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Randomized Controlled Trial
. 2022 May 13:13:853999.
doi: 10.3389/fendo.2022.853999. eCollection 2022.

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

Zhongjian Bao  1 , Guangdong Li  2 , Rongxiang Wang  3 , Songguo Xue  3 , Yong Zeng  4 , Shoulong Deng  5
Affiliations
Randomized Controlled Trial

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

Zhongjian Bao et al. Front Endocrinol (Lausanne). .

Abstract

Objective: In this study, two experiments were performed to assess the effect and the role of melatonin on human in vitro embryo quality.

Methods: 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 (10-7 M melatonin added to the culture medium; n=48) were compared with the previous non-MT cycles group (n=133), following by in vitro 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 (10-7 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 GPX1, CAT, Mn-SOD, Cu/Zn-SOD, BCL-2, BAX gene expression levels were analyzed.

Results: Experiment I: Results showed that the rate of Day 3 high-quality embryos (29.6% vs.19.5%) in the MT cycles group was significantly higher than that in the non-MT cycles group (P<0.05). The rate of available blastocysts (17.1% vs.12.7%) and clinical pregnancy rate (25.0% vs.17.1%) were in tendency higher in the group treated with melatonin (P>0.05). Experiment II:Results showed that the blastocyst rates in the melatonin administered group were significantly higher than in control group (42.25% vs.26.38%, P<0.05). There were no significant differences in high-quality blastocyst rates. In addition, quantitative PCR showed that the expression of CAT was significantly upregulated by melatonin treatment (P<0.05), while there were no significant differences in the expression of GPX1, Mn-SOD, Cu/Zn-SOD, BAX and BCL-2 gene as well as the levels of ROS.

Conclusion: 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.

Clinical trial registration: identifier [ChiCTR2200059773].

Keywords: embryo quality; human; in vitro culture; melatonin; repeated-poor; vitrified-warmed.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The experimental flowchart.
Figure 2
Figure 2
Effects of melatonin on the ROS levels of culture media culturing vitrified-warmed human cleavage-stage embryos for 72 h. Control: the ROS levels of culture media supplemented with no melatonin; Melatonin: the ROS levels of culture media supplemented with 10-7 M melatonin.
Figure 3
Figure 3
Effects of melatonin on the gene expression of BCL-2, BAX, CAT, GPX1, Mn-SOD and Cu/Zn-SOD in vitrified-warmed human cleavage-stage embryos cultured for 72 h. *P < 0.05 compared with the control group.
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