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Clinical outcomes of preimplantation genetic testing for aneuploidy in high-risk patients: A retrospective cohort study

  • Jun Woo Kim (In Vitro Fertilization Center, Maria S Fertility Hospital) ;
  • So Young Lee (In Vitro Fertilization Center, Maria S Fertility Hospital) ;
  • Chang Young Hur (In Vitro Fertilization Center, Maria S Fertility Hospital) ;
  • Jin Ho Lim (In Vitro Fertilization Center, Maria S Fertility Hospital) ;
  • Choon Keun Park (Department of Applied Animal Science, College of Animal Life Sciences, Kangwon National University)
  • 투고 : 2023.07.28
  • 심사 : 2023.10.05
  • 발행 : 2024.03.31

초록

Objective: The purpose of this study was to evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on clinical outcomes among high-risk patients. Methods: This retrospective study involved 1,368 patients and the same number of cycles, including 520 cycles with PGT-A and 848 cycles without PGT-A. The study participants comprised women of advanced maternal age (AMA) and those affected by recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or severe male factor infertility (SMF). Results: PGT-A was associated with significant improvements in the implantation rate (IR) and the ongoing pregnancy rate/live birth rate (OPR/LBR) per embryo transfer cycle in the AMA (39.3% vs. 16.2% [p<0.001] and 42.0% vs. 21.8% [p<0.001], respectively), RIF (41.7% vs. 22.0% [p<0.001] and 47.0% vs. 28.6% [p<0.001], respectively), and RPL (45.6% vs. 19.5% [p<0.001] and 49.1% vs. 24.2% [p<0.001], respectively) groups, as well as the IR in the SMF group (43.3% vs. 26.5%, p=0.011). Additionally, PGT-A was associated with lower overall incidence rates of early pregnancy loss in the AMA (16.7% vs. 34.3%, p=0.001) and RPL (16.7% vs. 50.0%, p<0.001) groups. However, the OPR/LBR per total cycle across all PGT-A groups did not significantly exceed that for the non-PGT-A groups. Conclusion: PGT-A demonstrated beneficial effects in high-risk patients. However, our findings indicate that these benefits are more pronounced in carefully selected candidates than in the entire high-risk patient population.

키워드

과제정보

The authors extend special thanks to their IVF laboratory colleagues and the clinicians at Maria S Fertility Hospital for their dedicated efforts throughout the study. Additionally, the authors are deeply grateful to their colleague Yejin Kim for providing valuable assistance with the statistical analysis using GraphPad Prism 9 software. This research did not receive any specific grant from funding agencies in the public, commercial, or non-profit sectors.

참고문헌

  1. Nagaoka SI, Hassold TJ, Hunt PA. Human aneuploidy: mechanisms and new insights into an age-old problem. Nat Rev Genet 2012;13:493-504. https://doi.org/10.1038/nrg3245
  2. Coticchio G, Dal Canto M, Mignini Renzini M, Guglielmo MC, Brambillasca F, Turchi D, et al. Oocyte maturation: gamete-somatic cells interactions, meiotic resumption, cytoskeletal dynamics and cytoplasmic reorganization. Hum Reprod Update 2015;21:427-54. https://doi.org/10.1093/humupd/dmv011
  3. Wang WH, Sun QY. Meiotic spindle, spindle checkpoint and embryonic aneuploidy. Front Biosci 2006;11:620-36. https://doi.org/10.2741/1822
  4. Campbell A, Fishel S, Bowman N, Duffy S, Sedler M, Thornton S. Retrospective analysis of outcomes after IVF using an aneuploidy risk model derived from time-lapse imaging without PGS. Reprod Biomed Online 2013;27:140-6. https://doi.org/10.1016/j.rbmo.2013.04.013
  5. Guerif F, Lemseffer M, Leger J, Bidault R, Cadoret V, Chavez C, et al. Does early morphology provide additional selection power to blastocyst selection for transfer? Reprod Biomed Online 2010;21:510-9. https://doi.org/10.1016/j.rbmo.2010.06.043
  6. Munne S, Sultan KM, Weier HU, Grifo JA, Cohen J, Rosenwaks Z. Assessment of numeric abnormalities of X, Y, 18, and 16 chromosomes in preimplantation human embryos before transfer. Am J Obstet Gynecol 1995;172(4 Pt 1):1191-201. https://doi.org/10.1016/0002-9378(95)91479-X
  7. van Echten-Arends J, Mastenbroek S, Sikkema-Raddatz B, Korevaar JC, Heineman MJ, van der Veen F, et al. Chromosomal mosaicism in human preimplantation embryos: a systematic review. Hum Reprod Update 2011;17:620-7. https://doi.org/10.1093/humupd/dmr014
  8. Gardner DK, Meseguer M, Rubio C, Treff NR. Diagnosis of human preimplantation embryo viability. Hum Reprod Update 2015;21:727-47. https://doi.org/10.1093/humupd/dmu064
  9. Rubio C, Navarro-Sanchez L, Garcia-Pascual CM, Ocali O, Cimadomo D, Venier W, et al. Multicenter prospective study of concordance between embryonic cell-free DNA and trophectoderm biopsies from 1301 human blastocysts. Am J Obstet Gynecol 2020;223:751.
  10. Rubio C, Rodrigo L, Garcia-Pascual C, Peinado V, Campos-Galindo I, Garcia-Herrero S, et al. Clinical application of embryo aneuploidy testing by next-generation sequencing. Biol Reprod 2019; 101:1083-90. https://doi.org/10.1093/biolre/ioz019
  11. Forman EJ, Hong KH, Ferry KM, Tao X, Taylor D, Levy B, et al. In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial. Fertil Steril 2013;100:100-7. https://doi.org/10.1016/j.fertnstert.2013.02.056
  12. Scott RT Jr, Upham KM, Forman EJ, Hong KH, Scott KL, Taylor D, et al. Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial. Fertil Steril 2013;100:697-703. https://doi.org/10.1016/j.fertnstert.2013.04.035
  13. Kang HJ, Melnick AP, Stewart JD, Xu K, Rosenwaks Z. Preimplantation genetic screening: who benefits? Fertil Steril 2016;106:597-602. https://doi.org/10.1016/j.fertnstert.2016.04.027
  14. Munne S, Kaplan B, Frattarelli JL, Child T, Nakhuda G, Shamma FN, et al. Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial. Fertil Steril 2019;112:1071-9. https://doi.org/10.1016/j.fertnstert.2019.07.1346
  15. Coughlan C, Ledger W, Wang Q, Liu F, Demirol A, Gurgan T, et al. Recurrent implantation failure: definition and management. Reprod Biomed Online 2014;28:14-38. https://doi.org/10.1016/j.rbmo.2013.08.011
  16. Practice Committee of the American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril 2012;98:1103-11. https://doi.org/10.1016/j.fertnstert.2012.06.048
  17. ESHRE Guideline Group on RPL; Bender Atik R, Christiansen OB, Elson J, Kolte AM, Lewis S, et al. ESHRE guideline: recurrent pregnancy loss. Hum Reprod Open 2018;2018:hoy004.
  18. Kim JW, Lee SY, Hur CY, Lim JH, Park CK. Comparison of clinical and preimplantation genetic testing for aneuploidy outcomes between in vitro fertilization and intracytoplasmic sperm injection in sibling mature oocytes from high-risk patients: a retrospective study. J Obstet Gynaecol Res 2023;49:2343-50. https://doi.org/10.1111/jog.15731
  19. Hur YS, Ryu EK, Song SH, Yoon SH, Lim KS, Lee WD, et al. A retrospective study of single frozen-thawed blastocyst transfer. Clin Exp Reprod Med 2016;43:106-11. https://doi.org/10.5653/cerm.2016.43.2.106
  20. Lee HL, McCulloh DH, Hodes-Wertz B, Adler A, McCaffrey C, Grifo JA. In vitro fertilization with preimplantation genetic screening improves implantation and live birth in women age 40 through 43. J Assist Reprod Genet 2015;32:435-44. https://doi.org/10.1007/s10815-014-0417-7
  21. Rubio C, Bellver J, Rodrigo L, Castillon G, Guillen 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;107:1122-9. https://doi.org/10.1016/j.fertnstert.2017.03.011
  22. Simopoulou M, Sfakianoudis K, Maziotis E, Tsioulou P, Grigoriadis S, Rapani A, et al. PGT-A: who and when?: a systematic review and network meta-analysis of RCTs. J Assist Reprod Genet 2021;38:1939-57. https://doi.org/10.1007/s10815-021-02227-9
  23. Mastenbroek S, Twisk M, van der Veen F, Repping S. Preimplantation genetic screening: a systematic review and meta-analysis of RCTs. Hum Reprod Update 2011;17:454-66. https://doi.org/10.1093/humupd/dmr003
  24. Ubaldi FM, Cimadomo D, Capalbo A, Vaiarelli A, Buffo L, Trabucco E, et al. Preimplantation genetic diagnosis for aneuploidy testing in women older than 44 years: a multicenter experience. Fertil Steril 2017;107:1173-80. https://doi.org/10.1016/j.fertnstert.2017.03.007
  25. Kort JD, McCoy RC, Demko Z, Lathi RB. Are blastocyst aneuploidy rates different between fertile and infertile populations? J Assist Reprod Genet 2018;35:403-8. https://doi.org/10.1007/s10815-017-1060-x
  26. Sato T, Sugiura-Ogasawara M, Ozawa F, Yamamoto T, Kato T, Kurahashi H, et al. Preimplantation genetic testing for aneuploidy: a comparison of live birth rates in patients with recurrent pregnancy loss due to embryonic aneuploidy or recurrent implantation failure. Hum Reprod 2019;34:2340-8. https://doi.org/10.1093/humrep/dez229
  27. Tong J, Niu Y, Wan A, Zhang T. Next-generation sequencing (NGS)-based preimplantation genetic testing for aneuploidy (PGT-A) of trophectoderm biopsy for recurrent implantation failure (RIF) patients: a retrospective study. Reprod Sci 2021;28:1923-9. https://doi.org/10.1007/s43032-021-00519-0
  28. Bhatt SJ, Marchetto NM, Roy J, Morelli SS, McGovern PG. Pregnancy outcomes following in vitro fertilization frozen embryo transfer (IVF-FET) with or without preimplantation genetic testing for aneuploidy (PGT-A) in women with recurrent pregnancy loss (RPL): a SART-CORS study. Hum Reprod 2021;36:2339-44. https://doi.org/10.1093/humrep/deab117
  29. Coates A, Hesla JS, Hurliman A, Coate B, Holmes E, Matthews R, et al. Use of suboptimal sperm increases the risk of aneuploidy of the sex chromosomes in preimplantation blastocyst embryos. Fertil Steril 2015;104:866-72. https://doi.org/10.1016/j.fertnstert.2015.06.033
  30. Mazzilli R, Cimadomo D, Vaiarelli A, Capalbo A, Dovere L, Alviggi E, et al. Effect of the male factor on the clinical outcome of intracytoplasmic sperm injection combined with preimplantation aneuploidy testing: observational longitudinal cohort study of 1,219 consecutive cycles. Fertil Steril 2017;108:961-72. https://doi.org/10.1016/j.fertnstert.2017.08.033
  31. Asoglu MR, Celik C, Serefoglu EC, Findikli N, Bahceci M. Preimplantation genetic testing for aneuploidy in severe male factor infertility. Reprod Biomed Online 2020;41:595-603. https://doi.org/10.1016/j.rbmo.2020.06.015
  32. Xu R, Ding Y, Wang Y, He Y, Sun Y, Lu Y, et al. Comparison of preimplantation genetic testing for aneuploidy versus intracytoplasmic sperm injection in severe male infertility. Andrologia 2021;53:e14065.