Recurrent Implantation Failure: History, Etiology, Advances and Ongoing Challenges

Infertility is the inability to conceive even after unprotected intercourse for more than 12 months. In India, the prevalence of infertility has been growing to the extent that 10-15 percent of couples experience this condition. Recurrent implantation failure (RIF) is a complex medical condition in which implantation becomes unsuccessful despite the advancements in Assisted Reproductive Technologies (ART). We lack a clear understanding of the definition and standardisation of RIF protocols. The etiology behind RIF is multifactorial, comprising both maternal and embryonic factors. Maternal factors include endometrial abnormalities, environmental exposure, physical aspects, and dysregulation of the immune system. Chromosomal aberrations such as aneuploidy are embryo-born factors that impede implantation. The latest studies have shed light on the novel mechanisms of RIF. Recent research has identified miRNA that can hinder the implantation processes, opening the door to many more avenues for targeted therapies, gene knockdown, and immune modulation. This review is a comprehensive overview of the history, causes, advancements, and challenges related to RIF.