## 1 Introduction  
Fetal demise can occur at any stage of pregnancy and may result from maternal, fetal, or placental factors. Pregnancy loss is categorized as miscarriage or stillbirth, depending on the timing of the loss. Definitions for these terms vary, with gestational age or fetal weight serving as key criteria. However, gestational age is considered a more reliable indicator of fetal maturity and viability compared to birth weight [1]. According to the European Society of Human Reproduction and Embryology, miscarriage is defined as pregnancy loss before 22 weeks of gestation, whereas the World Health Organization (WHO) defines it as the expulsion or removal of a fetus (or embryo) weighing less than 500 g, which aligns with approximately 22 weeks of gestation. Around 1-2% of couples attempting conception face unexplained recurrent pregnancy loss (uRPL), characterized by two or more spontaneous miscarriages without an identifiable cause [2; 3]. Intrauterine fetal demise (IUFD), also referred to as stillbirth, describes fetal death occurring at or beyond the 22 nd week of gestation [4]. Despite progress in understanding its causes, a significant proportion of stillbirths remain unexplained. Folates play a crucial role in amino acid and nucleic acid metabolism as well as in one-carbon metabolic pathways. It is widely recommended for women of reproductive age, pregnant individuals, and those with MTHFR polymorphism to take folate supplements. A daily intake of 400-800 mcg of folate is advised to reduce the risk of neural tube defects [5; 6]. Folic acid (FA), a synthetic form of vitamin B9, is commonly added to fortified foods and supplements. Within the body, it must be converted into the bioactive folate derivative (6S)-5-MTHF through cellular metabolism. Supplementing with (6S)-5-MTHF during pregnancy offers advantages over folic acid because it circumvents the metabolic block caused by enzyme polymorphisms, reducing the likelihood of unmetabolized folic acid (UMFA) accumulation [6]. Concerns regarding FA and its connection to UMFA syndrome have grown, as UMFA has been detected in umbilical cord blood and even in infants' circulation [7]. The bioavailability of folates depends not only on dietary intake but also on their absorption and transport within the body. During pregnancy, efficient folate transfer across the placenta is critical for fetal development. Folate transport primarily involves three key transporter types: the reduced folate carrier (RFC), high-affinity folate receptors (FOLRs), and the proton-coupled folate transporter (PCFT). These transporters are expressed in the human placenta, although their exact localization remains uncertain [8]. It is hypothesized that during pregnancy, when folate requirements are elevated, mutations in genes encoding folate transporters or receptors in either the mother or fetus may worsen folate deficiency or create a deficiency-like state, even with adequate folate intake [9]. The reduced folate carrier protein 1 (RFC1), encoded by the SLC19A1 gene (GeneID: 6573), plays a key role in regulating intracellular folate concentrations and is prominently expressed in tissues such as the liver and placenta [10]. Structurally, _SLC19A1_ belongs to the major facilitator superfamily (MFS), consisting of twelve transmembrane segments with both the N- and C-terminal regions positioned in the cytoplasm. Its transport activity relies on the outward movement of anionic metabolites along their concentration gradients to drive folate uptake [11]. The most studied single nucleotide polymorphism (SNP) in this gene is 80A>G (rs1051266), which results in a histidine-to-arginine substitution in exon 2, influencing folate uptake efficiency and altering metabolic pathways [12; 13]. Additionally, two other polymorphisms, -43T>C (rs1131596) near the transcription start site and 696C>T (rs12659) within the coding region, show strong linkage disequilibrium with the 80A>G variant [14; 15].