Does the quality of an embryo differ between long down-regulated and antagonist cycles among age and cycle day 3 FSH-matched women undergoing art?

Abstract

Objective: Lower pregnancy rates have been reported in gonadotropin releasing hormone (GnRH) antagonist cycles in comparison to those with agonist cycles. A non-significant difference of 3.3% in the pregnancy rate per cycle in favour of GnRH agonists was found. The possible difference between these two protocols could be a limiting factor. We aim to determine if the embryos developed in long down-regulated assisted reproductive technology (ART) cycles differ from the ones obtained in antagonist cycles among women matched for age and follicle-stimulating hormone (FSH) administered on cycle day 3.

Patients and Methods: Retrospective cohort analysis was done on a population from a university affiliated hospital. 193 women undergoing standard in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment were included. The age and cycle day 3 FSH matched women undergoing either long or short protocols were compared. Group A consisted of women who had long down-regulation with GnRH analogues, group B consisted of women who had used GnRH antagonists. The clinical and ongoing pregnancy rates were compared. Day 3 embryo scores were compared between the groups.

Results: Although mean number of aspirated and inseminated oocytes were similar for the groups and average embryo scores were comparable, clinical and ongoing pregnancy rates were higher in group A than in group B. The percentage of embryos with zero fragmentation and 8-10 blastomeres on day 3 was similar in antagonist and long agonist cycles.

Conclusion: Long protocol ART cycles will result in comparable percentages of day 3 embryos with symmetric 8-10 blastomeres with zero fragmentation to those in antagonist cycles.

Keywords: Gonadotropin releasing hormone agonist, Gonadotropin releasing hormone antagonist, Pregnancy, Embryo score, Day 3 embryo

Keywords

• Gonadotropin releasing hormone agonist, Gonadotropin releasing hormone antagonist, Pregnancy, Embryo score, Day 3 embryo

Yaş ve siklusun 3.günü FSH değerleri eşleşmiş kadınlarda uzun ve kısa YÜT’lerinde elde edilen embryo kalitesi farklı mıdır?

Abstract

Amaç: Gonadotropin salgılayıcı hormon (GnRH) antagonistlerinin kullanıldığı sikluslarda agonist sikluslarına göre daha düşük gebelik oranları bildirilmiştir. GnRH agonist sikluslarında anlamlı olmayan %3,3’ lük bir gebelik oranında artış vardır. Yaş ve üçüncü gün FSH değerleri eşleştirilmiş kadınlarda kısa ve uzun yardımcı üreme teknikleri (YÜT) sikluslarında embriyo gelişiminde farkın olup olmadığının araştırılması amaçlanmıştır. Hastalar ve Yöntem: Universiteye bağlı hastanenin YÜT merkezine başvuran 193 kadında retrospektif kohort analizi yapıldı. Yaş ve siklusun 3. günü serum folikül stimulan hormon (FSH) değeri benzer olan kısa ve uzun protokol ile klasik in vitro fertilizasyon (IVF) veya intrasitoplazmik sperm enjeksiyonu (ICSI) uygulanan hastalar dahil edildi. Group A, uzun GnRH analog protokolu, group B, ise kısa GnRh antagonist protokolü ile YÜT tedavisi aldı. Klinik ve devam eden gebelik oranları karşılaştırıldı. Üçüncü gün embriyo skorları gruplar arası karşılaştırıldı. Bulgular: Her iki grupta toplanan ve insemine edilen yumurta sayısı ve ortalama embriyo skorları benzer olmasına rağmen klinik ve devam eden gebelik oranları grup A’da grup B’ye göre daha yüksekti. Sıfır fragmentasyon ve 8-10 blastomer olan 3. gün embriyo yüzdesi gruplar arası benzer idi. Sonuç: Uzun protokol YÜT tedavilerinde, kısa protokolde elde edilenlere benzer oranda 8-10 blastomerli, simetrik ve sıfır fragmentasyonlu 3. gün embriyoları görülmektedir.

Keywords

• Gonadotropin salgılatıcı hormon agonisti, Gonadotropin salgılatıcı hormon antagonisti, Gebelik, Embryo skoru, 3.gün embryosu

References

1. 1. Fauser BC, van Heusden AM. Manipulation of human ovarian function: physiological concepts and clinical consequences. Endocr Rev 1997; 18: 71-106. doi: http://dx.doi.org/10.1210/ edrv.18.1.0290
2. 2. Pache TD, Wladimiroff JW, de Jong FH, Hop WC, Fauser BC. Growth patterns of nondominant ovarian follicles during the normal menstrual cycle. Fertil Steril 1990; 54: 638-42.
3. 3. van Santbrink EJ, Hop WC, van Dessel TJ, de Jong FH, Fauser BC. Decremental follicle-stimulating hormone and dominant follicle development during the normal menstrual cycle. Fertil Steril 1995; 64: 37-43.
4. 4. Fauser BC, Donderwinkel P, Schoot DC. The step-down principle in gonadotrophin treatment and the role of GnRH analogues. Baillieres Clin Obstet Gynaecol 1993; 7: 309-30. doi:10.1016/S0950-3552(05)80133-6
5. 5. Templeton A, Morris JK. Reducing the risk of multiple births by transfer of two embryos after in vitro fertilization. N Engl J Med 1998; 339: 573-7. doi: 10.1056/NEJM199808273390901
6. 6. Fauser BC, Devroey P. Reproductive biology and IVF: ovarian stimulation and luteal phase consequences. Trends Endocrinol Metabol 2003;14:236–42. doi:10.1016/S1043- 2760(03)00075-4
7. 7. Al Inany H, Aboulghar M. GnRH antagonist in assisted reproduction: a Cochrane review. Hum Reprod 2002;17: 874- 85. doi: 10.1093/humrep/17.4.874
8. 8. Fluker M, Grifo J, Leader A, et al. Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation. Fertil Steril 2001; 75: 38-45. doi:10.1016/S0015-0282(00)01638-1

9. 9. Ragni G, Vegetti W, Baroni E, et al. Comparison of luteal phase profile in gonadotrophin stimulated cycles with or without a gonadotrophin-releasing hormone antagonist. Hum Reprod 2001;16:2258–62. doi: 10.1093/humrep/16.11.2258
10. 10. Felberbaum RE, Diedrich K. Ovarian stimulation for IVF/ ICSI with gonadotrophins and GnRH analogues: agonist and antagonist. Hum Reprod 1999;14(Suppl 1):207–21.
11. 11. 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. doi: 10.1093/ humrep/deg407
12. 12. Hernandez ER. Embryo implantation: the Rubicon for GnRH antagonists. Hum Reprod 2000;15:1211-6. doi: 10.1093/ humrep/15.6.1211
13. 13. de Jong D, Macklon NS, Eijkemans MJ, Mannaerts BM, Coelingh Bennink HJ, Fauser BC, for the Ganirelix DoseFinding Study Group. Dynamics of the development of multiple follicles during ovarian stimulation for in vitro fertilization using recombinant follicle-stimulating hormone (Puregon) and various doses of the gonadotropin releasing hormone antagonist ganirelix (Orgalutran/Antagon). Fertil Steril 2001;75:688 –93. doi:10.1016/S0015-0282(00)01789-1
14. 14. Yoldemir T. The effect of prolongated time to achieve ovarian suppression before start of stimulation on pregnancy rates in ART cycles. Marmara Med J 2013;26:77-81. doi:10.5472/ MMJ.2013.02650.1
15. 15. Yoldemir T. The impact of pregnancy rates of using two different cut-off levels for high serum estradiol levels on the day of the hCG injection: Results from the same cohort of patients with long down-regulated ART cycles. Marmara Med J 2013; 26:122-6. doi: 10.5472/MMJ.2013.02675.0
16. 16. Tarlatzis BC, Grimbizis G, Pournaropoulos F, et al. Evaluation of two gonadotrophin-releasing hormones (GnRHa) analogues (leuprolide and buserelin) in short and long protocols for assisted reproduction techniques. J Assist Reprod Genet 1994; 11: 85–91. doi: 10.1007/BF02215993
17. 17. Tan SL. Gonadotrophin-releasing hormone agonists in assisted reproductive therapy. Hum Reprod 1996; 11 (Suppl. 4): 137–42.
18. 18. Kolibianakis E, Bourgain C, Albano C, et al. Effect of ovarian stimulation with recombinant follicle-stimulating hormone, gonadotropin releasing hormone antagonists, and human chorionic gonadotropin on endometrial maturation on the day of oocyte pick-up. Fertil Steril 2002; 78: 1025-9. doi: http:// dx.doi.org/10.1016/S0015-0282(02)03323-X
19. 19. Devroey P, Bourgain C, Macklon NS, Fauser BC. Reproductive biology and IVF: ovarian stimulation and endometrial receptivity. Trends Endocrinol Metab 2004; 15: 84-90. doi:10.1016/j.tem.2004.01.009
20. 20. Yoldemir T, Fraser IS. The effect of elevated serum estradiol levels on the day of human chorionic gonadotropin injection on pregnancy outcomes in an assisted reproduction program Aust N Z J Obstet Gynaecol 2009; 49:545–50. doi: 10.1111/j.1479-828X.2009.01061.x
21. 21. Beckers NG, Laven JS, Eijkemans MJ, Fauser BC. Follicular and luteal phase characteristics following early cessation of gonadotrophin-releasing hormone agonist during ovarian stimulation for in-vitro fertilization. Hum Reprod 2000;15: 43-9. doi: 10.1093/humrep/15.1.43
22. 22. de Jong D, Macklon NS, Fauser BC. A pilot study involving minimal ovarian stimulation for in vitro fertilization: extending the “follicle-stimulating hormone window” combined with the gonadotropin-releasing hormone antagonist cetrorelix. Fertil Steril 2000; 73: 1051-4. doi:10.1016/S0015-0282(00)00414-3
23. 23. Staessen C, Camus M, Bollen N, Devroey P, van Steirteghem AC. The relationship between embryo quality and the occurrence of multiple pregnancies. Fertil Steril 1992; 57: 626-30.
24. 24. Yoldemir T, Fraser IS. The effect of retrieved oocyte count on pregnancy outcomes in an assisted reproduction program. Arch Gynecol Obstet 2010;281:551-6. doi: 10.1007/s00404- 009-1221-y
25. 25. Yoldemir T, Fraser IS. Pregnancy rates in older poor responders who achieve embryo transfer in long-down regulated ART cycles are comparable to younger controls. J Obstet Gynaecol Can 2012; 34: 459–64.
26. 26. Hunault CC, Eijkemans MJ, Pieters MH, et al. A prediction model for selecting patients undergoing in vitro fertilization for elective single embryo transfer. Fertil Steril 2002;77: 725-32. doi:10.1016/S0015-0282(01)03243-5
27. 27. Han S W, Lei Z M, Rao Ch V. Up-regulation of cyclooxygenase-2 gene expression by chorionic gonadotropin during the differentiation of human endometrial stromal cells into decidua. Endocrinology 1996; 137: 1791–7. doi: http:// dx.doi.org/10.1210/endo.137.5.8612516
28. 28. Toth P, Li X, Rao Ch V. Expression of human chorionic gonadotropin (hCG)/luteinizing hormone receptors and regulation of cyclooxygenase-1 gene by exogenous hCG in human fetal membranes. J Clin Endocrinol Metab 1996; 81: 1283–8. doi: http://dx.doi.org/10.1210/jcem.81.3.8772613
29. 29. Fauser BC, Devroey P. Why is the clinical acceptance of gonadotropinreleasing hormone antagonist co-treatment during ovarian hyperstimulation for in vitro fertilization so slow? Fertil Steril 2005; 83:1607–11.
30. 30. Schipper I, Rommerts FF, Ten Hacken PM, Fauser BC. Low levels of follicle-stimulating hormone receptor-activation inhibitors in serum and follicular fluid from normal controls and anovulatory patients with or without polycystic ovary syndrome. J Clin Endocrinol Metab 1997; 82:1325-31. doi: http://dx.doi.org/10.1210/jcem.82.5.3922
31. 31. Giudice LC, Cataldo NA, van Dessel HJ, Yap OW, Chandrasekher YA. Growth factors in normal ovarian follicle development. Semin Reprod Endocrinol 1996;14:179-96.