Assesment of Vit D3 Level in Cases of Unexplaind Pregnancy Loss in Assiut

Recurrent pregnancy loss is defined as two or more consecutive pregnancy loss before 20 weekse of gestation (1). It affects about 1-5% of women of reproductive age. This not only causes significant physical and mental problems in families, but also a heavy economic burden on families and health systems (2, 3) Recurrent pregnancy loss (RPL) is a syndrome caused by multiple etiologies such as anatomical, endocrine, genetic, infectious, immunological, thrombotic and unexplained etiologies hence an investigation of underlying etiologies is often complicated When the conventional investigation scheme is applied, up to 60% of women with RPL remain unexplained (4). Recent studies have indicated that immune inflammatory and thrombotic conditions are two major under-lying pathologies for RPL (5). Approximately 20% of women with RPL have autoimmune conditions, such as antiphospholipid antibody (APA)(6),antinuclear antibody (ANA), anti-thyroperoxidase antibody and anti-thyroglobulin antibody(7,8).

Immune function in pregnancy From initial implantation of the conceptus, the maternal uterine endometrium undergoes decidualisation to support placental development and function. The resulting decidua is a tissue formed from the maternal endometrium, originating from epithelial and stromal cells, and is characterised by invasion from the extraembryonic fetal-derived trophoblasts and close 'cell-cell juxtaposition' of these different tissues The principal function of the decidua is to facilitate early fetal-maternal exchange of nutrients, gases and waste, while also acting as a secretory source of steroid hormones, cytokines and growth factors (9).However, the decidua also plays a key role in protecting pregnancy against maternal immune surveillance(10) .

Cellular infiltration is a key feature of immune function within decidua, and leukocytes comprise at least 40% of the total decidual stromal cell population(11) . The leukocyte subtypes present include decidual (uterine) natural killer (uNK) cells, macrophage subtypes, CD4C and CD8C T-lymphocytes (including T-regulatory cells (Tregs) and antigen-presenting cells (APCs) such as dendritic cells (DCs)(12) . There has been renewed interest in the role vitamin D, as key regulators of decidual immune cell function and its roles in fetal-maternal immune tolerance (13) .

• 3 - Vitamin D and autoimmunity Vitamin D, a steroid hormone, is well known to be involved in calcium and phosphate homeostasis and bone metabolism (14).The target organs for the non-classical actions of the vitamin D include immune systems, pancreatic b-cells, the heart and cardiovascular system, the brain and reproductive tissues. Tissue responses to vitamin D include regulation of hormone secretion modulation of immune responses, and a control of cellular proliferation and differentiation (15). Vitamin D was also reported to inhibit proliferation of T helper 1 (Th1) cells and limit their production of cytokines, such as interferon gamma (IFN-g), interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-a).Conversely, vitamin D induces T helper 2 (Th2) cytokines, such as IL-4, IL-5, IL-6, IL-9, IL-10 and IL-13 (16). Furthermore, in many studies vitamin D has been presented as a modifiable environmental factor for Th1-mediated autoimmune disease and appears to be important for susceptibility to and severity of the disease (17). Vitamin D also regulates B cell immunity. It down-regulates the proliferation and differentiation of B lymphocytes and inhibits IgG production (16).

Vitamin D deficiency in pregnant women is associated with increased risk of obstetrical complications such as pre-eclampsia (18), bacterial vaginosis associated preterm delivery (19), gestational diabetes mellitus (20) and small-for-gestational age births (21).