AUTHOR=Bao Zhongjian , Li Guangdong , Wang Rongxiang , Xue Songguo , Zeng Yong , Deng Shoulong 

TITLE=Melatonin Improves Quality of Repeated-Poor and Frozen-Thawed Embryos in Human, a Prospective Clinical Trial

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.853999

DOI=10.3389/fendo.2022.853999

ISSN=1664-2392

ABSTRACT=<sec><title>Objective</title><p>In this study, two experiments were performed to assess the effect and the role of melatonin on human <italic>in vitro</italic> embryo quality.</p></sec><sec><title>Methods</title><p>Experiment I: A total of 42 repeated-poor-quality-embryo patients were enrolled, with a total of 181 oocytes retrieval cycles. After IVF, for the same patient, the MT cycles group (10<sup>-7</sup> M melatonin added to the culture medium; n=48) were compared with the previous non-MT cycles group (n=133), following by <italic>in vitro</italic> culture to blastocyst stage and embryo transfer. 31 patients were transplanted with 65 embryo transfer, including 24 MT embryo transfer, 41 non-MT embryo transfer. Cycle outcomes were compared between the two groups. Experiment II:A total of 143 supernumerary human cleavage-stage embryos (from non-repeated-poor-quality-embryo patients) vitrified on Day 3 after IVF were warmed and randomized into two groups: melatonin group (10<sup>-7</sup> M melatonin added to the culture medium; n=71) and control group (n=72), and then cultured for 72 h. Rate of blastocyst and high-quality blastocyst, reactive oxygen species (ROS) levels of culture media as well as embryonic <italic>GPX1</italic>, <italic>CAT</italic>, <italic>Mn-SOD</italic>, <italic>Cu/Zn-SOD</italic>, <italic>BCL-2</italic>, <italic>BAX</italic> gene expression levels were analyzed.</p></sec><sec><title>Results</title><p>Experiment I: Results showed that the rate of Day 3 high-quality embryos (29.6% <italic>vs.</italic>19.5%) in the MT cycles group was significantly higher than that in the non-MT cycles group (<italic>P</italic>&lt;0.05). The rate of available blastocysts (17.1% <italic>vs.</italic>12.7%) and clinical pregnancy rate (25.0% <italic>vs.</italic>17.1%) were in tendency higher in the group treated with melatonin (<italic>P</italic>&gt;0.05). Experiment II:Results showed that the blastocyst rates in the melatonin administered group were significantly higher than in control group (42.25% <italic>vs.</italic>26.38%, <italic>P</italic>&lt;0.05). There were no significant differences in high-quality blastocyst rates. In addition, quantitative PCR showed that the expression of <italic>CAT</italic> was significantly upregulated by melatonin treatment (<italic>P</italic>&lt;0.05), while there were no significant differences in the expression of <italic>GPX1</italic>, <italic>Mn-SOD</italic>, <italic>Cu/Zn-SOD</italic>, <italic>BAX</italic> and <italic>BCL-2</italic> gene as well as the levels of ROS.</p></sec><sec><title>Conclusion</title><p>These data showed that melatonin supplement in the culture medium will improve Day 3 high-quality embryos rate of repeated-poor-quality-embryo patients and improve blastocyst rate of vitrified-warmed cleavage-stage embryos, suggesting that melatonin intervention may provide a potential rescue strategy for IVF failures.</p></sec><sec><title>Clinical Trial Registration</title><p>identifier [ChiCTR2200059773].</p></sec>