Parameters impacting the live birth rate per transfer after frozen single euploid blastocyst transfer

Autoři: Fazilet Kubra Boynukalin aff001;  Meral Gultomruk aff002;  Sabri Cavkaytar aff001;  Emre Turgut aff001;  Necati Findikli aff002;  Munevver Serdarogullari aff002;  Onder Coban aff002;  Zalihe Yarkiner aff003;  Carmen Rubio aff004;  Mustafa Bahceci aff001
Působiště autorů: Department of Reproductive Endocrinology and IVF Center, Bahceci Health Group, Istanbul, Turkey aff001;  Department of Embryology and R&D Center, Bahceci Health Group, Center, Istanbul, Turkey aff002;  Cyprus Science University, Kyrenia, Cyprus aff003;  Igenomix, Valencia, Spain aff004
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article



To assess the predictive value of patient characteristics, controlled ovarian stimulation and embryological parameters on the live birth outcome of single euploid frozen-warmed blastocyst transfer (FBT).


This was a retrospective cohort study including 707 single FBTs after preimplantation genetic testing for aneuploidy (PGT-A) that were performed from October 1, 2015, to January 1, 2018. The effects of patient-, cycle- and embryology-related parameters on the live birth outcome after FBT were assessed.


In the subgroup analysis based on live birth, patients who achieved a live birth had a significantly lower body mass index (BMI) than patients who did not achieve a live birth (22.7 (21.5–24.6) kg/m2 vs 27 (24–29.2) kg/m2, p<0.001). The percentage of blastocysts with inner cell mass (ICM) A or B was significantly higher among patients achieving a live birth, at 91.6% vs. 82.6% (p<0.001). Day-5 biopsies were also more prevalent among patients achieving a live birth, at 82.9% vs 68.1% (p<0.001). On the other hand, the mitochondrial DNA (mtDNA) levels were significantly lower among cases with a successful live birth, at 18.7 (15.45–23.68) vs 20.55 (16.43–25.22) (p = 0.001). The logistic regression analysis showed that BMI (p<0.001, OR: 0.789, 95% CI [0.734–0.848]), day of trophectoderm (TE) biopsy (p<0.001, OR: 0.336, 95% CI [0.189–0.598]) and number of previous miscarriages (p = 0.004, OR: 0.733, 95% CI [0.594–0.906]) were significantly correlated with live birth. Patients with elevated BMIs, cycles in which embryos were biopsied on day-6 and a higher number of miscarriages were at increased risks of reduced live birth rates.


A high BMI, an embryo biopsy on day-6 and a high number of miscarriages negatively affect the live birth rate after single euploid FBT.

Klíčová slova:

Biopsy – Birth rates – Blastocysts – Embryos – Miscarriage – Oocytes – Pregnancy – Aneuploidy


1. Rabinowitz M, Ryan A, Gemelos G, Hill M, Baner J, Cinnioglu C, et al. Origins and rates of aneuploidy in human blastomeres. Fertil Steril. 2012;97(2):395–401. doi: 10.1016/j.fertnstert.2011.11.034 22195772

2. Weissman A, Shoham G, Shoham Z, Fishel S, Leong M, Yaron Y. Preimplantation genetic screening: results of a worldwide web-based survey. Reprod Biomed Online. 2017;35(6):693–700. doi: 10.1016/j.rbmo.2017.09.001 28988928

3. Blockeel C, Schutyser V, De Vos A, Verpoest W, De Vos M, Staessen C, et al. Prospectively randomized controlled trial of PGS in IVF/ICSI patients with poor implantation. Reprod Biomed Online. 2008;17(6):848–54. doi: 10.1016/s1472-6483(10)60414-2 19079970

4. Hardarson T, Hanson C, Lundin K, Hillensjo T, Nilsson L, Stevic J, et al. Preimplantation genetic screening in women of advanced maternal age caused a decrease in clinical pregnancy rate: a randomized controlled trial. Hum Reprod. 2008;23(12):2806–12. doi: 10.1093/humrep/den217 18583331

5. Mastenbroek S, Twisk M, van Echten-Arends J, Sikkema-Raddatz B, Korevaar JC, Verhoeve HR, et al. In vitro fertilization with preimplantation genetic screening. N Engl J Med. 2007;357(1):9–17. doi: 10.1056/NEJMoa067744 17611204

6. Mersereau JE, Pergament E, Zhang X, Milad MP. Preimplantation genetic screening to improve in vitro fertilization pregnancy rates: a prospective randomized controlled trial. Fertil Steril. 2008;90(4):1287–9. doi: 10.1016/j.fertnstert.2007.08.010 18061593

7. Meyer LR, Klipstein S, Hazlett WD, Nasta T, Mangan P, Karande VC. A prospective randomized controlled trial of preimplantation genetic screening in the "good prognosis" patient. Fertil Steril. 2009;91(5):1731–8. doi: 10.1016/j.fertnstert.2008.02.162 18804207

8. Staessen C, Platteau P, Van Assche E, Michiels A, Tournaye H, Camus M, et al. Comparison of blastocyst transfer with or without preimplantation genetic diagnosis for aneuploidy screening in couples with advanced maternal age: a prospective randomized controlled trial. Hum Reprod. 2004;19(12):2849–58. doi: 10.1093/humrep/deh536 15471934

9. Staessen C, Verpoest W, Donoso P, Haentjens P, Van der Elst J, Liebaers I, et al. Preimplantation genetic screening does not improve delivery rate in women under the age of 36 following single-embryo transfer. Hum Reprod. 2008;23(12):2818–25. doi: 10.1093/humrep/den367 18930977

10. Rubio C, Bellver J, Rodrigo L, Bosch E, Mercader A, Vidal C, et al. Preimplantation genetic screening using fluorescence in situ hybridization in patients with repetitive implantation failure and advanced maternal age: two randomized trials. Fertil Steril. 2013;99(5):1400–7. doi: 10.1016/j.fertnstert.2012.11.041 23260857

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(1):100–7 e1. doi: 10.1016/j.fertnstert.2013.02.056 23548942

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(3):697–703. doi: 10.1016/j.fertnstert.2013.04.035 23731996

13. 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. doi: 10.1186/1755-8166-5-24 22551456

14. 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(5):1122–9. doi: 10.1016/j.fertnstert.2017.03.011 28433371

15. Vaegter KK, Lakic TG, Olovsson M, Berglund L, Brodin T, Holte J. Which factors are most predictive for live birth after in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) treatments? Analysis of 100 prospectively recorded variables in 8,400 IVF/ICSI single-embryo transfers. Fertil Steril. 2017;107(3):641–8 e2. doi: 10.1016/j.fertnstert.2016.12.005 28108009

16. European Orgalutran Study Group. 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, randomised, multicentre trial. Hum Reprod 2000;15:1490–8. doi: 10.1093/humrep/15.7.1490 10875855

17. Serdarogullari M, Coban O, Boynukalin FK, Bilgin EM, Findikli N, Bahceci M. Successful application of a single warming protocol for embryos cryopreserved by either slow freezing or vitrification techniques. Syst Biol Reprod Med. 2018:1–8.

18. Gardner DK, Schoolcraft WB. Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol. 1999;11(3):307–11. doi: 10.1097/00001703-199906000-00013 10369209

19. Zhao H, Tao W, Li M, Liu H, Wu K, Ma S. Comparison of two protocols of blastocyst biopsy submitted to preimplantation genetic testing for aneuploidies: a randomized controlled trial. Arch Gynecol Obstet. 2019 May;299(5):1487–1493. doi: 10.1007/s00404-019-05084-1 30737585

20. Devroey P, Pados G. Preparation of endometrium for egg donation. Hum Reprod Update. 1998 Nov-Dec;4(6):856–61. doi: 10.1093/humupd/4.6.856 10098476

21. Kung A, Munne S, Bankowski B, Coates A, Wells D. Validation of next-generation sequencing for comprehensive chromosome screening of embryos. Reprod Biomed Online. 2015;31(6):760–9. doi: 10.1016/j.rbmo.2015.09.002 26520420

22. Wells D, Kaur K, Grifo J, Glassner M, Taylor JC, Fragouli E, et al. Clinical utilisation of a rapid low-pass whole genome sequencing technique for the diagnosis of aneuploidy in human embryos prior to implantation. J Med Genet. 2014;51(8):553–62. doi: 10.1136/jmedgenet-2014-102497 25031024

23. Diez-Juan A, Rubio C, Marin C, Martinez S, Al-Asmar N, Riboldi M, Díaz-Gimeno P, Valbuena D, Simón C. Mitochondrial DNA content as a viability score in human euploid embryos: less is better. Fertil Steril. 2015 Sep;104(3):534–41.e1. doi: 10.1016/j.fertnstert.2015.05.022 26051102

24. Heffner LJ. Advanced maternal age—how old is too old? N Engl J Med. 2004;351(19):1927–9. doi: 10.1056/NEJMp048087 15525717

25. Nelson SM, Lawlor DA. Predicting live birth, preterm delivery, and low birth weight in infants born from in vitro fertilisation: a prospective study of 144,018 treatment cycles. PLoS Med. 2011;8(1):e1000386. doi: 10.1371/journal.pmed.1000386 21245905

26. Fragouli E, Spath K, Alfarawati S, Kaper F, Craig A, Michel CE, et al. Altered levels of mitochondrial DNA are associated with female age, aneuploidy, and provide an independent measure of embryonic implantation potential. PLoS Genet. 2015;11(6):e1005241. doi: 10.1371/journal.pgen.1005241 26039092

27. Kuliev A, Zlatopolsky Z, Kirillova I, Spivakova J, Cieslak Janzen J. Meiosis errors in over 20,000 oocytes studied in the practice of preimplantation aneuploidy testing. Reprod Biomed Online. 2011;22(1):2–8. doi: 10.1016/j.rbmo.2010.08.014 21115270

28. Dechaud H, Anahory T, Reyftmann L, Loup V, Hamamah S, Hedon B. Obesity does not adversely affect results in patients who are undergoing in vitro fertilization and embryo transfer. Eur J Obstet Gynecol Reprod Biol. 2006;127(1):88–93. doi: 10.1016/j.ejogrb.2005.12.009 16417960

29. Lashen H, Ledger W, Bernal AL, Barlow D. Extremes of body mass do not adversely affect the outcome of superovulation and in-vitro fertilization. Hum Reprod. 1999;14(3):712–5. doi: 10.1093/humrep/14.3.712 10221701

30. Maheshwari A, Stofberg L, Bhattacharya S. Effect of overweight and obesity on assisted reproductive technology—a systematic review. Hum Reprod Update. 2007;13(5):433–44. doi: 10.1093/humupd/dmm017 17584821

31. Schliep KC, Mumford SL, Ahrens KA, Hotaling JM, Carrell DT, Link M, et al. Effect of male and female body mass index on pregnancy and live birth success after in vitro fertilization. Fertil Steril. 2015;103(2):388–95. doi: 10.1016/j.fertnstert.2014.10.048 25497445

32. Styne-Gross A, Elkind-Hirsch K, Scott RT Jr., Obesity does not impact implantation rates or pregnancy outcome in women attempting conception through oocyte donation. Fertil Steril. 2005;83(6):1629–34. doi: 10.1016/j.fertnstert.2005.01.099 15950629

33. Bellver J, Ayllon Y, Ferrando M, Melo M, Goyri E, Pellicer A, et al. Female obesity impairs in vitro fertilization outcome without affecting embryo quality. Fertil Steril. 2010;93(2):447–54. doi: 10.1016/j.fertnstert.2008.12.032 19171335

34. Caillon H, Freour T, Bach-Ngohou K, Colombel A, Denis MG, Barriere P, et al. Effects of female increased body mass index on in vitro fertilization cycles outcome. Obes Res Clin Pract. 2015;9(4):382–8. doi: 10.1016/j.orcp.2015.02.009 25769458

35. Fedorcsak P, Dale PO, Storeng R, Ertzeid G, Bjercke S, Oldereid N, et al. Impact of overweight and underweight on assisted reproduction treatment. Hum Reprod. 2004;19(11):2523–8. doi: 10.1093/humrep/deh485 15319380

36. Fedorcsak P, Storeng R, Dale PO, Tanbo T, Abyholm T. Obesity is a risk factor for early pregnancy loss after IVF or ICSI. Acta Obstet Gynecol Scand. 2000;79(1):43–8. 10646815

37. Metwally M, Tuckerman EM, Laird SM, Ledger WL, Li TC. Impact of high body mass index on endometrial morphology and function in the peri-implantation period in women with recurrent miscarriage. Reprod Biomed Online. 2007;14(3):328–34. doi: 10.1016/s1472-6483(10)60875-9 17390512

38. Ozekinci M, Seven A, Olgan S, Sakinci M, Keskin U, Akar ME, et al. Does obesity have detrimental effects on IVF treatment outcomes? BMC Womens Health. 2015;15:61. doi: 10.1186/s12905-015-0223-0 26285703

39. Rittenberg V, Seshadri S, Sunkara SK, Sobaleva S, Oteng-Ntim E, El-Toukhy T. Effect of body mass index on IVF treatment outcome: an updated systematic review and meta-analysis. Reprod Biomed Online. 2011;23(4):421–39. doi: 10.1016/j.rbmo.2011.06.018 21885344

40. Robker RL. Evidence that obesity alters the quality of oocytes and embryos. Pathophysiology. 2008;15(2):115–21. doi: 10.1016/j.pathophys.2008.04.004 18599275

41. Sarais V, Pagliardini L, Rebonato G, Papaleo E, Candiani M, Vigano P. A Comprehensive Analysis of Body Mass Index Effect on in Vitro Fertilization Outcomes. Nutrients. 2016;8(3):109. doi: 10.3390/nu8030109 26907340

42. Veleva Z, Tiitinen A, Vilska S, Hyden-Granskog C, Tomas C, Martikainen H, et al. High and low BMI increase the risk of miscarriage after IVF/ICSI and FET. Hum Reprod. 2008;23(4):878–84. doi: 10.1093/humrep/den017 18281684

43. Wang JX, Davies M, Norman RJ. Body mass and probability of pregnancy during assisted reproduction treatment: retrospective study. BMJ. 2000;321(7272):1320–1. doi: 10.1136/bmj.321.7272.1320 11090515

44. Zander-Fox DL, Henshaw R, Hamilton H, Lane M. Does obesity really matter? The impact of BMI on embryo quality and pregnancy outcomes after IVF in women aged </ = 38 years. Aust N Z J Obstet Gynaecol. 2012;52(3):270–6. doi: 10.1111/j.1479-828X.2012.01453.x 22694077

45. Kawwass JF, Kulkarni AD, Hipp HS, Crawford S, Kissin DM, Jamieson DJ. Extremities of body mass index and their association with pregnancy outcomes in women undergoing in vitro fertilization in the United States. Fertil Steril. 2016;106(7):1742–50. doi: 10.1016/j.fertnstert.2016.08.028 27666564

46. Goldman KN, Hodes-Wertz B, McCulloh DH, Flom JD, Grifo JA. Association of body mass index with embryonic aneuploidy. Fertil Steril. 2015;103(3):744–8. doi: 10.1016/j.fertnstert.2014.11.029 25576217

47. Tremellen K, Pearce K, Zander-Fox D. Increased miscarriage of euploid pregnancies in obese women undergoing cryopreserved embryo transfer. Reprod Biomed Online. 2017;34(1):90–7. doi: 10.1016/j.rbmo.2016.09.011 27789185

48. Boots CE, Bernardi LA, Stephenson MD. Frequency of euploid miscarriage is increased in obese women with recurrent early pregnancy loss. Fertil Steril. 2014;102(2):455–9. doi: 10.1016/j.fertnstert.2014.05.005 24907916

49. Ahlstrom A, Westin C, Reismer E, Wikland M, Hardarson T. Trophectoderm morphology: an important parameter for predicting live birth after single blastocyst transfer. Hum Reprod. 2011;26(12):3289–96. doi: 10.1093/humrep/der325 21972253

50. Chen X, Zhang J, Wu X, Cao S, Zhou L, Wang Y, et al. Trophectoderm morphology predicts outcomes of pregnancy in vitrified-warmed single-blastocyst transfer cycle in a Chinese population. J Assist Reprod Genet. 2014;31(11):1475–81. doi: 10.1007/s10815-014-0317-x 25123128

51. Hill MJ, Richter KS, Heitmann RJ, Graham JR, Tucker MJ, DeCherney AH, et al. Trophectoderm grade predicts outcomes of single-blastocyst transfers. Fertil Steril. 2013;99(5):1283–9 e1. doi: 10.1016/j.fertnstert.2012.12.003 23312233

52. Goto S, Kadowaki T, Tanaka S, Hashimoto H, Kokeguchi S, Shiotani M. Prediction of pregnancy rate by blastocyst morphological score and age, based on 1,488 single frozen-thawed blastocyst transfer cycles. Fertil Steril. 2011;95(3):948–52. doi: 10.1016/j.fertnstert.2010.06.067 20674914

53. Richter KS, Harris DC, Daneshmand ST, Shapiro BS. Quantitative grading of a human blastocyst: optimal inner cell mass size and shape. Fertil Steril. 2001;76(6):1157–67. doi: 10.1016/s0015-0282(01)02870-9 11730744

54. Thompson SM, Onwubalili N, Brown K, Jindal SK, McGovern PG. Blastocyst expansion score and trophectoderm morphology strongly predict successful clinical pregnancy and live birth following elective single embryo blastocyst transfer (eSET): a national study. J Assist Reprod Genet. 2013;30(12):1577–81. doi: 10.1007/s10815-013-0100-4 24114628

55. Van den Abbeel E, Balaban B, Ziebe S, Lundin K, Cuesta MJ, Klein BM, et al. Association between blastocyst morphology and outcome of single-blastocyst transfer. Reprod Biomed Online. 2013;27(4):353–61. doi: 10.1016/j.rbmo.2013.07.006 23953585

56. Capalbo A, Rienzi L, Cimadomo D, Maggiulli R, Elliott T, Wright G, et al. Correlation between standard blastocyst morphology, euploidy and implantation: an observational study in two centers involving 956 screened blastocysts. Hum Reprod. 2014;29(6):1173–81. doi: 10.1093/humrep/deu033 24578475

57. Sunkara SK, Siozos A, Bolton VN, Khalaf Y, Braude PR, El-Toukhy T. The influence of delayed blastocyst formation on the outcome of frozen-thawed blastocyst transfer: a systematic review and meta-analysis. Hum Reprod. 2010;25(8):1906–15. doi: 10.1093/humrep/deq143 20542896

58. Yang H, Yang Q, Dai S, Li G, Jin H, Yao G, et al. Comparison of differences in development potentials between frozen-thawed D5 and D6 blastocysts and their relationship with pregnancy outcomes. J Assist Reprod Genet. 2016;33(7):865–72. doi: 10.1007/s10815-016-0712-6 27098058

59. Ferreux L, Bourdon M, Sallem A, Santulli P, Barraud-Lange V, Le Foll N, et al. Live birth rate following frozen-thawed blastocyst transfer is higher with blastocysts expanded on Day 5 than on Day 6. Hum Reprod. 2018;33(3):390–8. doi: 10.1093/humrep/dey004 29394365

60. Irani M, O'Neill C, Palermo GD, Xu K, Zhang C, Qin X, et al. Blastocyst development rate influences implantation and live birth rates of similarly graded euploid blastocysts. Fertil Steril. 2018;110(1):95–102 e1. doi: 10.1016/j.fertnstert.2018.03.032 29908774

61. Murugappan G, Shahine LK, Perfetto CO, Hickok LR, Lathi RB. Intent to treat analysis of in vitro fertilization and preimplantation genetic screening versus expectant management in patients with recurrent pregnancy loss. Hum Reprod. 2016;31(8):1668–74. doi: 10.1093/humrep/dew135 27278003

62. Rubio C, Buendia P, Rodrigo L, Mercader A, Mateu E, Peinado V, et al. Prognostic factors for preimplantation genetic screening in repeated pregnancy loss. Reprod Biomed Online. 2009;18(5):687–93. doi: 10.1016/s1472-6483(10)60015-6 19549449

63. Ryynanen M, Leskinen S, Heinonen S, Kirkinen P. Recurrence risk of a serious, noninherited chromosomal abnormality. Fertil Steril. 1997;68(3):439–42. doi: 10.1016/s0015-0282(97)00224-0 9314911

64. Marquard K, Westphal LM, Milki AA, Lathi RB. Etiology of recurrent pregnancy loss in women over the age of 35 years. Fertil Steril. 2010;94(4):1473–7. doi: 10.1016/j.fertnstert.2009.06.041 19643401

65. Warburton D, Kline J, Stein Z, Hutzler M, Chin A, Hassold T. Does the karyotype of a spontaneous abortion predict the karyotype of a subsequent abortion? Evidence from 273 women with two karyotyped spontaneous abortions. Am J Hum Genet. 1987;41(3):465–83. 3631080

66. Klimczak AM, Pacheco LE, Lewis KE, Massahi N, Richards JP, Kearns WG, et al. Embryonal mitochondrial DNA: relationship to embryo quality and transfer outcomes. J Assist Reprod Genet. 2018;35(5):871–7. doi: 10.1007/s10815-018-1147-z 29508122

67. Treff NR, Zhan Y, Tao X, Olcha M, Han M, Rajchel J, et al. Levels of trophectoderm mitochondrial DNA do not predict the reproductive potential of sibling embryos. Hum Reprod. 2017;32(4):954–62. doi: 10.1093/humrep/dex034 28333210

68. Veleva Z, Orava M, Nuojua-Huttunen S, Tapanainen JS, Martikainen H. Factors affecting the outcome of frozen-thawed embryo transfer. Hum Reprod. 2013;28(9):2425–31. doi: 10.1093/humrep/det251 23756705

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