Impact of Gonadotrophin Releasing Hormone Antagonist Duration on In-Vitro Fertilization Outcome

Abstract

Objective: To evaluate whether oocyte quality, implantation and pregnancy rates in intra-cytoplasmic sperm injection (ICSI) cycles are related to the duration of gonadotrophin-releasing hormone antagonist (GnRH-ant) use. Material and Method: A total of 138 patients who were treated with GnRH-ant protocol at the IVF Clinic from March 2010 to January 2012 were enrolled in this study. The patients were classified into three groups according to duration of GnRH-ant use. Group 1: 4 days (n=51); group 2:5 days (n=57); group 3:6 days (n=30) antagonist application. Main outcome measures were implantation rate, pregnancy rate, fertilization rate, number of oocytes retrieved (NOR), number of mature oocytes (NMO). Results: The NOR and NMO were the lowest in group 1, intermediate in group 2, and the highest in group 3 respectively. There is no statistically significant difference between the groups in regard to total gonadotrophins used, fertilization, implantation or pregnancy rates. The pregnancy rates per ET and cycle were 37.9% and 31.8%, respectively. Conclusion: We noticed that longer GnRH-ant use was associated with more oocytes retrieved and more mature oocytes, but no difference in fertilization, implantation or pregnancy rates concluding that longer GnRH-ant use does not have a detrimental effect on in vitro fertilization outcome.

Keywords

• GnRH antagonist duration, Fertilization, Implantation, Pregnancy.

Gonadotropin Salgılatıcı Hormon Antagonisti Uygulama Süresinin In-Vitro Fertilizasyon Sonuçlarına Etkisi

Öz

Amaç: Gonadotropin salgılatıcı hormon antagonisti (GnRH-ant) kullanım süresinin, in vitro fertilizasyon (IVF)/ intra-sitoplazmik sperm enjeksiyonu (ICSI) sikluslarında oosit kalitesi, implantasyon ve gebelik oranlarına etkisi olup olmadığını araştırmak. Gereç ve Yöntem: IVF kliniğimizde Mart 2010- Ocak 2012 tarihleri arasında GnRH-ant protokolü ile tedavi edilen 138 hasta çalışmaya dahil edildi. Hastalar GnRH-ant kullanım sürelerine göre 3 gruba ayrıldı. Grup 1: 4 gün (n=51); grup 2: 5 gün (n=57); grup 3: 6 gün (n=30). İmplantasyon, fertilizasyon ve gebelik oranları, toplanan oosit sayısı (TOS) ve matür oosit sayısı (MOS) bakılan ana parametrelerdir. Bulgular: Sonuçlara bakıldığında; TOS ve MOS grup1'de en düşük, grup 2'de orta ve grup 3'te en yüksek sayıda gözlendi. Gruplar arasında kullanılan toplam gonadotropin dozu, fertilizasyon oranı, implantasyon ve gebelik oranları açısından istatistiki anlamlı bir fark görülmedi. Siklus ve embriyo transferi başına görülen gebelik oranlarımız sırasıyla %31.8 ve %37.9 idi. Sonuç: Çalışmamızda GnRH-ant kullanım süresi uzadıkça toplanan oosit ve matür oosit sayısının arttığını, fakat fertilizasyon, implantasyon ve gebelik oranlarının fark etmemesi üzerinden, uzamış antagonist uygulamasının IVF sonucuna negatif etki oluşturmadığını gözlemledik.

Anahtar Kelimeler

• GnRH antagonist süresi, Fertilizasyon, İmplantasyon, Gebelik.

References

1. Fluker M, Grifo J, Leader A, et al. North American Ganirelix Study Group. Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation. Fertil Steril 2001; 75: 38-45.
2. Al-Inany HG, Youssef MA, Aboulghar M, et al. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev 2011; 5: CD001750.
3. Borm G, Mannaerts B. Treatment with the gonadotropinreleasing 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. The European Orgalutran Study Group. Hum Reprod 2000; 15: 1490-8.
4. Lindheim SR, Morales AJ. GnRH antagonists followed by a decline in serum estradiol results in adverse outcomes in donor oocyte cycles. Hum Reprod 2003; 18: 2048-51.
5. Al-Inany HG, Abou-Setta AM, Aboulghar M. Gonadotropinreleasing hormone antagonists for assisted conception. Cochrane Database Syst Rev 2006; 3: CD001750.
6. Hernandez ER. Embryo implantation and GnRH-antagonists. Rubicon for GnRH antagonists. Hum Reprod 2000; 15: 1211
7. Duijkers IJ, Klipping C, Willemsen WN, et al. Single and multiple dose pharmacokinetics and pharmacodynamics of the gonadotropin-releasing hormone antagonist cetrorelix in healthy female volunteers. Hum Reprod 1998; 13: 2392-8.
8. Detti L, Ambler DR, Yelian FD, Kruger ML, Diamond MP, Puscheck EE. Timing and duration of use of GnRH antagonist down-regulation for IVF/ICSI cycles have no impact on oocyte quality or pregnancy outcomes. J Assist Reprod Genet 2008; 25: 177-81.

9. Ludwig M, Katalinic A, Diedrich K. Use of GnRH antagonists in ovarian stimulation for assisted reproductive technologies compared to the long protocol. Meta-analysis. Arch Gynecol Obstet 2001; 265: 175-82.
10. Ortmann O, Diedrich K. Pituitary and extrapituitary actions of gonadotrophin- releasing hormone and its analogues. Hum Reprod 1999; 14: 194-206.
11. Kinay T, Tasci Y, Dilbaz S, Cinar O, Demir B, Haberal A. The relationship between endometrial thickness and pregnancy rates in GnRH antagonist down-regulated ICSI cycles. Gynecol Endocrinol 2010; 26: 833-7.
12. Serhal PF, Ranieri DM, Kinis A, Marchant S, Davies M, Khadum IM. Oocyte morphology predicts outcome of intracytoplasmic sperm injection. Hum Reprod 1997; 12: 1267-70.
13. Loutradis D, Drakakis P, Kallianidis K, Milingos S, Dendrinos S, Michalas S. Oocyte morphology correlates with embryo quality and pregnancy rate after intracytoplasmic sperm injection. Fertil Steril 1999; 72: 240-4.
14. Otsuki J, Okada A, Morimoto K, Nagai Y, Kubo H. The relationship between pregnancy outcome and smooth endoplasmic reticulum clusters in MII human oocytes. Hum Reprod 2004; 19: 1591-7.
15. Ebner T, Moser M, Sommergruber M, et al. Occurrence and developmental consequences of vacuoles throughout preimplantation development. Fertil Steril 2005; 83: 1635-40.
16. Ebner T, Moser M, Sommergruber M, Tews G. Selection based on morphological assessment of oocytes and embryos at different stages of preimplantation development: a review. Hum Reprod Update 2003; 9: 251-62.
17. Murber A, Fancsovits P, Ledó N, Gilán ZT, Rigó J Jr, Urbancsek J. Impact of GnRH analogues on oocyte/embryo quality and embryo development in in vitro fertilization/intracytoplasmic sperm injection cycles: a case control study. Reprod Biol Endocrinol 2009; 7: 103.
18. Depalo R, Lorusso F, Palmisano M, et al. Follicular growth and oocyte maturation in GnRH agonist and antagonist protocols for in vitro fertilisation and embryo transfer. Gynecol Endocrinol 2009; 25: 328-34.
19. Bahçeci M, Ulug U, Erden HF, Tosun S, Ciray N. Frozenthawed cleavage-stage embryo transfer cycles after previous GnRH agonist or antagonist stimulation. Reprod Biomed Online 2009; 18: 67-72.
20. Detti L, Yelian FD, Kruger ML, et al. Endometrial thickness is related to miscarriage rate, but not to the estradiol concentration, in cycles down-regulated with gonadotrophin-releasing hormone antagonist. Fertil Steril 2008; 89: 998-1001.
21. Papanikolaou EG, Camus M, Fatemi HM, et al. Early pregnancy loss is significantly higher after day 3 single embryo transfer than after day 5 single blastocyst transfer in GnRH antagonist stimulated IVF cycles. Reprod Biomed Online 2006; 12: 60-5.
22. Zikopoulos K, Kolibianakis EM, Camus M, et al. Duration of gonadotropin-releasing hormone antagonist administration does not affect the outcome of subsequent frozen-thawed cycles. Fertil Steril 2004; 81: 473-5.