Sciorio, R., Manna, C., Fauque, P., & Rinaudo, P. (2023). Can Cryopreservation in Assisted Reproductive Technology (ART) Induce Epigenetic Changes to Gametes and Embryos? Journal of clinical medicine. https://doi.org/10.3390/jcm12134444
Sciorio R, Manna C, Fauque P, Rinaudo P. Can Cryopreservation in Assisted Reproductive Technology (ART) Induce Epigenetic Changes to Gametes and Embryos? Journal of clinical medicine. 2023. doi:10.3390/jcm12134444
Sciorio, Romualdo, et al. "Can Cryopreservation in Assisted Reproductive Technology (ART) Induce Epigenetic Changes to Gametes and Embryos?" Journal of clinical medicine, 2023.
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Freezing eggs and embryos may alter their epigenetic marks
Freezing eggs and embryos by vitrification may alter epigenetic marks, a 2023 narrative review reports. The review draws on animal studies and a limited number of human studies. The human studies found few changes in DNA methylation. The authors consider it unclear whether any change affects the health of future children.
Key Findings
Several mouse and bovine studies reported altered expression or DNA methylation of imprinted genes in oocytes, early embryos, and blastocysts after oocyte vitrification.
Human studies of vitrified oocytes and embryos reported little or no change in DNA methylation or in the activity of imprinted genes.
A study of 16 donated mature human oocytes found 1987 genes expressed differently after vitrification and warming than in fresh oocytes: about 82% downregulated and 18% upregulated.
One study found lower survival, clinical pregnancy, and live birth rates in blastocysts stored more than six years than in those stored under three; miscarriage and ectopic pregnancy rates did not differ.
A meta-analysis of 26 studies reported higher birth weights and large-for-gestational-age singletons after freezing and thawing, and an increased risk of hypertensive disorders in those pregnancies.
Interpretation
The article is a narrative review that describes no search method. The review draws on mouse, bovine, fish, rooster, and ram studies and on human studies that the authors call limited. The authors state that the clinical consequences remain to be fully elucidated. The birth weight findings are associations. The authors write that it is unclear whether vitrification, cryoprotective agents, endometrial preparation drugs, or parental infertility is responsible.
RRM Context
IVF bypasses infertility and leaves the cause of failed conception unresolved. Freezing adds a step that exposes eggs, embryos, and sperm to cryoprotective agents. Restorative reproductive medicine is cause-based: it looks in both partners for the reason conception has not occurred and treats it. The review notes that birth weight has not differed after natural-cycle transfer, so the drugs that prepare the uterine lining may explain the higher birth weights.
Our editorial summary of this paper, not the article's abstract.
Abstract
Since the birth of Louise Brown in 1978, more than nine million children have been conceived using assisted reproductive technologies (ARTs). While the great majority of children are healthy, there are concerns about the potential epigenetic consequences of gametes and embryo manipulation. In fact, during the preimplantation period, major waves of epigenetic reprogramming occur. Epigenetic reprogramming is susceptible to environmental changes induced by ovarian stimulation, in-vitro fertilization, and embryo culture, as well as cryopreservation procedures. This review summarizes the evidence relating to oocytes and embryo cryopreservation and potential epigenetic regulation. Overall, it appears that the stress induced by vitrification, including osmotic shock, temperature and pH changes, and toxicity of cryoprotectants, might induce epigenetic and transcriptomic changes in oocytes and embryos. It is currently unclear if these changes will have potential consequences for the health of future offspring.
