Serum levels of copper, iron, and manganese in women with pregnancy, miscarriage, and primary infertility

Background: Iron (Fe), copper (Cu), and manganese (Mn) play a significant role in female reproduction and fetal development. At the same time, high levels of metals may exert toxic effects. Correspondingly, both excess and deficiency of essential trace elements were shown to be associated with female infertility and adverse pregnancy outcome, although the existing data are rather contradictory. Therefore, the objective of the present study was to reveal the potential role of altered iron, copper, and manganese status in female reproductive health problems through assessment of serum metal levels in healthy non-pregnant and pregnant women, as well as patients with miscarriage and primary infertility. Methods: A total of 150 healthy controls, 169 pregnant women (II trimester of pregnancy), 75 women with miscarriage, and 91 patients with primary infertility were enrolled. Serum metal levels were assessed using ICP-MS. Results: Pregnant women are characterized by a significant increase in serum Cu an Mn levels by 40% (p < 0.001) and 16% (p = 0.043) as compared to the controls, respectively. Serum Cu levels in women with miscarriage and infertility were 30% and 35% lower than those in pregnant women (p < 0.001). No significant difference in serum iron levels were observed between the control and pregnant women. Women who had miscarriage were characterized by 13% (p = 0.042) higher serum Fe levels as compared to the pregnant ones. Multiple regression analysis demonstrated that serum copper levels was significantly associated both with pregnancy (β = 0.436; p < 0.001) and reproductive health problems in women (β = −0.272; p < 0.001). The latter was improved significant after adjustment for serum Fe and Mn levels, age, and BMI (β = −0.431; p < 0.001). The model incorporating serum Cu, Fe, Mn, and anthropometric parameters accounted for 23% of variability in reproductive status (p < 0.001). Conclusions: It is proposed that the lack of pregnancy-associated increase in metal levels in miscarriage and infertility may be indicative of at least partial role of metal insufficiency in impaired pregnancy and reproductive function in general. However, detailed clinical studies as well as experimental investigations are required for assessment of the potential causes and mechanisms of the observed associations.