PREIMPLANTACIONI GENETSKI SKRINING EMBRIONA U PROCESU VANTELESNE OPLODNJE - PILOT STUDIJA

Ivana Stojić; Jelena Vukosavljević; Slobodan Maričić; Miloš R Vuković; Stefan Stojanoski; Aleksandra Trninić Pjević

doi:10.5937/mp70-21735

Ivana Stojić Univerzitet u Novom Sadu, Medicinski fakultet Klinički centar Vojvodine, Centar za radiologiju
Jelena Vukosavljević Klinički centar Vojvodine, Klinika za ginekologiju i akušerstvo
Slobodan Maričić 1. Univerzitet u Novom Sadu, Medicinski fakultet 2. Institut za onkologiju Vojvodine
Miloš R Vuković 1. Univerzitet u Novom Sadu, Medicinski fakultet 2. Institut za onkologiju Vojvodine
Stefan Stojanoski 1. Univerzitet u Novom Sadu, Medicinski fakultet 2. Institut za onkologiju Vojvodine
Aleksandra Trninić Pjević 1. Univerzitet u Novom Sadu, Medicinski fakultet 2. Klinički centar Vojvodine, Klinika za ginekologiju i akušerstvo

DOI: https://doi.org/10.5937/mp70-21735

Sažetak

Uvod: Još od prvih uspešnih začeća in vitro, odabir najvijabilnijih embriona za transfer je bio primarni fokus istraživanja u oblasti vantelesne oplodnje (VTO). Glavni uzrok neuspeha implantacije i gubitka trudnoće je prisustvo aneuploidije. Smatra se da uspešnost in vitro fertilizacije može da bude poboljšana selekcijom i transferom hromozomski normalnih embriona. Ova metoda je poznata kao preimplantacioni genetski skrining (PGS).

Cilj: Cilj našeg istraživanja je bio da se utvrdi klinički značaj komparativne genomske hibridizacije u formatu mikroniza (eng. array CGH) u okviru PGS, kao i mogućnost rutinske primene u cilju detekcije aneuploidija među embrionima dobijenim u postupku vantelesne oplodnje.

Materijal i metode: Sprovedena je delom retrospektivna, delom prospektivna studija u koju je uključeno 25 pacijentkinja kod kojih je izvršen postupak vantelesne oplodnje sa PGS na Klinici za ginekologiju i akušerstvo Kliničkog centra Vojvodine u periodu od marta 2015. do februara 2016.godine. Učinjena je biopsija embriona, nakon čega su uzorci slati u Institut za zdravstvenu zaštitu dece i omladine Vojvodine, gde je izvođena “array” CGH metoda.

Rezultati: Od 109 analiziranih uzoraka, uspešno su amplifikovana 63 uzorka, od kojih je dobijeno 26,98% (17/63) euploidnih i 73,02% (46/63) aneuploidnih embriona. Procenat aneuploidija je bio najviši (50%; 23/46) u starosnoj grupi od 31-36 godina. Kod tubarnog steriliteta procenat aneuploidije je bio najviši (36,9%; 17/46).

Zaključak: Pokazano je da su aneuploidije prisutne u visokom procentu kod pacijentkinja sa tubarnim sterilitetom i kod pacijentkinja u starosnoj grupi od 31-36 godina, što značajno snižava šansu za uspešan postupak VTO. Rutinski skrining embriona na aneuploidije u postupku VTO značajno bi smanjio emocionalne, finansijske i vremenske gubitke.

Biografije autora

Jelena Vukosavljević, Klinički centar Vojvodine, Klinika za ginekologiju i akušerstvo

Embriolog

Slobodan Maričić, 1. Univerzitet u Novom Sadu, Medicinski fakultet 2. Institut za onkologiju Vojvodine

dr Slobodan Maričić, lekar na specijalizaciji iz ginekologije i akušerstva

Student 2. god doktorskih studija, smer Klinička istraživanja, Medicinski fakultet Novi Sad

Miloš R Vuković, 1. Univerzitet u Novom Sadu, Medicinski fakultet 2. Institut za onkologiju Vojvodine

dr Miloš Vuković, lekar na specijalizaciji iz radiologije

Student 2. god doktorskih studija, smer Klinička istraživanja, Medicinski fakultet Novi Sad

Stefan Stojanoski, 1. Univerzitet u Novom Sadu, Medicinski fakultet 2. Institut za onkologiju Vojvodine

dr Stefan Stojanoski, lekar na specijalizaciji iz radiologije

Student 2. god doktorskih studija, smer Klinička istraživanja, Medicinski fakultet Novi Sad

Aleksandra Trninić Pjević, 1. Univerzitet u Novom Sadu, Medicinski fakultet 2. Klinički centar Vojvodine, Klinika za ginekologiju i akušerstvo

Prof.dr Aleksandra Trninić Pjević, vanredni profesor Medicinskog fakulteta Novi Sad

Specijalista ginekologije i akušerstva, subspecijalista steriliteta

Reference

Edwards RG, Purdy JM, Steptoe PC, Walters DE. The growth of human preimplantation embryos in vitro. Am J Obstet Gynecol. 1981;141(4):408–16.

Balaban B, Brison D, Calderon G, Catt J, Conaghan J, Cowan L, et al. Alpha scientists in reproductive medicine and ESHRE special interest group of embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011;26:1270–83.

Yang Z, Salem SA, Liu X, Kuang Y, Salem RD, Liu J. Selection of euploid blastocysts for cryopreservation with array comparative genomic hybridization (aCGH) results in increased implantation rates in subsequent frozen and thawed embryo transfer cycles. Mol Cytogenet. 2013;6(1):32.

Wintner EM, Hershko-Klement A, Tzadikevitch K, Ghetler Y, Gonen O, Wintner O, et al. Does the transfer of a poor quality embryo together with a good quality embryo affect the In Vitro Fertilization (IVF) outcome? J Ovarian Res. 2017;10(1):2.

Zhang JQ, Li XL, Peng Y, Guo X, Heng BC, Tong GQ. Reduction in exposure of human embryos outside the incubator enhances embryo quality and blastulation rate. Reprod Biomed Online. 2010;20(4):510–5.

Rodriguez-Purata J, Lee J, Whitehouse M, Duke M, Grunfeld L, Sandler B, et al. Reproductive outcome is optimized by genomic embryo screening, vitrification, and subsequent transfer into a prepared synchronous endometrium. J Assist Reprod Genet. 2016;33(3):401–12.

Alfarawati S, Fragouli E, Colls P, Stevens J, Gutiérrez-Mateo C, Schoolcraft WB, et al. The relationship between blastocyst morphology, chromosomal abnormality, and embryo gender. Fertil Steril. 2011;95(2):520–4.

Maurer M, Ebner T, Puchner M, Mayer RB, Shebl O, Oppelt P, et al. Chromosomal aneuploidies and early embryonic developmental arrest. Int J Fertil Steril. 2015;9(3):346.

Wang S, Kleckner N, Zhang L. Crossover maturation inefficiency and aneuploidy in human female meiosis. Cell Cycle. 2017;16(11):1017–9.

Wells D, Fragouli E. Preimplantation genetic diagnosis. Textb Clin Embryol. 2013;346.

Fiorentino F. Array comparative genomic hybridization: its role in preimplantation genetic diagnosis. Curr Opin Obstet Gynecol. 2012;24(4):203–9.

Lee C-I, Wu C-H, Pai Y-P, Chang Y-J, Chen C-I, Lee T-H, et al. Performance of preimplantation genetic testing for aneuploidy in IVF cycles for patients with advanced maternal age, repeat implantation failure, and idiopathic recurrent miscarriage. Taiwan J Obstet Gynecol. 2019;58(2):239–43.

Sermon K, Capalbo A, Cohen J, Coonen E, De Rycke M, De Vos A, et al. The why, the how and the when of PGS 2.0: current practices and expert opinions of fertility specialists, molecular biologists, and embryologists. MHR Basic Sci Reprod Med. 2016;22(8):845–57.

Khajuria R, Rodrigo L, Valbuena D, Rubio C, Simon C. Incidence of chromosomal aneuploidies at embryonic level with comparison based on type of biopsy and maternal age: first indian experience. Reprod Biomed Online. 2018;36:e22.

Franasiak JM, Forman EJ, Hong KH, Werner MD, Upham KM, Treff NR, et al. The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening. Fertil Steril. 2014;101(3):656–63.

Rubio C, Bellver J, Rodrigo L, Castillón G, Guillén A, Vidal C, et al. In vitro fertilization with preimplantation genetic diagnosis for aneuploidies in advanced maternal age: a randomized, controlled study. Fertil Steril. 2017;107(5):1122–9.

Penzias A, Bendikson K, Butts S, Coutifaris C, Fossum G, Falcone T, et al. Guidance on the limits to the number of embryos to transfer: a committee opinion. Fertil Steril. 2017;107(4):901–3.

Labs EGG on GP in IVF, De los Santos MJ, Apter S, Coticchio G, Debrock S, Lundin K, et al. Revised guidelines for good practice in IVF laboratories (2015). Hum Reprod. 2016;31(4):685–6.

van Loendersloot LL, Moolenaar LM, Repping S, Bossuyt PM, Hompes PGA, van der Veen F, et al. Cost-effectiveness of single versus double embryo transfer in IVF in relation to female age. Eur J Obstet Gynecol Reprod Biol. 2017;214:25–30.

Forman EJ, Tao X, Ferry KM, Taylor D, Treff NR, Scott Jr RT. Single embryo transfer with comprehensive chromosome screening results in improved ongoing pregnancy rates and decreased miscarriage rates. Hum Reprod. 2012;27(4):1217–22.

Ata B, Kaplan B, Danzer H, Glassner M, Opsahl M, Tan SL, et al. Array CGH analysis shows that aneuploidy is not related to the number of embryos generated. Reprod Biomed Online. 2012;24(6):614–20.

Fayek HK, Tawab N, Elrahman HA, Demiry Y, Aboulghar M, Serour G, et al. 44. Can PGT-A using array CGH improve IVF clinical results? (The Egyptian IVF-ET center experience). Reprod Biomed Online. 2019;39:e54.

Capalbo A, Cimadomo D, Rienzi L, Ubaldi FM. Comprehensive Chromosomal Screening from Polar Body Biopsy to Blastocyst Trophectoderm Sampling: Evidences and Considerations. In: Screening the Single Euploid Embryo. Springer; 2015. p. 89–102.

Victor AR, Griffin DK, Brake AJ, Tyndall JC, Murphy AE, Lepkowsky LT, et al. Assessment of aneuploidy concordance between clinical trophectoderm biopsy and blastocyst. Hum Reprod. 2018;34(1):181–92.

Orvieto R, Gleicher N. Should preimplantation genetic screening (PGS) be implemented to routine IVF practice? J Assist Reprod Genet. 2016;33(11):1445–8.

Mir P, Mateu E, Mercader A, Herrer R, Rodrigo L, Vera M, et al. Confirmation rates of array-CGH in day-3 embryo and blastocyst biopsies for preimplantation genetic screening. J Assist Reprod Genet. 2016;33(1):59–66.

Yang Z, Liu J, Collins GS, Salem SA, Liu X, Lyle SS, et al. Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study. Mol Cytogenet. 2012;5(1):24.