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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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.
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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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DOI: https://doi.org/10.1007/s10815-016-0850-x