Molecular Drivers of Developmental Arrest in the Human Preimplantation Embryo: A Systematic Review and Critical Analysis Leading to Mapping Future Research.

Developmental arrest of the preimplantation embryo is a multifactorial condition, characterized by lack of cellular division for at least 24 hours, hindering the in vitro fertilization cycle outcome. This systematic review aims to present the molecular drivers of developmental arrest, focusing on embryonic and parental factors. A systematic search in PubMed/Medline, Embase and Cochrane-Central-Database was performed in January 2021. A total of 76 studies were included. The identified embryonic factors associated with arrest included gene variations, mitochondrial DNA copy number, methylation patterns, chromosomal abnormalities, metabolic profile and morphological features. Parental factors included, gene variation, protein expression levels and infertility etiology. A valuable conclusion emerging through critical analysis indicated that genetic origins of developmental arrest analyzed from the perspective of parental infertility etiology and the embryo itself, share common ground. This is a unique and long-overdue contribution to literature that for the first time presents an all-inclusive methodological report on the molecular drivers leading to preimplantation embryos' arrested development. The variety and heterogeneity of developmental arrest drivers, along with their inevitable intertwining relationships does not allow for prioritization on the factors playing a more definitive role in arrested development. This systematic review provides the basis for further research in the field.

Efficient treatment of chronic endometritis through a novel approach of intrauterine antibiotic infusion: a case series.

BACKGROUND: Early diagnosis and efficient management of Chronic Endometritis (CE) in patients seeking fertility treatment are two components every practitioner wishes to address. With respect to endometrial restoration, antibiotic treatment appears to perform well. However, regarding the improvement of In Vitro Fertilization (IVF) success rates, literature evidence is inconclusive, and consensus on optimal treatment has yet to be reached. This manuscript uniquely brings to literature the first report on effective employment of intrauterine antibiotic infusion to treat CE and contribute to addressing the infertility related to it. CASE PRESENTATION: In this case series, we present 3 patients reporting numerous previous failed IVF attempts accompanied with diagnosed CE which failed to be properly treated in the past. Following initial assessment in our clinic and verification of CE findings, an oral antibiotic regime was administered based on the infectious agent detected. Re-evaluation concluded slightly improved microbiological environment in the endometrium but persisting inflammation. Antibiotic intrauterine infusion was proposed to the patients as an alternative practice. All our patients achieved a pregnancy shortly following intrauterine treatment with one patient reporting a live birth of twin babies and two patients currently reporting an ongoing pregnancy. CONCLUSIONS: The implications of this case series contribute to medical knowledge and extend to both effective treatment of CE and subsequent management of related infertility. The current line of treatment of CE through oral antibiotic regimes highlights the need for exploring new options and calls for larger studies on the clinical implication of their use. This novel approach enabled natural conception for patients presenting with established Recurrent Implantation Failure (RIF) having undergone numerous futile IVF attempts. The clinical impact from the practitioner's perspective is considerable allowing for an alternative line of treatment that merits further investigation.