Heber, M. F., & Ptak, G. E. (2021). The effects of assisted reproduction technologies on metabolic health and disease†. Biology of reproduction. https://doi.org/10.1093/biolre/ioaa224
Heber MF, Ptak GE. The effects of assisted reproduction technologies on metabolic health and disease†. Biology of reproduction. 2021. doi:10.1093/biolre/ioaa224
Heber, Maria Florencia, and Grażyna Ewa Ptak. "The effects of assisted reproduction technologies on metabolic health and disease†." Biology of reproduction, 2021.
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RRM Academy Synopsis
Studies report early metabolic changes in children conceived with ART
A narrative review reports early signs of metabolic change in children conceived with ART. The authors drew on human, animal and epigenetic studies. They say the changes could be early indicators of chronic adult disease, including metabolic syndrome. The changes do not appear to carry a high disease risk by themselves, and the authors call for long-term follow-up.
Key Findings
Some human studies of children and adolescents conceived by IVF or ICSI report higher blood pressure, higher fasting glucose, more body fat and, in a few studies, higher triglycerides.
Other human studies found no glucose changes, and the authors call the human evidence controversial because most children are still young and parental factors confound the results.
Several mouse studies of ART offspring report raised blood pressure, altered glucose metabolism and increased body weight and fat, with patterns that differ by sex and by procedure.
Most human epigenetic studies of IVF and ICSI placentas found decreased methylation of H19/IGF2 and SNRPN compared with naturally conceived pregnancies.
The review describes female ART offspring as more prone to early cardiovascular changes and obesity, and male offspring as showing more evident alterations later in life.
Interpretation
The paper is a narrative review. The authors summarize studies from several research areas without pooling the results. The human findings come from epidemiological studies of children. The authors note that procedure effects are hard to separate from parental factors. The authors say animal models can remove parental infertility, and the animals studied are mice and farm animals. The authors link ART to gestational diabetes, pregnancy hypertension, altered placental development and perinatal mortality. They call for long-term and transgenerational studies.
RRM Context
IVF and ICSI bypass the reproductive system and leave the cause of infertility in place. The review lists the steps they involve: ovarian stimulation, embryo culture, handling of eggs, sperm and embryos, and freezing. It places these steps in windows of epigenetic change. Restorative reproductive medicine treats the cause, so conception can occur without them. The review also names maternal and paternal obesity, stress and undernutrition among exposures linked to metabolic change in offspring.
Our editorial summary of this paper, not the article's abstract.
Abstract
The increasing prevalence of metabolic diseases places a substantial burden on human health throughout the world. It is believed that predisposition to metabolic disease starts early in life, a period of great susceptibility to epigenetic reprogramming due to environmental insults. Assisted reproductive technologies (ART), i.e., treatments for infertility, may affect embryo development, resulting in multiple adverse health outcomes in postnatal life. The most frequently observed alteration in ART pregnancies is impaired placental nutrient transfer. Moreover, consequent intrauterine growth restriction and low birth weight followed by catch-up growth can all predict future obesity, insulin resistance, and chronic metabolic diseases. In this review, we have focused on evidence of adverse metabolic alterations associated with ART, which can contribute to the development of chronic adult-onset diseases, such as metabolic syndrome, type 2 diabetes, and cardiovascular disease. Due to high phenotypic plasticity, ART pregnancies can produce both offspring with adverse health outcomes, as well as healthy individuals. We further discuss the sex-specific and age-dependent metabolic alterations reflected in ART offspring, and how the degree of interference of a given ART procedure (from mild to more severe manipulation of the egg) affects the occurrence and degree of offspring alterations. Over the last few years, studies have reported signs of cardiometabolic alterations in ART offspring that are detectable at a young age but that do not appear to constitute a high risk of disease and morbidity per se. These abnormal phenotypes could be early indicators of the development of chronic diseases, including metabolic syndrome, in adulthood. The early detection of metabolic alterations could contribute to preventing the onset of disease in adulthood. Such early interventions may counteract the risk factors and improve the long-term health of the individual.
