Defective Embryonic development
Defective Embryonic development :
- Genetic abnormalities [Male / Female / gametes/ embryos]
- Zona hardening
- Suboptimal culture conditions
- Chromosomal abnormalities of the male or female partner, the gametes or the developing embryo may burden embryogenesis.
- Increased frequency of female chromosomal abnormalities such as translocations, mosaics, inversion, deletion and chromosomal breakages, particularly at the centromere region in young women with implantation failure have been found.
- Increased incidence of sperm chromosomal abnormalities in patients with normal karyotype & Recurrent implantation failure was also observed.
- FISH for chromosomes 13,16,18,21,22, X & Y on blastomeres from biopsied embryos → showed % of embryonic aneuploidy higher in implantation failure group.
- 60% of the blastomere biopsies showed abnormalities in implantation failure groups.
- Disruption of chromosomal replication & segregation caused by maternal cytoplasmic factors or mutations in cell cycle control genes can be common causes for Recurrent implantation failure.
- Despite good morphology and development rate, chromosomally abnormal embryos fail to implant
- Zona pellucia which surrounds the mammalian oocyte, hardens naturally after fertilization to prevent polyspermic fertilization and to protect the integrity of the pre-implantation embryo.
- Increased zona thickness was associated with lower implantation rates
- Zona hardening induced by invitro culture or invivo aging affect hatching [failure of the zona to rupture] causing implantation failure
Treatment of the embryos :
- Preimplantation genetic screening
- Assisted hatching
- Zygote intra-fallopian transfer
- Blastocyst transfer
- Cytoplasmic transfer
- Improving ET technique
Suggested Methods for Treatment of Repeated Implantation failure :
Preimplantation Genetic Screening [PGS] :
Patients with implantation failure have high percentage of chromosomally abnormal embryos which fail to implant despite regular morphology and development rate. Using PGS and selecting chromosomally normal embryos for replacement significantly increased the implantation rates in implantation failure group .
PGS for chromosomes 13,16,18,21 and 22 are associated with improved outcome [PR -43%; delivery rate 32%] in implantation failure group.
However the role PGS is more determining to clarify the reason for recurrent failure.
Comparative Genomic hybridisation [CGH] also will enable to identify many chromosomal abnormalities that would have been missed by FISH.
Assisted Hatching :
Laser Assisted hatching has shown to significantly increase pregnancy rate in implantation failure group.
Zygote intrafallopian transfer :
ZIFT allows early embryonic growth in the natural tubal environment and transport of the embryos into the uterine cavity under natural physiologic regulation.
However due to the complexity and cost of ZIFT compared to IVF, led to discontinuation of this method in most IVF units. Other studies also showed that ZIFT had no superior results of implantation
Beneficial effects of the co-culture include secretion of embryotrophic factors such as nutrients, growth factors and cytokines. Detoxification of free radicals and potentially harmful substances.