A review of the pathophysiology of recurrent implantation failure

Fertil Steril. 2021 Dec;116(6):1436-1448. doi: 10.1016/j.fertnstert.2021.09.014. Epub 2021 Oct 19.


Implantation is a critical step in human reproduction. The success of this step is dependent on a competent blastocyst, receptive endometrium, and successful cross talk between the embryonic and maternal interfaces. Recurrent implantation failure is the lack of implantation after the transfer of several embryo transfers. As the success of in vitro fertilization has increased and failures have become more unacceptable for patients and providers, the literature on recurrent implantation failure has increased. While this clinical phenomenon is often encountered, there is not a universally agreed-on definition-something addressed in an earlier portion of this Views and Reviews. Implantation failure can result from several different factors. In this review, we discuss factors including the maternal immune system, genetics of the embryo and parents, anatomic factors, hematologic factors, reproductive tract microbiome, and endocrine milieu, which factors into embryo and endometrial synchrony. These potential causes are at various stages of research and not all have clear implications or immediately apparent treatment.

Keywords: Recurrent implantation failure; aneuploidy; endometrial receptivity; microbiome.

Publication types

  • Review

MeSH terms

  • Embryo Implantation / physiology*
  • Embryo Transfer / methods*
  • Embryo Transfer / trends
  • Endometriosis / genetics
  • Endometriosis / physiopathology
  • Endometrium / physiopathology*
  • Female
  • Fertilization in Vitro / methods
  • Fertilization in Vitro / trends
  • Humans
  • Pregnancy
  • Pregnancy Rate / trends
  • Recurrence
  • Treatment Failure*