Effect of Melatonin on Clinical Outcome of Patients with Repeated Cycles after Failed Cycles of In Vitro Fertilization and Intracytoplasmic Sperm Injection

Abstract Background: Melatonin (MT), as a powerful antioxidant, can effectively ameliorate the in vitro development of animal embryos, but few studies have been made on human embryos. Therefore, we investigated whether the application of MT in embryo cultures can improve embryonic development and clinical outcomes in patients with repeated cycles after failed in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles.Methods: Human immature oocytes from controlled ovarian hyperstimulation cycles were collected for in vitro maturation culture and ICSI fertilization. The obtained embryos were cultured in vitro in medium containing 0, 10-11, 10-9, 10-7 or 10-5 M MT, and 10-9 M was determined to be the optimal concentration. Subsequently, 140 patients who experienced failed IVF/ICSI cycles received 140 cycles of embryo culture in vitro with medium containing 10-9 M MT. High-quality blastocysts were collected and cryopreserved for three months before vitrified-warmed embryo transfer. These culture cycles served as the experimental (10-9 M) group. The control (0 M) group comprised previous failed cycles. The patients were further divided into subgroups of 1, 2 or ≥3 failed cycles. The fertilization and embryo development status were compared.Results: The fertilization, cleavage, high-quality embryo, blastocyst, and high-quality blastocyst rates of the 10-9 M group were significantly higher than 0 M (87.7% vs. 83.6%, p <0.01; 94.1% vs. 90.5%, p <0.01; 58.3% vs. 43.8%, 51.1% vs. 41.8%, 43.4% vs. 22.9%, all p <0.0001). A total of 50 vitrified-warmed cycle transfers were performed. A clinical pregnancy rate of 40% was obtained. Conclusion: The application of MT to embryo cultures in vitro improved embryonic development in patients with repeated cycles after failed IVF/ICSI cycles and obtained good clinical outcomes. The optimal concentration of MT was 10-9 M.Trial registration: Name of the registry: Effect of melatonin on clinical outcome of patients with repeated cycles after failed cycles of in vitro fertilization and intracytoplasmic sperm injection; registration number: ChiCTR2100045552; date of registration: April 19, 2021(Retrospectively registered); URL of trial registry record: www.medresman.org.cn.