Skip to main content
SpringerLink
Log in

A non-linear dose-response relation of female body mass index and in vitro fertilization outcomes

  • Assisted Reproduction Technologies
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Obesity, measured by body mass index (BMI), is implicated in adverse pregnancy outcomes for women seeking in vitro fertilization (IVF) care. However, the shape of the dose-response relationship between BMI and IVF outcomes remains unclear.

Methods

We therefore conducted a dose-response meta-analysis using a random effects model to estimate summary relative risk (RR) for clinical pregnancy (CPR), live birth (LBR), and miscarriage risk (MR) after IVF.

Results

A total of 18 cohort-based studies involving 975,889 cycles were included. For each 5-unit increase in BMI, the summary RR was 0.95 (95% CI: 0.94–0.97) for CPR, 0.93 (95% CI: 0.92-0.95) for LBR, and 1.09 (95% CI: 1.05-1.12) for MR. There was evidence of a non-linear association between BMI and CPR (Pnon-linearity < 10−5) with CPR decreasing sharply among obese women (BMI > 30). Non-linear dose-response meta-analysis showed a relatively flat curve over a broad range of BMI from 16 to 30 for LBR (Pnon-linearity = 0.0009). In addition, we observed a J-shaped association between BMI and MR (Pnon-linearity = 0.006) with the lowest miscarriage risk observed with a BMI of 22–25.

Conclusions

In conclusion, obesity contributed to increased risk of adverse IVF outcomes in a non-linear dose-response manner. More prospective trials in evaluating the effect of body weight control are necessary.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

Data analyzed in this study are openly available at locations cited in the reference section.

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.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Vahratian A. Prevalence of overweight and obesity among women of childbearing age: results from the 2002 National Survey of Family Growth. Matern Child Health J. 2009;13:268–73.

    Article  PubMed  Google Scholar 

  3. 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;8:109.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Legler J, Fletcher T, Govarts E, Porta M, Blumberg B, Heindel JJ, et al. Obesity, diabetes, and associated costs of exposure to endocrine-disrupting chemicals in the European Union. J Clin Endocrinol Metab. 2015;100(4):1278–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 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;106:1742–50.

    Article  PubMed  Google Scholar 

  6. Koning AMH, Kuchenbecker WKH, Groen H, Hoek A, Land JA, Khan KS, et al. Economic consequences of overweight and obesity in infertility: a framework for evaluating the costs and outcomes of fertility care. Hum Reprod Update. 2010;16:246–54.

    Article  CAS  PubMed  Google Scholar 

  7. Nohr EA, Bech BH, Davies MJ, Frydenberg M, Henriksen TB, Olsen J. Prepregnancy obesity and fetal death. Obstet Gynecol. 2005;106:250–9.

    Article  PubMed  Google Scholar 

  8. Aladashvili-Chikvaidze N, Kristesashvili J, Gegechkori M. Types of reproductive disorders in underweight and overweight young females and correlations of respective hormonal changes with BMI. Iran J Reprod Med. 2015;13:135–40.

    PubMed  PubMed Central  Google Scholar 

  9. Jungheim ES, Travieso JL, Hopeman MM. Weighing the impact of obesity on female reproductive function and fertility. Nutr Rev. 2013;71:3–8.

    Article  Google Scholar 

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

    Article  PubMed  Google Scholar 

  11. Maheshwari A, Stofberg L, Bhattacharya S. Effect of overweight and obesity on assisted reproductive technology—a systematic review. Hum Reprod Update. 2007;13:433–44.

    Article  CAS  PubMed  Google Scholar 

  12. Styne-Gross A, Elkind-Hirsch K, Scott RT. Obesity does not impact implantation rates or pregnancy outcome in women attempting conception through oocyte donation. Fertil Steril. 2005;83:1629–34.

    Article  PubMed  Google Scholar 

  13. 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;127:88–93.

    Article  PubMed  Google Scholar 

  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  PubMed  Google Scholar 

  15. Sermondade N, Huberlant S, Bourhis-Lefebvre V, Arbo E, Gallot V, Colombani M, et al. Female obesity is negatively associated with live birth rate following IVF: a systematic review and meta-analysis. Hum Reprod Update. 2019;25(4):439–51.

    Article  CAS  PubMed  Google Scholar 

  16. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–9 W264.

    Article  PubMed  Google Scholar 

  17. Greenland S, Longnecker MP. Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol. 1992;135:1301–9.

    Article  CAS  PubMed  Google Scholar 

  18. Orsini N, Bellocco R, Greenland S. Generalized least squares for trend estimation of summarized dose-response data. Stata J. 2006;6:40–57.

    Article  Google Scholar 

  19. Larsson SC, Orsini N, Wolk A. Dietary magnesium intake and risk of stroke: a meta-analysis of prospective studies. Am J Clin Nutr. 2012;95:362–6.

    Article  CAS  PubMed  Google Scholar 

  20. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.

    Article  CAS  PubMed  Google Scholar 

  21. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.

    Article  PubMed  Google Scholar 

  22. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bailey AP, Hawkins LK, Missmer SA, Correia KF, Yanushpolsky EH. Effect of body mass index on in vitro fertilization outcomes in women with polycystic ovary syndrome. Am J Obstet Gynecol. 2014;211:163–e1-e6.

    Article  PubMed  Google Scholar 

  24. 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;100:1050–8.

    Article  PubMed  Google Scholar 

  25. Cai J, Liu L, Zhang J, Qiu H, Jiang X, Li P, et al. Low body mass index compromises live birth rate in fresh transfer in vitro fertilization cycles: a retrospective study in a Chinese population. Fertil Steril. 2017;107:422–429.e2.

    Article  PubMed  Google Scholar 

  26. Christensen MW, Ingerslev HJ, Degn B, Kesmodel US, et al. PLoS One. 2016;11:e0163393.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Chueca A, Devesa M, Tur R, Mancini F, Buxaderas R, Barri PN. Should BMI limit patient access to IVF? Hum Reprod. 2010;25(Supplement 1):i283.

  28. Insogna IG, Lee MS, Reimers RM, Toth TL. Neutral effect of body mass index on implantation rate after frozen-thawed blastocyst transfer. Fertil Steril. 2017;108:770-776.e1.

  29. MacKenna A, Schwarze JE, Crosby JA, Zegers-Hochschild F. Outcome of assisted reproductive technology in overweight and obese women. JBRA Assist Reprod. 2017;21:79–83.

    PubMed  PubMed Central  Google Scholar 

  30. Oliveira JB, Dieamant F, Baruffi R, Petersen CG, Mauri AL, Vagnini LD, et al. Female body mass index (BMI) influences art outcomes: an evaluation of 3740 IVF/ICSI cycles. Fertil Steril. 2018;110:e120–1.

    Article  Google Scholar 

  31. Provost MP, Acharya KS, Acharya CR, Yeh JS, Steward RG, Eaton JL, Goldfarb JM, Muasher SJ Pregnancy outcomes decline with increasing body mass index: analysis of 239,127 fresh autologous in vitro fertilization cycles from the 2008 – 2010 Society for Assisted Reproductive Technology registry. Fertil Steril. 2016a;105: 663-669, Pregnancy outcomes decline with increasing body mass index: analysis of 239,127 fresh autologous in vitro fertilization cycles from the 2008–2010 Society for Assisted Reproductive Technology registry.

  32. Provost MP, Acharya KS, Acharya CR, Yeh JS, Steward RG, Eaton JL, Goldfarb JM, Muasher SJ Pregnancy outcomes decline with increasing recipient body mass index: an analysis of 22,317 fresh donor/recipient cycles from the 2008 – 2010 Society for Assisted Reproductive Technology Clinic Outcome Reporting System registry. Fertil Steril. 2016b;105:364-368, Pregnancy outcomes decline with increasing recipient body mass index: an analysis of 22,317 fresh donor/recipient cycles from the 2008–2010 Society for Assisted Reproductive Technology Clinic Outcome Reporting System registry.

  33. 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;103:388–95.

    Article  PubMed  Google Scholar 

  34. Wang JX, Davies M, Norman RJ. Body mass and probability of pregnancy during assisted reproduction treatment: retrospective study. BMJ. 2000;321:1320–1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wang JX, Davies MJ, Norman RJ. Obesity increases the risk of spontaneous abortion during infertility treatment. Obes Res. 2002;10:551–4.

    Article  PubMed  Google Scholar 

  36. Zhang J, Liu H, Mao X, Chen Q, Fan Y, Xiao Y, et al. Effect of body mass index on pregnancy outcomes in a freeze-all policy: an analysis of 22,043 first autologous frozen-thawed embryo transfer cycles in China. BMC Med. 2019;17:114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Qiu MT, Tao Y, Kuang YP, Wang Y. Effect of body mass index on pregnancy outcomes with the freeze-all strategy in women with polycystic ovarian syndrome. Fertil Steril. 2019;112:1172–9.

    Article  CAS  PubMed  Google Scholar 

  38. Catteau A, Caillon H, Barrière P, Denis MG, Masson D, Fréour T. Leptin and its potential interest in assisted reproduction cycles. Hum Reprod Update. 2016;22:320–41.

    Article  CAS  PubMed  Google Scholar 

  39. Broughton DE, Moley KH. Obesity and female infertility: potential mediators of obesity’ s impact. Fertil Steril. 2017;107:840–7.

    Article  PubMed  Google Scholar 

  40. Goldman KN, Hodes-Wertz B, McCulloh DH, Flom JD, Grifo JA. Association of body mass index with embryonic aneuploidy. Fertil Steril. 2015;103:744–8.

    Article  PubMed  Google Scholar 

  41. Comstock IA, Kim S, Behr B, Lathi RB. Increased body mass index negatively impacts blastocyst formation rate in normal responders undergoing in vitro fertilization. J Assist Reprod Genet. 2015;32:1299–304.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Boots CE, Bernardi LA, Stephenson MD. Frequency of euploid miscarriage is increased in obese women with recurrent early pregnancy loss. Fertil Steril. 2014;102:455–9.

    Article  PubMed  Google Scholar 

  43. Goldman KN, Hodes-wertz B, Mcculloh DH, Flom JD. Association of body mass index with embryonic aneuploidy. Fertil Steril. 2013;15:1–5.

    Google Scholar 

  44. Adamson GD, de Mouzon J, Chambers GM, Zegers-Hochschild F, Mansour R, Ishihara O, et al. International Committee for Monitoring Assisted Reproductive Technology: world report on assisted reproductive technology, 2011. Fertil Steril. 2018;110(6):1067–80.

    Article  PubMed  Google Scholar 

  45. 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  PubMed  Google Scholar 

  46. Milone M, Sosa Fernandez LM, Sosa Fernandez LV, Manigrasso M, Elmore U, De Palma GD, et al. Does bariatric surgery improve assisted reproductive technology outcomes in obese infertile women? Obes Surg. 2017;27:2106–12.

    Article  PubMed  Google Scholar 

  47. Mutsaerts MA, van Oers AM, Groen H, Burggraaff JM, Kuchenbecker WK, Perquin DA, et al. Randomized trial of a lifestyle program in obese infertile women. N Engl J Med. 2016;374:1942–53.

    Article  CAS  PubMed  Google Scholar 

  48. Einarsson S, Bergh C, Friberg B, Pinborg A, Klajnbard A, Karlström PO, et al. Weight reduction intervention for obese infertile women prior to IVF: a randomized controlled trial. Hum Reprod. 2017;32:1621–30.

    Article  PubMed  Google Scholar 

  49. Wellons MF, Fujimoto VY, Baker VL, Barrington DS, Broomfield D, Catherino WH, et al. Race matters: a systematic review of racial/ethnic disparity in Society for Assisted Reproductive Technology reported outcomes. Fertil Steril. 2012;98:406–9.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Dr. Gitte Lindved Petersen and Dr. Veronica Sarais for making their data available for the present study.

Author information

Authors and Affiliations

  1. Prenatal Diagnosis Center, Department of Clinical Laboratory, Changning Maternity and Infant Health Hospital, East China Normal University, #786 Yuyuan Road, Shanghai, 200051, China

    Kefu Tang, Yuanqing Guo, Lei Wu, Ying Luo, Bo Gong & Liyun Feng

  2. Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200135, China

    Kefu Tang

Authors
  1. Kefu Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuanqing Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lei Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ying Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bo Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Liyun Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kefu Tang.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethics approval

Not applicable.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tang, K., Guo, Y., Wu, L. et al. A non-linear dose-response relation of female body mass index and in vitro fertilization outcomes. J Assist Reprod Genet 38, 931–939 (2021). https://doi.org/10.1007/s10815-021-02082-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-021-02082-8

Keywords

Search

Navigation