Table II.
Subgroup analyses and meta regression for the effects of stem-cell based therapy on FSH, E2 and follicle counts in animal models of POF.
| Index/subgroup | Studies (n) | SMD/RR (95% CI) | P-value for subgroup outcomes/interactions | I2 (%) | Heterogeneity P-value |
|---|---|---|---|---|---|
| FSH | |||||
| Delivery method | |||||
| ITV | 1 | −1.98 (−3.76, −0.20) | 0.029 | – | – |
| Non-ITV | 7 | −1.27 (−2.09, −0.45) | 0.002 | 85.1 | 0.000 |
| Follow-up duration | |||||
| Per week | 8 | 1.22 (1.18, 8.34) | 0.805 | 84.7 | |
| Cell amount | |||||
| Per 1×106 | 8 | 1.47 (0.21, 10.1) | 0.640 | 85.1 | |
| Units | |||||
| IU/l | 6 | −1.65 (−2.60, −0.70) | 0.001 | 84.4 | 0.000 |
| pg/ml | 2 | −0.52 (−1.11, 0.07) | 0.085 | 0.0 | 0.459 |
| Details of the animal model | |||||
| Chemotherapy | 7 | −0.989 (−1.526, −0.452) | 0.000 | 55.3 | 0.037 |
| Radiotherapy | 1 | −2.867 (−3.540, −2.195) | 0.000 | – | – |
| Study design | |||||
| Case control | 6 | −1.149 (−1.735, −0.562) | 0.000 | 48.3 | 0.085 |
| RCT | 2 | −1.602 (−4.076, 0.873) | 0.205 | 96.6 | 0.000 |
| Cell type | |||||
| UCMSCs | 3 | −1.980 (−2.724, −1.236) | 0.000 | 0.0 | 0.997 |
| OGLCs-iPSCs | 1 | −0.685 (−1.423, 0.053) | 0.069 | – | – |
| HCMNCs | 1 | −2.867 (−3.540, −2.195) | 0.000 | – | – |
| EnSCs | 1 | −1.049 (−1.815, −0.282) | 0.007 | – | – |
| miR-17-3p-iPS | 1 | −0.221 (−1.204, 0.763) | 0.660 | – | – |
| BMMSCs | 1 | −0.342 (−0.967, 0.282) | 0.283 | – | – |
| Stem cell origin | |||||
| Human | 7 | −1.498 (−2.308, −0.687) | 0.000 | 80.0 | 0.000 |
| Rat | 1 | −0.342 (−0.967, 0.282) | 0.283 | – | |
| E2 | |||||
| Delivery method | |||||
| ITV | 3 | 3.15 (0.34, 5.95) | 0.028 | 82.6 | 0.003 |
| Non-ITV | 8 | 2.19 (1.01, 3.37) | 0.000 | 92.1 | 0.000 |
| Follow-up duration | |||||
| Per week | 11 | 0.76 (0.04, 12.95) | 0.831 | 91.0 | |
| Cell amount | |||||
| Per 1×106 | 11 | 1.01 (0.06, 16.56) | 0.991 | 90.8 | |
| Details of the animal model | |||||
| Chemotherapy | 10 | 1.877 (1.112, 2.643) | 0.000 | 80.7 | 0.000 |
| Radiotherapy | 1 | 4.990 (4.029, 5.951) | 0.000 | – | – |
| Study design | |||||
| Case control | 7 | 2.689 (1.439, 3.939) | 0.000 | 82.9 | 0.000 |
| RCT | 4 | 1.822 (0.072, 3.573) | 0.041 | 95.3 | 0.000 |
| Cell type | |||||
| UCMSCs | 4 | 2.683 (0.853, 4.514) | 0.004 | 83.8 | 0.000 |
| ADSCs | 1 | 0.704 (−0.037, 1.444) | 0.063 | – | – |
| OGLCs-iPSCs | 1 | 0.561 (−0.169, 1.292) | 0.132 | – | – |
| HCMNCs | 1 | 4.990 (4.029, 5.951) | 0 | – | – |
| EnSCs | 1 | 1.624 (0.791, 2.456) | 0 | – | – |
| BMMSCs | 2 | 3.367 (−2.439, 9.174) | 0.256 | 90.9 | 0.001 |
| miR-17-3p-iPS | 1 | 2.630 (1.248, 4.011) | 0 | – | |
| Stem cell origin | |||||
| Human | 8 | 2.546 (0.310, 3.782) | 0 | 90.3 | 0.000 |
| Rat | 3 | 1.410 (−0.002, 2.822) | 0.05 | 81.9 | 0.004 |
| Follicle count | |||||
| Delivery method | |||||
| ITV | 16 | 1.747 (0.749, 2.744) | 0.001 | 88.0 | 0.000 |
| Non-ITV | 16 | 1.968 (1.097, 2.840) | 0 | 91.6 | 0.000 |
| Follow-up duration | |||||
| Per week | 32 | 0.93 (0.15, 5.73) | 0.938 | 90.2 | |
| Cell amount | |||||
| Per 1×106 | 32 | 1.09 (0.14, 8.48) | 0.933 | 90.3 | |
| Details of the animal model | |||||
| Chemotherapy | 31 | 1.670 (1.101, 2.240) | 0 | 86.7 | 0.000 |
| Radiotherapy | 1 | 7.977 (6.557, 9.397) | 0 | – | – |
| Study design | |||||
| Case control | 21 | 1.489 (0.671, 2.308) | 0 | 86.7 | 0.000 |
| RCT | 11 | 2.530 (1.420, 3.640) | 0 | 93.8 | 0.000 |
| Cell type | |||||
| UCMSCs | 10 | 2.056 (0.989, 3.123) | 0 | 72.0 | 0.000 |
| ADSCs | 1 | 2.678 (1.675, 3.681) | 0 | – | – |
| OGLCs-iPSCs | 1 | −0.649 (−1.385, 0.086) | 0.084 | – | – |
| HAECs | 9 | 1.349 (−0.055, 2.753) | 0.06 | 92.0 | 0.000 |
| HCMNCs | 1 | 7.977 (6.557, 9.397) | 0 | – | – |
| BMMSCs | 10 | 1.532 (0.876, 2.188) | 0 | 78.5 | 0.000 |
| Stem cell origin | |||||
| Human | 21 | 1.884 (0.852, 2.916) | 0 | 92.0 | 0.000 |
| Rat | 10 | 1.634 (0.943, 2.325) | 0 | 82.3 | 0.000 |
| Mouse | 1 | 2.169 (0.431, 3.906) | 0.014 | – | – |
| Follicle stage | |||||
| Primordial | 6 | 1.93 (−0.06, 3.92) | 0.057 | 95.1 | 0.000 |
| Primary | 5 | 1.57 (−0.16, 3.92) | 0.075 | 89.9 | 0.000 |
| Secondary | 5 | 2.91 (0.64, 5.71) | 0.012 | 91.0 | 0.000 |
| Antral | 7 | 2.17 (1.23, 3.10) | 0 | 74.3 | 0.000 |
| Atretic | 3 | −1.50 (−4.06, 1.05) | 0.248 | 93.9 | 0.000 |
| Total follicles | 2 | 4.48 (3.38, 5.58) | 0 | 0 | 0.384 |
| Mature | 1 | 0.28 (−0.86, 1.42) | 0.629 | – | – |
| Preantral | 1 | 1.03 (0.01, 2.04) | 0.047 | – | – |
| Primordial and primary | 1 | 2.83 (1.47, 4.20) | 0 | – | – |
| Immature | 1 | 2.17 (0.43, 3.91) | 0.014 | – | – |
ITV, intra-tail venous; RCT, randomized controlled trial; UCMSCs, human umbilical cord mesenchymal stem cells; ADSCs, adipose-derived stem cells; OGLCs-iPSCs, ovarian granulosa-like cells derived from human induced pluripotent stem cells; HAECs, human amniotic epithelial cells; HCMNCs, human cord blood mononuclear cells; EnSCs, human endometrial mesenchymal stem cells; BMMSCs, bone marrow derived mesenchymal stem cells; miR-17-3p-iPS, microRNA-17-3p-transfected human-induced pluripotent stem cells; SMD, standard mean difference; CI, confidence interval; RR, risk ratios.