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Does coenzyme Q10 supplementation improve fertility outcomes in women undergoing assisted reproductive technology procedures? A systematic review and meta-analysis of randomized-controlled trials

Abstract

Objective

Increased oxidative stress has been identified as a pathogenetic mechanism in female infertility. However, the effect of specific antioxidants, such as coenzyme Q10 (CoQ10), on the outcomes after assisted reproductive technologies (ART) has not been clarified. The aim of this study was to systematically review and meta-analyze the best available evidence regarding the effect of CoQ10 supplementation on clinical pregnancy (CPR), live birth (LBR), and miscarriage rates (MR) compared with placebo or no-treatment in women with infertility undergoing ART.

Methods

A comprehensive literature search was conducted in PubMed (MEDLINE), Cochrane, and Scopus, from inception to March 2020. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). The I2 index was employed for heterogeneity.

Results

Five randomized-controlled trials fulfilled eligibility criteria (449 infertile women; 215 in CoQ10 group and 234 in placebo/no treatment group). Oral supplementation of CoQ10 resulted in an increase of CPR when compared with placebo or no-treatment (28.8% vs. 14.1%, respectively; OR 2.44, 95% CI 1.30–4.59, p = 0.006; I2 32%). This effect remained significant when women with poor ovarian response and polycystic ovarian syndrome were analyzed separately. No difference between groups was observed regarding LBR (OR 1.67, 95% CI 0.66–4.25, p = 0.28; I2 34%) and MR (OR 0.61, 95% CI 0.13–2.81, p = 0.52; I2 0%).

Conclusions

Oral supplementation of CoQ10 may increase CPR when compared with placebo or no-treatment, in women with infertility undergoing ART procedures, without an effect on LBR or MR.

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Data availability

Not applicable.

Abbreviations

IVF:

In vitro fertilization

ICSI:

Intracytoplasmic sperm injection

hCG:

Human chorionic gonadotropin

PCOS:

Polycystic ovary syndrome

POR:

Poor ovarian response

References

  1. Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, et al. The International Glossary on Infertility and Fertility Care, 2017. Hum Reprod. 2017;32(9):1786–801. https://doi.org/10.1093/humrep/dex234.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Farquhar C, Marjoribanks J. Assisted reproductive technology: an overview of Cochrane Reviews. Cochrane Database Syst Rev. 2018;8:CD010537. https://doi.org/10.1002/14651858.CD010537.pub5.

    Article  PubMed  Google Scholar 

  3. Showell MG, Mackenzie-Proctor R, Jordan V, Hart RJ. Antioxidants for female subfertility. Cochrane Database Syst Rev. 2017;7:Cd007807. https://doi.org/10.1002/14651858.CD007807.pub3.

    Article  PubMed  Google Scholar 

  4. Sasaki H, Hamatani T, Kamijo S, Iwai M, Kobanawa M, Ogawa S, et al. Impact of oxidative stress on age-associated decline in oocyte developmental competence. Front Endocrinol. 2019;10:811. https://doi.org/10.3389/fendo.2019.00811.

    Article  Google Scholar 

  5. Xu Y, Nisenblat V, Lu C, Li R, Qiao J, Zhen X, et al. Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in low-prognosis young women with decreased ovarian reserve: a randomized controlled trial. Reprod Biol Endocrinol. 2018;16(1):29. https://doi.org/10.1186/s12958-018-0343-0.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Banerjee P, Bhattacharya J. Impact of oxidative stress on infertility, with emphasis on infertility management strategies. Glob J Fertil Res. 2019;4(1):10–8. https://doi.org/10.17352/gjfr.000012.

    Article  Google Scholar 

  7. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39(1):44–84. https://doi.org/10.1016/j.biocel.2006.07.001.

    Article  PubMed  CAS  Google Scholar 

  8. Shkolnik K, Tadmor A, Ben-Dor S, Nevo N, Galiani D, Dekel N. Reactive oxygen species are indispensable in ovulation. Proc Natl Acad Sci U S A. 2011;108(4):1462–7. https://doi.org/10.1073/pnas.1017213108.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Fujii J, Iuchi Y, Okada F. Fundamental roles of reactive oxygen species and protective mechanisms in the female reproductive system. Reprod Biol Endocrinol. 2005;3:43. https://doi.org/10.1186/1477-7827-3-43.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Lu J, Wang Z, Cao J, Chen Y, Dong Y. A novel and compact review on the role of oxidative stress in female reproduction. Reprod Biol Endocrinol. 2018;16(1):80. https://doi.org/10.1186/s12958-018-0391-5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Kurutas EB. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutr J. 2016;15(1):71. https://doi.org/10.1186/s12937-016-0186-5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Rodick T, Seibels D, Jeganathan R, Huggins K, Ren G, Mathews S. Potential role of coenzyme Q10 in health and disease conditions. Nutr Diet Suppl. 2018;10:1–11. https://doi.org/10.2147/NDS.S112119.

    Article  CAS  Google Scholar 

  13. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535. https://doi.org/10.1136/bmj.b2535.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. https://doi.org/10.1136/bmj.d5928.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Tufanaru C, Munn Z, Stephenson M, Aromataris E. Fixed or random effects meta-analysis? Common methodological issues in systematic reviews of effectiveness. Int J Evid Based Healthc. 2015;13:196–207. https://doi.org/10.1097/XEB.0000000000000065.

    Article  PubMed  Google Scholar 

  16. El Refaeey A, Selem A, Badawy A. Combined coenzyme Q10 and clomiphene citrate for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome. Reprod BioMed Online. 2014;29(1):119–24. https://doi.org/10.1016/j.rbmo.2014.03.011.

    Article  PubMed  CAS  Google Scholar 

  17. Bentov Y, Hannam T, Jurisicova A, Esfandiari N, Casper RF. Coenzyme Q10 Supplementation and Oocyte Aneuploidy in Women Undergoing IVF-ICSI Treatment. Clin Med Insights Reprod Health. 2014;8:31–6. https://doi.org/10.4137/cmrh.S14681.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Caballero T, Fiameni F, Valcarcel A, Buzzi J. Dietary supplementation with coenzyme Q10 in poor responder patients undergoing IVF-ICSI Treatment. Fertil Steril. 2016;106(3):e58. https://doi.org/10.1016/j.fertnstert.2016.07.177.

    Article  Google Scholar 

  19. Sen SD. Co-enzyme q10-a mitochondrial antioxidant -a new hope for success in infertility in clomiphene-citrate-resistant polycystic ovary syndrome. CENTRAL. 2019;2019(3). https://doi.org/10.1111/1471-0528.2_14571.

  20. Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011;26(7):1616–24. https://doi.org/10.1093/humrep/der092.

    Article  PubMed  CAS  Google Scholar 

  21. The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81(1):19–25. https://doi.org/10.1016/j.fertnstert.2003.10.004.

    Article  Google Scholar 

  22. Ben-Meir A, Kim K, McQuaid R, Esfandiari N, Bentov Y, Casper RF, et al. Co-enzyme Q10 supplementation rescues cumulus cells dysfunction in a maternal aging model. Antioxidants. 2019;8(3):58. https://doi.org/10.3390/antiox8030058.

    Article  PubMed Central  CAS  Google Scholar 

  23. Zhang M, ShiYang X, Zhang Y, Miao Y, Chen Y, Cui Z, et al. Coenzyme Q10 ameliorates the quality of postovulatory aged oocytes by suppressing DNA damage and apoptosis. Free Radic Biol Med. 2019;143:84–94. https://doi.org/10.1016/j.freeradbiomed.2019.08.002.

    Article  PubMed  CAS  Google Scholar 

  24. Ozcan P, Ficicioglu C, Kizilkale O, Yesiladali M, Tok OE, Ozkan F, et al. Can coenzyme Q10 supplementation protect the ovarian reserve against oxidative damage? J Assist Reprod Genet. 2016;33(9):1223–30. https://doi.org/10.1007/s10815-016-0751-z.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Lafuente R, González-Comadrán M, Solà I, López G, Brassesco M, Carreras R, et al. Coenzyme Q10 and male infertility: a meta-analysis. J Assist Reprod Genet. 2013;30(9):1147–56. https://doi.org/10.1007/s10815-013-0047-5.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Agarwal A, Sharma A, Master K, Sharma R, Henkel R. Meta-analysis of double-blind placebo control trials evaluating the role of coenzyme Q10 on semen parameters. Fertil Steril. 2018;110(4):e167–e8. https://doi.org/10.1016/j.fertnstert.2018.07.497.

    Article  Google Scholar 

  27. Smits RM, Mackenzie-Proctor R, Yazdani A, Stankiewicz MT, Jordan V, Showell MG. Antioxidants for male subfertility. Cochrane Database Syst Rev. 2019;(3). https://doi.org/10.1002/14651858.CD007411.pub4.

  28. Agarwal A, Gupta S, Sharma RK. Role of oxidative stress in female reproduction. Reprod Biol Endocrinol. 2005;3:28. https://doi.org/10.1186/1477-7827-3-28.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Wu X, Iguchi T, Itoh N, Okamoto K, Takagi T, Tanaka K, et al. Ascorbic acid transported by sodium-dependent vitamin C transporter 2 stimulates steroidogenesis in human choriocarcinoma cells. Endocrinol. 2008;149(1):73–83. https://doi.org/10.1210/en.2007-0262.

    Article  CAS  Google Scholar 

  30. Vural P, Akgul C, Yildirim A, Canbaz M. Antioxidant defence in recurrent abortion. Clin Chim Acta. 2000;295(1-2):169–77. https://doi.org/10.1016/s0009-8981(99)00255-7.

    Article  PubMed  CAS  Google Scholar 

  31. Ledee-Bataille N, Olivennes F, Lefaix JL, Chaouat G, Frydman R, Delanian S. Combined treatment by pentoxifylline and tocopherol for recipient women with a thin endometrium enrolled in an oocyte donation programme. Hum Reprod. 2002;17(5):1249–53. https://doi.org/10.1093/humrep/17.5.1249.

    Article  PubMed  CAS  Google Scholar 

  32. Takasaki A, Tamura H, Taniguchi K, Asada H, Taketani T, Matsuoka A, et al. Luteal blood flow and luteal function. J Ovarian Res. 2009;2:1. https://doi.org/10.1186/1757-2215-2-1.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Thomson RL, Spedding S, Buckley JD. Vitamin D in the aetiology and management of polycystic ovary syndrome. Clin Endocrinol. 2012;77(3):343–50. https://doi.org/10.1111/j.1365-2265.2012.04434.x.

    Article  CAS  Google Scholar 

  34. Nestler JE. Inositolphosphoglycans (IPGs) as Mediators of Insulin's Steroidogenic Actions. J Basic Clin Physiol Pharmacol. 2011;9(2-4):197–204. https://doi.org/10.1515/JBCPP.1998.9.2-4.197.

    Article  Google Scholar 

  35. Gaskins AJ, Chiu YH, Williams PL, Ford JB, Toth TL, Hauser R, et al. Association between serum folate and vitamin B-12 and outcomes of assisted reproductive technologies. Am J Clin Nutr. 2015;102(4):943–50. https://doi.org/10.3945/ajcn.115.112185.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. AbdulameerYahya A, Abdulridha MK, Al-Rubuyae BJ, Al-Atar HA. The effect of vitamin D and co-enzyme Q10 replacement therapy on hormonal profile and ovulation statusin women with clomiphene citrate resistant polycystic ovary syndrome. J Pharm Sci Res. 2019;11(1):208–15 https://www.researchgate.net/publication/330811147_The_Effect_of_Vitamin_D_and_Co-enzyme_Q10_Replacement_Therapy_on_Hormonal_Profile_and_Ovulation_Statusin_Women_with_Clomiphene_Citrate_Resistant_Polycystic_Ovary_Syndrome.

    Google Scholar 

  37. Pritchard N, Healey M, Sorby KL, Sivapalan S, Osianlis T, Jatkar S, et al. A case control study of melatonin with or without coenzyme Q10 in improving oocyte quality and outcomes in in vitro fertilization. Reprod Biol Insights. 2015;8:1–7. https://doi.org/10.4137/RBI.S27776.

    Article  Google Scholar 

  38. Gat I, Blanco Mejia S, Balakier H, Librach CL, Claessens A, Ryan EA. The use of coenzyme Q10 and DHEA during IUI and IVF cycles in patients with decreased ovarian reserve. Gynecol Endocrinol. 2016;32(7):534–7. https://doi.org/10.3109/09513590.2015.1137095.

    Article  PubMed  CAS  Google Scholar 

  39. Bhagavan HN, Chopra RK. Coenzyme Q10: Absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006;40(5):445–53. https://doi.org/10.1080/10715760600617843.

    Article  PubMed  CAS  Google Scholar 

  40. Miles MV, Horn P, Miles L, Tang P, Steele P, DeGrauw T. Bioequivalence of coenzyme Q10 from over-the-counter supplements. Nutr Res. 2002;22(8):919–29. https://doi.org/10.1016/S0271-5317(02)00402-5.

    Article  CAS  Google Scholar 

  41. Jones K, Hughes K, Mischley L, McKenna DJ. Coenzyme Q-10: Efficacy, safety, and use. Altern Ther Health Med. 2002;8(3):42–55 quiz 6, 138. https://search.proquest.com/docview/204823988?accountid=8359.

    PubMed  Google Scholar 

  42. Langsjoen PH, Langsjoen PH, Folkers K. Long-term efficacy and safety of coenzyme Q10 therapy for idiopathic dilated cardiomyopathy. Am J Cardiol. 1990;65(7):521–3.

    Article  CAS  PubMed  Google Scholar 

  43. Gouveia F, Costa R, Lemos T. Coenzyme Q10 and polycitic ovary syndrome: systematic review. CMI. 2018;3. https://doi.org/10.15761/CMI.1000168.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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PF designed the research, searched the literature, extracted and analyzed the data, and wrote the first draft of the paper. PT searched the literature, extracted the data, and was responsible for the statistical analysis. PA and MC reviewed the manuscript and provided critical scientific input. DGG resolved discrepancies regarding the quality of the studies included in the meta-analysis, provided critical scientific input, and had the primary responsibility for the paper’s final content.

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Correspondence to Michail Chourdakis.

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Florou, P., Anagnostis, P., Theocharis, P. et al. Does coenzyme Q10 supplementation improve fertility outcomes in women undergoing assisted reproductive technology procedures? A systematic review and meta-analysis of randomized-controlled trials. J Assist Reprod Genet 37, 2377–2387 (2020). https://doi.org/10.1007/s10815-020-01906-3

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  • DOI: https://doi.org/10.1007/s10815-020-01906-3

Keywords

  • Coenzyme Q10
  • CoQ10
  • Female infertility
  • Assisted reproduction
  • Pregnancy outcomes
  • Meta-analysis