The Effect Of Melatonin On The Development Of Human Embryos Derived From In Vitro-matured Oocytes Obtained From Controlled Ovarian Hyperstimulation Cycles

Background: The efficiency of in vitro maturation(IVM) technology remains to be improved. Melatonin, a powerful antioxidant, which can scavenge extra reactive oxygen species(ROS) and inhibit oxidative stress generated in vitro culture condition, may provide a sally port for the protocol of IVM.Methods: A total of 353 immature oocytes were collected from patients younger than35 years old who underwent intracytoplasmic sperm injection(ICSI) cycles at the Reproductive Medicine Center in the First Affiliated Hospital of Anhui Medical University between March 2015 and December 2015. Immature oocytes were cultured in IVM medium with 10-5 M melatonin. After maturation and ICSI, the embryos were distributed randomly into five different treatment groups having 0, 10-11, 10-9, 10-7 or10-5 M melatonin. Finally, the high-quality blastocysts were screened for aneuploidy of embryos by array CGH to evaluate the safety of melatonin supplementation in both maturation medium and embryo culture medium.Results: After 24~26 h of in vitro incubation, 290 mature oocytes were used to evaluate the effects of melatonin on the development of in vitro embryos. There was no significant difference in cleavage rate and high-quality blastocyst rate among all five groups. Blastocyst rate of four melatonin-treated groups had no significant difference with the untreated group. But the highest blastocyst rate was yielded at 10-9 M melatonin, which was significantly higher with 10-5 M concentration(47.1% versus14.7%, P=0.002). In the GV subgroup, blastocyst rate at 0 M group was highest(42.9%),and the lowest(13.6%) was at 10-5 M. High-quality blastocyst rate at 0 M was highest(19.0%), the lowest(4.5%) at 10-5 M. In the MⅠsubgroup, blastocyst rate at 10-9 M(64.0%) was highest, the lowest at 10-5 M(16.7%). High-quality blastocyst rate at 10-9M group(24.0%) was highest, the lowest at 10-7 M group(8.0%). The incidence rate of aneuploidy in melatonin-treated groups(12.5%, 2/16) was slightly lower than that in the control group without melatonin supplementation(16.7%, 1/6) despite that there was no significant difference between two rates.Conclusions: The supplementation of melatonin in embryo culture medium might be less beneficial for the development of human embryo. There is a tendency for low concentration(0, 10-11, 10-9M) to increase blastocyst formation. But the high concentration(10-7M, 10-5M) might even retard the formation of blastocyst, and melatonin dose not increase the aneuploidy rate for human embryo culture.