Implantation failure can be divided into three 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] :-
Decreased endometrial receptivity :
- Uterine cavity abnormalities
- Thin endometrium
- Altered expression of adhesive molecules
- Immunological factors
- 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.