Meta-analysis of the relevance between sperm parameters and serum vitamin D levels in infertile men

To systematically estimate the relevance between sperm parameters and serum vitamin D levels and the subsequent reproductive outcomes in men. PubMed, Web of Science and other databases were searched for studies that examined a possible correlation between serum vitamin D levels and sperm parameters and reproductive outcomes. The documents were screened according to the corresponding inclusion and exclusion criteria. Selection criteria included all published randomised and controlled trials and non-randomised studies that focus on vitamin D and the reproductive function of men The patients were classified into observation/intervention and control groups, the intervention group was given vitamin D supplementation and the control group was not. The meta-analysis was conducted using Stata 16.0 software. A meta-analysis of 11 clinical studies that enrolled a total of 1356 patients, revealed that the clinical pregnancy rate in the observation group was no statistically different in the control group. A meta-analysis of 8 studies demonstrated that there was no statistically difference in sperm concentration between the experimental group and the control group. A meta-analysis of 8 studies found that sperm progressive motility in the experimental group was greater than that in the control group by using a random-effects model. The mean concentration of vitamin D was significantly lower in the control group. Appropriate vitamin D supplement intervention in infertile men improves sperm progressive motility. Interpretation of these results should be done with caution due to the significant heterogeneity of the included studies. Furthermore, Well-conducted prospective cohort studies are needed to better explain the relationship between vitamin D and sperm parameters in infertile men.

Male infertility; Semen parameters; Serum vitamin D; Reproductive outcome

[1] Arab A, Rafie N, Mansourian M, Miraghajani M, Hajianfar H. Dietary patterns and semen quality: a systematic review and meta-analysis of observational studies. Andrology. 2018; 6: 20–28.

[2] Fainberg J, Kashanian JA. Recent advances in understanding and managing male infertility. F1000Research. 2019; 8: 670.

[3] Kim MJ, Hwang HR, Kim Y, Lee S, Lee J, Jeong D, et al. Association between serum 25-hydroxyvitamin D levels and dry eye in Korean adults: a study based on Korean national health and nutrition examination survey, 2010–2011. Korean Journal of Family Medicine. 2017; 38: 81–85.

[4] Meng YF, Lu J, Xing Q, Tao JJ, Xiao P. Lower serum vitamin D level was associated with risk of dry eye syndrome. Medical Science Monitor. 2017; 23: 2211–2216.

[5] Shetty R, Sethu S, Deshmukh R, Deshpande K, Ghosh A, Agrawal A, et al. Corneal dendritic cell density is associated with subbasal nerve plexus features, ocular surface disease index, and serum vitamin D in evaporative dry eye disease. BioMed Research International. 2016; 2016: 1–10.

[6] Yang C, Albietz J, Harkin DG, Kimlin MG, Schmid KL. Impact of oral vitamin D supplementation on the ocular surface in people with dry eye and/or low serum vitamin D. Contact Lens and Anterior Eye. 2018; 41: 69–76.

[7] Wang EY, Huang Y, Du QY, Yao GD, Sun YP. Body mass index effects sperm quality: a retrospective study in Northern China. Asian Journal of Andrology. 2017; 19: 234–237.

[8] Blomberg Jensen M, Nielsen JE, Jørgensen A, Rajpert-De Meyts E, Kristensen DM, Jørgensen N, et al. Vitamin D receptor and vitamin D metabolizing enzymes are expressed in the human male reproductive tract. Human Reproduction. 2010; 25: 1303–1311.

[9] Corbett ST, Hill O, Nangia AK. Vitamin D receptor found in human sperm. Urology. 2006; 68: 1345–1349.

[10] Aquila S, Guido C, Perrotta I, Tripepi S, Nastro A, Andò S. Human sperm anatomy: ultrastructural localization of 1alpha, 25-dihydroxyvitamin D receptor and its possible role in the human male gamete. Journal of Anatomy. 2008; 213: 555–564.

[11] Aquila S, Guido C, Middea E, Perrotta I, Bruno R, Pellegrino M, et al. Human male gamete endocrinology: 1alpha, 25-dihydroxyvitamin D3 (1, 25(OH)2D3) regulates different aspects of human sperm biology and metabolism. Reproductive Biology and Endocrinology. 2009; 7: 140.

[12] de Angelis C, Galdiero M, Pivonello C, Garifalos F, Menafra D, Cariati F, et al. The role of vitamin D in male fertility: a focus on the testis. Reviews in Endocrine and Metabolic Disorders. 2017; 18: 285–305.

[13] Banks N, Sun F, Krawetz SA, Coward RM, Masson P, Smith JF, et al. Male vitamin D status and male factor infertility. Fertility and Sterility. 2021; 116: 973–979.

[14] Neville G, Martyn F, Kilbane M, O’Riordan M, Wingfield M, McKenna M, et al. Vitamin D status and fertility outcomes during winter among couples undergoing in vitro fertilization/intracytoplasmic sperm injection. International Journal of Gynecology & Obstetrics. 2016; 135: 172–176.

[15] Blomberg Jensen M, Lawaetz JG, Petersen JH, Juul A, Jørgensen N. Effects of vitamin D supplementation on semen quality, reproductive hormones, and live birth rate: a randomized clinical trial. The Journal of Clinical Endocrinology & Metabolism. 2018; 103: 870–881.

[16] Jiang L, Ji L, Song J, Qian K. The effect of serum vitamin D levels in couples on embryo development and clinical outcomes. Reproductive Biomedicine Online. 2019; 38: 699–710.

[17] Dovnik A, Mujezinović F. The association of vitamin D levels with common pregnancy complications. Nutrients. 2018; 10: 876.

[18] Menkveld R, Wong WY, Lombard CJ, Wetzels AM, Thomas CM, Merkus HM, et al. Semen parameters, including WHO and strict criteria morphology, in a fertile and subfertile population: an effort towards standardization of in-vivo thresholds. Human Reproduction. 2001; 16: 1165–1171.

[19] Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. International Journal of Surgery. 2010; 8: 336–341.

[20] Yu X, Dong LH, Zhao JL. Effect of vitamin D intervention on semen quality of infertile men. Journal of Ningxia Medical University. 2020; 42: 782–-786.

[21] Wadhwa L, Priyadarshini S, Fauzdar A, Wadhwa SN, Arora S. Impact of Vitamin D supplementation on semen quality in vitamin D-deficient infertile males with oligoasthenozoospermia. The Journal of Obstetrics and Gynecology of India. 2020; 70: 44–49.

[22] Akhavizadegan H, Karbakhsh M. Comparison of serum vitamin D between fertile and infertile men in a vitamin D deficient endemic area: a case-control study. Urologia Journal. 2017; 84: 218–220.

[23] Tirabassi G, Cutini M, Muscogiuri G, Delli Muti N, Corona G, Galdiero M, et al. Association between vitamin D and sperm parameters: clinical evidence. Endocrine. 2017; 58: 194–198.

[24] Hollis BW. Assessment and interpretation of circulating 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in the clinical environment. Endocrinology and Metabolism Clinics of North America. 2010; 39: 271–286.

[25] Zhu CL, Xu QF, Li SX, Wei YC, Zhu GC, Yang C, et al. Investigation of serum vitamin D levels in Chinese infertile men. Andrologia. 2016; 48: 1261–1266.

[26] Abbasihormozi S, Kouhkan A, Alizadeh AR, Shahverdi AH, Nasr-Esfahani MH, Sadighi Gilani MA, et al. Association of vitamin D status with semen quality and reproductive hormones in Iranian subfertile men. Andrology. 2017; 5: 113–118.

[27] Rosen CJ, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, et al. IOM committee members respond to endocrine society vitamin D guideline. The Journal of Clinical Endocrinology & Metabolism. 2012; 97: 1146–1152.

[28] Tartagni M, Matteo M, Baldini D, Tartagni MV, Alrasheed H, De Salvia MA, et al. Males with low serum levels of vitamin D have lower pregnancy rates when ovulation induction and timed intercourse are used as a treatment for infertile couples: results from a pilot study. Reproductive Biology and Endocrinology. 2015; 13: 127.

[29] Rehman R, Lalani S, Baig M, Nizami I, Rana Z, Gazzaz ZJ. Association between vitamin D, reproductive hormones and sperm parameters in infertile male subjects. Frontiers in Endocrinology. 2018; 9: 607.

[30] Azizi E, Naji M, Shabani-Nashtaei M, Aligholi A, Najafi A, Amidi F. Association of serum content of 25-hydroxy vitamin D with semen quality in normozoospermic and oligoasthenoteratozoospermic men. International Journal of Reproductive Biomedicine. 2018; 16: 689–696.

[31] Rahnavard Z, Eybpoosh S, Homami MR, Meybodi HA, Azemati B, Heshmat R, et al. Vitamin d deficiency in healthy male population: results of the Iranian multi-center osteoporosis study. Iranian Journal of Public Health. 2010; 39: 45–52.

[32] Alzoubi A, Mahdi H, Al Bashir S, Halalsheh O, Al Ebbini M, Alzarir M, et al. Normalization of serum vitamin D improves semen motility parameters in patients with idiopathic male infertility. Acta Endocrinologica. 2017; 13: 180–187.

[33] Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J. Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ Journal of Surgery. 2003; 73: 712–716.

[34] Calagna G, Catinella V, Polito S, Schiattarella A, De Franciscis P, D’Antonio F, et al. Vitamin D and male reproduction: updated evidence based on literature review. Nutrients. 2022; 14: 3278.

[35] Deeks JJ, Hopewell S, Moher D, Higgins JP, Moons KG, Chandler J, et al. Doug Altman’s legacy to Cochrane and evidence synthesis. The Cochrane Database of Systematic Reviews. 2018; 8: ED000127.

[36] Arab A, Hadi A, Moosavian SP, Askari G, Nasirian M. The association between serum vitamin D, fertility and semen quality: a systematic review and meta-analysis. International Journal of Surgery. 2019; 71: 101–109.

[37] Maghsoumi-Norouzabad L, Zare Javid A, Mansoori A, Dadfar M, Serajian A. Evaluation of the effect of vitamin D supplementation on spermatogram, seminal and serum levels of oxidative stress indices in asthenospermia infertile men: a study protocol for a triple-blind, randomized controlled trial. Nutrition Journal. 2021; 20: 49.

[38] Lian J, Cheng Z. A commentary on “The association between serum vitamin D, fertility and semen quality: a systematic review and meta-analysis” (Int J Surg 2019; 71:101–109). International Journal of Surgery. 2021; 92: 106034.

[39] Maghsoumi-Norouzabad L, Labibzadeh M, Zare Javid A, Ahmad Hosseini S, Abbas Kaydani G, Dastoorpur M. The association of vitamin D, semen parameters, and reproductive hormones with male infertility: a cross-sectional study. International Journal of Reproductive Biomedicine. 2022; 20: 331–338.

[40] Homayouni-Meymandi M, Sotoodehnejadnematalahi F, Nasr-Esfahani MH. Relationship between serum vitamin D in male, sperm function and clinical outcomes in infertile men candidate for ICSI: a cohort study. International Journal of Fertility & Sterility. 2022; 16: 115–121.

[41] Blomberg Jensen M, Gerner Lawaetz J, Andersson A, Petersen JH, Nordkap L, Bang AK, et al. Vitamin D deficiency and low ionized calcium are linked with semen quality and sex steroid levels in infertile men. Human Reproduction. 2016; 31: 1875–1885.

[42] Hammoud AO, Wayne Meikle A, Matthew Peterson C, Stanford J, Gibson M, Carrell DT. Association of 25-hydroxy-vitamin D levels with semen and hormonal parameters. Asian Journal of Andrology. 2012; 14: 855–859.

[43] Blomberg Jensen M, Bjerrum PJ, Jessen TE, Nielsen JE, Joensen UN, Olesen IA, et al. Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa. Human Reproduction. 2011; 26: 1307–1317.

[44] Deng X, Song Y, Manson JE, Signorello LB, Zhang SM, Shrubsole MJ, et al. Magnesium, vitamin D status and mortality: results from us national health and nutrition examination survey (NHANES) 2001 to 2006 and NHANES III. BMC Medicine. 2013; 11: 187.

[45] Savastano S, Barrea L, Savanelli MC, Nappi F, Di Somma C, Orio F, et al. Low vitamin D status and obesity: role of nutritionist. Reviews in Endocrine and Metabolic Disorders. 2017; 18: 215–225.

[46] Zeng W, Avelar GF, Rathi R, Franca LR, Dobrinski I. The length of the spermatogenic cycle is conserved in porcine and ovine testis xenografts. Journal of Andrology. 2006; 27: 527–533.

[47] Blomberg Jensen M, Jørgensen A, Nielsen JE, Bjerrum PJ, Skalkam M, Petersen JH, et al. Expression of the vitamin D metabolizing enzyme CYP24A1 at the annulus of human spermatozoa may serve as a novel marker of semen quality. International Journal of Andrology. 2012; 35: 499–510.