Increased risk of large-for-gestational age birthweight in singleton siblings conceived with in vitro fertilization in frozen versus fresh cycles
- 475 Downloads
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.
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).
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).
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.
KeywordsAssisted reproductive technology Siblings Fresh and thawed cycles Birth outcomes
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.
Compliance with ethical standards
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.
- 4.Shih W, Rushford DD, Bourne H, Garrett C, McBain JC, Healy DL, et al. Factors affecting low birthweight after assisted reproduction technology: difference between transfer of fresh and cryopreserved embryos suggests an adverse effect of oocyte collection. Hum Reprod. 2008;23:1644–53.CrossRefPubMedGoogle Scholar
- 8.Nakashima A, Araki R, Tani H, Ishihara O, Kuwahara A, Irahara M, et al. Implications of assisted reproductive technologies on term singleton birth weight: an analysis of 25,777 children in the national assisted reproduction registry of Japan. Fertil Steril. 2013;99:450–5.CrossRefPubMedGoogle Scholar
- 21.Center for Disease Control and Prevention, American Society for Reproductive Medicine, and Society for Assisted Reproductive Technology. Assisted reproductive technology success rates: national summary and fertility clinic reports. Washington, DC: US Dept. of Health and Human Services; 2012. p. 2014.Google Scholar
- 26.Institute of Medicine. Weight gain during pregnancy: reexamining the guidelines. Washington, DC: National Academies Press; 2009.Google Scholar
- 38.Yeh JS, Steward RG, Dude AM, Shah AA, Goldfarb JM, Muasher SJ. Pregnancy rates in donor oocyte cycles compared to similar autologous in vitro fertilization cycles: an analysis of 26,457 fresh cycles from the Society for Assisted Reproductive Technology. Fertil Steril. 2014;102:399–404.CrossRefPubMedGoogle Scholar
- 41.Maheshwari A, Pandey S, Shetty A, Hamilton M, Bhattacharya S. Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of frozen thawed versus fresh embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril. 2012;98:368–77.CrossRefPubMedGoogle Scholar
- 46.Korosec S, Frangez HB, Verdenik I, Kladnik U, Kotar V, Virant-Klun I, Bokal EV. Singleton pregnancy outcomes after in vitro fertilization with fresh or frozen-thawed embryo transfer and incidence of placenta previa. BioMed Res Int. 2014; article ID 431797. Doi.org/ 10.1155/2014/431797.
- 49.Pinborg A, Loft A, Noergaard L, Henningsen AA, Rasmussen S, Nyboe Andersen A. Singletons born after frozen embryo transfer (FET) have an increased risk of being large of gestational age—Danish national controlled cohort study of 15,078 singletons. [abstract] Human Reprod. 2011 (suppl. 1): O-230.Google Scholar
- 54.Parsons TJ, Power C, Logan S, Summerbell CD. Childhood predictors of adult obesity: a systematic review. Int J Obes. 1999;23(Supplement 8):S1–107.Google Scholar
- 59.Olivennes F, Schneider Z, Remy V, Blanchet V, Kerbrat V, Fanchin R, et al. Perinatal outcome and follow-up of 82 children aged 1–9 years old conceived from cryopreserved embryos. Hum Reprod. 1996;11:1665–8.Google Scholar