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.
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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 19.
Pasquali R. Obesity and androgens: facts and perspectives. Fertil Steril. 2006;85(5):1319–40.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 28.
Bellver J. Impact of bodyweight and lifestyle on IVF outcome. Expert Rev Obstet Gynecol. 2008;3:607–25.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: World Health Organization; 2010.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
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.
- 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.
- 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.
- 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.
- 47.
Irtue S, Vidal-Puig A. Adipose tissue expandability, lipotoxicity and the metabolic syndrome—an allostatic perspective. Biochim Biophys Acta. 2010;1801:338–49.
- 48.
Broughton DE, Jungheim ES. A focused look at obesity and the preimplantation trophoblast. Semin Reprod Med. 2016;34:5–10.
- 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.
- 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.
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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 61.
Bouloumié A, Drexler HC, Lafontan M, Busse R. Leptin, the product of Ob gene, promotes angiogenesis. Circ Res. 1998;83(10):1059–66.
- 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.
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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