Table 2.

Clinical studies on heavy metals/metalloids and reproductive concerns.

Heavy metals/metalloids	Study design	Study population/country	Biomarker of exposure	Study duration	Findings	Quality score	References
Al, Mg, Pb	Case-control study	97 pregnant women with offspring were diagnosed with congenital heart defects (CHD group) and 194 pregnant women whose offspring had no CHD (control group) (China)	Umbilical cord blood	2 years	Significantly increased levels of Al, Mg, and Pb during pregnancy correlated with increased risk of CHD in offspring	6	(36)
Pb, Cd, Sb, Ni	Cross-sectional study	206 apparently healthy women administered for prenatal care and monitored for spontaneous abortions (SA) in Iran	Blood	19 months	Only Sb showed a significant positive correlation with the risk of SA (OR: 1.65, 95% CI: 1.08–2.52, p value: 0.02)	5	(37)
Pb	Case-control study	300 pregnant women attending a hospital monitored for effects of blood lead levels (BLLs) on spontaneous abortion in China	Blood	2 years	Positive correlations of increased blood Pb levels with spontaneous abortion in five blood lead levels (P1 = 0.64, P2 = 0.02, P3 = 0.01, P4 = 0.02, and P5 = 0.00	5	(38)
Hg	Prospective cohort study	1,204 women in a National Health and Nutrition Examination Survey monitored for Uterine Leiomyomata and Endometriosis (USA)	Blood and urine	5 years	Hg was found positively associated with Uterine leiomyomata (UL) (OR: 1.91, 95% CI: 1.14, 3.25).	5	(39)
Pb, Cd	Prospective cohort study	female workers (n = 26,542) who underwent a lead- and cadmium associated special medical examination for endometriosis (EM) (Korea)	blood	3 years	Increased standard admission rate (SAR) (1.24 [95% (CI): 1.03–1.48] and admission odds ratio (OR) [1.44 (95% CI: 1.11–1.85)] in Pb-exposed workers compared to the general population. Co-exposure to lead and cadmium has a synergistic effect with EM.	5	(40)
Cd, Pb, Hg, As	Case control study	33 women with unexplained infertility and 32 fertile women (Turkey)	Endometrial biopsy specimens	20 months	Cd was found in 91% of women with unexplained infertility, compared with 34% of fertile women. Pb was found in 15% of women with unexplained infertility compared with 3% of fertile women. Hg and As were undetected in samples from both groups.	5	(41)
Cd, Cr, Hg, Se, As	Case control	95 pregnant women with history of miscarriage and 100 with no history of miscarriage (control) (China)	Whole blood and urine	2 years	Blood Cd and urine Cr levels were elevated in women with history of miscarriage	5	(42)
Pb, Cd, Hg	Case control	29 pregnant women with history of spontaneous abortion and 20 healthy pregnant women (Turkey)	Blood	8 months	Higher blood Pb levels (p = 0.038) were found in the pregnant women with history of spontaneous abortion; no difference in Cd and Hg levels in both groups.	4	(43)
Pb, Cd	Prospective cohort	45 pregnant women diagnosed with threatened abortion and 40 non-pregnant apparently healthy women (Turkey)	Serum	Not available	Significantly increased (p < 0.001) serum concentrations of Pb and Cd in cases of threatened abortion	4	(44)
Cd, Pb	Case control	83 women with history of miscarriage and 35 women with no history of miscarriage (control) (Poland)	Blood and fragments of placental tissue	Not available	Higher levels of Cd and Pb in the blood and placenta of pregnant women with miscarriage compared to control	5	(45)
As, Cd, Pb, Hg	Case- control	56 women with PCOS and 50 women without PCOS (control) (Saudi Arabia)	Serum	26 months	Significantly (p < 0.001) high levels of Serum As, Cd, Pb, Hg and decreased levels of GSH and SOD in PCOS group compared to the control group -elevated oxidative stress parameters in PCOS women compared to control	5	(46)
Pb, Cd, As, Ba, Hg, U	Prospective cohort study	Male partners (61 infertile and 55 fertile) of infertile women who attended fertility clinic (Lebanon)	Blood and seminal fluid	6 years	Participants with low-quality semen had significantly higher Cd and Ba levels in the seminal fluid compared to participants with normal-quality semen. Significant correlations between low sperm viability and higher blood Cd and B and higher seminal Pb, Cd, Ba, and U	6	(47)
Cd, Pb	Case-control study	35 pregnant women with history of recurrent spontaneous abortion and 35 pregnant women without history of recurrent spontaneous abortion (Nigeria)	Blood	17 months	Significant elevation (p < 0.05) in Pb, Cd levels in cases compared with control	4	(48)
Cd	Case control	50 women with medically unexplained recurrent spontaneous abortion and 30 healthy fertile women (control group), with no history of spontaneous abortion (Egypt)	Blood	Not available	Higher level of cadmium in blood samples of women with unexplained recurrent spontaneous abortion compared to control	5	(49)