Effect of stem cell transplantation of premature ovarian failure in animal models and patients: A meta-analysis and case report

Lei Chen, Shilei Guo, Cui Wei, Honglan Li, Haiya Wang, Yan Xu, Lei Chen, Shilei Guo, Cui Wei, Honglan Li, Haiya Wang, Yan Xu

Abstract

Stem cell transplantation has been considered a promising therapeutic approach for premature ovarian failure (POF). However, to date, no quantitative data analysis of stem cell therapy for POF has been performed. Therefore, the present study performed a meta-analysis to assess the efficacy of stem cell transplantation in improving ovarian function in animal models of POF. In addition, a case report of a patient with POF subjected to stem cell treatment was included to demonstrate that stem cell therapy also contributes to the recovery of ovarian function in patients. Published studies were identified by a systematic review of the PubMed, Embase, and Cochrane's library databases, and references cited in associated reviews were also considered. Data regarding follicle-stimulating hormone (FSH), estradiol (E2), ovarian weight, follicle count, the number of pregnancies and other parameters, including delivery route and cell type, were extracted. Pooled analysis, sensitivity analyses, subgroup analyses and meta-regression were performed. In the case of POF, transvaginal ultrasound (TVS), abdominal ultrasound (TAS) and color Doppler flow imaging (CDFI) were performed to observe the endometrial morphology and blood flow signals in the patient. Overall, pooled results from 16 pre-clinical studies demonstrated that stem cell-based therapy significantly improved FSH levels [standardized mean difference (SMD)=-1.330; 95% confidence interval (CI), -(2.095-0.565); P=0.001], E2 levels (SMD=2.334; 95% CI, 1.350-3.319; P<0.001), ovarian weight (SMD=1.310; 95% CI, 0.157-2.463; P=0.026), follicle count (SMD=1.871; 95% CI, 1.226-2.516; P<0.001), and the number of pregnancies (risk ratio=1.715, 95% CI, 1.213-2.424; P=0.002). The results of TVS and TAS demonstrated improved ovarian size and endometrial thickness in the patient with POF after MSC treatment. Of note, a rich blood flow signal in the endometrium was observed on CDFI. It appeared that stem cell-based therapy may be an effective method for the resumption of ovarian function in a patient and in animal models of POF; however, large-scale and high-quality future studies are required to confirm the present findings due to heterogeneity.

Keywords: cell transplantation; meta-analysis; ovarian function; premature ovarian failure; stem cell.

Figures

Figure 1.
Figure 1.
Identification process for eligible studies.
Figure 2.
Figure 2.
Forest plot demonstrating the effect of stem cell therapy on follicle stimulating hormone improvement compared with controls. SMD, standardized mean difference; CI, confidence interval; SD, standard deviation; ITV, intra-tail venous.
Figure 3.
Figure 3.
Forest plot presenting the effect of stem cell therapy on estradiol improvement compared with controls. SMD, standardized mean difference; CI, confidence interval; SD, standard deviation; ITV, intra-tail venous.
Figure 4.
Figure 4.
Forest plot presenting the effect of stem cell therapy on ovarian weight improvement compared with controls. SMD, standardized mean difference; CI, confidence interval; SD, standard deviation; ITV, intra-tail venous.
Figure 5.
Figure 5.
Forest plot illustrating the effect of stem cell therapy on follicles count improvement compared with controls. SMD, standardized mean difference; CI, confidence interval; SD, standard deviation; ITV, intra-tail venous.
Figure 6.
Figure 6.
Forest plot presenting the effect of stem cell therapy on the number of pregnancy improvement compared with controls. RR, risk ratio; CI, confidence interval; SD, standard deviation; ITV, intra-tail venous.
Figure 7.
Figure 7.
Funnel plot of the SMD for estradiol in animal models of premature ovarian failure assigned to the stem cell-based therapy or control groups. SMD, standardized mean difference.
Figure 8.
Figure 8.
Funnel plot of the SMD for follicle count of premature ovarian failure in animal models of premature ovarian failure assigned to the stem cell-based therapy or control groups. SMD, standardized mean difference.
Figure 9.
Figure 9.
Funnel plot of the SMD for follicle-stimulating hormone in animal models of premature ovarian failure assigned to the stem cell-based therapy or control groups. SMD, standardized mean difference.
Figure 10.
Figure 10.
Transabdominal ultrasound and transvaginal ultrasound detection of endometrial morphology on March 6, 2014. The (A) endometrial thickness was 0.3 cm and, sizes of (B) right and (C) left ovary were 2.2×1.0 and 1.9×1.3 cm, respectively.
Figure 11.
Figure 11.
Transabdominal ultrasound and transvaginal ultrasound detection of endometrial morphology on May 15, 2014. (A) The endometrial thickness was 0.6 cm. The sizes of (B) right and (C) left ovary were 2.3×1.9 and 2.3×1.6 cm, respectively.
Figure 12.
Figure 12.
Transvaginal color Doppler flow imaging and transabdominal ultrasound detection of endometrial morphology on July, 24 2014. (A) Abundant blood flow signals in the endometrium were detected. The sizes of the left and right ovary were 3.3×2.0 and 2.7×1.2 cm, respectively. (B) Endometrial thickness was 0.75 cm.

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