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Increased risk of large-for-gestational age birthweight in singleton siblings conceived with in vitro fertilization in frozen versus fresh cycles

  • Assisted Reproduction Technologies
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Abstract

Background

Children born from fresh in vitro fertilization (IVF) cycles are at greater risk of being born smaller and earlier, even when limited to singletons; those born from frozen cycles have an increased risk of large-for-gestational age (LGA) birthweight (z-score ≥1.28). This analysis sought to overcome limitations in other studies by using pairs of siblings, and accounting for prior cycle outcomes, maternal characteristics, and embryo state and stage.

Methods

Pairs of singleton births conceived with IVF and born between 2004 and 2013 were identified from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database, matched for embryo stage (blastocyst versus non-blastocyst) and infant gender, categorized by embryo state (fresh versus frozen) in 1st and 2nd births (four groups).

Results

The data included 7795 singleton pairs. Birthweight z-scores were 0.00–0.04 and 0.24–0.26 in 1st and 2nd births in fresh cycles, and 0.25–0.34 and 0.50–0.55 in frozen cycles, respectively. LGA was 9.2–9.8 and 14.2–15.4% in 1st and 2nd births in fresh cycles, and 13.1–15.8 and 20.8–21.0% in 1st and 2nd births in frozen cycles. The risk of LGA was increased in frozen cycles (1st births, adjusted odds ratios (AOR) 1.74, 95% CI 1.45, 2.08; and in 2nd births when the 1st birth was not LGA, AOR 1.70, 95% CI 1.46, 1.98 for fresh/frozen and 1.40, 1.11, 1.78 for frozen/frozen).

Conclusions

Our results with siblings indicate that frozen embryo state is associated with an increased risk for LGA. The implications of these findings for childhood health and risk of obesity are unclear, and warrant further investigation.

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Authors’ roles

BL and MBB contributed to the conception and design of the study, drafted the manuscript, and revised it. MBB performed the statistical analyses. BL, JE, and EW linked IVF cycles in the SART CORS database. All the authors contributed to the interpretation of the data and approved the final version of the manuscript.

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Authors and Affiliations

  1. Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, 965 Fee Road, East Fee Hall, Room 628, East Lansing, MI, 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. Department of Obstetrics and Gynecology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA

    Judy E. Stern

  5. Atlanta Center for Reproductive Medicine, Atlanta, GA, USA

    James P. Toner

  6. Division of Reproductive Endocrinology and Infertility, Mayo Clinic, Rochester, MN, USA

    Charles C. Coddington III

Authors
  1. Barbara Luke
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  2. Morton B. Brown
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  3. Ethan Wantman
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  4. Judy E. Stern
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  5. James P. Toner
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  6. Charles C. Coddington III
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Corresponding author

Correspondence to Barbara Luke.

Ethics declarations

This study was approved by the Committees for the Protection of Human Subjects at the Dartmouth College, Michigan State University, and University of Michigan.

Conflict of interest

BL is a research consultant to the Society for Assisted Reproductive Technology (SART). EW is under contract with SART to maintain the SART CORS database. MBB, JES, JPT, and CCC have no conflicts to declare.

Additional information

Capsule Frozen embryo state is associated with an increased risk for LGA; the implications of these findings for childhood health and obesity risk are unclear.

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Luke, B., Brown, M.B., Wantman, E. et al. Increased risk of large-for-gestational age birthweight in singleton siblings conceived with in vitro fertilization in frozen versus fresh cycles. J Assist Reprod Genet 34, 191–200 (2017). https://doi.org/10.1007/s10815-016-0850-x

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