Parental Dysbiosis and Nutritional Imbalance in Recurrent Implantation Failure: Potential Microbiome–Epigenome Links in Early Embryonic Programming

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Abstract
Parental microbiome composition and nutritional and metabolic status have been studied in relation to in vitro fertilization (IVF), but their contribution to recurrent implantation failure (RIF) remains uncertain. This narrative review examines maternal and paternal microbial profiles, nutrition, inflammation, oxidative stress, and epigenetic regulation, distinguishing human observational and interventional findings from animal experiments, in vitro studies, and proposed mechanisms. The literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science, covering publications from 2000 to 2026. Search concepts included “in vitro fertilization”, “recurrent implantation failure”, “reproductive tract microbiota”, “gut microbiome”, “parental nutrition”, “oxidative stress”, and “sperm epigenetics”. Associations between reproductive-tract microbial profiles and pregnancy outcomes vary across populations and analytical methods. Endometrial findings require particular caution because low microbial biomass increases susceptibility to contamination. Evidence linking parental gut microbiota to epigenetic programming of human preimplantation embryos remains indirect, and paternal gut–testis mechanisms are supported predominantly by experimental research. Randomized probiotic studies have produced inconsistent results and have not established a reproducible improvement in implantation or live birth across IVF populations. Nutritional adequacy and management of relevant metabolic disorders belong within established preconception care, whereas microbiome testing, targeted microbial manipulation, and proposed epigenetic interventions remain investigational for RIF. The available evidence supports further study of these relationships but does not establish parental dysbiosis as a cause of RIF or demonstrate that microbiome modification prevents implantation failure.

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