Recurrent Implantation Failure-update overview on etiology, diagnosis, treatment and future directions

Asher Bashiri, Katherine Ida Halper*, Raoul Orvieto

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


Recurrent implantation failure (RIF) refers to cases in which women have had three failed in vitro fertilization (IVF) attempts with good quality embryos. The definition should also take advanced maternal age and embryo stage into consideration. The failure of embryo implantation can be a consequence of uterine, male, or embryo factors, or the specific type of IVF protocol. These cases should be investigated to determine the most likely etiologies of the condition, as this is a complex problem with several variables. There are multiple risk factors for recurrent implantation failure including advanced maternal age, smoking status of both parents, elevated body mass index, and stress levels. Immunological factors such as cytokine levels and presence of specific autoantibodies should be examined, as well as any infectious organisms in the uterus leading to chronic endometritis. Uterine pathologies such as polyps and myomas as well as congenital anatomical anomalies should be ruled out. Sperm analysis, pre-implantation genetic screening and endometrial receptivity should be considered and evaluated, and IVF protocols should be tailored to specific patients or patient populations. Treatment approaches should be directed toward individual patient cases. In addition, we suggest considering a new initial step in approach to patients with RIF, individualized planned activities to activate the brain's reward system in attempt to improve immunological balance in the body.

Original languageEnglish
Article number121
JournalReproductive Biology and Endocrinology
Issue number1
StatePublished - 5 Dec 2018


  • Chronic endometritis
  • Endometrial scratching
  • IVIG
  • Low molecular weight heparin
  • Preimplantation Genetic Screening- PGS
  • Progesterone
  • Recurrent implantation failure-RIF
  • Reward system


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