Molecular regulators of human blastocyst development and hatching: Their significance in implantation and pregnancy outcome

In humans, blastocyst hatching and implantation events are two sequential, critically linked and rate-limiting events for a prospective pregnancy. These events are regulated by embryo-endometrium derived molecular factors which include hormones, growth factors, cytokines, immune-modulators, cell adhesion molecules and proteases. Due to poor viability of blastocysts, they fail to hatch and implant, leading to a low ‘Live Birth Rates’, majorly contributing to infertility. Here, embryo-derived biomarkers analysis plays a key role to assess potential biological viability of blastocysts which are capable of implantation and prospective pregnancy. Thus far, embryo-derived biomarkers examined are mostly immune-modulators which are thought to be associated with blastocyst development-implantation and progression of pregnancy, leading to live births. There is an urgent need to develop a quantitative and a reliable non-invasive approach aiding embryo selection for elective single embryo transfer and to minimize recurrent pregnancy loss and multiple pregnancies. In this article, we provide a comprehensive review on our current knowledge and understanding of potential embryo-derived molecular regulators, that is, biomarkers, of development of human blastocysts, their hatching and implantation. We discuss their potential implications in the assessment of blastocyst implantation potential and pregnancy outcome in terms of live births in humans.