Khan, H.L.Bhatti, S.Abbas, S.Kaloglu, C.Qurat-ul-Ain Zahra, S.Khan, Y.L.Aydin, H.H.2020-12-012020-12-0120201058-04681058-0468https://doi.org/10.1007/s10815-020-02010-2https://hdl.handle.net/11454/61736Purpose: Intrafollicular fluid (IFF) melatonin plays a decisive role in maintaining granulosa cells’ DNA integrity and protects them against apoptosis. It reduces oxidative stress and improves the oocyte quality with a higher fertilization rate. Method: This prospective study investigated the antioxidant property of IFF melatonin and its impact on IVF outcome parameters. We also explored the relative expression of five microRNAs (miR-663b, miR-320a, miR-766-3p, miR-132-3p, miR-16-5p) and levels of cell-free DNA (cfDNA) by real-time PCR in unexplained infertile patients. We collected 425 follicular fluid (FF) samples containing mature oocytes from 295 patients undergoing IVF. Results: Patients were subgrouped based on IFF melatonin concentration (group A ? 30 pg/mL, group B > 70 to ? 110 pg/mL, group C > 111 to ? 385 pg/mL). Our results showed that patients with ? 30 pg/mL IFF melatonin levels have significantly higher oxidative stress markers, cfDNA levels, and lower relative expression of miR-663b, miR-320a, miR-766-3p, miR-132-3p, and miR-16-5p compared to other subgroups (p < 0.001). Similarly, they have a low fertilization rate and a reduced number of high-quality day 3 embryos. Conclusion: Findings suggest that the therapeutic use of melatonin produces a considerable rise in the number of mature oocytes retrieved, fertilization rate, and good-quality embryo selection. Furthermore, miRNA signature enhances the quality of embryo selection, thus, may allow us to classify them as non-invasive biomarkers to identify good-quality embryos. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.en10.1007/s10815-020-02010-2info:eu-repo/semantics/closedAccessCell-free DNAEmbryo qualityFollicular fluidMelatoninmiRNA expressionUnexplained infertilityArticle2-s2.0-8509644193333226531Q2