2022, Vol. 26 ›› Issue (25): 4084-4092

Stem cell transplantation in the treatment of premature ovarian failure: a meta-analysis based on 13 animal studies

Zhao Shuying1, Guo Guangling2, Liu Chenchen1, Zhang Chao3, Dong Sirui2, Gong Qinqin2, Ji Luwei2   

Abstract: OBJECTIVE: In recent years, the incidence of premature ovarian failure has been on the rise, showing the young trend. Because of the complex etiology of premature ovarian failure and poor clinical outcome, there is an urgent need to find a safe and effective treatment modality. This study systemically assessed the effectivity of stem cell transplantation of premature ovarian failure animal models.
METHODS: PubMed, The Cochrane Library, EMbase, CBM, CNKI, Wanfang, and VIP were retrieved before June 10, 2020. A series of studies on the treatment of premature ovarian failure animal models by stem cells were collected. Two evaluators independently screened the literature and extracted the data. The SYRCLE risk of bias assessment scale for animal experiments was used to evaluate the quality of the literature. The primary outcome indicators were analyzed using RevMan 5.3 software for meta-analysis.
RESULTS: (1) A total of 13 randomized controlled animal experimental studies were included, with 348 mice, and overall quality was moderate. Stem cell group (n=184) only received stem cell transplantation, and control group (n=164) only received blank control, normal saline or PBS intervention. (2) Meta-analysis results showed that compared with the control group, serum estrogen level (SMD=3.02, 95%CI: 1.87-4.18, P < 0.000 01), serum anti-Müllerian hormone level (ng/mL subgroup: SMD=4.77, 95%CI: 0.95-8.59, P=0.01; pg/mL subgroup: SMD=4.94, 95%CI: 0.91-8.97, P=0.02), serum luteinizing hormone level (SMD=-1.47, 95%CI: -1.73 to -1.22, P < 0.000 01), the number of follicles at all levels (SMD=1.91, 95%CI: 0.85-2.97, P=0.000 4) and fertility rate increased (RR=2.07, 95%CI: 1.39-3.09, P=0.000 4), but serum follicle-stimulating hormone level decreased (P < 0.000 1) in the stem cell group. The number of follicles at all levels was significantly higher in the stem cell group than that in the control group (P < 0.05). Subgroup analysis showed that with the increase of follow-up time, the number of primordial follicles, primary follicles and secondary follicles was significantly increased (P < 0.05), and the number of atresic follicles was significantly decreased (P < 0.05). Different types of stem cell transplantation could improve the serum estrogen level, and the recovery of serum estrogen level was more significant with the increase of unit dose of stem cell injection (P < 0.05).  
CONCLUSION: Available evidence from animal studies suggests that stem cell transplantation is effective in treating premature ovarian failure model mice. Stem cell transplantation induces an increase in estrogen levels, a decrease in follicle-stimulating hormone levels, and an improvement in follicle numbers at all levels in premature ovarian failure. Stem cells have some restorative effects on the ovary, but large samples and high quality human trials are still needed to verify clinical application effects.
Key words: stem cell, mice, ovarian failure, estrogen, follicle stimulating hormone, anti-mullerian hormone, follicle, meta-analysis