PREİMPLANTASYON EMBRİYO GELİŞİM DURAKLAMASININ YARDIMLA ÜREME TEDAVİSİ SONUÇLARI ÜZERİNE ETKİSİ

Öz

Amaç: Yardımla üreme tedavileri sırasında, insan preimplantasyon embriyoları genellikle in vitro kültür ortamı, hasta yaşı, ovarian stimülasyon protokolleri ve gametlere bağlı nedenlerle gelişimin çeşitli aşamalarında duraklayabilmektedir. Gelişimsel duraklamanın (arrest) gözlendiği çiftlerde normal gelişim gösteren diğer embriyoların transfer edilmesinden sonra implantasyon başarısızlığı ve düşük gözlenebilmektedir. Diğer yandan, embriyonik arrestin altında yatan nedenler kesin olarak açıklanabilmiş değildir. Bu çalışmada amacımız, erken dönem embriyonik arrestin yardımla üreme teknikleri başarısı üzerine etkisinin araştırılmasıdır. Gereç ve Yöntem: Bu retrospektif çalışma kapsamında, 2010 ve 2018 yılları arasında yardımla üreme tedavisi gören ve ovulatuvar faktör, tubal faktör, endometriozis, açıklanamayan infertilite, ve erkek faktörü tanısı konulmuş olan 620 infertil çiftin intrasitoplazmik sperm enjeksiyonu-embriyo transferi (ICSI-ET) siklusu değerlendirilmiştir. Çalışma grupları, embriyonik arrest gözlenen hastalar ve tüm embriyoları duraklamadan normal hızda gelişim gösteren (kontrol) hastalardan oluşmaktadır. Çalışma datası, tek-yönlü değişken analizi (ANOVA) ve Ki-kare testi kullanılarak analiz edilmiştir. Bulgular: Çalışma toplumunda, kullanılan ilaç dozu, oosit sayısı, fertilizasyon oranı, iyi kaliteli (GI) ve düşük kaliteli (GIII) embriyo oranları anlamlı olarak arrest yönünde artmışken, gebelik oranlarının azaldığı (p<0,0001) ve canlı doğum oranlarında iki grup arasında bir farklılığın olmadığı (p=0,449) tespit edilmiştir. Sonuç: Embriyo kohortunda arrest embriyoların bulunmasının yardımla üreme teknikleri başarısı üzerine olumsuz etkilerinin olduğu çeşitli çalışmalarda belirtilmiştir. Çalışmamızda elde edilen bulgular bu doğrultudadır. 

Anahtar Kelimeler

• Preimplantasyon dönem embriyo,yardımla üreme teknikleri,gelişimsel duraklama

THE EFFECT OF PREIMPLANTATION EMBRYO DEVELOPMENT ARREST ON ASSISTED REPRODUCTIVE TREATMENT RESULTS

Öz

Objective: During assisted reproductive treatments, human preimplantation embryo’s development can sometimes may stop cleavage at various stages due to in vitro culture media, patient age, ovarian stimulation protocols, and gametes. Implantation failure and abortion can be observed after the transfer of other embryos, which have normal development, in couples with developmental arrest. On the other hand, the underlying causes of embryonic arrest cannot be explained clearly. The aim of this study was to investigate the effect of early embryonic arrest on the success of assisted reproductive techniques. Materials and Methods: In this retrospective study of intracytoplasmic sperm injection-embryo transfer (ICSI-ET), the cycle of 620 infertile couples diagnosed with ovulatory factor, tubal factor, endometriosis, unexplained infertility, and male factor between 2010 and 2018 were evaluated. The study groups consisted of patients with embryonic arrest and control patients whose embryos developed at normal speed without interruption. The study data was analyzed using the uni-directional variable analysis (ANOVA) and the Chi-square test. Results: In the study population, the drug dose, oocyte count, fertilization rate, and high and low grade embryo ratios were increased in the direction of arrest. On the one hand, pregnancy rates decreased (p<0.0001). On the other hand, there was no difference between the two groups in live birth rates (p=0.449). Conclusion: In several studies, it was stated that the presence of arrested embryos in the embryo cohort had negative effects on the success of assisted reproductive techniques. The findings of this study support that claim. 

Anahtar Kelimeler

• Preimplantation stage embryo,assisted reproductive techniques,arrest

Kaynakça

1. 1. Wang X, Song D, Mykytenko D, Kuang Y, Lv Q, Li B, Chen B, et al. Novel mutations in genes encoding subcortical maternal complex proteins may cause human embryonic developmental arrest. Reprod Biomed Online 2018;36(6):698-704.
2. 2. Special ASiRMaE and Embryology IGo. The Istanbul consensus workshop on embryo as-sessment: proceedings of an expert meeting. Hum Reprod 2011;26:1270-83.
3. 3. Lan KC, Huang FJ, Lin YC, Kung FT, Hsieh CH, Huang HW, et al. The predictive value of using a combined Z-score and day 3 embryo morphology score in the assessment of embryo survival on day 5. Hum Reprod 2003;18:1299-306.
4. 4. Favetta LA, St John EJ, King WA, Betts DH. High levels of p66shc and intracellular ROS in permanently arrested early embryos. Free Radic Biol Med 2007;4:1201-10.
5. 5. Qi ST, Liang LF, Xian YX, Liu JQ, Wang E. Arrested human embryos are more likely to have abnormal chromosomes than developing embryos from women of advanced maternal age. J Ovarian Res 2014;7:65.
6. 6. Lin YH, Chou CK, Hung YC, Yu IS, Pan HA, Lin SW, et al. SEPT12 deficiency causes sperm nucleus damage and developmental arrest of preimplantation embryos. Fertil Steril 2011;95:363-5.
7. 7. Burruel V, Klooster KL, Chitwood J, Ross PJ, Meyers SA. Oxidative damage to rhesus macaque spermatozoa results in mitotic arrest and transcript abundance changes in early embryos. Biol Reprod 2013;89:72.
8. 8. Zamora RB, Sánchez RV, Pérez JG, Díaz RR, Quintana DB, Bethencourt JC. Human zygote morphological indicators of higher rate of arrest at the first cleavage stage. Zygote 2011;19(4):339-44.

9. 9. Munne S, Dailey T, Sultan KM, Grifo J, Cohen J. The use of first polar bodies for pre-implantation diagnosis of aneuploidy. Hum Reprod 1995;10:1014-20.
10. 10. Marquez C, Sandalinas M, Bahce M, Alikani M, Munne S. Chromosome abnormalities in 1255 cleavage-stage human embryos. Reprod Biomed Online 2000;1:17-26.
11. 11. Memili E, First NL. Zygotic and embryonic gene expression in cow: a review of timing and mechanisms of early gene expression as compared with other species. Zygote 2000;8:87-96.
12. 12. Betts DH, Madan P. Permanent embryo arrest: molecular and cellular concepts. Mol Hum Reprod 2008;14:445-53.
13. 13. Hardy K, Spanos S, Becker D, Iannelli P, Winston RML, Stark J. From cell death to embryo arrest: mathematical models of human preimplantation embryo development. Dev Biol 2001;98:1655-60.
14. 14. Benkhalifa M, Kahraman S, Caserta D, Domez E, Qumsiyeh MB. Morphological and cytogenetic analysis of intact oocytes and blocked zygotes. Prenat Diagn 2003;23:397404.
15. 15. Liu L, Cai J, Chen PLY, Sha A, Ren J. Clinical outcome of IVF/ ICSI cycles with an arrested embryo on day 3. Int J Clin Exp Med 2016;9(8):16414-24.
16. 16. Jun SH, Choi B, Shahine L, Westphal LM, Behr B, Reijo Pera RA et al. Defining human embryo phenotypes by cohort-specific prognostic factors. PLoS One 2008;3:e2562.
17. 17. Daughtry BL, Chavez SL. Chromosomal instability in mammalian pre-implantation embryos: potential causes, detection methods, and clinical consequences. Cell Tissue Res 2016;363(1):201-25.
18. 18. Johnson MH, Nasr-Esfahani MH. Radical solutions and cultural problems: could free oxygen radicals be responsible for the impaired development of preimplantation mammalian embryos in vitro? Bioessays 1994;16(1):31-8.
19. 19. Betts DH, King WA. Genetic regulation of embryo death and senescence. Theriogenology 2001;55:171-91.
20. 20. Favetta LA, Robert C, St John EJ, Betts DH, King WA. p66shc, but not p53, is involved in early arrest of in vitro-produced bovine embryos. Mol Hum Reprod 2004;10(6):383-92.
21. 21. Chi L, de Jesus E, Adler A, Grifo JA, Berkeley AS, Krey LC. 2-cell stage arrest in human embryos: incidence and developmental potential in different culture media. Fertil Steril 2000;74(S1.1):S222.
22. 22. Almeida PA, Bolton VN. Cytogenetic analysis of human preimplantation embryos following developmental arrest in vitro. Reprod Fertil Dev 1998;10(6):505-13.
23. 23. Miller JE, Smith TT. The effect of intracytoplasmic sperm injection and semen parameters on blastocyst development in vitro. Hum Reprod 2001;16(5):918-24.
24. 24. Van Loendersloot LL, Van Wely M, Limpens J, Bossuyt PM, Repping S, Van der Veen F. Predictive factors in in vitro fertilization (IVF): a systematic review and meta-analysis. Hum Reprod Update 2010;16:577-589.
25. 25. Cai QF, Wan F, Huang R, Zhang HW. Factors predicting the cumulative outcome of IVF/ICSI treatment: a multivariable analysis of 2450 patients. Hum Reprod 2011;26:2532-40.
26. 26. Steward RG, Lan L, Shah AA, Yeh JS, Price TM, Goldfarb JM, et al. Oocyte number as a predictor for ovarian hyperstimulation syndrome and live birth: an analysis of 256,381 in vitro fertilization cycles. Fertil Steril 2014;101:967-73.
27. 27. Biase FH, Everts RE, Oliveira R, Santos-Biase WK, Fonseca Merighe GK, Smith LC, et al. Messenger RNAs in metaphase II oocytes correlate with successful embryo development to the blastocyst stage. Zygote 2014;22:69-79.
28. 28. Tosti E, Boni R, Gallo A, Silvestre F. Ion currents modulating oocyte maturation in animals. Syst Biol Reprod Med 2013;59:61-8.
29. 29. Yurttas P, Morency E, Coonrod SA. Use of proteomics to identify highly abundant ma-ternal factors that drive the egg-to-embryo transition. Reproduction 2010;139:809-23.
30. 30. Ingman WV, Robker RL, Woittiez K, Robertson SA. Null mutation in transforming growth factor ß1 disrupts ovarian function and causes oocyte incompetence and early embryo arrest. Endocrinology 2006;147:835-45.
31. 31. Meirelles FV, Caetano AR, Watanabe YF, Ripamonte P, Carambula SF, Merighe GK, et al. Genome activation and developmental block in bovine embryos. Anim Reprod Sci 2004;82-83:13-20.
32. 32. Marteil G, Richard-Parpaillon L, Kubiak JZ. Role of oocyte quality in meiotic maturation and embryonic development. Reprod Biol 2009;9:203-24.
33. 33. Hourvitz AME, Brengauz M, Machtinger R, Dor J. In vitro maturation for patients with repeated in vitro fertilization failure due to “oocyte maturation abnormalities”. Fertil Steril 2010;94:496-501.
34. 34. Sa R, Cunha M, Silva J, Luis A, Oliveira C, Teixeira da Silva J, et al. Ultrastructure of tubular smooth endoplasmic reticulum aggregates in human metaphase II oocytes and clinical implications. Fertil Steril 2011;96:143-9.