Diagnostic and therapeutic options in recurrent implantation failure [version 1; peer review: 2 approved]

Recurrent implantation failure (RIF) is an uncommon, imprecisely defined clinical disorder characterized by failure to achieve pregnancy after repeated embryo transfers. The diverse etiologies and incomplete understanding of RIF provide significant diagnostic and therapeutic challenges to patients and providers. Careful clinical evaluation prior to assisted reproduction can uncover many treatable causes, including thyroid dysfunction, submucosal myomas, and tobacco use. The more-subtle causes often require a more-targeted assessment. Undetected, small polyps or small areas of intrauterine synechiae are relatively common and easily treated contributors to RIF. Molecular and cellular abnormalities pose a greater therapeutic challenge. Putative causes of RIF, including progesterone resistance, shifted window of receptivity, decreased integrin expression, and immunologic disturbances, should be considered in the evaluation of a patient with otherwise unexplained RIF. It may also be true that a more complex and standardized definition of RIF would be helpful in these cases. In this paper, we review the diagnostic and therapeutic approaches to RIF, with emphasis on disorders of endometrial receptivity.