Implantation failure can be divided into five areas.
  • Problems with the embryos
  • Problems with “host” uterus
  • Problems in the interaction between embryo and uterus.
  • Failure to achieve a pregnancy following 2-3 IVF cycles in which reasonably good [ high grade embryos] embryos were transferred is termed as implantation failure.
  • Embryonic loss which occurs repeatedly after Assisted Reproduction may be attributed to many factors.

These are grouped into three categories
  • Decreased endometrial receptivity
  • Embryonic defect
  • Factors with combined effect.
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Assumed etiologies for repeated implantation failure [RIF]
  • Uterine cavity abnormalities
  • Thin endometrium
  • Altered expression of adhesive molecules
  • Immunological factors
  • Thrombophilas
  • 18-27% women reveal uterine abnormalities, mainly hyperplasia polyps, endometritis, synechiae and leiomyomata Effect of leiomyomata on implantation is uncertain
  • Impact of intramural lesions or myomas < 4 cm on implantation failure remain controversial
  • Presence of thin or hyperechogenic endometrium or persistent endometrial fluid impaired the outcome in tubal factor
  • Local dysregulation of the normal expression or action of various cytokines are related to implantation failure
  • Elevated endometrial NK cells
  • Dys regulation of interleukin [IL] 12,15 & 18
  • High IL –Iβ and low interferon –γ & IL-10 are associated with implantation failure
  • Failure of appearance of a specific integrin – α V β 3 in endometrium at the time of implantation can cause implantation failure.
  • High levels of aromatase p450 mRNA
  • Changes in pinopodes expression
  • High matrix metalloproteinases are associated with implantation failure
  • Role of immunological causes and thrombophilia in implantation failure 18 specific antiphospholipid antibodies
  • β 2- glycoprotein – I antibodies are related to IVF failure
  • Antibodies to annexin –V, which acts as an inhibitor of phospholipid –dependant coagulation and also necessary for trophoblast differentiation lead to implantation failure.
  • T-helper 1 & 2 [Th1,Th2] intracellular cytokine expression was increased in peripheral lymphocytes.
  • Presence of natural killer cells also leads to implantation failure.
  • Couples sharing HLA alleles are at high risk of recurrent implantation failure & biochemical pregnancies.
  • Prevalence of PAT-1 mutation & multiple thrombophilic gene mutations higher in implantation failure group.
  • Significantly decreased expression of specific endometrial molecules suggested that functional, not only
  • morphological endometrial defects may be associated with unexplained infertility.
  • Suggested methods for investigation and treatment of Recurrent implantation failure.