Childhood growth of term singletons born after frozen compared with fresh embryo transfer

Terho, A; Pelkonen, S.; Toikkanen, Ronja; Koivurova, Sari; Salo, Jarmo A.; Nuojua-Huttunen, Sinikka; Pokka, Tytti; Gissler, Mika; Tiitinen, Aila; Martikainen, Hannu

doi:10.1016/j.rbmo.2021.08.002

Cited by 5 publications

(4 citation statements)

References 31 publications

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“…The results from our large national cohort study suggest that newborn twins conceived by fresh ET have a significantly lower birth weight than NC twins, whereas FET twins are heavier, consistent with singleton studies ( Hann et al , 2018 ; Maheshwari et al , 2018 ; Laval et al , 2020 ; Terho et al , 2021b ). Contrary to what was observed in singletons from the same cohort ( Hann et al , 2018 ), FET twins grow faster than NC and fresh ET twins after the first assessment, and by school entry, FET twins are heavier than NC and fresh ET twins.…”

Section: Discussionsupporting

confidence: 86%

“…Specific ART procedures, particularly frozen embryo transfer (FET) and fresh embryo transfer (ET), have been linked to differences in outcomes within the ART cohort. Several studies have reported that singleton fresh ET babies are smaller at birth, while FET babies are larger than their naturally conceived (NC) counterparts ( Maheshwari et al , 2018 ; Castillo et al , 2019 ; Laval et al , 2020 ; Terho et al ., 2021a ). Some smaller ART growth studies have reported inconsistent differences in growth for fresh ET, FET, and NC babies ( Ludwig et al , 2006 ; Sakka et al , 2010 ; Yeung et al , 2016 ; Magnus et al , 2021 ; Terho et al , 2021b ).…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have reported that singleton fresh ET babies are smaller at birth, while FET babies are larger than their naturally conceived (NC) counterparts ( Maheshwari et al , 2018 ; Castillo et al , 2019 ; Laval et al , 2020 ; Terho et al ., 2021a ). Some smaller ART growth studies have reported inconsistent differences in growth for fresh ET, FET, and NC babies ( Ludwig et al , 2006 ; Sakka et al , 2010 ; Yeung et al , 2016 ; Magnus et al , 2021 ; Terho et al , 2021b ). Two recent large cohort studies demonstrated that small fresh ET singletons show catch-up growth and weigh the same as FET and NC singletons by ∼5 years old or adolescence ( Hann et al , 2018 ; Turner et al , 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Growth of twins conceived using assisted reproductive treatments up to 5 years old: a national growth cohort

et al. 2023

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STUDY QUESTION Do twins conceived through assisted reproductive treatments (ART) grow differently from naturally conceived (NC) twins in early life? SUMMARY ANSWER Assessments at 6–8 weeks old and at school entry show that ART twins conceived from frozen embryo transfer (FET) grow faster than both NC twins and ART twins conceived from fresh embryo transfer (ET). WHAT IS KNOWN ALREADY Singletons born from fresh ET grow more slowly in utero and in the first few weeks of life but then show postnatal catch-up growth by school age, compared to NC and FET babies. Evidence on early child growth of ART twins relative to NC twins is inconsistent; most studies are small and do not distinguish FET from fresh ET cycles. STUDY DESIGN, SIZE, DURATION This cohort study included 13 528 live-born twin babies conceived by ART (fresh ET: 2792, FET: 556) and NC (10 180) between 1991 and 2009 in Scotland. The data were obtained by linking Human Fertilisation and Embryology Authority ART register data to the Scottish Morbidity Record (SMR02) and Scottish child health programme datasets. Outcome data were collected at birth, 6–8 weeks (first assessment), and school entry (4–7 years old) assessments. The primary outcome was growth, measured by weight at the three assessment points. Secondary outcomes were length (at birth and 6–8 weeks) or height (at school entry), BMI, occipital circumference, gestational age at birth, newborn intensive care unit admission, and growth rates (between birth and 6–8 weeks and between 6–8 weeks and school entry). PARTICIPANTS/MATERIALS, SETTING, METHODS All twins in the linked dataset (born between 1991 and 2009) with growth data were included in the analysis. To determine outcome differences between fresh ET, FET, and NC twins, linear mixed models (or analogous logistic regression models) were used to explore the outcomes of interest. All models were adjusted for available confounders: gestational age/child age, gender, maternal age and smoking, Scottish Index of Multiple Deprivation, year of treatment, parity, ICSI, and ET stage. MAIN RESULTS AND THE ROLE OF CHANCE In the primary birth weight models, the average birth weight of fresh ET twins was lower [–35 g; 95% CI: (−53, −16)g] than NC controls, while FET twins were heavier [71 g; 95% CI (33, 110) g] than NC controls and heavier [106 g; 95% CI (65, 146) g] than fresh ET twins. However, the difference between FET and NC twins was not significant when considering only full-term twins (≥37 weeks gestation) [26 g; 95% CI (–30, 82) g], while it was significantly higher in preterm twins [126 g; 95% CI (73, 179) g]. Growth rates did not differ significantly for the three groups from birth to 6–8 weeks. However, FET twins grew significantly faster from 6 to 8 weeks than NC (by 2.2 g/week) and fresh ET twins (by 2.1 g/week). By school entry, FET twins were 614 g [95% CI (158, 1070) g] and 581 g [95% CI (100, 1063) g] heavier than NC and fresh ET twins, respectively. Length/height and occipital frontal circumference did not differ significantly at any time point. LIMITATIONS, REASONS FOR CAUTION Although the differences between ART and NC reflect the true ART effects, these effects are likely to be mediated partly through the different prevalence of mono/dizygotic twins in the two groups. We could not explore the mediating effect of zygosity due to the unavailability of data. The confounding variables included in the study were limited to those available in the datasets. WIDER IMPLICATIONS OF THE FINDINGS Live-born twins from FET cycles are heavier at birth, grow faster than their fresh ET and NC counterparts, and are still heavier at school entry. This differs from that observed in singletons from the same cohort, where babies in the three conception groups had similar weights by school entry age. The results are reassuring on known differences in FET versus fresh ET and NC twin outcomes. However, FET twins grow faster and are consistently larger, and more ART twins depict catch-up growth. These may lead to an increased risk profile for non-communicable diseases in later life. As such, these twin outcomes require careful evaluation using more recent and comprehensive cohorts. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the EU H2020 Marie Sklodowska-Curie Innovative Training Networks (ITN) grant Dohartnet (H2020-MSCA-ITN-2018-812660). The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER N/A.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Growth of twins conceived using assisted reproductive treatments up to 5 years old: a national growth cohort

et al. 2023

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“…They found no effect of FET versus fresh ET on neonatal weight and childhood weight gain trajectory [29]. An observational cohort study by Hannu et al suggested that childhood growth did not differ between term singletons after FET versus fresh ET when correcting for exact age at measurement and adjusting for maternal BMI and paternal height [30]. These results provide evidence that FET does not cause a clinically signi cant effect on long-term growth of the offspring and reassurance of the safety and feasibility of the steadily increasing use of FET in assisted reproduction.…”

Section: Discussionmentioning

confidence: 98%

Reduced live birth rate after frozen compared to fresh single poor cleavage-stage embryo transfer cycles: a retrospective study

Li²,

Liu³

et al. 2022

Preprint

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Purpose The ongoing debate focuses on whether the freeze-all strategy is suitable for the general population or may be offered to specific subgroups of patients. This study aimed to compare the pregnancy and neonatal outcomes between FET and fresh ET and evaluate the effectiveness of the embryo freezing strategy for a specific group of patients undergoing single poor cleavage-stage embryo transfer. Methods A total of 1,819 ET cycles that underwent single poor cleavage-stage embryo transfer between January 2014 and December 2020 were enrolled in this study and categorized into two groups according to the embryo processing methods: fresh ET group (n = 1124) and frozen ET group (n = 695). Results We found that the clinical pregnancy and live birth rates were significantly higher in the fresh cycles than in the frozen cycles (32.38% vs. 22.30%, p = 0.000; 25.62% vs. 16.12%, p = 0.000, respectively). The multivariate logistic regression model showed that the cycle type (fresh or frozen) still had a significant impact on the live birth rate (OR 1.62, 95% CI: 1.19–2.21, p = 0.002) after adjusting for potential confounders. Discussion FET was associated with a significantly lower risk of clinical pregnancy and live birth rates. For patients who are more likely to develop poor-quality cleavage embryos, such as women with previous low response or reduced ovarian reserve, it is suggested that fresh ET should be given priority to achieve better pregnancy and neonatal outcomes than FET if there are no special circumstances.

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Association between frozen embryo transfer and childhood allergy: a retrospective cohort study

Luo,

Su,

Dong

et al. 2024

Reproductive BioMedicine Online

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Childhood growth of term singletons born after frozen compared with fresh embryo transfer

Abstract: He has practised infertility treatments for over 35 years and published more than 150 peer-reviewed papers. His main interest is the safety of infertility treatments, including single embryo transfer in fresh and frozen cycles.

Cited by 5 publications

References 31 publications

Growth of twins conceived using assisted reproductive treatments up to 5 years old: a national growth cohort

Growth of twins conceived using assisted reproductive treatments up to 5 years old: a national growth cohort

Reduced live birth rate after frozen compared to fresh single poor cleavage-stage embryo transfer cycles: a retrospective study

Association between frozen embryo transfer and childhood allergy: a retrospective cohort study

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