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.
Assumed etiologies for repeated implantation failure [RIF]
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.
