Role of P53 p.Arg72Pro Variant in Recurrent Pregnancy Loss, Recurrent Implantation Failure and IVF Outcome

The role of p53 p.Arg72Pro variant in recurrent pregnancy loss, recurrent implantation failure and IVF outcome is controversial and research so far has yielded inconsistent results. This systematic review aims to summarise the literature on the role of TP53 p.Arg72Pro variant in recurrent pregnancy loss following natural and assisted conception. A comprehensive literature search was conducted on MEDLINE, EMBASE and CENTRAL electronic databases for literature published between 1998 and April 2020. Inclusion and exclusion criteria and search terms were established. References of retrieved articles were hand searched to identify other relevant papers including conference abstracts. In total, 9 case control studies (1041 patients), 6 case control studies (382 patients) and 7 studies (3403) were included examining the role of TP53 p.Arg72Pro variant in recurrent pregnancy loss, recurrent implantation failure and IVF outcome respectively. Combined genotype frequencies suggest that there may be an association between Pro/Pro genotype and recurrent pregnancy loss and Arg/Pro genotype and recurrent implantation failure. However, the association between TP53 p.Arg72Pro variant and recurrent pregnancy loss, recurrent implantation failure or IVF outcomes has not been clearly established. In conclusion, genotyping patients for the TP53 variant may enable us to identify an aetiology for patients experiencing unexplained recurrent pregnancy loss and detect individuals at risk of recurrent implantation failure before IVF treatment is initiated. Furthermore, exploring the mechanisms of action of the p53 protein may provide us with an insight into potential treatments.

[1]  Yulin Jia,et al.  Maternal genetic polymorphisms and unexplained recurrent miscarriage: a systematic review and meta‐analysis , 2017, Clinical genetics.

[2]  Ying Luo,et al.  Influence of TP53 Codon 72 Polymorphism Alone or in Combination with HDM2 SNP309 on Human Infertility and IVF Outcome , 2016, PloS one.

[3]  J. Chen,et al.  Associations between the codon 72 polymorphism of the TP53 gene and the risk of recurrent implantation failure , 2016, The journal of obstetrics and gynaecology research.

[4]  Yuan-yuan Wu 吴媛媛,et al.  Association between p53 polymorphism at codon 72 and recurrent spontaneous abortion , 2016, Journal of Huazhong University of Science and Technology [Medical Sciences].

[5]  S. K. Lee,et al.  No association of p53 codon 72 polymorphism with idiopathic recurrent pregnancy loss in Korean population. , 2015, European journal of obstetrics, gynecology, and reproductive biology.

[6]  Xiaorong Yang,et al.  Association between p53 Arg72Pro polymorphism and recurrent pregnancy loss: an updated systematic review and meta-analysis. , 2015, Reproductive biomedicine online.

[7]  Martina Müller,et al.  p53 Family and Cellular Stress Responses in Cancer , 2014, Front. Oncol..

[8]  R. Baruffi,et al.  The tp53 codon 72 polymorphism (RS1042522) in women is not associated with pregnancy outcomes after ART , 2014 .

[9]  N. Raine-Fenning,et al.  What exactly do we mean by 'recurrent implantation failure'? A systematic review and opinion. , 2014, Reproductive biomedicine online.

[10]  T. Gurgan,et al.  Recurrent implantation failure: definition and management. , 2014, Reproductive biomedicine online.

[11]  P. Ashton-Prolla,et al.  p53 signaling pathway polymorphisms associated to recurrent pregnancy loss , 2014, Molecular Biology Reports.

[12]  J. Llácer,et al.  Negative effect of P72 polymorphism on p53 gene in IVF outcome in patients with repeated implantation failure and pregnancy loss , 2014, Journal of Assisted Reproduction and Genetics.

[13]  R. Baruffi,et al.  A prospective evaluation of the effect of single nucleotide polymorphisms (SNPs) of genes involved in human reproduction on recurrent implantation failure (RIF) , 2013 .

[14]  R. Baruffi,et al.  Association of single nucleotide polymorphisms with recurrent miscarriage , 2013 .

[15]  Definitions of infertility and recurrent pregnancy loss: a committee opinion. , 2020, Fertility and sterility.

[16]  M. Bortolini,et al.  TP53 PIN3 and PEX4 polymorphisms and infertility associated with endometriosis or with post-in vitro fertilization implantation failure , 2012, Cell Death and Disease.

[17]  M. Torloni,et al.  Genetic Polymorphisms and Recurrent Spontaneous Abortions: An Overview of Current Knowledge , 2012, American journal of reproductive immunology.

[18]  Sheng-Hsiang Lin,et al.  Genetic association studies of angiogenesis- and vasoconstriction-related genes in women with recurrent pregnancy loss: a systematic review and meta-analysis. , 2011, Human reproduction update.

[19]  V. Wiwanitkit Null effect of p53 codon 72 polymorphism on recurrent pregnancy loss and recurrent implantation failure: A summative assessment , 2011, Indian journal of human genetics.

[20]  Ying Luo,et al.  p53 codon 72 polymorphism and recurrent pregnancy loss: a meta-analysis , 2011, Journal of Assisted Reproduction and Genetics.

[21]  A. Levine,et al.  Regulation of female reproduction by p53 and its family members , 2011, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[22]  O. Christiansen,et al.  A genome-wide scan in affected sibling pairs with idiopathic recurrent miscarriage suggests genetic linkage. , 2011, Molecular human reproduction.

[23]  Wenwei Hu,et al.  Regulation of Fertility by the p53 Family Members. , 2011, Genes & cancer.

[24]  L. Smeenk,et al.  Behind the scenes: unravelling the molecular mechanisms of p53 target gene selectivity (Review). , 2010, International journal of oncology.

[25]  G. Patounakis,et al.  The p53 codon 72 single nucleotide polymorphism lacks a significant effect on implantation rate in fresh in vitro fertilization cycles: an analysis of 1,056 patients. , 2009, Fertility and sterility.

[26]  G. Atwal,et al.  Single-nucleotide polymorphisms in the p53 pathway regulate fertility in humans , 2009, Proceedings of the National Academy of Sciences.

[27]  Ghasemi Nasrin,et al.  Association of p53 polymorphism with ICSI/IVF failure and recurrent pregnancy loss , 2009, The Australian & New Zealand journal of obstetrics & gynaecology.

[28]  R. Jeyendran,et al.  P53 tumor suppressor factor, plasminogen activator inhibitor, and vascular endothelial growth factor gene polymorphisms and recurrent implantation failure. , 2008, Fertility and sterility.

[29]  K. Aittomäki,et al.  Study of p53 gene mutations and placental expression in recurrent miscarriage cases. , 2009, Reproductive biomedicine online.

[30]  G. Atwal,et al.  p53: A new player in reproduction , 2008, Cell cycle.

[31]  C. Kay,et al.  p53 tumour suppressor gene polymorphism is associated with recurrent implantation failure. , 2006, Reproductive biomedicine online.

[32]  C. Kay,et al.  Role of p53 codon 72 polymorphism in recurrent pregnancy loss. , 2006, Reproductive biomedicine online.

[33]  L. Hefler,et al.  Recurrent pregnancy failure is associated with a polymorphism in the p53 tumour suppressor gene. , 2005, Human reproduction.

[34]  S. Agrawal,et al.  An update in recurrent spontaneous abortion , 2005, Archives of Gynecology and Obstetrics.

[35]  D. Pim,et al.  p53 polymorphic variants at codon 72 exert different effects on cell cycle progression , 2004, International journal of cancer.

[36]  K. Baek,et al.  Expression of angiogenesis‐ and apoptosis‐related genes in chorionic villi derived from recurrent pregnancy loss patients , 2003, Molecular reproduction and development.

[37]  M. Murphy,et al.  The codon 72 polymorphic variants of p53 have markedly different apoptotic potential , 2003, Nature Genetics.

[38]  M. Makris,et al.  Recurrent miscarriage: aetiology, management and prognosis. , 2002, Human reproduction update.

[39]  G. Prendergast,et al.  The polyproline region of p53 is required to activate apoptosis but not growth arrest , 1997, Oncogene.

[40]  M. Stephenson,et al.  Current Clinical Options for Diagnosis and Treatment of Recurrent Spontaneous Abortion , 1997, American journal of reproductive immunology.