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      Birthweights and Down syndrome in neonates that were delivered after frozen‐thawed embryo transfer: The 2007‐2012 Japan Society of Obstetrics and Gynecology National Registry data in Japan

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          Abstract

          Aim

          To evaluate the use of frozen embryos on the outcome of assisted reproductive technology ( ART), a retrospective study of the Japanese Assisted Reproductive Technology Registry data during the years 2007‐2012 was conducted.

          Methods

          A total of 124 946 singleton neonates who reached term gestation following ART from 2007‐2012, with 80 660 achieved through frozen‐thawed embryo transfer ( ET) and 44 286 being achieved through fresh ET, were analyzed for their birthweights and chromosomal abnormalities.

          Results

          The birthweight of the neonates from the frozen‐thawed ETs was significantly higher than that of those from the fresh ETs throughout all the study years. The frequency of Down syndrome was 0.17% for the fresh ETs and 0.13% for the frozen‐thawed ETs in the period 2007‐2012. This study showed that frozen‐thawed ETs result in a constant increase of the average birthweight between 37 and 41 weeks gestational age and lower frequencies of Down syndrome.

          Conclusion

          Frozen‐thawed ETs were comparable to the fresh ET method, with the exceptions of higher birthweights and a lower frequency of Down syndrome in the neonates that were born from frozen‐thawed ET. The increase in birthweights was not proportional to the gestational ages. This cannot be explained with any well‐known mechanism. The frequency of chromosomal abnormalities needs detailed data for analysis.

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          Most cited references17

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          Assisted reproductive technology in Europe, 2010: results generated from European registers by ESHRE†.

          The 14th European IVF--monitoring (EIM) report presents the results of medically assisted reproduction treatments including assisted reproductive technology (ART) cycles and intrauterine insemination (IUI) cycles initiated in Europe during 2010: are there changes in the trends compared with previous years?
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            Perinatal outcomes of children born after frozen-thawed embryo transfer: a Nordic cohort study from the CoNARTaS group.

            What are the risks of adverse outcomes in singletons born after frozen-thawed embryo transfer (FET)? Singletons born after FET have a better perinatal outcome compared with singletons born after fresh IVF and ICSI as regards low birthweight (LBW) and preterm birth (PTB), but a worse perinatal outcome compared with singletons born after spontaneous conception. Previous studies have shown a worse perinatal outcome in children born after IVF in general compared with children born after spontaneous conception. In singletons born after FET, a lower rate of PTB and LBW and a higher rate of large for gestational age (LGA) compared with singletons born after fresh IVF have been shown. A retrospective Nordic population-based cohort study of all singletons conceived after FET in Denmark, Norway and Sweden until December 2007 was performed. Singletons born after FET (n = 6647) were compared with a control group of singletons born after fresh IVF and ICSI (n = 42 242) and singletons born after spontaneous conception (n = 288 542). Data on perinatal outcomes were obtained by linkage to the national Medical Birth Registries. Odds ratios were calculated for several perinatal outcomes and adjustments were made for maternal age, parity, year of birth, offspring sex and country of origin. Singletons born after FET had a lower risk of LBW (adjusted odds ratio (aOR) 0.81, 95% confidence interval (CI) 0.71-0.91), PTB (aOR 0.84, 95% CI 0.76-0.92), very PTB (VPTB; aOR 0.79, 95% CI 0.66-0.95) and small for gestational age (SGA; aOR 0.72, 95% CI 0.62-0.83), but a higher risk of post-term birth (aOR 1.40, 95% CI 1.27-1.55), LGA (aOR 1.45, 95% CI 1.27-1.64), macrosomia (aOR 1.58, 95% CI 1.39-1.80) and perinatal mortality (aOR 1.49, 95% CI 1.07-2.07) compared with singletons born after fresh IVF and ICSI. Compared with children conceived after spontaneous conception, singletons born after FET had a higher risk of LBW (aOR 1.27, 95% CI 1.13-1.43), very LBW (aOR 1.69, 95% CI 1.33-2.15), PTB (aOR 1.49, 95% CI 1.35-1.63), VPTB (aOR 2.68, 95% CI 2.24-3.22), SGA (aOR 1.18, 95% CI 1.03-1.35), LGA (aOR 1.29, 95% CI 1.15-1.45), macrosomia (aOR 1.29, 95% CI 1.15-1.45) and perinatal (aOR 1.39, 95% CI 1.03-1.87) neonatal (aOR 1.87, 95% CI 1.23-2.84) and infant mortality (aOR 1.92, 95% CI 1.36-2.72). When analyzing trends over time, the risk of being born LGA increased over time for singletons born after FET compared with singletons born after fresh IVF and ICSI (P = 0.04). As in all observational studies, the possible role of residual confounding factors and bias should be considered. In this study, we were not able to control for confounding factors, such as BMI, smoking and reason for, or length of, infertility. Perinatal outcomes in this large population-based cohort of children born after FET from three Nordic countries compared with fresh IVF and ICSI and spontaneous conception were in agreement with the literature.
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              Infant outcome of 957 singletons born after frozen embryo replacement: the Danish National Cohort Study 1995-2006.

              To examine infant outcome of singletons born after cryopreservation of embryos (Cryo). National population-based controlled follow-up study. Denmark, 1995-2007. The study population was 957 Cryo singletons (Cryo-IVF, n=660; Cryo-ICSI, n=244; Cryo-IVF/-ICSI, n=53). The first control group was all singletons born after fresh IVF or intracytoplasmic sperm injection (ICSI) during the same period (IVF, n=6904; ICSI, n=3425). The second control group comprised a random sample of non-assisted reproductive technology (ART) singletons (n=4800). All observations were obtained from national registers. Low birth weight (LBW; <2500 g), preterm birth (PTB; <37 weeks), congenital malformations, mortality, and morbidity. Birth weight was higher in Cryo (mean=3578 g, SD=625) versus fresh (mean=3373 g, SD=648) and in Cryo versus non-ART (mean=3537 g, SD=572), and this was also the case for first birth only. Lower adjusted risk of LBW (odds ratio [OR]=0.63; 95% confidence interval [CI], 0.45-0.87) and PTB (OR=0.70; 95% CI, 0.53-0.92) was observed in Cryo versus fresh. Similar LBW and PTB rates were observed when comparing Cryo with non-ART, but the perinatal mortality rate was doubled in Cryo (1.6%) compared with non-ART (0.8%) singletons, and the adjusted risks of very preterm birth (<34 weeks) and neonatal admittance were also significantly increased. No significant differences in the prevalence rates of birth defects, neurological sequelae, malignancies, and imprinting-related diseases were observed between the Cryo and the two control groups. However higher malformation and cerebral palsy rates were observed in the total Fresh vs. non-ART group. Cryo singletons have better neonatal outcome than offspring after fresh ET but poorer compared with non-ART singletons. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                miyado-k@ncchd.go.jp
                saitou-hi@ncchd.go.jp
                Journal
                Reprod Med Biol
                Reprod. Med. Biol
                10.1111/(ISSN)1447-0578
                RMB2
                Reproductive Medicine and Biology
                John Wiley and Sons Inc. (Hoboken )
                1445-5781
                1447-0578
                10 April 2017
                April 2017
                : 16
                : 2 ( doiID: 10.1111/rmb2.2017.16.issue-2 )
                : 228-234
                Affiliations
                [ 1 ] Department of Perinatal Medicine and Maternal Care National Center for Child Health and Development Tokyo Japan
                [ 2 ] Department of Reproductive Biology National Research Institute for Child Health and Development Tokyo Japan
                [ 3 ] Department of Molecular Endocrinology National Research Institute for Child Health and Development Tokyo Japan
                [ 4 ] Department of Life Sciences School of Agriculture Meiji University Kawasaki Japan
                Author notes
                [*] [* ] Correspondence

                Kenji Miyado, Department of Reproductive Biology, National Research Institute for Child Health and Development, Tokyo, Japan.

                Email: miyado-k@ 123456ncchd.go.jp

                Hidekazu Saito, Department of Perinatal Medicine and Maternal Care, National Center for Child Health and Development, Tokyo, Japan.

                Email: saitou-hi@ 123456ncchd.go.jp

                Article
                RMB212033
                10.1002/rmb2.12033
                5661821
                3d122842-473f-4bda-a0c4-4a0fb5f4fb73
                © 2017 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 October 2016
                : 10 February 2017
                Page count
                Figures: 3, Tables: 1, Pages: 7, Words: 4631
                Funding
                Funded by: National Center for Child Health and Development
                Award ID: 24‐6
                Funded by: Ministry of Education, Culture, Sports, Science and Technology
                Award ID: 26293363
                Award ID: 26670733
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                rmb212033
                April 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.7 mode:remove_FC converted:04.12.2017

                assisted reproductive technology,birthweight,chromosomal abnormalities,down syndrome,frozen‐thawed embryo transfer

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