The health of children conceived by ART: ‘the chicken or the egg?’

Berntsen, Sine; Söderström‐Anttila, Viveca; Wennerholm, Ulla‐Britt; Laivuori, Hannele; Loft, Anne; Oldereid, Nan Birgitte; Romundstad, Liv Bente; Bergh, Christina; Pinborg, Anja

doi:10.1093/humupd/dmz001

Cited by 321 publications

(265 citation statements)

References 186 publications

(224 reference statements)

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“…Several studies have own, on the contrary, either better or similar results after ICSI treatment compared with IVF treatment (5,13,(37)(38)(39). As ICSI has mainly been used when male infertility is present, this might be an explanation for the advantage of ICSI, because the women are not necessarily infertile (40).…”

Section: Discussionmentioning

confidence: 99%

Mortality from infancy to adolescence in singleton children conceived from assisted reproductive techniques versus naturally conceived singletons in Sweden

Rodriguez‐Wallberg

Lundberg

Ekberg

et al. 2020

Fertility and Sterility

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Objective: To assess infant (<1 year) and childhood (1-18 years) mortality in singletons conceived through assisted reproductive techniques (ART) versus naturally conceived singletons. Design: Nationwide prospective study. Setting: Sweden. Patient(s): All singleton liveborn infants born from 1983 to 2012 in Sweden identified using the Medical Birth Register (N ¼ 2,847,108), of whom 43,506 were conceived through ART treatments including in vitro fertilization with and without intracytoplasmic sperm injection. Intervention(s): None. Main Outcome Measures(s): Infant (<1 year) and childhood (1-18 years) mortality. Result(s): Data on ART treatment and covariates were retrieved from population-based registers using the unique personal identity number assigned to all permanent residents in Sweden. Cox proportional hazards models estimated the hazard ratios (HRs) with 95% confidence intervals (CIs) as measures of association between ART treatments and death. The analyses were adjusted for maternal characteristics, infertility, child sex, and birth cohort and were restricted to individuals with complete information on covariates for fully adjusted analysis. Compared with naturally conceived singletons, higher infant mortality risks were seen in infants conceived through ART (adjusted HR 1.45; 95% CI, 1.19-1.77), especially after transfer of cryopreserved embryos (adjusted HR 2.30; 95% CI, 1.46-3.64). Early neonatal mortality risk (deaths during the first week) was increased in children born after transfer of blastocysts (HR 2.40; 95% CI, 1. 05-5.48). No increased mortality risk was observed between the ages of 1 and 18 years. Conclusion(s): Singletons conceived through ART had an increased risk of infant mortality from birth up to 1 year of life, predominantly in the early neonatal period and in pregnancies after transfer of frozen and thawed embryos. (Fertil Steril Ò 2020;113:524-32. Ó2019 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.

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Section: Discussionmentioning

confidence: 99%

Mortality from infancy to adolescence in singleton children conceived from assisted reproductive techniques versus naturally conceived singletons in Sweden

Rodriguez‐Wallberg

Lundberg

Ekberg

et al. 2020

Fertility and Sterility

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“…This suggests that even though superovulation produces abnormal oocytes that initiate altered expression of imprinted genes in embryos, compensatory mechanisms regulating imprinted gene networks are able to restore proper levels of gene expression during development. Although, as highlighted across the literature, the alterations in DNA methylation following ART procedures are not always striking and vary between studies (reviewed in Berntsen et al, 2019), in part because of distinctions in treatments used. It was recently reported that human placenta, but not cord blood, from IVF/ICSI showed decreased DNA methylation levels for imprinted loci H19/IGF2 and KCNQ1OT1, as well as for specific repetitive elements (Choux et al, 2018), whereas in another recent study, no obvious overall differences in genome-wide DNA methylation differences in placental tissues were associated with ART (Choufani et al, 2019).…”

Section: Art Proceduresmentioning

confidence: 99%

DNA methylation, environmental exposures and early embryo development

2019

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The first crucial step in the developmental program occurs during pre-implantation, the time after the oocyte has been fertilized and before the embryo implants in the uterus. This period represents a vulnerable window as the epigenome undergoes dynamic changes in DNA methylation profiles. Alterations in the early embryonic reprogramming wave can impair DNA methylation patterns and induce permanent changes to the developmental program, leading to the onset of adverse health outcomes in offspring. Although there is an increasing body of evidence indicating that harmful exposures during preimplantation embryo development can trigger lasting epigenetic alterations in offspring, the mechanisms are still not fully understood. Since physiological or pathological changes in DNA methylation can occur as a response to environmental cues, proper environmental milieu plays a critical role in the success of embryonic development. In this review, we depict the mechanisms behind the embryonic epigenetic reprogramming of DNA methylation and highlight how maternal environmental stressors (e.g., alcohol, heat stress, nutrient availability) during pre-implantation and assisted reproductive technology procedures affect development and DNA methylation marks.

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“…In the past 40 years, more than 7 million babies have been conceived by assisted reproductive technologies (ART) treatment, mainly through in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) (1). Increasing evidence suggests that ART treatment is associated with adverse obstetric and perinatal outcomes, which may be related to the genetic factors of patients, multiple pregnancies and ART procedures per se (1,2). To avoid multiple pregnancies, a single embryo transfer policy has been implemented in many IVF centers.…”

Section: Introductionmentioning

confidence: 99%

“…However, even singletons conceived by ART are also at increased risk of adverse pregnancy outcomes such as low birth weight, preterm birth, small for gestational age, stillbirth, perinatal mortality and gestational diabetes compared with singletons conceived spontaneously (1,2).…”

Section: Introductionmentioning

confidence: 99%

Fresh versus frozen single embryo transfer in Chinese women of advanced age undergoing IVF/ICSI: a study protocol for a randomized controlled trial

Chen¹,

Huang²,

Liu³

et al. 2020

Preprint

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Background: Elective frozen cleavage embryo transfer resulted in significantly higher live birth rate in patients with polycystic ovary syndrome but not in ovulatory women compared with fresh embryo transfer. Further, elective single frozen blastocyst transfer had significantly higher live birth rate in ovulatory women compared with single fresh blastocyst transfer. However, it is unknown whether single frozen cleavage embryo transfer results in higher cumulative live birth rate in women of advanced age undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). The aim of this study is to compare the effectiveness of frozen cleavage embryo transfer with fresh cleavage embryo transfer in Chinese women of advanced age. Methods: This study is a double-blind randomized controlled clinical trial (1:1 treatment ratio of frozen embryo transfer vs. fresh embryo transfer). A total of 840 women of advanced age with normal ovarian reserve undergoing the first cycle of IVF or ICSI will be enrolled and randomized into two parallel groups. Participants in group A will undergo frozen single cleavage embryo transfer, and participants in group B will undergo fresh single cleavage embryo transfer. The primary outcome is the cumulative live birth rate of the trial IVF/ICSI cycle within 12 months after randomization. This study is powered to detect an absolute difference of 8% (23% vs 15%) at the significance level of 0.05 and 80% statistical power based on a two-sided test. Discussion: The results of this study will provide evidence for the efficacy and safety of frozen cleavage embryo transfer compared with fresh cleavage embryo transfer in women of advanced age undergoing IVF/ICSI. Trial registration: Chinese Clinical Trial Registry, ChiCTR2000029330. Registered on 25 Jan 2020. Keywords: Frozen embryo transfer, advanced age, in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), live birth, randomized controlled trial.

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The health of children conceived by ART: ‘the chicken or the egg?’

Cited by 321 publications

References 186 publications

Mortality from infancy to adolescence in singleton children conceived from assisted reproductive techniques versus naturally conceived singletons in Sweden

Mortality from infancy to adolescence in singleton children conceived from assisted reproductive techniques versus naturally conceived singletons in Sweden

DNA methylation, environmental exposures and early embryo development

Fresh versus frozen single embryo transfer in Chinese women of advanced age undergoing IVF/ICSI: a study protocol for a randomized controlled trial

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