Maternal body mass index affects embryo morphokinetics: a time-lapse study

Abstract

Purpose

To assess the effect of body mass index (BMI) on morphokinetic parameters of human embryos evaluated with time-lapse technology during in vitro culture.

Methods

A retrospective analysis of ART cycles utilizing time-lapse technology was undertaken to assess the potential impact of maternal BMI on morphokinetic and static morphological parameters of embryo development. The cohort of patients was divided into four groups: 593 embryos from 128 underweight women in group A; 5248 embryos from 1107 normal weight women in group B; 1053 embryos from 226 overweight women in group C; and 286 embryos from 67 obese women in group D.

Results

After adjusting for maternal age, paternal age, and cause of infertility, time to reach five blastomeres (t5) and time to reach eight blastomeres (t8) were longer in obese women compared with normoweight women [50.84 h (46.31–55.29) vs. 49.24 h (45.69–53.22) and 57.89 h (51.60–65.94) vs. 55.66 h (50.89–62.89), adjusted p < 0.05 and adjusted p < 0.01, respectively]. In addition, t8 was also delayed in overweight compared with normoweight women [56.72 h (51.83–63.92) vs. 55.66 h (50.89–62.89), adjusted p < 0.01]. No significant differences were observed among groups with regard to embryo morphology and pregnancy rate. Miscarriage rate was higher in underweight compared with normoweight women (OR = 2.1; 95% CI 1.12–3.95, adjusted p < 0.05).

Conclusion

Assessment with time-lapse technology but not by classical static morphology evidences that maternal BMI affects embryo development. Maternal obesity and overweight are associated with slower embryo development.

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References

  1. 1.

    Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384:766–81.

    Article  Google Scholar 

  2. 2.

    Flegal KM. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010. JAMA. 2012;307:491–7.

    Article  Google Scholar 

  3. 3.

    Rich-Edwards JW, Spiegelman D, Garland M, Hertzmark E, Hunter DJ, Colditz GA, et al. Physical activity, body mass index, and ovulatory disorder infertility. Epidemiology. 2002;13:184–90.

    Article  Google Scholar 

  4. 4.

    Van der Steeg JW, Steures P, Eijkemans MJ, Habbema JD, Hompes PG, Burggraaff JM, et al. Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women. Hum Reprod. 2008;23:324–8.

    Article  Google Scholar 

  5. 5.

    Polotsky AJ, Hailpern SM, Skurnick JH, Lo JC, Sternfeld B, Santoro N. Association of adolescent obesity and lifetime nulliparity—the study of Women’s health across the nation (SWAN). Fertil Steril. 2010;93:2004–11.

    Article  Google Scholar 

  6. 6.

    Boots C, Stephenson MD. Does obesity increase the risk of miscarriage in spontaneous conception: a systematic review. Semin Reprod Med. 2011;29:507–13.

    Article  Google Scholar 

  7. 7.

    Weiss JL, Malone FD, Emig D, Ball RH, Nyberg DA, Comstock CH, et al. Obesity, obstetric complications and cesarean delivery rate—a population-based screening study. Am J Obstet Gynecol. 2004;190:1091–7. https://doi.org/10.1016/j.ajog.2003.09.058.

    Article  PubMed  Google Scholar 

  8. 8.

    Rajasingam D, Seed PT, Briley AL, Shennan AH, Poston L. A prospective study of pregnancy outcome and biomarkers of oxidative stress in nulliparous obese women. Am J Obstet Gynecol. 2009;200:395.e1–9. https://doi.org/10.1016/j.ajog.2008.10.047.

    CAS  Article  Google Scholar 

  9. 9.

    Orvieto R, Meltcer S, Nahum R, Rabinson J, Anteby EY, Ashkenazi J. The influence of body mass index on in vitro fertilization outcome. Int J Gynaecol Obstet. 2009;104(1):53–5. https://doi.org/10.1016/j.ijgo.2008.08.012.

    Article  PubMed  Google Scholar 

  10. 10.

    Ben-Haroush A, Sirota I, Salman L, Son WY, Tulandi T, Holzer H, et al. The influence of body mass index on pregnancy outcome following single-embryo transfer. J Assist Reprod Genet. 2018;35(7):1295–300. https://doi.org/10.1007/s10815-018-1186-5 Epub 2018 May 28.

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Orvieto R. The effect of female body mass index on in vitro fertilization cycle outcomes. J Assist Reprod Genet. 2018;35(11):2081. https://doi.org/10.1007/s10815-018-1299-x.

    Article  PubMed  Google Scholar 

  12. 12.

    Metwally M, Ong KJ, Ledger WL, Li TC. Does high body mass index increase the risk of miscarriage after spontaneous and assisted conception? A meta-analysis of the evidence. Fertil Steril. 2008;90:714–26.

    Article  Google Scholar 

  13. 13.

    Bellver J, Ayllón 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;93:447–54.

    Article  Google Scholar 

  14. 14.

    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;23:421–39.

    Article  Google Scholar 

  15. 15.

    Kudesia R, Wu H, Hunter Cohn K, Tan L, Lee JA, Copperman AB, et al. The effect of female body mass index on in vitro fertilization cycle outcomes: a multi-center analysis. J Assist Reprod Genet. 2018;35(11):2013–23. https://doi.org/10.1007/s10815-018-1290-6.

    Article  PubMed  Google Scholar 

  16. 16.

    Talmor A, Dunphy B. Female obesity and infertility. Best Pract Res Clin Obstet Gynaecol. 2015;29:498–506. https://doi.org/10.1016/j.bpobgyn.2014.10.014.

    Article  PubMed  Google Scholar 

  17. 17.

    Shah DK, Missmer SA, Berry KF, Racowsky C, Ginsburg ES. Effect of obesity on oocyte and embryo quality in women undergoing in vitro fertilization. Obstet Gynecol. 2011;118:63–70.

    Article  Google Scholar 

  18. 18.

    Valckx SD, de Pauw I, de Neubourg D, Inion I, Berth M, Fransen E, et al. BMI-related metabolic composition of the follicular fluid of women undergoing assisted reproductive treatment and the consequences for oocyte and embryo quality. Hum Reprod. 2012;27:3531–9.

    CAS  Article  Google Scholar 

  19. 19.

    Pasquali R. Obesity and androgens: facts and perspectives. Fertil Steril. 2006;85(5):1319–40.

    CAS  Article  Google Scholar 

  20. 20.

    Levens ED, Skarulis MC. Assessing the role of endometrial alteration among obese patients undergoing assisted reproduction. Fertil Steril. 2008;89:1606–8. https://doi.org/10.1016/j.fertnstert.2007.03.079.

    Article  PubMed  Google Scholar 

  21. 21.

    Ou XH, Li S, Wang ZB, Li M, Quan S, Xing F, et al. Maternal insulin resistance causes oxidative stress and mitochondrial dysfunction in mouse oocytes. Hum Reprod. 2012;27(7):2130–45. https://doi.org/10.1093/humrep/des137.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Turner N, Robker RL. Developmental programming of obesity and insulin resistance: does mitochondrial dysfunction in oocytes play a role? Mol Hum Reprod. 2015;21(1):23–30. https://doi.org/10.1093/molehr/gau042.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Zhang X, Wu XQ, Lu S, Guo YL, Ma X. Deficit of mitochondria-derived ATP during oxidative stress impairs mouse MII oocyte spindles. Cell Res. 2006;16(10):841–50.

    CAS  Article  Google Scholar 

  24. 24.

    Robker RL, Akison LK, Bennett BD, Thrupp PN, Chura LR, Russell DL, et al. Obese women exhibit differences in ovarian metabolites, hormones, and gene expression compared with moderate-weight women. J Clin Endocrinol Metab. 2009;94:1533–40. https://doi.org/10.1210/jc.2008-2648.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Provost M, Acharya K, Acharya C. Pregnancy outcomes decline with increasing BMI: an analysis of 239,127 cycles from the 2008–2010 SART registry. Fertil Steril. 2014;102:e18.

    Article  Google Scholar 

  26. 26.

    Luke B, Brown MB, Stern JE, Missmer SA, Fujimoto VY, Leach R. Female obesity adversely affects assisted reproductive technology (ART) pregnancy and live birth rates. Hum Reprod. 2011;26:245–52.

    Article  Google Scholar 

  27. 27.

    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. https://doi.org/10.1111/j.1479-828X.2012.01453.x.

    Article  PubMed  Google Scholar 

  28. 28.

    Bellver J. Impact of bodyweight and lifestyle on IVF outcome. Expert Rev Obstet Gynecol. 2008;3:607–25.

    Article  Google Scholar 

  29. 29.

    Meseguer M, Rubio I, Cruz M, Basile N, Marcos J, Requena A. Embryo incubation and selection in a time-lapse monitoring system improves pregnancy outcome compared with a standard incubator: a retrospective cohort study. Fertil Steril. 2012;98(6):1481–9.e10. https://doi.org/10.1016/j.fertnstert.2012.08.016.

    Article  PubMed  Google Scholar 

  30. 30.

    Basile N, Vime P, Florensa M, Aparicio Ruiz B, Garcia Velasco JA, Remohi J, et al. The use of morphokinetics as a predictor of implantation: a multicentric study to define and validate an algorithm for embryo selection. Hum Reprod. 2015;30:276–83.

    CAS  Article  Google Scholar 

  31. 31.

    Dal Canto M, Coticchio G, Mignini Renzini M, De Ponti E, Novara PV, Brambillasca F, et al. Cleavage kinetics analysis of human embryos predicts development to blastocyst and implantation. Reprod BioMed Online. 2012;25(5):474–80. https://doi.org/10.1016/j.rbmo.2012.07.016.

    Article  PubMed  Google Scholar 

  32. 32.

    Meseguer M, Herrero J, Tejera A, Hilligsoe KM, Ramsing NB, Remoh J. The use of morphokinetics as a predictor of embryo implantation. Hum Reprod. 2011 Advanced Access publication on August 9, 2011;26(10):2658–71. https://doi.org/10.1093/humrep/der256.

    Article  PubMed  Google Scholar 

  33. 33.

    Bellver J, Mifsud A, Grau N, Privitera L, Meseguer M. Similar morphokinetic patterns in embryos derived from obese and normoweight infertile women: a time-lapse study. Hum Reprod. 2013;28(3):794–800. https://doi.org/10.1093/humrep/des438.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Leary C, Leese HJ, Sturmey RG. Human embryos from overweight and obese women display phenotypic and metabolic abnormalities. Hum Reprod. 2015;30(1):122–32. https://doi.org/10.1093/humrep/deu276.

    Article  PubMed  Google Scholar 

  35. 35.

    World Health Organization BMI Classification. Accessed on 22 February 2016. Available online: http://apps.who.int/bmi/index.jsp?introPage=intro_3.html.

  36. 36.

    World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: World Health Organization; 2010.

    Google Scholar 

  37. 37.

    Dal Canto M, Brambillasca F, Mignini Renzini M, Coticchio G, Merola M, Lain M, et al. Cumulus cell-oocyte complexes retrieved from antral follicles in IVM cycles: relationship between COCs morphology, gonadotropin priming and clinical outcome. J Assist Reprod Genet. 2012;29(6):513–9. https://doi.org/10.1007/s10815-012-9766-2.

    Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Fadini R, Coticchio G, Brambillasca F, Mignini Renzini M, Novara PV, Brigante C, et al. Clinical outcomes from mature oocytes derived from preovulatory and antral follicles: reflections on follicle physiology and oocyte competence. J Assist Reprod Genet. 2015;32:255–61 Springer US.

    Article  Google Scholar 

  39. 39.

    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 Oxford University Press.

    Article  Google Scholar 

  40. 40.

    Practice Committee of American Society for Reproductive Medicine. Criteria for number of embryos to transfer: a committee opinion. Fertil Steril. 2013;99(1):44–6.

    Article  Google Scholar 

  41. 41.

    Sarais V, Pagliardini L, Rebonato G, Papaleo E, Candiani M, Viganò P. A comprehensive analysis of body mass index effect on in vitro fertilization outcomes. Nutrients. 2016;8(3):109. https://doi.org/10.3390/nu8030109.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  42. 42.

    G*Power: Statistical power analyses for Windows and Mac. Available online: http://www.psycho.uni-duesseldorf.de/abteilungen/aap/gpower3/. Accessed on 22 February 2016.

  43. 43.

    Metwally M, Cutting R, Tipton A, Skull J, Ledger WL, Li TC. Effect of increased body mass index on oocyte and embryo quality in IVF patients. Reprod BioMed Online. 2007;15(5):532–8.

    CAS  Article  Google Scholar 

  44. 44.

    Igosheva N, Abramov AY, Poston L, Eckert JJ, Fleming TP, Duchen MR, et al. Maternal diet-induced obesity alters mitochondrial activity and redox status in mouse oocytes and zygotes. PLoS One. 2010;5:e10074.

    Article  Google Scholar 

  45. 45.

    Wickramasinghe D, Ebert KM, Albertini DF. Meiotic competence acquisition is associated with the appearance of M-phase characteristics in growing mouse oocytes. Dev Biol. 1991;143:162–72.

    CAS  Article  Google Scholar 

  46. 46.

    Valckx SD, Van Hoeck V, Arias-Alvarez M, Maillo V, Lopez-Cardona AP, Gutierrez-Adan A, et al. Elevated non-esterified fatty acid concentrations during in vitro murine follicle growth alter follicular physiology and reduce oocyte developmental competence. Fertil Steril. 2014;102(6):1769–76.e1. https://doi.org/10.1016/j.fertnstert.2014.08.018.

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Irtue S, Vidal-Puig A. Adipose tissue expandability, lipotoxicity and the metabolic syndrome—an allostatic perspective. Biochim Biophys Acta. 2010;1801:338–49.

    Article  Google Scholar 

  48. 48.

    Broughton DE, Jungheim ES. A focused look at obesity and the preimplantation trophoblast. Semin Reprod Med. 2016;34:5–10.

    Article  Google Scholar 

  49. 49.

    Luzzo KM, Wang Q, Purcell SH, Chi M, Jimenez PT, Grindler N, et al. High fat diet induced developmental defects in the mouse: oocyte meiotic aneuploidy and fetal growth retardation/brain defects. PLoS One. 2012;7:e49217.

    CAS  Article  Google Scholar 

  50. 50.

    Keefe DL. Telomeres and genomic instability during early development. Eur J Med Genet. 2019. https://doi.org/10.1016/j.ejmg.2019.03.002.

  51. 51.

    Bellver J, Pellicer A, García-Velasco JA, Ballesteros A, Remohí J, Meseguer M. Obesity reduces uterine receptivity: clinical experience from 9,587 first cycles of ovum donation with normal weight donors. Fertil Steril. 2013;100(4):1050–8. https://doi.org/10.1016/j.fertnstert.2013.06.001.

    Article  PubMed  Google Scholar 

  52. 52.

    Matalliotakis I, Cakmak H, Sakkas D, Mahutte N, Koumantakis G, Arici A. Impact of body mass index on IVF and ICSI outcome: a retrospective study. Reprod BioMed Online. 2008;16:778–83. https://doi.org/10.1016/S1472-6483(10)60142-3.

    Article  PubMed  Google Scholar 

  53. 53.

    Vilarino FL, Bianco B, Christofolini DM, Barbosa CP. Impact of body mass index on in vitro fertilization outcomes. Rev Bras Ginecol Obstet. 2010;32:536–40. https://doi.org/10.1590/S0100-72032010001100004.

    Article  PubMed  Google Scholar 

  54. 54.

    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.

    CAS  Article  Google Scholar 

  55. 55.

    Wang JX, Davies MJ, Norman RJ. Polycystic ovarian syndrome and the risk of spontaneous abortion following assisted reproductive technology treatment. Hum Reprod. 2001;16(12):2606–9.

    CAS  Article  Google Scholar 

  56. 56.

    Roth D, Grazi RV, Lobel SM. Extremes of body mass index do not affect first-trimester pregnancy outcome in patients with infertility. Am J Obstet Gynecol. 2003;188(5):1169–70.

    Article  Google Scholar 

  57. 57.

    Veleva Z, Tiitinen A, Vilska S, Hydén-Granskog C, Tomás 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. https://doi.org/10.1093/humrep/den017.

    Article  PubMed  Google Scholar 

  58. 58.

    Lage M, Garcia-Mayor RV, Tomé MA, Cordido F, Valle-Inclan F, Considine RV, et al. Serum leptin levels in women throughout pregnancy and the postpartum period and in women suffering spontaneous abortion. Clin Endocrinol. 1999;50(2):211–6.

    CAS  Article  Google Scholar 

  59. 59.

    Andrico S, Gambera A, Specchia C, Pellegrini C, Falsetti L, Sartori E. Leptin in functional hypothalamic amenorrhoea. Hum Reprod. 2002;17(8):2043–8.

    CAS  Article  Google Scholar 

  60. 60.

    Cervero A, Horcajadas JA, MartIn J, Pellicer A, Simón CJ. The leptin system during human endometrial receptivity and preimplantation development. Clin Endocrinol Metab. 2004;89(5):2442–51.

    CAS  Article  Google Scholar 

  61. 61.

    Bouloumié A, Drexler HC, Lafontan M, Busse R. Leptin, the product of Ob gene, promotes angiogenesis. Circ Res. 1998;83(10):1059–66.

    Article  Google Scholar 

  62. 62.

    Laird SM, Quinton ND, Anstie B, Li TC, Blakemore AI. Leptin and leptin-binding activity in women with recurrent miscarriage: correlation with pregnancy outcome. Hum Reprod. 2001;16(9):2008–13.

    CAS  Article  Google Scholar 

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Correspondence to Mariabeatrice Dal Canto.

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Bartolacci, A., Buratini, J., Moutier, C. et al. Maternal body mass index affects embryo morphokinetics: a time-lapse study. J Assist Reprod Genet 36, 1109–1116 (2019). https://doi.org/10.1007/s10815-019-01456-3

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Keywords

  • BMI
  • Embryo development
  • Morphokinetics
  • Time-lapse