Table I.
Studies investigating vitamin D and RPL.
| Authors (year) (Ref.) | Research objective | Research type | Number of experimental group vs. control group | Type of samples | Vitamin D supplementation | Conclusions |
|---|---|---|---|---|---|---|
| Tavakoli et al (2011) (33) | To assess the influence of 1,25 (OH)2D3 on cytokines. | Case control study (in vitro) | n=8 women with RPL vs. n=8 healthy women | Endometrium | 10−7 M 1,25(OH)2D3 for 6 h | Vitamin D3 lowered IFN-γ/IL-10 ratio and reduced IL-6, TGF-β and IL-10 production. |
| Ibrahim et al (2013) (72) | To evaluate the role of vitamin D3 in prevention of RPL. | Randomized controlled trial (in vitro) | 40 pregnant women with RPL, n=20 (study group) vs. n=20 (control group) | Peripheral blood | 0.25 mcg vitamin D3 given twice daily after pregnancy was documented till delivery. | Vitamin D3 supplementation resulted in a lower risk of pregnancy loss among women with RPL. |
| Ota et al (2014) (29) | To investigate the relationship between autoimmune or cellular immunity and vitamin D. | Retrospective cross sectional study (in vitro) | 133 females with RPL: VDN (n=70) vs. VDL (n=63) | Peripheral blood | 10 and 100 nM vitamin D3 | VDD was associated with autoimmune or cellular immune abnormalities in RPL. |
| Ota et al (2015) (27) | To study the influence of vitamin D upon NK cells. | Case-control study (in vitro) | 18 women with RPL vs. 16 healthy women | Peripheral blood | 10 and 100 nM 1,25(OH)2D3 | 1,25 (OH)2D3 has immunomodulatory influence upon NK cell cytotoxicity, cytokine production, the process of degranulation and TLR4 expression. |
| Rafiee et al (2015) (77) | To research the impact of vitamin D3 upon Th17 and Treg cells. | A double-blind placebo-controlled study (in vivo) | 44 women with RPL: n=22 (experimental group) vs. n=22 (control group) | Peripheral blood | 300,000 IU vitamin D3 | Vitamin D3 decreased the number of Th17 cells and the ratio of Th17/Treg in RPL. |
| Chen et al (2016) (2) | To study the function of vitamin D on cellular immunity in RPL. | Prospective study (in vivo) | 99 women with RPL: VDN (n=35) vs. VDI (n=51) vs. VDD (n=13). | Peripheral blood | 1,25(OH)2D 0.5 µg/day for 2 months | Abnormal cellular immune reactions were shown in RPL cases with low vitamin D levels. |
| Samimi et al (2017) (79) | To examine the influence of vitamin D supplementation on RPL. | A double-blind randomized and controlled clinical trial (in vivo) | 77 pregnant women with RPL: n=39 (experimental group) vs. n=38 (control group) | Peripheral blood | 400 IU/day | Vitamin D3 leads to decreased IL-23 and lower morbidity of abortion among patients with RPL. |
| Ji et al (2019) (76) | To identify the relationship between vitamin D and Treg/Th17. | Clinical trial (in vivo) and a case control study (in vitro) | Patients with RPL (n=107) vs. healthy pregnant women (n=48) | Peripheral blood | In vivo: 2,000 IU/day for 2 months; In vitro: 1, 10 and 100 nmol/l for 4.5 days | The Treg/Th17 imbalance observed in patients with RPL can be restored by vitamin D supplementation. |
| Abdollahi et al (2020) (75) | To study the function of 1,25(OH)2D3 on Tregs and Th17. | Case control study | Non-pregnant women with RPL (n=20) vs. healthy non-pregnant women (n=20) | Peripheral blood | 1,25(OH)2D3 50 nM for 16 h | 1,25 (OH)2D3 supplementation substantially enhanced the proportion of Treg cells in patients with RPL. |
VDN, vitamin D normal; VDI, vitamin D insufficient; VDD, vitamin D deficiency; VDL, vitamin D low; TLR4, Toll like receptor 4.; Treg, regulatory T; Th, T helper; RPL, recurrent pregnant loss; NK, natural killer.