Relation between Selenium and Female Fertility: A Systematic Review

Data sourceA search was performed in the following databases: MEDLINE, Web of Science, Scopus, SciELO, LILACS, MDPI, ScienceDirect, and Europe PMC. The descriptors selected were “selenium” AND “female” AND “fertility”. The search interval was from 1996 to 2021.

Study selectionThe evaluation was performed independently by two reviewers, and a third reviewer confirmed the inclusion of papers in case of divergence between the first two reviewers. Papers were selected after the title and abstract were read, and those that met the eligibility criteria had the full text read.

Data collectionThe following data was extracted: author, year of publication, country, type of study, objective, method, sample size, follow-up period, patients' mean age, inclusion and exclusion criteria, and concentration of serum and capillary selenium. The data was organized in chronological order of paper publication.

Data synthesisThe number of papers identified totaled 3,800, out of which 7 were included in the systematic review. The studies indicated a positive correlation between serum selenium and antioxidant concentration in the follicular fluid, reduction in antithyroid antibodies, oocyte production and follicle number.

Conclusion

Selenium supplementation is promising in women with this micronutrient deficiency to promote improvement of the reproductive efficiency and prevent damage to the pregnancy. Further studies on this theme are still required.

Keywords
selenium; fertility agents, female; reproduction

Author/Year of publication	Country	Type of study	Mean age (years)	Sample size	Study aim	Methodological quality
Kim et al. (2018)²⁹29 Kim K, Wactawski-Wende J, Michels KA. , Schliep KC, Plowden TC, Chaljub EN, Mumford SL. Dietary minerals, reproductive hormone levels and sporadic anovulation: associations in healthy women with regular menstrual cycles. Br J Nutr 2018; 120 (01) 81-89 DOI: 10.1017/S0007114518000818. https://doi.org/10.1017/S000711451800081...	United States	Prospective cohort	18–44¹	259	To investigate the association between 10 minerals and reproduction hormones	Moderate quality *
Dickerson et al. (2011)³⁰30 Dickerson EH, Sathyapalan T, Knight R. , Maguiness SM, Killick SR, Robinson J, Atkin SL. Endocrine disruptor & nutritional effects of heavy metals in ovarian hyperstimulation. J Assist Reprod Genet 2011; 28 (12) 1223-1228 DOI: 10.1007/s10815-011-9652-3. https://doi.org/10.1007/s10815-011-9652-...	United Kingdom	Prospective cohort	32.7	30	To assess the exposure to mercury, zinc, and selenium in the gonadal response in IVF	Moderate quality *
Singh et al. (2013)³¹31 Singh AK, Chattopadhyay R, Chakravarty B, Chaudhury K. Markers of oxidative stress in follicular fluid of women with endometriosis and tubal infertility undergoing IVF. Reprod Toxicol 2013; 42: 116-124 DOI: 10.1016/j.reprotox.2013.08.005. https://doi.org/10.1016/j.reprotox.2013....	India	Prospective Cohort	32.1	340	To evaluate the relation between oxidative stress and elements of the follicular fluid in women subjected to IVF	High quality *
Ambroziak et al. (2017)³²32 Ambroziak U, Hybsier S, Shahnazaryan U. , Krasnodębska-Kiljańska M, Rijntjes E, Bartoszewicz Z, et al. Severe selenium deficits in pregnant women irrespective of autoimmune thyroid disease in an area with marginal selenium intake. J Trace Elem Med Biol 2017; 44: 186-191 DOI: 10.1016/j.jtemb.2017.08.005. https://doi.org/10.1016/j.jtemb.2017.08....	Poland	Prospective Cohort	29.6	74	To determine whether selenium is associated to the AITD during pregnancy	High quality *
Lozano et al. (2020)³³33 Lozano M, Murcia M, Soler-Blasco R. , Iñiguez C, Irizar A, Lertxundi A, et al. Prenatal Se concentrations and anthropometry at birth in the INMA study (Spain). Environ Res 2020; 181: 108943 DOI: 10.1016/j.envres.2019.108943. https://doi.org/10.1016/j.envres.2019.10...	Spain	Prospective Cohort	30.7	1,249	To investigate the association between maternal selenium serum levels and their babies' anthropometry	High quality*
Thomas et al. (2013)³⁴34 Thomas VV, Knight R, Haswell SJ, Lindow SW, van der Spuy ZM. Maternal hair selenium levels as a possible long-term nutritional indicator of recurrent pregnancy loss. BMC Womens Health 2013; 13: 40 DOI: 10.1186/1472-6874-13-40. https://doi.org/10.1186/1472-6874-13-40...	South Africa	Case-control	32.75	48	To evaluate whether selenium deficiency is found in women with RPL	Moderate quality *
Mantovani et al. (2019)³⁵35 Mantovani G, Isidori AM, Moretti C. , Di Dato C, Greco E, Ciolli P, et al. Selenium supplementation in the management of thyroid autoimmunity during pregnancy: results of the “SERENA study”, a randomized, double-blind, placebo-controlled trial. Endocrine 2019; 66 (03) 542-550 DOI: 10.1007/s12020-019-01958-1. https://doi.org/10.1007/s12020-019-01958...	Italy	Randomized clinical trial	31.9	45	To investigate whether selenium supplementation has a protective effect on thyroid during and after pregnancy	High quality **

Study	Design	Selection	Comparability	Outcome	Total
Kim et al. (2018)²⁹29 Kim K, Wactawski-Wende J, Michels KA. , Schliep KC, Plowden TC, Chaljub EN, Mumford SL. Dietary minerals, reproductive hormone levels and sporadic anovulation: associations in healthy women with regular menstrual cycles. Br J Nutr 2018; 120 (01) 81-89 DOI: 10.1017/S0007114518000818. https://doi.org/10.1017/S000711451800081...	Prospective cohort	4	1	1	6
Dickerson et al. (2011)³⁰30 Dickerson EH, Sathyapalan T, Knight R. , Maguiness SM, Killick SR, Robinson J, Atkin SL. Endocrine disruptor & nutritional effects of heavy metals in ovarian hyperstimulation. J Assist Reprod Genet 2011; 28 (12) 1223-1228 DOI: 10.1007/s10815-011-9652-3. https://doi.org/10.1007/s10815-011-9652-...	Prospective cohort	3	1	3	7
Singh et al. (2013)³¹31 Singh AK, Chattopadhyay R, Chakravarty B, Chaudhury K. Markers of oxidative stress in follicular fluid of women with endometriosis and tubal infertility undergoing IVF. Reprod Toxicol 2013; 42: 116-124 DOI: 10.1016/j.reprotox.2013.08.005. https://doi.org/10.1016/j.reprotox.2013....	Prospective cohort	4	2	3	9
Ambroziak et al. (2017)³²32 Ambroziak U, Hybsier S, Shahnazaryan U. , Krasnodębska-Kiljańska M, Rijntjes E, Bartoszewicz Z, et al. Severe selenium deficits in pregnant women irrespective of autoimmune thyroid disease in an area with marginal selenium intake. J Trace Elem Med Biol 2017; 44: 186-191 DOI: 10.1016/j.jtemb.2017.08.005. https://doi.org/10.1016/j.jtemb.2017.08....	Prospective cohort	4	2	3	9
Lozano et al. (2020)³³33 Lozano M, Murcia M, Soler-Blasco R. , Iñiguez C, Irizar A, Lertxundi A, et al. Prenatal Se concentrations and anthropometry at birth in the INMA study (Spain). Environ Res 2020; 181: 108943 DOI: 10.1016/j.envres.2019.108943. https://doi.org/10.1016/j.envres.2019.10...	Prospective cohort	4	2	3	9
Thomas et al. (2013)³⁴34 Thomas VV, Knight R, Haswell SJ, Lindow SW, van der Spuy ZM. Maternal hair selenium levels as a possible long-term nutritional indicator of recurrent pregnancy loss. BMC Womens Health 2013; 13: 40 DOI: 10.1186/1472-6874-13-40. https://doi.org/10.1186/1472-6874-13-40...	Case-control	4	2	2	8

Study	PEDro scale criteria
Study	2	3	4	5	6	7	8	9	10	11
Mantovani et al. (2019)³⁵35 Mantovani G, Isidori AM, Moretti C. , Di Dato C, Greco E, Ciolli P, et al. Selenium supplementation in the management of thyroid autoimmunity during pregnancy: results of the “SERENA study”, a randomized, double-blind, placebo-controlled trial. Endocrine 2019; 66 (03) 542-550 DOI: 10.1007/s12020-019-01958-1. https://doi.org/10.1007/s12020-019-01958...	Y	N	Y	N	N	N	Y	Y	Y	Y

Pregnancy trimester	Mean serum Se concentration (μg/L)	SD
1st trimester
Healthy pregnant women³²32 Ambroziak U, Hybsier S, Shahnazaryan U. , Krasnodębska-Kiljańska M, Rijntjes E, Bartoszewicz Z, et al. Severe selenium deficits in pregnant women irrespective of autoimmune thyroid disease in an area with marginal selenium intake. J Trace Elem Med Biol 2017; 44: 186-191 DOI: 10.1016/j.jtemb.2017.08.005. https://doi.org/10.1016/j.jtemb.2017.08....	64.60	14.60
Healthy pregnant women³³33 Lozano M, Murcia M, Soler-Blasco R. , Iñiguez C, Irizar A, Lertxundi A, et al. Prenatal Se concentrations and anthropometry at birth in the INMA study (Spain). Environ Res 2020; 181: 108943 DOI: 10.1016/j.envres.2019.108943. https://doi.org/10.1016/j.envres.2019.10...	79.57	9.64
AITD pregnant women³²32 Ambroziak U, Hybsier S, Shahnazaryan U. , Krasnodębska-Kiljańska M, Rijntjes E, Bartoszewicz Z, et al. Severe selenium deficits in pregnant women irrespective of autoimmune thyroid disease in an area with marginal selenium intake. J Trace Elem Med Biol 2017; 44: 186-191 DOI: 10.1016/j.jtemb.2017.08.005. https://doi.org/10.1016/j.jtemb.2017.08....	66.60	12.60
Placebo pregnant women³⁵35 Mantovani G, Isidori AM, Moretti C. , Di Dato C, Greco E, Ciolli P, et al. Selenium supplementation in the management of thyroid autoimmunity during pregnancy: results of the “SERENA study”, a randomized, double-blind, placebo-controlled trial. Endocrine 2019; 66 (03) 542-550 DOI: 10.1007/s12020-019-01958-1. https://doi.org/10.1007/s12020-019-01958...	70.26	29.06
Supplemented pregnant women³⁵35 Mantovani G, Isidori AM, Moretti C. , Di Dato C, Greco E, Ciolli P, et al. Selenium supplementation in the management of thyroid autoimmunity during pregnancy: results of the “SERENA study”, a randomized, double-blind, placebo-controlled trial. Endocrine 2019; 66 (03) 542-550 DOI: 10.1007/s12020-019-01958-1. https://doi.org/10.1007/s12020-019-01958...	70.09	30.95
2nd trimester
Healthy pregnant women³²32 Ambroziak U, Hybsier S, Shahnazaryan U. , Krasnodębska-Kiljańska M, Rijntjes E, Bartoszewicz Z, et al. Severe selenium deficits in pregnant women irrespective of autoimmune thyroid disease in an area with marginal selenium intake. J Trace Elem Med Biol 2017; 44: 186-191 DOI: 10.1016/j.jtemb.2017.08.005. https://doi.org/10.1016/j.jtemb.2017.08....	57.80	14.00
AITD pregnant women³²32 Ambroziak U, Hybsier S, Shahnazaryan U. , Krasnodębska-Kiljańska M, Rijntjes E, Bartoszewicz Z, et al. Severe selenium deficits in pregnant women irrespective of autoimmune thyroid disease in an area with marginal selenium intake. J Trace Elem Med Biol 2017; 44: 186-191 DOI: 10.1016/j.jtemb.2017.08.005. https://doi.org/10.1016/j.jtemb.2017.08....	59.00	9.90
Placebo pregnant women³⁵35 Mantovani G, Isidori AM, Moretti C. , Di Dato C, Greco E, Ciolli P, et al. Selenium supplementation in the management of thyroid autoimmunity during pregnancy: results of the “SERENA study”, a randomized, double-blind, placebo-controlled trial. Endocrine 2019; 66 (03) 542-550 DOI: 10.1007/s12020-019-01958-1. https://doi.org/10.1007/s12020-019-01958...	56.24	19.48
Supplemented pregnant women³⁵35 Mantovani G, Isidori AM, Moretti C. , Di Dato C, Greco E, Ciolli P, et al. Selenium supplementation in the management of thyroid autoimmunity during pregnancy: results of the “SERENA study”, a randomized, double-blind, placebo-controlled trial. Endocrine 2019; 66 (03) 542-550 DOI: 10.1007/s12020-019-01958-1. https://doi.org/10.1007/s12020-019-01958...	91.53	25.49
3rd trimester
Healthy pregnant women³²32 Ambroziak U, Hybsier S, Shahnazaryan U. , Krasnodębska-Kiljańska M, Rijntjes E, Bartoszewicz Z, et al. Severe selenium deficits in pregnant women irrespective of autoimmune thyroid disease in an area with marginal selenium intake. J Trace Elem Med Biol 2017; 44: 186-191 DOI: 10.1016/j.jtemb.2017.08.005. https://doi.org/10.1016/j.jtemb.2017.08....	48.40	11.30
AITD pregnant women³²32 Ambroziak U, Hybsier S, Shahnazaryan U. , Krasnodębska-Kiljańska M, Rijntjes E, Bartoszewicz Z, et al. Severe selenium deficits in pregnant women irrespective of autoimmune thyroid disease in an area with marginal selenium intake. J Trace Elem Med Biol 2017; 44: 186-191 DOI: 10.1016/j.jtemb.2017.08.005. https://doi.org/10.1016/j.jtemb.2017.08....	52.20	11.60
6 months postpartum
Placebo women³⁵35 Mantovani G, Isidori AM, Moretti C. , Di Dato C, Greco E, Ciolli P, et al. Selenium supplementation in the management of thyroid autoimmunity during pregnancy: results of the “SERENA study”, a randomized, double-blind, placebo-controlled trial. Endocrine 2019; 66 (03) 542-550 DOI: 10.1007/s12020-019-01958-1. https://doi.org/10.1007/s12020-019-01958...	71.80	18.83
Supplemented women³⁵35 Mantovani G, Isidori AM, Moretti C. , Di Dato C, Greco E, Ciolli P, et al. Selenium supplementation in the management of thyroid autoimmunity during pregnancy: results of the “SERENA study”, a randomized, double-blind, placebo-controlled trial. Endocrine 2019; 66 (03) 542-550 DOI: 10.1007/s12020-019-01958-1. https://doi.org/10.1007/s12020-019-01958...	93.54	23.53

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[1] Address for correspondence Luiz Gustavo Lima, Medical Student, Av. General Carlos Cavalcanti, 4748, 84030900, Uvaranas, Ponta Grossa, PR, Brazil (e-mail: luizlima742@gmail.com).