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Background: Louise Brown’s delivery in 1978 was the mark of a successful IVF program that has now been in practice for more than 40 years. The technology has delivered more than 8 million babies. Many breakthrough innovations were established to answer the problem in ART services. Optimizing ART biomarkers and cross border reproductive care have become a rising issue in ART services. Disruptive innovation disrupts the existing condition and takes the lead in the new market, including to change our patient behavior in health services. National health services addressed new issues about the impact of 4.0 industrial revolution on health workforce and our daily practices. Every disruptive innovation today is enhanced by a combination of physical, digital, and biological domain. The advancement in the area of the internet of things, artificial intelligence, virtual reality, nanotechnology, cloud computing, big data, deep learning, machine learning, robotics, and gene editing could potentially support us to innovate. And to improve the quality and outcome of ART, the introduction of the latest technology, such as robotics and artificial intelligence, has become an essential approach. A recent study discovered that the use of artificial intelligence would remove the embryologist’s subjectivity and improve the way we choose the best embryo for implantation. The next challenging issue in ART is improving the success rate through optimizing noninvasive biomarkers development. Many biological products such as blood, tissue, organ fluid can be assessed and considered to be used as IVF biomarkers. Proteomic tools were used and are needed to analyze a sample from subjects before it was created as a biomarker for improving the IVF services quality. Conclusion: The development of IVF over 40 years has brought about many distinct achievements in the laboratory and in clinic. Industrial revolution 4.0 has generated many innovations that have helped improve the quality of ART services, including AUGMENT social egg freezing, artificial intelligence, and genome editing. In this era, precision medicine looks very promising for bridging the gap and increasing the accuracy and efficacy of promotive, preventive, diagnostic, and treatment approaches in reproductive medicine.