Review of Genetic Profile of Recurrent Implantation Failure
Review of Genetic Profile of Recurrent Implantation Failure
Leila kooshesh,1,*
1. Department of Genetics, Fars Academic Center for Education, Culture and Research, ACECR, Shiraz, Iran koosheshle@yahoo.com
Introduction: Introduction: Successful implantation is a complex and imperative process in which a mature blastocyst-stage embryo attaches and invades the receptive endometrium for placentation and achieving an ongoing pregnancy. Implantation can occur during a short and restricted period, known as the window of implantation (WOI) (days 20–24 of the cycle, during the secretory phase), depends on high endometrial receptivity. During WOI, a synchronization between embryo development and endometrial status, as well as a proper two-way interaction between them are critical that depend on many molecular, physiological and genetic factors involved in this process.
Compared to other mammals, human implantation success is quite inefficient. According to studies, 75% of women that suffer from recurrent pregnancy loss are diagnosed as recurrent implantation failure (RIF) and among patients under infertility treatment, 15% experience RIF. Regarding to the complexity of the implantation process, there are some causes for RIF, which one of most important of them is genomic and epigenomic factors that could be also divided into uterine and embryo genetic factors. This review tries to summarize these genomic factors involved in RIF.
Regarding evidence has demonstrated a role for genetic and epigenetic regulation in endometrial function and embryo development and survival both in physiological and pathological conditions so, many genomic factors involved in the embryo implantation and various single-nucleotide polymorphisms (SNPs) have been reported to be associated with RIF.
Several studies have analyzed some epigenetic modifications, focusing on long non-coding RNAs (lncRNAs) or microRNAs (miRNA) in RIF. Revel et al. (2011) first showed a different miRNA expression profile in the secretory endometrium from women with RIF in compared with fertile women. Then investigations indicated that some miRNAs regulating molecular pathways and target genes crucial for implantation (endometrial receptivity and embryo development and survival) are dysregulated in patients with RIF. Polymorphisms of microRNAs such as
miR-449bA>G, miR-27a rs895819 and miR-449b rs10061133 involved in the expression of several implantation genes might be related to RIF pathogenesis. Also, according to several analyses, it was revealed that inherited thrombophilia could be a risk factor of RIF. It was observed that the presence of factor V Leiden and mutation of methylene tetrahydrofolate reductase (MTHFR) were associated with RIF and 68.9% of patients with RIF after the first IVF-embryo transfer cycle had inherited thrombophilia. However, there were some analysis that did not reveal this relation. Moreover, some variants of p53 gene, as regulator of cell growth and inducer of angiogenesis, are linked with RIF. Furthermore, some recent studies have shown an association between p53 rs1042522 (R72P, G/C) and p53 rs17878362 (Ins16bp, N/D) polymorphism and the risk of implantation failure. In addition, it was also investigated that polymorphism of human leukocyte antigen (HLA)-G, an important factor of the immunomodulatory system and implantation, such as rs1632947, rs1233334, rs371194629 HLA-G, as well as, HLA-G 14-bp polymorphism were significantly correlated with RIF occurrence. Also, several variants of VEGF, an angiogenetic factor involved in implantation process, such as –1154A>G were indicated as a significant risk factor of RIF. Finally, another genetic factor associated with RIF is several variants of the estrogen receptor 1 (ESR1) gene such as ESR1/AA (rs12199722) genotype, which was common in the RIF group compared with women who became pregnant on their first cycle of IVF/intracytoplasmic sperm injection.
Methods: Method: In this literature review, publications available in PubMed and Scopus databases, as well as in Google Scholar were taken into account. Eligibility criteria included studies on genomic and epigenomic factors of recurrent implantation failure.
Results: Genetic and epigenetic polymorphisms of all genes involved in embryo development and survival, as well as endometrial receptivity could lead to impossibility of embryo nesting and recurrent implantation failure occurrence that is a great challenge for human reproductive medicine.
Conclusion: Conclusion: Genetic and epigenetic polymorphisms of all genes involved in embryo development and survival, as well as endometrial receptivity could lead to impossibility of embryo nesting and recurrent implantation failure occurrence that is a great challenge for human reproductive medicine.