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Risks of nonchromosomal birth defects, small-for-gestational age birthweight, and prematurity with in vitro fertilization: effect of number of embryos transferred and plurality at conception versus at birth

  • Assisted Reproduction Technologies
  • Published:
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Abstract

Purpose

Excess embryos transferred (ET) (> plurality at birth) and fetal heartbeats (FHB) at 6 weeks’ gestation are associated with reductions in birthweight and gestation, but prior studies have been limited by small sample sizes and limited IVF data. This analysis evaluated associations between excess ET, excess FHB, and adverse perinatal outcomes, including the risk of nonchromosomal birth defects.

Methods

Live births conceived via IVF from Massachusetts, New York, North Carolina, and Texas included 138,435 children born 2004–2013 (Texas), 2004–2016 (Massachusetts and North Carolina), and 2004–2017 (New York) were classified by ET and FHB. Major birth defects were reported by statewide registries within the first year of life. Logistic regression was used to estimate adjusted odds ratios (AORs) and 95% CIs of the risks of a major nonchromosomal birth defect, small-for-gestational age birthweight (SGA), low birthweight (LBW), and preterm birth (≤36 weeks), by excess ET, and excess ET + excess FHB, by plurality at birth (singletons and twins).

Results

In singletons with [2 ET, FHB =1] and [≥3 ET, FHB=1], risks [AOR (95% CI)] were increased, respectively, for major nonchromosomal birth defects [1.13 (1.00–1.27) and 1.18 (1.00–1.38)], SGA [1.10 (1.03–1.17) and 1.15 (1.05–1.26)], LBW [1.09 (1.02–1.13) and 1.17 (1.07–1.27)], and preterm birth [1.06 (1.00–1.12) and 1.14 (1.06–1.23)]. With excess ET + excess FHB, risks of all adverse outcomes except major nonchromosomal birth defects increased further for both singletons and twins.

Conclusion

Excess embryos transferred are associated with increased risks for nonchromosomal birth defects, reduced birthweight, and prematurity in IVF-conceived births.

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Data availability

The data used in this analysis were obtained from private (SART CORS) and public (vital records, birth defects registries) sources, under data use agreements and confidentiality pledges assuring that the data would not be shared or distributed, and therefore are not available to other investigators.

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Acknowledgements

The authors thank the Society for Assisted Reproductive Technology and all of its members for providing clinical information to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for use by patients and researchers. Without the efforts of their members, this research would not have been possible.

Funding

This project was supported by grant R01 HD084377 from the National Institute of Child Health and Human Development National Institutes of Health, USA (Barbara Luke, Principal Investigator).

Author information

Authors and Affiliations

  1. Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, 965 Wilson Road, East Fee Hall, Room 628, East Lansing, MI, 48824, USA

    Barbara Luke

  2. Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA

    Morton B. Brown

  3. Redshift Technologies, Inc., New York, NY, USA

    Ethan Wantman

  4. Birth Defects Monitoring Program, State Center for Health Statistics, North Carolina Department of Health and Human Services, Raleigh, NC, USA

    Nina E. Forestieri

  5. Birth Defects Research Section, New York State Department of Health, Albany, NY, USA

    Marilyn L. Browne & Sarah C. Fisher

  6. Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, Rensselaer, NY, USA

    Marilyn L. Browne

  7. Massachusetts Center for Birth Defects Research and Prevention, Massachusetts Department of Public Health, Boston, MA, USA

    Mahsa M. Yazdy & Mary K. Ethen

  8. Birth Defects Epidemiology and Surveillance Branch, Texas Department of State Health Services, Austin, TX, USA

    Mark A. Canfield

  9. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA

    Hazel B. Nichols

  10. Virginia Beach, USA

    Sergio Oehninger

  11. Center for Assisted Reproduction, Bedford, TX, USA

    Kevin J. Doody

  12. UCL Great Ormond Street Institute of Child Health, University College London, London, UK

    Alastair G. Sutcliffe & Carrie Williams

  13. Division of Male Reproductive Medicine and Surgery, Department of Urology, Stanford University School of Medicine, Palo Alto, CA, USA

    Michael L. Eisenberg

  14. Division of Reproductive Endocrinology and Infertility, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Valerie L. Baker

  15. Massachusetts General Hospital Fertility Center and Harvard Medical School, Boston, MA, USA

    Caitlin R. Sacha

  16. Epidemiology Program, Texas Children’s Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, USA

    Philip J. Lupo

Authors
  1. Barbara Luke
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Contributions

Drs. Luke and Brown had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Luke and Brown

Acquisition, analysis, or interpretation of data: All authors

Drafting of the manuscript: Luke, Brown

Critical revision of the manuscript for important intellectual content: All authors

Statistical analysis: Brown

Obtained funding: Luke, Brown

Administrative, technical, or material support: All authors

Supervision: Luke

Corresponding author

Correspondence to Barbara Luke.

Ethics declarations

Ethics approval

This study was approved by the Institutional Review Boards at Michigan State University, the University of Michigan, and each of the four study State Departments of Health.

Conflict of interest

Drs. Luke and Brown reported receiving grants from NIH during the conduct of the study. Ms. Forestieri, Dr. Yazdy, and Dr. Browne reported receiving NIH grant support from Michigan State University during the conduct of the study. Mr. Wantman reported receiving personal fees from SART, being a data vendor of SART, and maintaining the SART CORS database during the course of the study; and personal fees from NYU Fertility, MyEggBank, Prelude Fertility, Shady Grove Fertility, Northwell Health Fertility, and Mass General Fertility outside the submitted work. No other disclosures were reported.

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Luke, B., Brown, M.B., Wantman, E. et al. Risks of nonchromosomal birth defects, small-for-gestational age birthweight, and prematurity with in vitro fertilization: effect of number of embryos transferred and plurality at conception versus at birth. J Assist Reprod Genet 38, 835–846 (2021). https://doi.org/10.1007/s10815-021-02095-3

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