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Implantation factors
- 1. Gili Paz Harel and Michael Mullokandov
- 2. Maternal – fetal interface
- 4. Gametes • Hormone imbalance • Organ abnormalities • Genetic disorders • Metabolic disorders • Lifestyle
- 5. Fertilization • 2PN • 1 day after oocyte retrieval
- 6. The embryo
- 7. Which Embryo is Disease-Free?
- 8. Embryo biopsy Blastomere biopsy PB biopsy Blastocyst biopsy
- 9. PGS / PGD • Preimplantation genetic screening / diagnosis • Single gene defects • Balanced translocations • Advanced maternal age (aneuploidy) • Repetitive IVF failure • Recurrent pregnancy loss
- 10. •Achondroplasia •ADPKD1 •ADPKD2 •Adrenoleukodystroph •Age-related aneuploidies •Alpha-thalassemia •Alpha-1-antitrypsin •Alport disease •Amyloid precursor protein (APP) mutation •ARPKD •Becker muscular dystrophy •Beta-thalassemia •Charcot Marie Tooth disease •Chromosomal translocations •Congenital adrenal hyperplasia •Cystic fibrosis •Down syndrome •Duchenne muscular dystophy •Dystonia •Epidermolysis bullosa •Familial dysautonomia •Fanconi anemia •FAP •Fragile X syndrome •Gaucher disease •Hemophilia A and B •HLA genotyping •HSNF5 mutation •Huntington disease •Hypophosphatasia •Incontinentia pigmenti •Kell disease •Klinefelter syndrome •LCHAD •Lesch Nyhan syndrome •Marfan syndrome •Multiple epiphysial dysplasia •Myotonic dystophy •Myotubular myopathy •NF1 and NF2 •Norrie disease •Osteogenesis imperfecta •OTC deficiency •P53 mutations •PKU •Retinitis pigmentosa •SCA6 •Sickle cell anemia •Sonic hedgehog mutations •Spinal muscular atrophy (SMA) •Tay-Sachs disease •Tuberous sclerosis •Turner syndrome •Von Hippel Lindau •X-linked hydrocephaly •X-linked hyper IgM syndrome
- 11. FISH – fluorescence in situ hybridization
- 12. Summary • To date, PGS is the only commonly available testing procedure that can provide useful information on embryo quality, in addition to morphology. • The technical execution of biopsy requires a high level of training. The technique includes PB biopsy, blastomere biopsy and trophectoderm cells from blastocyst biopsy. • The benefit of PGS has been strongly debated. However, PGD is a solid diagnostic tool. • Technological improvements, such as the use of microarrays are developed. • Ethical issues should be considered.
- 13. Blastocyst Implantation Essential Factors (BIEFs) The blastocyst implantation essential factors (BIEFs) are a collective name given to the molecules that are indispensable for successful implantation of a mature and healthy blastocyst. Paracrine, juxtacrine or autocrine mechanisms. Expressed in the luminal epithelium in the entire uterus during the receptive state. Estrogen, estrogen receptor a (ERa), progesterone and its receptor (PR), Hoxa-10, and amphiregulin… Heparin-binding epidermal growth factor- like growth factor (HB-EGF), epiregulin and amphiregulin… Systemic vs. Local BIEFs Koji Yoshinaga 2010
- 14. Leukemia Inhibitory Factor (LIF) • LIF is an interleukin 6 class cytokine that affects cell growth by inhibiting differentiation. • High LIF expression is an indicator of a receptive endometrium in fertile women. • In the LIF-null mice, the luminal epithelial surface fails to produce pinopods, thus LIF appears to play an important role in the loss of polarity that occurs in the receptive luminal epithelial cells.
- 15. p53 regulates LIF expression LIF was identified as a potential p53 target gene with a putative p53-binding element in intron 1 of both mouse and human LIF genes. - Day 0 - Day 4 Wenwei Hu et. al. 2007
- 16. Administration of LIF (day 4) to pregnant p53 -/- mice restores maternal reproduction by improving implantation. Wenwei Hu et. al. 2007 Day 5 Day 7 Clinical study ???
- 17. N – normal M – treated with mifepristone A – acupuncture treatment P – progestin treatment Immunohistochemical protein levels
- 18. How it looks like?
- 20. Thank you