Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cedars Sinai Medical Center, Los Angeles, California.
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Cedars Sinai Medical Center, Los Angeles, California; David Geffen School of Medicine at UCLA, Los Angeles, California.
Fertil Steril. 2024 Jan;121(1):80-94. doi: 10.1016/j.fertnstert.2023.10.007. Epub 2023 Oct 10.
Because analytic technologies improve, increasing amounts of data on methylation differences between assisted reproductive technology (ART) and unassisted conceptions are available. However, various studies use different tissue types and different populations in their analyses, making data comparison and integration difficult.
To compare and integrate data on genome-wide analyses of methylation differences due to ART, allowing exposure of overarching themes.
All studies undertaking genome-wide analysis of human methylation differences due to ART or infertility in any tissue type across the lifespan were assessed for inclusion.
Seventeen studies were identified that met the inclusion criteria. One study assessed trophectoderm biopsies, 2 first-trimester placenta, 1 first-trimester fetal tissue, 2 term placenta, 7 cord blood, 3 newborn dried blood spots, 1 childhood buccal smears, 1 childhood peripheral blood, and 2 adult peripheral blood. Eleven studies compared tissues from in vitro fertilization (IVF) conceptions with those of unassisted conceptions, 4 compared intracytoplasmic sperm injection with unassisted conceptions, 4 compared non-IVF fertility treatment (NIFT) with unassisted conceptions, 4 compared NIFT with IVF, and 5 compared an infertile population (conceiving via various methods) with an unassisted presumably fertile population. In studies assessing placental tissue, 1 gene with potential methylation changes due to IVF when compared with unassisted conceptions was identified by 2 studies. In blood, 11 potential genes with methylation changes due to IVF compared with unassisted conceptions were identified by 2 studies, 1 of which was identified by 3 studies. Three potentially affected genes were identified by 2 studies involving blood between intracytoplasmic sperm injection and unassisted populations. There were no overlapping genes identified in any tissue type between NIFT and unassisted populations, between NIFT and IVF, or the infertility combined population when compared with the unassisted fertile population.
Comparing studies is challenging due to differing variables between analyses. However, even in similar tissue types and populations, overlapping methylation changes are limited, suggesting that differences due to ART are minimal.
Information from this systematic review is significant for providers and patients who provide and use ART to understand methylation risks that may be associated with the technology.
由于分析技术的进步，越来越多的关于辅助生殖技术 (ART) 和非辅助受孕之间甲基化差异的数据分析可用。然而，各种研究在分析中使用不同的组织类型和不同的人群，使得数据比较和整合变得困难。
比较和整合由于 ART 导致的全基因组甲基化差异分析数据，揭示总体主题。
评估了所有涉及人类在一生中任何组织类型由于 ART 或不孕而导致的全基因组甲基化差异的分析研究，以确定其是否符合纳入标准。
确定了 17 项符合纳入标准的研究。一项研究评估了滋养层活检，2 项研究评估了早期胎盘，1 项研究评估了早期胎儿组织，2 项研究评估了足月胎盘，7 项研究评估了脐带血，3 项研究评估了新生儿干血斑，1 项研究评估了儿童口腔拭子，1 项研究评估了儿童外周血，2 项研究评估了成人外周血。11 项研究比较了体外受精 (IVF) 受孕组织与非辅助受孕组织，4 项研究比较了胞浆内精子注射与非辅助受孕组织，4 项研究比较了非 IVF 生育治疗 (NIFT) 与非辅助受孕组织，4 项研究比较了 NIFT 与 IVF，5 项研究比较了不孕人群（通过各种方法受孕）与非辅助受孕的可能生育人群。在评估胎盘组织的研究中，有 2 项研究确定了 1 个因 IVF 而导致的潜在甲基化变化的基因。在血液中，有 2 项研究确定了 11 个因 IVF 而导致的潜在甲基化变化的基因，其中 1 个基因被 3 项研究确定。有 2 项涉及胞浆内精子注射与非辅助人群的血液的研究确定了 3 个潜在受影响的基因。在 NIFT 与非辅助人群之间、NIFT 与 IVF 之间，或不孕综合人群与非辅助生育人群之间，在任何组织类型中都没有发现重叠的基因。
由于分析之间存在不同的变量，因此比较研究具有挑战性。然而，即使在类似的组织类型和人群中，重叠的甲基化变化也是有限的，这表明 ART 导致的差异很小。
这项系统综述的信息对提供和使用辅助生殖技术的提供者和患者具有重要意义，让他们了解可能与该技术相关的甲基化风险。
