{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T05:33:25Z","timestamp":1791869605845,"version":"4.3.4"},"reference-count":119,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,18]],"date-time":"2021-09-18T00:00:00Z","timestamp":1631923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Currently, infertility affects 8\u201312% of reproductive age couples worldwide, a problem that also affects women suffering from recurrent implantation failure (RIF). RIF is a complex condition resulting from many physiological and molecular mechanisms involving dynamic endometrium\u2013blastocyst interaction. The most important are the endometrial receptivity process, decidualization, trophoblast invasion, and blastocyst nesting. Although the exact multifactorial pathogenesis of RIF remains unclear, many studies have suggested the association between hormone level imbalance, disturbances of angiogenic and immunomodulatory factors, certain genetic polymorphisms, and occurrence of RIF. These studies were performed in quite small groups. Additionally, the results are inconsistent between ethnicities. The present review briefly summarizes the importance of factors involved in RIF development that could also serve as diagnostic determinants. Moreover, our review could constitute part of a new platform for discovery of novel diagnostic and therapeutic solutions for RIF.<\/jats:p>","DOI":"10.3390\/ijms221810082","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T08:04:23Z","timestamp":1632211463000},"page":"10082","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Biomolecular Markers of Recurrent Implantation Failure\u2014A Review"],"prefix":"10.3390","volume":"22","author":[{"given":"Aleksandra E.","family":"Mrozikiewicz","sequence":"first","affiliation":[{"name":"Department of Infertility and Reproductive Endocrinology, Poznan University of Medical Sciences, Polan 33, 60-535 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2305-3116","authenticated-orcid":false,"given":"Marcin","family":"O\u017carowski","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Institute of Natural Fibres and Medicinal Plants\u2014State Research Institute, Wojska Polskiego 71B, 60-630 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"J\u0119drzejczak","sequence":"additional","affiliation":[{"name":"Department of Infertility and Reproductive Endocrinology, Poznan University of Medical Sciences, Polan 33, 60-535 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"619437","DOI":"10.3389\/fendo.2021.619437","article-title":"Determining diagnostic criteria of unexplained recurrent implantation failure: A ret-rospective study of two vs. three or more implantation failure","volume":"12","author":"Sun","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.bpobgyn.2018.07.004","article-title":"What to do when good-quality embryos repeatedly fail to implant","volume":"53","author":"Coughlan","year":"2018","journal-title":"Best Pr. Res. Clin. Obstet. Gynaecol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s43032-019-00031-6","article-title":"Association of miR-27aA>G, miR-423C>a, miR-449bA>G, and miR-604A>G Polymorphisms with Risk of Recurrent Implantation Failure","volume":"27","author":"Kim","year":"2020","journal-title":"Reprod. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.rbmo.2019.10.014","article-title":"How common is real repeated implantation failure? An indirect estimate of the prevalence","volume":"40","author":"Busnelli","year":"2020","journal-title":"Reprod. Biomed. Online"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1093\/humrep\/deaa317","article-title":"Definition, diagnostic and therapeutic options in recurrent implantation failure: An international survey of clinicians and embryologists","volume":"36","author":"Cimadomo","year":"2021","journal-title":"Hum. Reprod."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.rbmo.2013.08.011","article-title":"Recurrent implantation failure: Definition and management","volume":"28","author":"Coughlan","year":"2014","journal-title":"Reprod. Biomed. Online"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s12958-018-0414-2","article-title":"Recurrent Implantation Failure-update overview on etiology, diagnosis, treatment and future directions","volume":"16","author":"Bashiri","year":"2018","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_8","first-page":"169","article-title":"Uterine factors and infertility","volume":"51","author":"Sanders","year":"2006","journal-title":"J. Reprod. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/aji.12234","article-title":"Immunological Modes of Pregnancy Loss: Inflammation, Immune Effectors, and Stress","volume":"72","author":"Bao","year":"2014","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jri.2014.12.009","article-title":"Where and when should natural killer cells be tested in women with repeated implantation failure?","volume":"108","author":"Lozano","year":"2015","journal-title":"J. Reprod. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1210\/mend.14.8.0498","article-title":"Dysregulation of EGF Family of Growth Factors and COX-2 in the Uterus during the Preattachment and Attachment Reactions of the Blastocyst with the Luminal Epithelium Correlates with Implantation Failure in LIF- Deficient Mice","volume":"14","author":"Song","year":"2000","journal-title":"Mol. Endocrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4365","DOI":"10.1210\/endo.141.12.7855","article-title":"Leukemia Inhibitory Factor Can Substitute for Nidatory Estrogen and Is Essential to Inducing a Receptive Uterus for Implantation But Is Not Essential for Subsequent Embryogenesis1","volume":"141","author":"Chen","year":"2000","journal-title":"Endocrinology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"968141","DOI":"10.1155\/2014\/968141","article-title":"Diverse Roles of Prostaglandins in Blastocyst Implantation","volume":"2014","author":"Salleh","year":"2014","journal-title":"Sci. World J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.fertnstert.2017.11.026","article-title":"p53 and reproduction","volume":"109","author":"Kang","year":"2018","journal-title":"Fertil. Steril."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1177\/1933719117718276","article-title":"Dysregulation of GdA Expression in Endometrium of Women With Endometriosis: Implication for Endometrial Receptivity","volume":"25","author":"Focarelli","year":"2017","journal-title":"Reprod. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s12522-013-0144-2","article-title":"Glycodelin in reproduction","volume":"12","author":"Uchida","year":"2013","journal-title":"Reprod. Med. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"36999","DOI":"10.1074\/jbc.M112.385336","article-title":"Glycodelin-A Stimulates Interleukin-6 Secretion by Human Monocytes and Macrophages through L-selectin and the Extracellular Signal-regulated Kinase Pathway","volume":"287","author":"Lee","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e03242-19","DOI":"10.1128\/mBio.03242-19","article-title":"Alterations in Vaginal Microbiota and Associated Metabolome in Women with Recurrent Implantation Failure","volume":"11","author":"Fu","year":"2020","journal-title":"MBio"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.fertnstert.2018.04.041","article-title":"Relevance of assessing the uterine microbiota in infertility","volume":"110","author":"Moreno","year":"2018","journal-title":"Fertil. Steril."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"643422","DOI":"10.3389\/fmicb.2021.643422","article-title":"Role of Vaginal Microbiota Dysbiosis in Gynecological Diseases and the Potential Interventions","volume":"12","author":"Han","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S0015-0282(02)03298-3","article-title":"Increased frequency of female partner chromosomal abnormalities in patients with high-order implantation failure after in vitro fertilization","volume":"78","author":"Raziel","year":"2002","journal-title":"Fertil. Steril."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1016\/j.fertnstert.2006.11.043","article-title":"High incidence of complex chromosome abnormality in cleavage embryos from patients with repeated implantation failure","volume":"87","author":"Voullaire","year":"2007","journal-title":"Fertil. Steril."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S0015-0282(02)03219-3","article-title":"Increased sperm nuclear DNA damage in normozoospermic infertile men: A prospective study","volume":"78","author":"Saleh","year":"2002","journal-title":"Fertil. Steril."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1007\/s43032-020-00253-z","article-title":"Immunoendocrine Markers of Stress in Seminal Plasma at IVF\/ICSI Failure: A Preliminary Study","volume":"28","author":"Nikolaeva","year":"2021","journal-title":"Reprod. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1093\/humrep\/deh069","article-title":"Increased rates of thrombophilia in women with repeated IVF failures","volume":"19","author":"Azem","year":"2004","journal-title":"Hum. Reprod."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0015-0282(01)01832-5","article-title":"Inherited thrombophilia and in vitro fertilization implantation failure","volume":"76","author":"Grandone","year":"2001","journal-title":"Fertil. Steril."},{"key":"ref_27","first-page":"467","article-title":"Recurrent IVF failure and hereditary thrombophilia","volume":"12","author":"Safdarian","year":"2014","journal-title":"Iran. J. Reprod. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.fertnstert.2021.01.055","article-title":"A novel platform for discovery of differentially expressed microRNAs in patients with repeated implantation failure","volume":"116","author":"Chen","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s00404-021-06072-0","article-title":"Polymorphisms of vascular endothelial growth factor and recurrent implantation failure: A systematic review and meta-analysis","volume":"304","author":"Zeng","year":"2021","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/ng1093","article-title":"The codon 72 polymorphic variants of p53 have markedly different apoptotic potential","volume":"33","author":"Dumont","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.3389\/fimmu.2019.02982","article-title":"Association of Soluble HLA-G Plasma Level and HLA-G Genetic Polymorphism With Pregnancy Outcome of Patients Undergoing in vitro Fertilization Embryo Transfer","volume":"10","author":"Nowak","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e13243","DOI":"10.1111\/aji.13243","article-title":"Potential impact of maternal vitamin D status on peripheral blood and endometrium cellular immunity in women with recurrent implantation failure","volume":"84","author":"Chen","year":"2020","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Schr\u00f6der-Heurich, B., Springer, C.J.P., and Von Versen-H\u00f6ynck, F. (2020). Vitamin D Effects on the Immune System from Periconception through Pregnancy. Nutrients, 12.","DOI":"10.3390\/nu12051432"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"613277","DOI":"10.3389\/fcell.2021.613277","article-title":"Approaches to Improve Endometrial Receptivity in Case of Repeated Implantation Failures","volume":"9","author":"Makrigiannakis","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s43032-021-00599-y","article-title":"The Role of Immune Cells in Recurrent Spontaneous Abortion","volume":"28","author":"Li","year":"2021","journal-title":"Reprod. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ticconi, C., Pietropolli, A., Di Simone, N., Piccione, E., and Fazleabas, A. (2019). Endometrial Immune Dysfunction in Recurrent Pregnancy Loss. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215332"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.jfma.2017.03.011","article-title":"M1 macrophages decrease in the deciduae from normal pregnancies but not from spontaneous abortions or unexplained recurrent spontaneous abortions","volume":"117","author":"Tsao","year":"2018","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1111\/j.1600-0897.2010.00813.x","article-title":"The Contribution of Macrophages to Normal and Pathological Pregnancies","volume":"63","author":"Nagamatsu","year":"2010","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.placenta.2016.07.004","article-title":"HLA-G expression is regulated by miR-365 in trophoblasts under hypoxic conditions","volume":"45","author":"Mori","year":"2016","journal-title":"Placenta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1093\/humrep\/dez194","article-title":"Endometrial uNK cell counts do not predict successful implantation in an IVF population","volume":"34","author":"Donoghue","year":"2019","journal-title":"Hum. Reprod."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e12784","DOI":"10.1111\/aji.12784","article-title":"The role of immunological testing and intervention in reproductive medicine: A fertile collaboration?","volume":"79","author":"Ali","year":"2018","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1093\/humrep\/deh450","article-title":"Human chorionic gonadotropin and growth factors at the embryonic-endometrial interface control leukemia inhibitory factor (LIF) and interleukin 6 (IL-6) secretion by human endometrial epithelium","volume":"19","author":"Berndt","year":"2004","journal-title":"Hum. Reprod."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1093\/humupd\/dml004","article-title":"Endometrial receptivity markers, the journey to successful embryo implantation","volume":"12","author":"Achache","year":"2006","journal-title":"Hum. Reprod. Updat."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4097","DOI":"10.1210\/en.2005-0380","article-title":"In vivo infusion of interleukin-1beta and chorionic gonadotropin induces endometrial changes that mimic early pregnancy events in the baboon","volume":"146","author":"Strakova","year":"2005","journal-title":"Endocrinology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.fertnstert.2017.07.006","article-title":"Clinical validation of pinopode as a marker of endometrial receptivity: A randomized controlled trial","volume":"108","author":"Qiong","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref_46","first-page":"877","article-title":"The Regulation of Leukemia Inhibitory Factor","volume":"2","author":"Yue","year":"2015","journal-title":"Cancer Cell Microenviron."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/359076a0","article-title":"Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor","volume":"359","author":"Stewart","year":"1992","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"201514","DOI":"10.1155\/2014\/201514","article-title":"Leukemia Inhibitory Factor: Roles in Embryo Implantation and in Nonhormonal Contraception","volume":"2014","author":"Salleh","year":"2014","journal-title":"Sci. World J."},{"key":"ref_49","first-page":"721","article-title":"p53 regulates maternal reproduction through LIF","volume":"450","author":"Hu","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"bqz005","DOI":"10.1210\/endocr\/bqz005","article-title":"Levonorgestrel Inhibits Embryo Attachment by Eliminating Uterine Induction of Leukemia Inhibitory Factor","volume":"161","author":"Matsuo","year":"2019","journal-title":"Endocrinology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8680","DOI":"10.1073\/pnas.151180898","article-title":"Dual control of LIF expression and LIF receptor function regulate Stat3 activation at the onset of uterine receptivity and embryo implantation","volume":"98","author":"Cheng","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"15523","DOI":"10.1038\/s41598-020-72640-0","article-title":"Differential roles of uterine epithelial and stromal STAT3 coordinate uterine receptivity and embryo attachment","volume":"10","author":"Hiraoka","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Choi, Y., Kim, H.-R., Lim, E.J., Park, M., Yoon, J.A., Kim, Y.S., Kim, E.-K., Shin, J.-E., Kim, J.H., and Kwon, H. (2016). Integrative Analyses of Uterine Transcriptome and MicroRNAome Reveal Compromised LIF-STAT3 Signaling and Progesterone Response in the Endometrium of Patients with Recurrent\/Repeated Implantation Failure (RIF). PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157696"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1210\/me.2013-1086","article-title":"Uterine Deletion ofGp130orStat3Shows Implantation Failure with Increased Estrogenic Responses","volume":"27","author":"Sun","year":"2013","journal-title":"Mol. Endocrinol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Lee, J., Ahn, E., Park, H., Kim, J., Kim, Y., Lee, W., and Kim, N. (2021). Association between HOX Transcript Antisense RNA Single-Nucleotide Variants and Recurrent Implantation Failure. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063021"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.rbmo.2012.03.004","article-title":"Glycodelin suppresses endometrial cell migration and invasion but stimulates spheroid attachment","volume":"24","author":"So","year":"2012","journal-title":"Reprod. Biomed. Online"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.fertnstert.2009.10.009","article-title":"Glycodelin-A modulates cytokine production of peripheral blood natural killer cells","volume":"94","author":"Lee","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jri.2011.04.007","article-title":"Glycodelin-A as a paracrine regulator in early pregnancy","volume":"90","author":"Lee","year":"2011","journal-title":"J. Reprod. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"102625","DOI":"10.1016\/j.jri.2019.102625","article-title":"Glycodelin regulates the numbers and function of peripheral natural killer cells","volume":"137","author":"Dixit","year":"2020","journal-title":"J. Reprod. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1111\/aji.12471","article-title":"The Pleiotropic Effect of Glycodelin-A in Early Pregnancy","volume":"75","author":"Lee","year":"2016","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1111\/j.1600-0897.2008.00647.x","article-title":"Glycodelin-A induces a tolerogenic phenotype in monocyte-derived dendritic cells in vitro","volume":"60","author":"Scholz","year":"2008","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/j.fertnstert.2015.01.025","article-title":"Role of Mucin 1 and Glycodelin A in recurrent implantation failure","volume":"103","author":"Bastu","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1093\/humrep\/13.3.720","article-title":"The window for embryo transfer in oocyte donation cycles depends on the duration of progesterone therapy","volume":"13","author":"Prapas","year":"1998","journal-title":"Hum. Reprod."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"178","DOI":"10.3892\/etm.2020.9308","article-title":"Endometrial changes in estrogen and progesterone receptor expression during implantation in an oocyte donation program","volume":"20","author":"Klonos","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"9744","DOI":"10.1073\/pnas.1732707100","article-title":"Defective mammary gland morphogenesis in mice lacking the progesterone receptor B isoform","volume":"100","author":"Lydon","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"49","DOI":"10.4238\/gmr.15027849","article-title":"Endometrial expression of telomerase, progesterone, and estrogen receptors during the implantation window in patients with recurrent implantation failure","volume":"15","author":"Long","year":"2016","journal-title":"Genet. Mol. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.fertnstert.2018.11.016","article-title":"Association between estrogen receptor 1 (ESR1) and leukemia inhibitory factor (LIF) polymorphisms can help in the prediction of recurrent implantation failure","volume":"111","author":"Vagnini","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_68","first-page":"624","article-title":"p63 protects the female germ line during meiotic arrest","volume":"444","author":"Suh","year":"2006","journal-title":"Nat. Cell Biol."},{"key":"ref_69","first-page":"34","article-title":"Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1\u03b1","volume":"14","author":"Ravi","year":"2000","journal-title":"Genome Res."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Guo, X., Yi, H., Li, T., Wang, Y., Wang, H., and Chen, X. (2021). Role of Vascular Endothelial Growth Factor (VEGF) in Human Embryo Implantation: Clinical Implications. Biomolecules, 11.","DOI":"10.3390\/biom11020253"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.fertnstert.2011.06.048","article-title":"Progestins inhibit estradiol-induced vascular endothelial growth factor and stromal cell\u2013derived factor 1 in human endometrial stromal cells","volume":"96","author":"Okada","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1182\/blood-2002-11-3423","article-title":"Mechanism of monocyte activation and expression of proinflammatory cytochemokines by placenta growth factor","volume":"102","author":"Selvaraj","year":"2003","journal-title":"Blood"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4267","DOI":"10.4049\/jimmunol.178.7.4267","article-title":"Genetic Deletion of Placenta Growth Factor in Mice Alters Uterine NK Cells","volume":"178","author":"Tayade","year":"2007","journal-title":"J. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1093\/humrep\/der376","article-title":"Localization of angiogenic growth factors and their receptors in the human endometrium throughout the menstrual cycle and in recurrent miscarriage","volume":"27","author":"Lash","year":"2012","journal-title":"Hum. Reprod."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.repbio.2014.10.001","article-title":"Luteal phase defect is associated with impaired VEGF mRNA expression in the secretory phase endometrium","volume":"15","author":"Sadekova","year":"2015","journal-title":"Reprod. Biol."},{"key":"ref_76","first-page":"1","article-title":"Circulating MMP-7 and VEGF as potential predictive biomarkers for recurrent implantation failures","volume":"9","author":"Benkhalifa","year":"2021","journal-title":"Zygote"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e12693","DOI":"10.1111\/aji.12693","article-title":"Physiological and pathological angiogenesis in endometrium at the time of embryo implantation","volume":"78","author":"Chen","year":"2017","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_78","first-page":"280","article-title":"Elevated Levels of Serum Vascular Endothelial Growth Factor-A Are Not Related to NK Cell Parameters in Recurrent IVF Failure","volume":"18","author":"Bansal","year":"2017","journal-title":"J. Reprod. Infertil."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.preteyeres.2018.10.006","article-title":"The role of placental growth factor (PlGF) and its receptor system in retinal vascular diseases","volume":"69","author":"Etienne","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Albonici, L., Benvenuto, M., Focaccetti, C., Cifaldi, L., Miele, M.T., Limana, F., Manzari, V., and Bei, R. (2020). PlGF Immunological Impact during Pregnancy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228714"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Ukah, U.V., Payne, B.A., Hutcheon, J.A., Chappell, L., Seed, P.T., Conti-Ramsden, F.I., Ansermino, J.M., Magee, L.A., and Von Dadelszen, P. (2020). Placental growth factor for the prognosis of women with preeclampsia (fullPIERS model extension): Context matters. BMC Pregnancy Childbirth, 20.","DOI":"10.1186\/s12884-020-03332-w"},{"key":"ref_82","first-page":"1823","article-title":"Angiogenic Growth Factor Messenger Ribonucleic Acids in Uterine Natural Killer Cells1","volume":"86","author":"Li","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Rah, H., Chung, K.W., Ko, K.H., Kim, E.S., Kim, J.O., Sakong, J.H., Kim, J.H., Lee, W.S., and Kim, N.K. (2017). miR-27a and miR-449b polymorphisms associated with a risk of idiopathic recurrent pregnancy loss. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177160"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2694","DOI":"10.1093\/humrep\/del203","article-title":"Acquired and inherited thrombophilia: Implication in recurrent IVF and embryo transfer failure","volume":"21","author":"Qublan","year":"2006","journal-title":"Hum. Reprod."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1159\/000165776","article-title":"Repeated in vitro Fertilization Failure and Its Relation with Thrombophilia","volume":"67","author":"Simur","year":"2009","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1007\/s00404-020-05851-5","article-title":"Association between MTHFR polymorphisms (MTHFR C677T, MTHFR A1298C) and recurrent implantation failure: A systematic review and meta-analysis","volume":"303","author":"Zeng","year":"2021","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"a006452","DOI":"10.1101\/cshperspect.a006452","article-title":"VEGF-Directed Blood Vessel Patterning: From Cells to Organism","volume":"2","author":"Bautch","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.cell.2004.11.022","article-title":"A Single Nucleotide Polymorphism in the MDM2 Promoter Attenuates the p53 Tumor Suppressor Pathway and Accelerates Tumor Formation in Humans","volume":"119","author":"Bond","year":"2004","journal-title":"Cell"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"9761","DOI":"10.1073\/pnas.0904280106","article-title":"Single-nucleotide polymorphisms in the p53 pathway regulate fertility in humans","volume":"106","author":"Kang","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","first-page":"169","article-title":"Negative effect of P72 polymorphism on p53 gene in IVF outcome in patients with repeated implantation failure and pregnancy loss","volume":"31","author":"Turienzo","year":"2013","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.1007\/s11033-019-04748-0","article-title":"Evaluation of clinical utility of P53 gene variations in repeated implantation failure","volume":"46","author":"Mohammadzadeh","year":"2019","journal-title":"Mol. Biol. Rep."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1080\/14647273.2018.1524935","article-title":"Prevalence of candidate single nucleotide polymorphisms on p53, IL-11, IL-10, VEGF and APOE in patients with repeated implantation failure (RIF) and pregnancy loss (RPL)","volume":"23","author":"Turienzo","year":"2018","journal-title":"Hum. Fertil."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1007\/s10815-017-0994-3","article-title":"The HLA-G 14-bp polymorphism and recurrent implantation failure: A meta-analysis","volume":"34","author":"Fan","year":"2017","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3389\/fmed.2018.00181","article-title":"The Vaginal Microenvironment: The Physiologic Role of Lactobacilli","volume":"5","author":"Amabebe","year":"2018","journal-title":"Front. Med."},{"key":"ref_95","first-page":"1031","article-title":"Microbial Changes during Pregnancy, Birth, and Infancy","volume":"7","author":"Neuman","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1097\/GCO.0000000000000626","article-title":"The vaginal microbiome as a tool to predict IVF success","volume":"32","author":"Schoenmakers","year":"2020","journal-title":"Curr. Opin. Obstet. Gynecol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.resmic.2017.04.001","article-title":"The role of lactic acid production by probiotic Lactobacillus species in vaginal health","volume":"168","author":"Tachedjian","year":"2017","journal-title":"Res. Microbiol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Gong, Z., Luna, Y., Yu, P., and Fan, H. (2014). Lactobacilli Inactivate Chlamydia trachomatis through Lactic Acid but Not H2O2. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107758"},{"key":"ref_99","first-page":"13","article-title":"Lactobacillus by-products inhibit the growth and virulence of uropathogenic Escherichia coli","volume":"60","author":"Cadieux","year":"2009","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1128\/AEM.66.5.2001-2005.2000","article-title":"Lactic Acid Permeabilizes Gram-Negative Bacteria by Disrupting the Outer Membrane","volume":"66","author":"Alakomi","year":"2000","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1093\/jac\/dkt156","article-title":"Vaginal concentrations of lactic acid potently inactivate HIV","volume":"68","author":"Aldunate","year":"2013","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"4610","DOI":"10.1172\/JCI57172","article-title":"Vaginal microbiome and sexually transmitted infections: An epidemiologic perspective","volume":"121","author":"Brotman","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ygyno.2015.04.036","article-title":"The vaginal and gastrointestinal microbiomes in gynecologic cancers: A review of applications in etiology, symptoms and treatment","volume":"138","author":"Chase","year":"2015","journal-title":"Gynecol. Oncol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s10815-011-9694-6","article-title":"The dynamics of the vaginal microbiome during infertility therapy with in vitro fertilization-embryo transfer","volume":"29","author":"Hyman","year":"2012","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.ajog.2016.09.075","article-title":"Evidence that the endometrial microbiota has an effect on implantation success or failure","volume":"215","author":"Moreno","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_106","first-page":"1","article-title":"The impact of the female genital tract microbiome in women health and reproduction: A review","volume":"38","author":"Labarta","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1080\/19396368.2017.1390007","article-title":"Regulatory T cells improve pregnancy rate in RIF patients after additional IVIG treatment","volume":"63","author":"Ahmadi","year":"2017","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5653\/cerm.2017.44.1.1","article-title":"Intravenous immunoglobulin G in women with reproductive failure: The Korean Society for Reproductive Immunology practice guidelines","volume":"44","author":"Sung","year":"2017","journal-title":"Clin. Exp. Reprod. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"103313","DOI":"10.1016\/j.jri.2021.103313","article-title":"Unexplained recurrent implantation failures: Predictive factors of pregnancy and therapeutic management from a French multicentre study","volume":"145","author":"Kolanska","year":"2021","journal-title":"J. Reprod. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1080\/08923973.2020.1835951","article-title":"Effects of treatment with hydroxychloroquine on the modulation of Th17\/Treg ratio and pregnancy outcomes in women with recurrent implantation failure: Clinical trial","volume":"42","author":"Sadeghpour","year":"2020","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.rbmo.2016.04.008","article-title":"The risk of embryo-endometrium asynchrony increases with maternal age after ovarian stimulation and IVF","volume":"33","author":"Shapiro","year":"2016","journal-title":"Reprod. Biomed. Online"},{"key":"ref_112","unstructured":"National Centers for Disease Control and Prevention and Health Promotion of the Centers for Disease Control and Prevention in Consultation with the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology (2017). Assisted Reproductive Technology National Summary Report."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.ijgo.2008.08.012","article-title":"The influence of body mass index on in vitro fertilization outcome","volume":"104","author":"Orvieto","year":"2008","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.fertnstert.2012.04.004","article-title":"The effect of body mass index on the outcomes of first assisted reproductive technology cycles","volume":"98","author":"Moragianni","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1093\/humupd\/dmn046","article-title":"Effects of cigarette smoking upon clinical outcomes of assisted reproduction: A meta-analysis","volume":"15","author":"Waylen","year":"2008","journal-title":"Hum. Reprod. Updat."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Anblagan, D., Jones, N.W., Costigan, C., Parker, A.J.J., Allcock, K., Aleong, R., Coyne, L.H., Deshpande, R., Raine-Fenning, N., and Bugg, G. (2013). Maternal Smoking during Pregnancy and Fetal Organ Growth: A Magnetic Resonance Imaging Study. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067223"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0015-0282(02)04664-2","article-title":"Semen quality of male smokers and nonsmokers in infertile couples","volume":"79","author":"Mueller","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3938","DOI":"10.1073\/pnas.0511183103","article-title":"Cortisol levels and very early pregnancy loss in humans","volume":"103","author":"Nepomnaschy","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1590\/S1415-47572012000600008","article-title":"The TP53 fertility network","volume":"35","author":"Paskulin","year":"2012","journal-title":"Genet. Mol. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/10082\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:01:40Z","timestamp":1760166100000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/10082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,18]]},"references-count":119,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijms221810082"],"URL":"https:\/\/doi.org\/10.3390\/ijms221810082","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,18]]}}}