Haroon Latif Khan1, Shahzad Bhatti2,3,4,5, Sana Abbas1, Celal Kaloglu6, Syeda Qurat-Ul-Ain Zahra7, Yousaf Latif Khan1,8, Zahira Hassan9, Nilgün Öztürk Turhan10, Hikmet Hakan Aydin11. 1. Lahore Institute of Fertility and Endocrinology, Hameed Latif Hospital, 14-Abu Bakar Block, New Garden Town, Lahore, 54800, Pakistan. 2. Lahore Institute of Fertility and Endocrinology, Hameed Latif Hospital, 14-Abu Bakar Block, New Garden Town, Lahore, 54800, Pakistan. drshahzadbhatti@yahoo.com. 3. Department of Human Genetics and Molecular biology, University of Health Sciences, Lahore, 54600, Pakistan. drshahzadbhatti@yahoo.com. 4. Department of Medical Education, Rashid Latif Medical College, Lahore, Pakistan. drshahzadbhatti@yahoo.com. 5. Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore, 54800, Pakistan. drshahzadbhatti@yahoo.com. 6. Department of Histology and Embryology, Faculty of Medicine, Sivas-Cumhuriyet University, 58140, Sivas, Turkey. 7. Department of Biochemistry, Kinnaird College, Lahore, Pakistan. 8. Department of Gynecology and Obstetrics, Hameed Latif Hospital, 14 - Abu Bakar Block, New Garden Town, Lahore, 54800, Pakistan. 9. Department of Cellular Pathology, Royal Free Hospital, London, NW3 2QG, UK. 10. Bayındır Hastanesi, Department of Obstetrics and Gynecology, Nispetiye Mah. Aydın sokak No:8, 34340, Beşiktaş, Istanbul, Turkey. 11. Department of Medical Biochemistry, Ege University School of Medicine, Bornova, Izmir, Turkey.
Abstract
PURPOSE: 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.
PURPOSE: 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.
Authors: Araceli Diez-Fraile; Tim Lammens; Kelly Tilleman; Wojciech Witkowski; Bruno Verhasselt; Petra De Sutter; Yves Benoit; Marc Espeel; Katharina D'Herde Journal: Hum Fertil (Camb) Date: 2014-03-31 Impact factor: 2.767
Authors: I Antolín; C Rodríguez; R M Saínz; J C Mayo; H Uría; M L Kotler; M J Rodríguez-Colunga; D Tolivia; A Menéndez-Peláez Journal: FASEB J Date: 1996-06 Impact factor: 5.191