grubunda siklus başına kimyasal gebelik oranı %40,3 iken antagonist protokol grubunda %28,5?tir (p<0,001). Agonist protokol grubunda klinik gebelik oranı %31,4 devam eden gebelik oranı %27,2 iken antagonist grupta sırasıyla %27,2 ve %25,1?di(sırasıyla p=0,179 ve p=0,115). Agonist ve antagonist protokol grubunda transfer başına kimyasal gebelik oranı agonist protokol grubunda %42,1,antagonist protokol grubunda %32,8 idi . Agonist protokol grubunda bu oran istatistiksel olarak anlamlı derecede yüksek bulundu (p=0,08). Agonist protokol grubunda transfer başına klinik gebelik oranı %32,8,devam eden gebelik oranı %28,4?tü. Antagonist protokol grubunda bu oranlar sırasıyla %31,4,%28,9?du. Her iki protokol grubunda agonist gruptaki bu yükseklik istatistiksel olarak anlamlı değildi (sırasıyla p=0,660 ve p=0,873). Çalışmamızda klinik gebelik üzerine her iki protokol grubunun etkileri benzer bulunmuştur (OR=0,814,%95 CI=0,603-1,099;p=0,18). Kimyasal gebelik üzerinde GnRH agonist protokol daha başarılı bulunmuştur (OR =1,696,%95 CI=1,272-2,262;p<0,001). Devam eden gebelik üzerine etkisine bakıldığında her iki protokolün etkisinin benzer olduğu bulunmuştur (OR=1,115,%95 CI=0,817-1,523 ;p=493).
Sonuç:GnRH agonist ve GnRH antagonist protokol grubunda benzer klinik ve devam eden gebelik oranları bulunmuştur. GnRH agonist protokolün uzun stimülasyon süresi ve OHSS görülme sıklığı nedeniyle son yıllarda GnRH antagonist protokol seçimi tedavilerde öncelikle tercih edilmektedir.

Anahtar Kelimeler

GnRH agonist protokol, GnRH antagonist protokol, in vitro fertilizasyon, klinik gebelik oranı, overyan hiperstimülasyon sendromu

Is GnRH agonist protocol as effective as GnRH antagonist protocol in IVF cycles?

Öz

Objective:Aim of this study is to compare effectiveness of gonadotrophin releasing hormone (GnRH) agonist in-vitro fertilization(IVF) cycles compared to GnRH antagonist IVF cycles
Methods:In all, 1000 fresh cycles were used in analysis.GnRH agonist and GnRH antagonist were compared. Primary outcome measure of the study was ongoing pregnancy rate after 12 weeks of gestation.
Results:Agonist cycles had significantly more cases of coasting and OHSS (p<0,001). Cycle cancellation rates were more common in GnRH antagonist group (p<0,001).Biochemical pregnancy rates were higher in the GnRH agonist group (40.3% vs 28.5%) (p<0,001). Clinical pregnancy and ongoing pregnancy rates were higher in the GnRH agonist group (31,4% and 27,2% respectively) compared to GnRH antagonist group (27,2%, and 25,1% respectively)(p=0,179 and p=0,115 ). Biochemical pregnancy rates per cycle were higher in the GnRH agonist group (42,1% vs 32,8%) (p=0,008). Clinical pregnancy and ongoing pregnancy rates per cycle in GnRH agonist group (32,8% and 28,4%) were higher compared to GnRH antagonist group (31,4% and 28,9%,) (p=0,660) We found no significant difference in clinical pregnancy between groups(OR=0,814, 95% CI=0,603-1,099;p=0,18). GnRH agonist protocol was more succesful in biochemical pregnancy OR =1,696, 95 %CI=1,272-2,262;p<0,001). The ongoing pregnancy rates were similar between groups (OR=1,115, 95% CI=0,817-1,523 ;p=493).
Conclusion:GnRH agonist cycles have longer induction duration, and higher rates of OHSS, and similar pregnancy rates with antagonist cycles. GnRH agonist use in IVF cycles is falling behind GnRH antagonist use in contemporary practice.

Anahtar Kelimeler

GnRH agonist protocol, GnRH antagonist protocol, in vitro fertilisation, clinical pregnancy rate, overian hyperstimulation syndrome

Kaynakça

• 1. Gnoth C, Godehardt D, Godehardt E, Frank-Herrmann P, Freundl G. Time to pregnancy: results of the German prospective study and impact on the management of infertility. Hum Reprod 2003;18: 1959-66.
• 2. Vayena E, Rowe PJ,P.Griffin PD. Current Practices and Controversies in Assisted Reproduction. WHO Press 2002;83-101.
• 3. Steptoe PC, Edwards RG. Reimplantation of a human embryo with subsequent tubal pregnancy. Lancet;1976;31:750-751.
• 4. Steptoe PC, Edwards RG. Birth after reimplantation of a human embryo. Lancet;1978;12;2:366.
• 5. Janssens RM, Brus L,Cahill DJ,Huirne JA,Schoemaker J,Lambalk CB. Direct ovarian effects and safety aspects of GnRH agonists and antagonists. Hum Reprod Update 2000;6:505-18.
• 6. ART factsheet. European Society of Human Reproduction and Embryology. 2014.
• 7. Daya S, Maheshwari A, Siristatidis CS, Bhattacharya S, Gibreel AF. Gonadotropin-releasing hormone agonist protocols for pituitary desensitization in in vitro fertilization and gamete intrafallopian transfer cycles. Cochrane Database Systematic Review, 2000;(2):CD001299.
• 8.Sunkara SK, Coomarasamy A, Faris F,Braude P, Khalaf Y. Long gonadotropn-releasing hormone agonist versus short agonist versus antagonist regimens in poorresponders undergoing in in vitro fertilization: a randomized controlled trial. Fertil Steril 2014; 101(1):147–153.
• 9.Albuquerque LE, Tso LO, Saconato H, Albuquerque MC, Macedo CR. Depot versus daily administration of gonadotrophin-releasing hormone agonist protocols for pituitary down regulation in assisted reproduction cycles. Cochrane Database Syst Rev. 2013;1:CD002808.
• 10. Assisted Reproductive Technology National Summary Report. National Center for Chronic Disease Prevention and Health Promotion.2012;1:82 (https://www.cdc.gov/art/pdf/2012-report/art-2012-fertility-clinic-report.pdf).
• 11. CARTR Plus 2013 Report. The Canadian Assisted Reproductive Technologies Register(CARTR). (https://cfas.ca/cartr-annual-reports.html).
• 12.Wang YA, Healy D, Black D, Sullivan AD. Age-specific success rate for women undertaking their first assisted reproduction technology treatment using their own oocytes in Australia, 2002– 2005. Hum Reprod. 2008; 23(7):1633-8.
• 13.van Loendersloot LL, van Wely M, Limpens J, Bossuyt PM, Repping S. Predictive factors in in vitro fertilization(IVF) : a systematic review and meta-analysis. Hum Reprod Update. 2010;16(6):577-89.
• 14.Gesink Law DC, Maclehose RF, Longnecker MP. Obesity and time to pregnancy. Hum Reprod 2007;22(2):414–420.
• 15. Maheshwari A, Stofberg L, Bhattacharya S. Effect of overweight and obesity on assisted reproductive technology—a systematic review. Hum Reprod Update 2007;13(5):433–444.
• 16. Griesinger G, Felberbaum R, Diedrich K. GnRH antagonists in ovarian stimulation:a treatment regimen of clinicians' second choice? Data from the German national IVF registry. Hum Reprod 2005;20(9):2373-75.
• 17. Al-Inany HG, Abou-Setta AM, Aboulghar M. Gonadotrophin-releasing hormone antagonists for assisted conception: a Cochrane review. Reprod Biomed Online 2007:14(5):640-9.
• 18. Albano C, Felberbaum RE, Smitz J, et al. 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. European Cetrorelix Study Group. Hum Reprod. 2000;15(3):526–531.
• 19. Al Inany HG, Youssef MAFM, Aboulghar M, Broekmans FJ, Sterrenburg MD, Smit JG, Abou‐Setta AM. Gonadotrophin‐releasing hormone antagonists for assisted reproductive technology. Cochrane Database of Systematic Reviews 2011;5:CD001750.
• 20. Pundir J, Sunkara SK, El-Toukhy T, Khalaf Y. Meta-analysis of GnRH antagonist protocols: do they reduce the risk of OHSS in PCOS? Reproductive BioMedicine Online 2012;24:6-22.
• 21. Xiao JS, Su CM, Zeng XT. Comparisons of GnRH antagonist versus GnRH agonist protocol in supposed normal ovarian responders undergoing IVF: a systematic review and meta-analysis. PLoS One. 2014;9(9):e106854.
• 22. Griesinger G, Diedrich K, Devroey P, Kolibianakis EM. GnRH agonist for triggering final oocyte maturation in the GnRH antagonist ovarian hyperstimulation protocol: a systematic review and meta-analysis. Hum Reprod Update 2006;12(2),159–168.
• 23.Humaidan P, Bredkjaer HE, Bungum L, et al. GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study. Hum Reprod. 2005;20(5):1213–1220.
• 24. Youssef MAFM, Van der Veen F, Al‐Inany HG, Mochtar MH, Griesinger G, Nagi Mohesen M, Aboulfoutouh I, van Wely M. Gonadotropin‐releasing hormone agonist versus HCG for oocyte triggering in antagonist‐assisted reproductive technology. Cochrane Database of Systematic Reviews 2014;10:CD008046.
• 25. Humaidan P, Polyzos NP. Human chorionic gonadotropin vs. gonadotropin-releasing hormone agonist trigger in assisted reproductive technology—“The king is dead, long live the king!”. Fertil Steril 2014;102(2):339-341.
• 26. The European and Middle East Orglutron Study Group. Comparable clinical outcome using the GnRH antagonist ganirelix or a long protocol of the GnRH agonist triptorelin for the prevention of premature LH surges in women undergoing ovarian stimulation. Hum Reprod 2001;16(4): 644-51.
• 27. Kolibianakis M, Collins J, Tarlatzis BC, Devroey P, Diedrich K, Griesinger G. Among patients treated for IVF with gonadotropins and GnRH analogues, is the probability of live birth dependent on the type of analogue used? A systematic review and meta-analysis. Hum Reprod Update 2006;12(6):651-71.
• 28. Badrawi A, Al-Inany H, Hussein M, Zaki S, Ramzy AM. Agonist versus antagonist in ICSI cycles :a randomized trial and cost effectiveness analysis. Middle East Society Journal 2005;10(1):49-54.
• 29. Xavier P, Gamboa C, Calejo L, et al. A randomised study of GnRH antagonist (cetrorelix) versus agonist (busereline) for controlled ovarian stimulation: effect on safety and efficacy. Eur J Obstet Gynecol Reprod Biol. 2005;120(2):185–189
• 30. Luo S, Li S, Li X, Bai Y, Jin S. Effect of gonadotropin-releasing hormone antagonists on intrauterine insemination cycles in women with polycystic ovary syndrome: a meta-analysis. Gynecological Endocrinology 2014;30(4):255-259.
• 31. Al-Inany H, Aboulghar MA. GnRH antagonist in assisted reproduction Cochrane systematic review. Hum Reprod 2002;17(4):874-85.
• 32. Practice Committee of the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile female: a committee opinion. Fertil Steril. 2015;103(6):44–50.
• 33. Schally AV, Arimura A, Kastin AJ. Gonadotropin-releasing hormone:one polypeptide regulates secretion of luteinizing and follicle stimulating hormones. Science 1971;173:1036-8.
• 34. The Practice Committee of the American Society for Reproductive Medicine. Ovarian hyperstimulation syndrome. Fertil Steril 2008;90(3):188-93.