Short‐ and long‐term outcomes in children born after assisted reproductive technology

Pinborg, Anja

doi:10.1111/1471-0528.15437

Cited by 34 publications

(28 citation statements)

References 25 publications

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“…In 2010, 48.5 million couples worldwide were estimated to be affected by infertility [ 1 ]. The use of in vitro fertilization (IVF) and other assisted reproductive technologies (ART) is expanding rapidly, accounting for more than seven million births worldwide [ 2 ]. The advancement of treatments and changes in protocols have also reshaped the landscape of fertility practice in recent years.…”

Section: Introductionmentioning

confidence: 99%

Assisted reproductive technology and hypertensive disorders of pregnancy: systematic review and meta-analyses

Chih

Elias

Gaudet

et al. 2021

BMC Pregnancy Childbirth

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Background Hypertensive disorders of pregnancy (HDP) is one of the most common pregnancy complications and causes of maternal morbidity and mortality. Assisted reproductive technology (ART) has been associated with adverse pregnancy outcomes, including HDP. However, the impact of multiple pregnancies, oocyte donation, as well as fresh and frozen embryo transfer needs to be further studied. We conducted a systematic review and meta-analyses to evaluate the association between ART and HDP or preeclampsia relative to spontaneous conception (SC). Methods We identified studies from EMBASE, MEDLINE, and Cochrane Library (up to April 8, 2020) and manually using structured search strategies. Cohort studies that included pregnancies after in vitro fertilization (IVF) with or without intracytoplasmic sperm fertilization (ICSI) relative to SC with HDP or preeclampsia as the outcome of interest were included. The control group was women who conceived spontaneously without ART or fertility medications. The pooled results were reported in odds ratios (OR) with 95% confidence intervals based on random effects models. Numbers needed to harm (NNH) were calculated based on absolute risk differences between exposure and control groups. Results Eighty-five studies were included after a screening of 1879 abstracts and 283 full text articles. Compared to SC, IVF/ICSI singleton pregnancies (OR 1.70; 95% CI 1.60–1.80; I2 = 80%) and multiple pregnancies (OR 1.34; 95% CI 1.20–1.50; I2 = 76%) were both associated with higher odds of HDP. Singleton pregnancies with oocyte donation had the highest odds of HDP out of all groups analyzed (OR 4.42; 95% CI 3.00–6.51; I2 = 83%). Frozen embryo transfer resulted in higher odds of HDP (OR 1.74; 95% CI 1.58–1.92; I2 = 55%) than fresh embryo transfer (OR 1.43; 95% CI 1.33–1.53; I2 = 72%). The associations between IVF/ICSI pregnancies and SC were similar for preeclampsia. Most interventions had an NNH of 40 to 100, while singleton and multiple oocyte donation pregnancies had particularly low NNH for HDP (16 and 10, respectively). Conclusions Our meta-analysis confirmed that IVF/ICSI pregnancies are at higher odds of HDP and preeclampsia than SC, irrespective of the plurality. The odds were especially high in frozen embryo transfer and oocyte donation pregnancies.

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Section: Introductionmentioning

confidence: 99%

Assisted reproductive technology and hypertensive disorders of pregnancy: systematic review and meta-analyses

Chih

Elias

Gaudet

et al. 2021

BMC Pregnancy Childbirth

View full text Add to dashboard Cite

show abstract

“…For instance, the occurrence of autism and cerebral palsy in IVF/ICSI-derived children was found to be increased in some (Stromberg et al 2002, Lehti et al 2013, Sandin et al 2013, Kamowski-Shakibai et al 2015, Schieve et al 2017, Goldsmith et al 2018 but not all studies (Kallen et al 2010, Reid et al 2010. Both autism (Fountain et al 2015) and cerebral palsy (Goldsmith et al 2018) have been strongly associated with multiple births in ART pregnancies highlighting the need to reduce multiple pregnancies in women undergoing ART (Pinborg 2019).…”

Section: Assisted Reproductive Technologiesmentioning

confidence: 99%

“…Also, a critical step in elucidating the long-term effects of ART in human populations is the development of databases for ART surveillance (i.e. health monitoring of ART-derived offspring), something that has been implemented in just a few countries (Pinborg 2019). The first ART-derived baby turned 40 years just recently, hence the long-term repercussions (or lack of) of ART for healthy ageing are far from being elucidated.…”

Section: Assisted Reproductive Technologiesmentioning

confidence: 99%

Periconceptional environment and the developmental origins of disease

Velazquez

Fleming

Watkins

2019

Journal of Endocrinology

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The concept emerging from Professor David Barker’s seminal research on the developmental origins of later-life disease has progressed in many directions since it was first published. One critical question being when during gestation might environment alter the developmental programme with such enduring consequences. Here, we review the growing consensus from clinical and animal research that the period around conception, embracing gamete maturation and early embryogenesis might be the most vulnerable period. We focus on four types of environmental exposure shown to modify periconceptional reproduction and offspring development and health: maternal overnutrition and obesity; maternal undernutrition; paternal diet and health; and assisted reproductive technology. These conditions may act through diverse epigenetic, cellular and physiological mechanisms to alter gene expression and cellular signalling and function in the conceptus affecting offspring growth and metabolism leading to increased risk for cardiometabolic and neurological disease in later life.

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Section: Introductionmentioning

confidence: 99%

“…In developed countries, 1-6% of children are currently conceived by ART, mostly IVF and ICSI (Calhaz-Jorge et al, 2015;Goisis et al, 2019;Pinborg et al, 2019). Even though these procedures are generally considered to be safe, there are remaining concerns about their longterm health consequences (Celermajer, 2012;Calhaz-Jorge et al, 2015, Goisis et al, 2019Pinborg et al, 2019). As recently reviewed, several studies have suggested that individuals conceived by ART might be at risk of developing increased adiposity, glucose intolerance and hypertension, although there is no general agreement on these findings and correction for confounding factors such as maternal hormonal environment following ovarian stimulation, embryo culture conditions, fresh or frozen embryo transfer, single or multiple embryo replacement and parental age and/or infertility (Pinborg et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Decreased pulmonary vascular distensibility in adolescents conceived by in vitro fertilization

et al. 2019

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STUDY QUESTION What is the functional relevance of decreased pulmonary vascular distensibility in adolescents conceived by IVF? SUMMARY ANSWER Children born by IVF have a slight decrease in pulmonary vascular distensibility observed during normoxic exercise that is not associated with altered right ventricular function and aerobic exercise capacity. WHAT IS KNOWN ALREADY General vascular dysfunction and increased hypoxic pulmonary hypertension have been reported in ART children as compared to controls. Pulmonary hypertension or decreased pulmonary vascular distensibility may affect right ventricular function and thereby possibly limit maximal cardiac output and aerobic exercise capacity. STUDY DESIGN, SIZE, DURATION This prospective case-control study enrolled 15 apparently healthy adolescents conceived by IVF/ICSI after fresh embryo transfer paired in a 2 to 1 ratio to 30 naturally conceived adolescents between March 2015 and May 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS Fifteen IVF/ICSI adolescents and 30 controls from singleton gestations matched by age, gender, weight, height and physical activity underwent exercise echocardiography, lung diffusion capacity measurements and a cycloergometer cardiopulmonary exercise test. A pulmonary vascular distensibility coefficient α was determined from the pulmonary arterial pressure (PAP) versus cardiac output (Q) relationships. Pulmonary capillary volume (Vc) was calculated from single breath nitric oxide and carbon monoxide lung diffusion capacity measurements (DLCO and DLNO) at rest and during exercise (100 W). Eight of the IVF subjects and eight controls underwent a 30 min hypoxic challenge at rest with a fraction of inspired oxygen of 0.12 to assess hypoxic pulmonary vasoconstriction. MAIN RESULTS AND THE ROLE OF CHANCE In normoxia, oxygen uptake (VO2), blood pressure, DLCO, DLNO, echocardiographic indices of right ventricular function, Q and PAP at rest and during exercise were similar in both groups. However, IVF children had a lower pulmonary vascular distensibility coefficient α (1.2 ± 0.3 versus 1.5 ± 0.3%/mmHg, P = 0.02) and a blunted exercise-induced increase in Vc (24 versus 32%, P < 0.05). Hypoxic-induced increase in pulmonary vascular resistance in eight IVF subjects versus eight controls was similar. LIMITATIONS, REASONS FOR CAUTION The IVF cohort was small, and thus type I or II errors could have occurred in spite of careful matching of each case with two controls. ART evolved over the years, so that it is not certain that the presently reported subtle changes will be reproducible in the future. As the study was limited to singletons born after fresh embryo transfers, our observations cannot be extrapolated to singletons born after frozen embryo transfer. WIDER IMPLICATIONS OF THE FINDINGS The present study suggests that adolescents conceived by IVF have preserved right ventricular function and aerobic exercise capacity despite a slight alteration in pulmonary vascular distensibility as assessed by two entirely different methods, i.e. exercise echocardiography and lung diffusing capacity measurements. However, the long-term prognostic relevance of this slight decrease in pulmonary vascular distensibility needs to be evaluated in prospective large scale and long-term outcome studies. STUDY FUNDING/COMPETING INTEREST(S) Dr Caravita was supported by an ERS PAH short term research training fellowship (STRTF2014-5264). Dr Pezzuto was funded by an Italian Society of cardiology grant. Dr Motoji was supported by a grant from the Cardiac Surgery Funds, Belgium. All authors have no conflicts of interests to declare.

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Short‐ and long‐term outcomes in children born after assisted reproductive technology

Cited by 34 publications

References 25 publications

Assisted reproductive technology and hypertensive disorders of pregnancy: systematic review and meta-analyses

Assisted reproductive technology and hypertensive disorders of pregnancy: systematic review and meta-analyses

Periconceptional environment and the developmental origins of disease

Decreased pulmonary vascular distensibility in adolescents conceived by in vitro fertilization

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