Effect of frozen/thawed embryo transfer on birthweight, macrosomia, and low birthweight rates in US singleton infants

• Type of Material: Article
• Authors: Julia F. Litzky, Dartmouth College; Sheree Boulet, Emory University; Navid Esfandiari, Dartmouth College; Yujia Zhang, Centers for Disease Control & Prevention; Dmitry M. Kissin, Emory University; Regan N. Theiler, Dartmouth College; Carmen Marsit, Emory University
• Language: English
• Date: 2018-04-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Elsevier Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ajog.2017.12.223
• Title of Journal or Parent Work: American Journal of Obstetrics and Gynecology
• ISSN: 0002-9378
• Volume: 218
• Issue: 4
• Start Page: 433.e1
• End Page: 433.e10
• Grant/Funding Information: This study was supported by grants from the National Institutes of Health (NIH-NIMH R01MH094609, NIH-NIEHS R01ES022223, P01 ES022832), and the Environmental Protection Agency (EPA RD8354420).; Grants were all received by Dr Marsit.; The funding sources were not involved in the design of the study or in the analysis or interpretation of the data.
• Keywords: Obstetrics & Gynecology; COHORT; in vitro fertilization; low birthweight; TECHNOLOGY; birthweight; Life Sciences & Biomedicine; FROZEN; National ART Surveillance System; frozen/ thawed embryo transfer; OVARIAN STIMULATION; IN-VITRO FERTILIZATION; fresh embryo transfer; Science & Technology; CYCLES; IMPACT; PERINATAL OUTCOMES; FRESH; macrosomia; CHILDREN BORN
• Research Categories: Health Sciences, Human Development; Health Sciences, Obstetrics and Gynecology

Abstract

Background: Singleton infants conceived using assisted reproductive technology have lower average birthweights than naturally conceived infants and are more likely to be born low birthweight (<2500 gr). Lower birthweights are associated with increased infant and child mortality and poor adult health outcomes, including cardiovascular disease, hypertension, and diabetes. Data from registry and single-center studies suggest that frozen/thawed embryo transfer may be associated with larger birthweights. To date, however, a nationwide, full-population study on United States infants born using frozen/thawed embryo transfer has not been reported. Objectives: The objective of this study was to compare the effect of frozen/thawed vs fresh embryo transfer on birthweight outcomes for singleton, term infants conceived using in vitro fertilization in the United States between 2007 and 2014, including average birthweight and the risks of both macrosomia (>4000 g) and low birthweight (<2500 g). Study Design: We used data from the Centers for Disease Control and Prevention's National Assisted Reproductive Technology Surveillance System to compare birthweight outcomes of live-born singleton, autologous oocyte, term (37-43 weeks) infants. Generalized linear models for all infants and stratified by infant sex were used to assess the relationship between frozen/thawed embryo transfer and birthweight, in grams. Infertility diagnosis, year of treatment, maternal age, maternal obstetric history, maternal and paternal race, and infant gestational age and sex were included in the models. Missing race data were imputed. The adjusted relative risks for macrosomia and low birthweight were evaluated using multivariable predicted marginal proportions from logistic regression models. Results: In total, 180,184 singleton, term infants were included, with 55,898 (31.02%) having been conceived from frozen/thawed embryos. Frozen/thawed embryo transfer was associated with, on average, a 142 g increase in birthweight compared with infants born after fresh embryo transfer (P <.001). An interaction between infant sex and embryo transfer type was significant (P <.0001), with frozen/thawed embryo transfer having a larger effect on male infants by 16 g. The adjusted risk of a macrosomic infant was 1.70 times higher (95% confidence interval, 1.64–1.76) following frozen/thawed embryo transfer than fresh embryo transfer. However, adjusted risk of low birthweight following frozen/thawed embryo transfer was 0.52 (95% confidence interval, 0.48–0.56) compared with fresh embryo transfer. Conclusion: Frozen/thawed embryo transfer, in comparison with fresh embryo transfer, was associated with increased average birthweight in singleton, autologous oocytes, term infants born in the United States, with a significant interaction between frozen/thawed embryo transfer and infant sex. The risk of macrosomia following frozen/thawed embryo transfer was greater than that following fresh embryo transfer, but the risk of low birthweight among frozen/thawed embryo transfer infants was significantly decreased in comparison with fresh embryo transfer infants.