Do high levels of folic acid in women’s blood impact the outcome of IVF?

Of significant scientific and practical interest is the relationship between the blood plasma levels of folic acid at preconception and the outcome of pregnancy. A phase III clinical trial on the efficacy and safety of the biosimilar follitropin alfa has recently been completed within the ongoing assisted reproductive technology (ART) programs. The results confirmed the therapeutic equivalence of the investigational agent to the reference drug. In this trial, women with tubal infertility or male factor infertility were included. The study did not include women with endometriosis and polycystic ovary syndrome. A total of 118 patients were recruited; of those, 110 were randomized; then the 110 women underwent hormonal stimulation and 98 of them underwent embryo transfer. Blood samples were taken within a period not exceeding 28 days before the start of the stimulation; the samples were analyzed for folic acid (FA), trace elements and hormones. The results were grouped by quartiles (Q) according to the levels of FA in the blood serum: Q1 – 2.9–10.7 ng/ml, Q2 – 10.8–20.5 ng/ml, Q3 – 20.6–32.9 ng/ml, and Q4 ≥ 33.0 ng/ml. In addition, group distribution was also made according to the WHO recommendations: possible FA deficiency – 3.0–5.9 ng/ml, normal – 6.0–20.0 ng/ml, and elevated levels – more than 20 ng/ml. A significant decrease in the number of fertilized oocytes, clinical pregnancies and live births in Q4 (increased FA) compared with Q1 was found. Also, in women with high levels of FA, the number of aspirated oocytes was significantly lower than that in women with normal or decreased FA levels. We also found a significant inverse relationship between the number of aspirated oocytes and the levels of estradiol and serum FA. Plasma FA levels > 20 ng/ml detected prior to the IVF procedure may be associated with a low number of aspirated oocytes, and FA levels > 33 ng/ml – with a reduced number of fertilized oocytes, clinical pregnancies and live births. Thus, the excessive content of FA in the body can contribute to a worse outcome of IVF programs.