Paternal Exposure to Non-essential Heavy Metal Affects Embryo Cleavage and Implantation in Intracytoplasmic Sperm Injection (ICSI) Cycles: Evidence for a Paradoxical Effect.

Although the adverse effects of non-essential heavy metals on semen quality have been demonstrated in experimental animal models and occupational human exposure studies, little is known about the reproductive efficiency of exposed sperm during the process of intracytoplasmic sperm injection (ICSI). Our study aims to evaluate the effect of paternal exposure to non-essential heavy metals on embryo efficiency outcomes (embryo cleavage, fragmentation, implantation, and live birth) in ICSI cycle. Ninety-five heterosexual couples who underwent 95 ICSI cycles and 78 fresh embryo transfers between January 2003 and December 2009 were evaluated. Men whose female partner was undergoing ICSI were asked to provide semen and blood samples. Heavy metal levels (Pb, Cd, As, Hg, Ba, and U) were analyzed using an ion-coupled plasma-mass spectrometry (ICP-MS; Agilent 7500 ce, Agilent Technologies, Germany) equipped with a cell dynamic range (CDR). Paternal exposure to trace heavy metals was found to influence intermediate reproductive endpoints in ICSI cycles. After adjusting for paternal and maternal confounders, paternal blood concentrations of Cd [-0.30(-0.11,-0.02)], As [-0.26(-0.16,-0.11)], and U [-0.22(-0.24,-0.02)] were inversely associated with embryo cell cleavage on day 3. Counterintuitively, paternal blood and semen Pb levels [0.26(0.01,0.22); 0.25(0.03,0.14)] as well as semen U levels [0.27(0.01,0.19)] were positively associated with the proportion of implanted embryos. There were no significant associations observed for clinical pregnancy and live birth rates with any paternal heavy metal concentrations in semen and blood. These findings highlight the importance of paternal health for embryo efficiency outcomes in ICSI treatment cycles and the need for more male partner inclusive counseling in fertility practice. They also underline a paradoxical positive association between some heavy metal pollutants at low exposure levels and reproductive outcomes.