P-608 Blood levels of heavy metals among the infertile and fertile population: a case-control study

Abstract Study question What is the impact of blood concentration of metals like lead, aluminium, and zinc on female fertility? Summary answer lead levels, even lower than the exposure reference levels, negatively impact female fertility. Zinc had a protective effect, aluminum was not found to impact What is known already Centre for Disease Control and Prevention (CDC) recent guidelines define 3.5 μg/dL of lead as the reference value in humans. In humans, only a few published studies support the association between heavy metals and an increased incidence of female infertility. Still, other researchers have found no link between heavy metals and female fertility. This discrepancy underscores the need for further comprehensive research to elucidate the role of lead and other heavy metals in female fertility. As a result, this case-control study was designed to explore the association between heavy metals in unexplained and anovulatory infertility in females. Study design, size, duration This case-control study was conducted at a tertiary-level hospital over 2 years of duration after institutional ethical approval. A total sample size of 246 participants (123 in each group) was estimated based on the results of the study conducted by Chang and colleagues at a 95% confidence interval, 80% power, and 10% adjustments for dropouts. Participants/materials, setting, methods 123 women (aged< 35 years) attending the infertility clinic suffering from anovulatory or unexplained infertility and an equal number of apparently healthy pregnant women, with no self-reported history of infertility, were enrolled for the study. Whole blood Pb, Al, and Zinc levels were estimated using graphite furnace atomic absorption spectrometry (GFAAS ICE 3400, Thermo Fischer, USA). Quality control was conducted using CLIN Check Whole Blood Control Levels I, II, and III (Recipe, Germany). Main results and the role of chance The median blood lead level (BLL) was significantly higher (2.4 μg/dL) among the cases compared to the controls (1.80 μg/dL) (Mann-Whitney test, P = 0.0005). There was no significant association found between consuming dairy products and high blood lead levels. Individuals who consumed a non-vegetarian diet proportionally had higher lead levels, which was statistically significant (p-value of 0.05, OR 2.2). The study revealed a weak non-significant correlation between lead levels and reproductive hormones (LH, FSH). The median zinc level was significantly lower (0.90 mg/L) among infertile women compared to the fertile females (1.30 mg/L)(Mann-Whitney U test, p = 0.0002). The median aluminium level was significantly higher among the infertile women (15 μg/dL) as compared to the fertile women (9.40 μg/dL) (p = 0.003). In the logistic regression model on the likelihood of infertility, lead, and Zn levels contributed significantly. The overall model demonstrated statistical significance with the null model (χ2(7) = 102.791, p < 0.0001), explaining 45% of the variation in infertility (Nagelkerke R2 = 0.4554) Limitations, reasons for caution The study is prone to the inherent limitations of single-center cross-sectional design. Simultaneous estimation of urinary metal levels was not performed. Further longitudinal prospective research is needed to provide a definitive answer to the research question. Wider implications of the findings The presence of BLL, lower than the exposure reference levels, negatively impacts female fertility suggesting that even lower levels are detrimental to female fertility. The detrimental effect of lead was only partially explained by its impact on female reproductive hormones. Zinc levels showed a positive impact on female fertility. Trial registration number No