Micronutrientes en el tratamiento de la infertilidad masculina idiopática

Micronutrient supplementation to treat idiopathic male infertility

La evidencia sobre la asociación entre dieta y fertilidad humana ha aumentado en forma exponencial en la última década, lo que ha permitido identificar algunos hallazgos claros. La infertilidad masculina es un problema común que está incrementando. Aunque algunos pacientes tienen causas hormonales anatómicas o funcionales reconocidas, la etiología exacta en un gran número de casos es desconocida. En diferentes condiciones de infertilidad masculina, generalmente asociadas a anomalías morfofuncionales de los espermatozoides, existen pruebas claras de daño celular causados por el estrés oxidativo. En las últimas 5 décadas, varias investigaciones han intentado comprobar si la suplementación de micronutrientes puede tener efectos positivos en los parámetros cualitativos/cuantitativos del semen y la frecuencia de embarazo. Las vitaminas C y E, junto con la L-carnitina, han demostrado ser eficaces. Sin embargo, otros micronutrientes han sido menos estudiados. Existe la necesidad de realizar más investigaciones con estudios controlados aleatorios para confirmar la eficacia y seguridad de los suplementos antioxidantes en el tratamiento médico de la infertilidad masculina idiopática. El objetivo de esta revisión fue evaluar los efectos de los micronutrientes en el tratamiento de la infertilidad masculina.

1. Vander Borght M, Wyns C. Fertility and infertility: Definition and epidemiology. Clin Biochem. 2018;62:2-10. doi: 10.1016/j.clinbiochem.2018.03.012.
2. Winkelman WD, Katz PP, Smith JF, Rowen TS; Infertility outcomes program project group. the sexual impact of infertility among women seeking fertility care. Sex Med. 2016;4(3):e190-7. doi: 10.1016/j.esxm.2016.04.001.
3. Krausz C, Cioppi F, Riera-Escamilla A. Testing for genetic contributions to infertility: potential clinical impact. Expert Rev Mol Diagn. 2018;18(4):331-346. doi: 10.1080/14737159.2018.1453358.
4. de Sousa Filho EP, Christofolini DM, Barbosa CP, Glina S, Bianco B. Y chromosome microdeletions and varicocele as aetiological factors of male infertility: A cross-sectional study. Andrologia. 2018;50(3):211-218. doi: 10.1111/and.12938.
5. Levine H, Jørgensen N, Martino-Andrade A, Mendiola J, Weksler-Derri D, Mindlis I, Pinotti R, Swan SH. Temporal trends in sperm count: a systematic review and meta-regression analysis. Hum Reprod Update. 2017;23(6):646-659. doi: 10.1093/humupd/dmx022.
6. Onofre J, Geenen L, Cox A, Van Der Auwera I, Willendrup F, Andersen E, Campo R, Dhont N, Ombelet W. Simplified sperm testing devices: a possible tool to overcome lack of accessibility and inconsistency in male factor infertility diagnosis. An opportunity for low- and middle- income countries. Facts Views Vis Obgyn. 2021;13(1):79-93. doi: 10.52054/FVVO.13.1.011.
7. Zhu Q, Li X, Ge RS. Toxicological Effects of Cadmium on Mammalian Testis. Front Genet. 2020;11:527. doi: 10.3389/fgene.2020.00527
8. Yuan HF, Shangguan HF, Zheng Y, Meng TQ, Xiong CL, Guan HT. Decline in semen concentration of healthy Chinese adults: evidence from 9357 participants from 2010 to 2015. Asian J Androl. 2018;20(4):379-384. doi: 10.4103/aja.aja_80_17.
9. Vinolas C, Raad J, Sonigo C, Sifer C, Sermondade N, Grynberg M. Medical techniques of fertility preservation in the male and female. J Visc Surg. 2018;155 Suppl 1:S3-S9. doi: 10.1016/j.jviscsurg.2018.03.009.
10. Wu X, Lin D, Sun F, Cheng CY. Male Infertility in Humans: An Update on Non-obstructive Azoospermia (NOA) and Obstructive Azoospermia (OA). Adv Exp Med Biol. 2021;1288:161-173. doi: 10.1007/978-3-030-77779-1_8.
11. Colpi GM, Francavilla S, Haidl G, Link K, Behre HM, Goulis DG, Krausz C, Giwercman A. European Academy of Andrology guideline Management of oligo-astheno-teratozoospermia. Andrology. 2018;6(4):513-524. doi: 10.1111/andr.12502.
12. Kumar N, Singh AK. Reactive oxygen species in seminal plasma as a cause of male infertility. J Gynecol Obstet Hum Reprod. 2018;47(10):565-572.
13. Saito Y, Nishio K, Yoshida Y, Niki E. Cytotoxic effect of formaldehyde with free radicals via increment of cellular reactive oxygen species. Toxicology. 2005;210(2-3):235-45.
14. De Luca MN, Colone M, Gambioli R, Stringaro A, Unfer V. Oxidative Stress and Male Fertility: Role of Antioxidants and Inositols. Antioxidants (Basel). 2021;10(8):1283. doi: 10.3390/antiox10081283.
15. Gharagozloo P, Gutiérrez-Adán A, Champroux A, Noblanc A, Kocer A, Calle A, Pérez-Cerezales S, Pericuesta E, Polhemus A, Moazamian A, Drevet JR, Aitken RJ. A novel antioxidant formulation designed to treat male infertility associated with oxidative stress: promising preclinical evidence from animal models. Hum Reprod. 2016;31(2):252-62. doi: 10.1093/humrep/dev302.
16. Majzoub A, Agarwal A. Antioxidant therapy in idiopathic oligoasthenoteratozoospermia. Indian J Urol. 2017;33(3):207-214. doi: 10.4103/iju.IJU_15_17.
17. Agarwal A, Rana M, Qiu E, AlBunni H, Bui AD, Henkel R. Role of oxidative stress, infection and inflammation in male infertility. Andrologia. 2018;50(11):e13126. doi: 10.1111/and.13126.
18. Zandieh Z, Vatannejad A, Doosti M, Zabihzadeh S, Haddadi M, Bajelan L, Rashidi B, Amanpour S. Comparing reactive oxygen species and DNA fragmentation in semen samples of unexplained infertile and healthy fertile men. Ir J Med Sci. 2018;187(3):657-662. doi: 10.1007/s11845-017-1708-7.
19. Puzuka A, Alksere B, Gailite L, Erenpreiss J. Idiopathic Infertility as a Feature of Genome Instability. Life (Basel). 2021;11(7):628. doi: 10.3390/life11070628.
20. Esteves SC, Zini A, Coward RM, Evenson DP, Gosálvez J, Lewis SEM, Sharma R, Humaidan P. Sperm DNA fragmentation testing: Summary evidence and clinical practice recommendations. Andrologia. 2021;53(2):e13874. doi: 10.1111/and.13874.
21. Sacha CR, Vagios S, Hammer K, Fitz V, Souter I, Bormann CL. The effect of semen collection location and time to processing on sperm parameters and early IVF/ICSI outcomes. J Assist Reprod Genet. 2021;38(6):1449-1457. doi: 10.1007/s10815-021-02128-x.
22. Dietrich C. Antioxidant functions of the aryl hydrocarbon receptor. Stem Cells Int. 2016;2016:7943495. doi: 10.1155/2016/7943495
23. Opuwari CS, Henkel RR. An update on oxidative damage to spermatozoa and oocytes. Biomed Res Int. 2016;2016:9540142. doi: 10.1155/2016/9540142.
24. Pujianto DA, Oktarina M, Sharma Sharaswati IA, Yulhasri. Hydrogen Peroxide Has Adverse Effects on Human Sperm Quality Parameters, Induces Apoptosis, and Reduces Survival. J Hum Reprod Sci. 2021;14(2):121-128. doi: 10.4103/jhrs.jhrs_241_20.
25. Bossi RL, Cabral M, Oliveira M, Lopes S, Hurtado R, Sampaio M, Geber S. Ultrastructural analysis of Lyophilized Human Spermatozoa. JBRA Assist Reprod. 2021;25(3):473-479. doi: 10.5935/1518-0557.20210028.
26. Boehm F, Edge R, Truscott TG, Witt C. A dramatic effect of oxygen on protection of human cells against γ-radiation by lycopene. FEBS Lett. 2016;590(8):1086-93. doi: 10.1002/1873-3468.12134.
27. Gvozdjáková A, Kucharská J, Dubravicky J, Mojto V, Singh RB. Coenzyme Q₁₀, α-tocopherol, and oxidative stress could be important metabolic biomarkers of male infertility. Dis Markers. 2015;2015:827941. doi: 10.1155/2015/827941.
28. Cirilli I, Damiani E, Dludla PV, Hargreaves I, Marcheggiani F, Millichap LE, Orlando P, Silvestri S, Tiano L. Role of Coenzyme Q10 in Health and Disease: An Update on the Last 10 Years (2010-2020). Antioxidants (Basel). 2021;10(8):1325. doi: 10.3390/antiox10081325.
29. Mancini A, Milardi D, Conte G, Bianchi A, Balercia G, De Marinis L, Littarru GP. Coenzyme Q10: another biochemical alteration linked to infertility in varicocele patients? Metabolism. 2003;52(4):402-6.
30. Agarwal A, Sengupta P, Durairajanayagam D. Role of L-carnitine in female infertility. Reprod Biol Endocrinol. 2018;16(1):5. doi: 10.1186/s12958-018-0323-4.
31. Ghyasvand T, Goodarzi MT, Amiri I, Karimi J, Ghorbani M. Serum levels of lycopene, beta-carotene, and retinol and their correlation with sperm DNA damage in normospermic and infertile men. Int J Reprod Biomed (Yazd). 2015;13(12):787-92.
32. Sofimajidpour H, Ghaderi E, Ganji O. Comparison of the Effects of Varicocelectomy and Oral L-carnitine on Sperm Parameters in Infertile Men with Varicocele. J Clin Diagn Res. 2016;10(4):PC07-10. doi: 10.7860/JCDR/2016/18464.7557.
33. Zhang X, Cui Y, Dong L, Sun M, Zhang Y. The efficacy of combined l-carnitine and l-acetyl carnitine in men with idiopathic oligoasthenoteratozoospermia: A systematic review and meta-analysis. Andrologia. 2020;52(2):e13470. doi: 10.1111/and.13470.
34. Wei G, Zhou Z, Cui Y, Huang Y, Wan Z, Che X, Chai Y, Zhang Y. A Meta-Analysis of the Efficacy of L-Carnitine/L-Acetyl-Carnitine or N-Acetyl-Cysteine in Men With Idiopathic Asthenozoospermia. Am J Mens Health. 2021;15(2):15579883211011371. doi: 10.1177/15579883211011371.
35. Haseen Ahmed SD, Ahsan S, Iqbal T, Ahmed Burney SI. Relationship of seminal free L-Carnitine with functional spermatozoal characteristics: Results from an observational study conducted in a tertiary care hospital of Karachi, Pakistan. J Pak Med Assoc. 2017;67(2):280-284.
36. Stukenborg JB, Mitchell RT, Söder O. Endocrine disruptors and the male reproductive system. Best Pract Res Clin Endocrinol Metab. 2021:101567. doi: 10.1016/j.beem.2021.101567.
37. Mostafa T, Abdel-Hamid IA. Ejaculatory dysfunction in men with diabetes mellitus. World J Diabetes. 2021;12(7):954-974. doi: 10.4239/wjd.v12.i7.954.
38. Vanderhout SM, Rastegar Panah M, Garcia-Bailo B, Grace-Farfaglia P, Samsel K, Dockray J, Jarvi K, El-Sohemy A. Nutrition, genetic variation and male fertility. Transl Androl Urol. 2021;10(3):1410-1431. doi: 10.21037/tau-20-592.
39. Aitken RJ, Baker MA. The Role of Genetics and Oxidative Stress in the Etiology of Male Infertility-A Unifying Hypothesis? Front Endocrinol (Lausanne). 2020;11:581838. doi: 10.3389/fendo.2020.581838.
40. Agarwal A, Cho CL, Esteves SC, Majzoub A. Development of treatment strategies in men with vulnerable sperm. Transl Androl Urol. 2017;6(Suppl 4):S476-S478. doi: 10.21037/tau.2017.04.28.
41. Yan F, Dou X, Zhu G, Xia M, Liu Y, Liu X, Wu G, Wang H, Zhang B, Shao Q, Wang Y. Cistanoside of Cistanche Herba ameliorates hypoxia-induced male reproductive damage via suppression of oxidative stress. Am J Transl Res. 2021;13(5):4342-4359.
42. Suleiman SA, Ali ME, Zaki ZM, el-Malik EM, Nasr MA. Lipid peroxidation and human sperm motility: protective role of vitamin E. J Androl. 1996;17(5):530-7.
43. Matorras R, Pérez-Sanz J, Corcóstegui B, Pérez-Ruiz I, Malaina I, Quevedo S, Aspichueta F, Crisol L, Martinez-Indart L, Prieto B, Expósito A. Effect of vitamin E administered to men in infertile couples on sperm and assisted reproduction outcomes: a double-blind randomized study. F S Rep. 2020;1(3):219-226. doi: 10.1016/j.xfre.2020.09.006.
44. Keskes-Ammar L, Feki-Chakroun N, Rebai T, Sahnoun Z, Ghozzi H, Hammami S, Zghal K, Fki H, Damak J, Bahloul A. Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men. Arch Androl. 2003;49(2):83-94. doi: 10.1080/01485010390129269
45. Isoyama R, Baba Y, Harada H, Kawai S, Shimizu Y, Fujii M, Fujisawa S, Takihara H, Koshido Y, Sakatoku J. Clinical experience of methylcobalamin (CH3-B12)/clomiphene citrate combined treatment in male infertility. Hinyokika Kiyo. 1986;32(8):1177-83.
46. Banihani SA. Vitamin B12 and Semen Quality. Biomolecules. 2017;7(2):42. doi: 10.3390/biom7020042.
47. Garolla A, Petre GC, Francini-Pesenti F, De Toni L, Vitagliano A, Di Nisio A, Foresta C. Dietary Supplements for Male Infertility: A Critical Evaluation of Their Composition. Nutrients. 2020;12(5):1472. doi: 10.3390/nu12051472.
48. Nalbanski B, Protich M, Barov D, Stanislavov R. Treatment of oligoasthenozoospermia with vitamin B12. Akush Ginekol (Sofiia). 1986;25(3):71-4.
49. Maiorino M, Roveri A, Benazzi L, Bosello V, Mauri P, Toppo S, Tosatto SC, Ursini F. Functional interaction of phospholipid hydroperoxide glutathione peroxidase with sperm mitochondrion-associated cysteine-rich protein discloses the adjacent cysteine motif as a new substrate of the selenoperoxidase. J Biol Chem. 2005;280(46):38395-402.
50. Fernandez MC, O'Flaherty C. Peroxiredoxin 6 is the primary antioxidant enzyme for the maintenance of viability and DNA integrity in human spermatozoa. Hum Reprod. 2018;33(8):1394-1407. doi: 10.1093/humrep/dey221.
51. Agarwal A, Majzoub A, Baskaran S, Panner Selvam MK, Cho CL, Henkel R, Finelli R, Leisegang K, Sengupta P, Barbarosie C, Parekh N, Alves MG, Ko E, Arafa M, Tadros N, Ramasamy R, Kavoussi P, Ambar R, Kuchakulla M, Robert KA, Iovine C, Durairajanayagam D, Jindal S, Shah R. Sperm DNA Fragmentation: A New Guideline for Clinicians. World J Mens Health. 2020;38(4):412-471. doi: 10.5534/wjmh.200128.
52. Aljaser F, Tabassum H, Fatima S, Abudawood M, Banu N. Effect of trace elements on the seminal oxidative status and correlation to sperm motility in infertile Saudi males. Saudi J Biol Sci. 2021;28(8):4455-4460. doi: 10.1016/j.sjbs.2021.04.042.
53. Roy AC, Karunanithy R, Ratnam SS. Lack of correlation of selenium level in human semen with sperm count/motility. Arch Androl. 1990;25(1):59-62.
54. Wolfe RR, Cifelli AM, Kostas G, Kim IY. Optimizing protein intake in adults: interpretation and application of the recommended dietary allowance compared with the acceptable macronutrient distribution range. Adv Nutr. 2017;8(2):266-275. doi: 10.3945/an.116.013821.
55. Kumalic SI, Klun IV, Bokal EV, Pinter B. Effect of the oral intake of astaxanthin on semen parameters in patients with oligo-astheno-teratozoospermia: a randomized double-blind placebo-controlled trial. Radiol Oncol. 2020;55(1):97-105. doi: 10.2478/raon-2020-0062.
56. Scaruffi P, Licata E, Maccarini E, Massarotti C, Bovis F, Sozzi F, Stigliani S, Dal Lago A, Casciano I, Rago R, Anserini P. Oral Antioxidant Treatment of Men Significantly Improves the Reproductive Outcome of IVF Cycles. J Clin Med. 2021;10(15):3254. doi: 10.3390/jcm10153254.