Advertisement

The Effect of Subclinical Varicocele on Pregnancy Rates and Semen Parameters: a Systematic Review and Meta-Analysis

  • Taylor P. Kohn
  • Samuel J. Ohlander
  • Jake S. Jacob
  • Tina M. Griffin
  • Larry I. Lipshultz
  • Alexander W. Pastuszak
Andrology and Infertility (L Lipshultz, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Andrology and Infertility

Abstract

Purpose of Review

Current guidelines recommend against surgical repair of subclinical varicoceles (SCVs) for infertility; several studies demonstrate mixed fertility results after SCV correction. To determine whether surgical correction of SCV improves semen parameters and/or reproductive outcomes, we performed a systematic review and meta-analysis. Seven biomedical literature databases were searched through January 2018 for studies that assessed reproductive outcomes and/or change in semen parameters in men with corrected SCV compared to either (1) uncorrected SCV or (2) corrected clinical varicocele. Estimates were pooled using random-effects meta-analysis.

Recent Findings

Data were extracted from 13 studies involving 1357 men. Overall, the risk of bias for included studies was high and without a consistent SCV definition across studies. Surgical correction of SCV was associated with a minor increase in sperm density and total motile sperm count (TMSC) compared to uncorrected SCV. This increase in semen parameters is not clinically significant, as men prior to varicocelectomy were on average normospermic nor was correction of a SCV associated with an increase in pregnancy rates when compared to men with uncorrected SCV. Comparing corrected SCV to corrected clinical varicocele, SCV correction resulted in a smaller increase in TMSC but no difference in average annual pregnancy rate.

Summary

The risk of bias within and heterogeneity between studies assessing SCV correction are high, yet overall very little clinical benefit is derived from SCV correction.

Keywords

Semen analysis Varicocele Pregnancy Meta-analysis Varicocelectomy 

Notes

Role of Funding Source

A.W.P. is a National Institutes of Health K12 Scholar supported by a Male Reproductive Health Research Career Development Physician-Scientist Award (HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Program (to Dolores J. Lamb).

Compliance with Ethical Standards

Conflict of Interest

Taylor P. Kohn, Samuel J. Ohlander, Jake S. Jacob, Tina M. Griffin, Larry I. Lipshultz, and Alexander W. Pastuszak each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Clarke BG. Incidence of varicocele in normal men and among men of different ages. JAMA. 1966;198:1121–2.CrossRefPubMedGoogle Scholar
  2. 2.
    Gorelick JI, Goldstein M. Loss of fertility in men with varicocele. Fertil Steril. 1993;59:613–6.CrossRefPubMedGoogle Scholar
  3. 3.
    Kohn TP, Kohn JR, Pastuszak AW. Varicocelectomy before assisted reproductive technology: are outcomes improved? Fertil Steril. 2017;108:385–91.CrossRefPubMedGoogle Scholar
  4. 4.
    Shiraishi K, Takihara H, Matsuyama H. Elevated scrotal temperature, but not varicocele grade, reflects testicular oxidative stress-mediated apoptosis. World J Urol. 2010;28:359–64.CrossRefPubMedGoogle Scholar
  5. 5.
    Dubin L, Amelar RD. Varicocele size and results of varicocelectomy in selected subfertile men with varicocele. Fertil Steril. 1970;21:606–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Narayan P, Amplatz K, Gonazlez R. Varicocele and male subfertility. Fertil Steril. 1981;36:92–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Yarborough MA, Burns JR, Keller FS. Incidence and clinical significance of subclinical scrotal varicoceles. J Urol. 1989;141:1372–4.CrossRefPubMedGoogle Scholar
  8. 8.
    •• ASRM. Report on varicocele and infertility: a committee opinion. Fertil Steril. 2014;102:1556–60. This guideline report published by ASRM recommends against correction of a subclinical varicocele for the sake of improving fertility. CrossRefGoogle Scholar
  9. 9.
    Alshehri FM, Akbar MH, Altwairgi AK, AlThaqufi OJ. Preoperative duplex ultrasound parameters predicting male fertility after successful varicocelectomy. Saudi Med J. 2015;36:1439–45.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    • Cantoro U, Polito M, Muzzonigro G. Reassessing the role of subclinical varicocele in infertile men with impaired semen quality: a prospective study. Urology. 2015;85:826–30. Only recently published studies assessing the role of correcting a subclinical varicocele. This prospective study demonstrated a significant improvement in semen parameters and pregnancy rate after embolization. CrossRefPubMedGoogle Scholar
  11. 11.
    Dhabuwala CB, Hamid S, Moghissi KS. Clinical versus subclinical varicocele: improvement in fertility after varicocelectomy. Fertil Steril. 1992;57:854–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Donkol RH, Salem T. Paternity after varicocelectomy: preoperative sonographic parameters of success. J Ultrasound Med Off J Am Inst Ultrasound Med. 2007;26:593–9.CrossRefGoogle Scholar
  13. 13.
    Jarow JP, Ogle SR, Eskew LA. Seminal improvement following repair of ultrasound detected subclinical varicoceles. J Urol. 1996;155:1287–90.CrossRefPubMedGoogle Scholar
  14. 14.
    Ketabchi AA, Ahmadinejad M, Ehsan M. Comparison of the effects of varicocelectomy on the spermiogram of patients with subclinical versus clinical varicocele. Acta Medica Iranica. 2005;43:249–52.Google Scholar
  15. 15.
    Marsman JWP, Brand R, Schats R, Bernardus RE. Clinical and subclinical varicocele: a useful distinction? Eur J Obstet Gynecol Reprod Biol. 1995;60:165–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Pierik FH, Vreeburg JTM, Stijnen T, Van Roijen JH, Dohle GR, Laméris JS, et al. Improvement of sperm count and motility after ligation of varicoceles detected with colour Doppler ultrasonography. Int J Androl. 1998;21:256–60.CrossRefPubMedGoogle Scholar
  17. 17.
    Seo JT, Kim KT, Moon MH, Kim WT. The significance of microsurgical varicocelectomy in the treatment of subclinical varicocele. Fertil Steril. 2010;93:1907–10.CrossRefPubMedGoogle Scholar
  18. 18.
    Tinga DJ, Jager S, Bruijnen CL, Kremer J, Mensink HJ. Factors related to semen improvement and fertility after varicocele operation. Fertil Steril. 1984;41:404–10.CrossRefPubMedGoogle Scholar
  19. 19.
    Unal D, Yeni E, Verit A, Karatas OF. Clomiphene citrate versus varicocelectomy in treatment of subclinical varicocele: a prospective randomized study. Int J Urol Off J Japan Urol Assoc. 2001;8:227–30.Google Scholar
  20. 20.
    Vermeulen A, Vandeweghe M. Improved fertility after varicocele correction: fact or fiction? Fertil Steril. 1984;42:249–56.CrossRefPubMedGoogle Scholar
  21. 21.
    Yamamoto M, Hibi H, Hirata Y, Miyake K, Ishigaki T. Effect of varicocelectomy on sperm parameters and pregnancy rate in patients with subclinical varicocele: a randomized prospective controlled study. J Urol. 1996;155:1636–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–9. w64CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Bjorndahl L, Barratt CL, Mortimer D, Jouannet P. ‘How to count sperm properly’: checklist for acceptability of studies based on human semen analysis. Hum Reprod. 2016;31:227–32.PubMedGoogle Scholar
  24. 24.
    Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5.CrossRefPubMedGoogle Scholar
  25. 25.
    Borenstein M, Hedges LV, Higgins JP, Rothstein HR. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synthesis Methods. 2010;1:97–111.CrossRefGoogle Scholar
  26. 26.
    Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.CrossRefPubMedGoogle Scholar
  27. 27.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ (Clin Res Ed). 2003;327:557–60.CrossRefGoogle Scholar
  28. 28.
    R-Core-Team. R: A Language and Environment for Statistical Computing. In. Vol. 2015. Vienna, Austria: R Foundation for Statistical Computing.Google Scholar
  29. 29.
    Trum JW, Gubler FM, Laan R, van der Veen F. The value of palpation, varicoscreen contact thermography and colour Doppler ultrasound in the diagnosis of varicocele. Hum Reprod. 1996;11:1232–5.CrossRefPubMedGoogle Scholar
  30. 30.
    •• Dubin JM, Greer AB, Kohn TP, Masterson TA, Ji L, Ramasamy R. Men with severe oligospermia appear to benefit from varicocele repair: a cost-effectiveness analysis of assisted reproductive technology. Urology. 2018;111:99–103. This cost-effectiveness analysis determines that correcting a varicocele with semen parameters < 2 million total motile sperm with subsequent improvement to > 10 million total motile sperm is more cost-effective than simply starting with IVF. CrossRefPubMedGoogle Scholar
  31. 31.
    Trussell JC, Christman GM, Ohl DA, Legro RS, Krawetz SA, Snyder PJ, et al. Recruitment challenges of a multicenter randomized controlled varicocelectomy trial. Fertil Steril. 2011;96:1299–305.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    te Velde ER, Eijkemans R, Habbema HD. Variation in couple fecundity and time to pregnancy, an essential concept in human reproduction. Lancet (Lond Engl). 2000;355:1928–9.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Taylor P. Kohn
    • 1
  • Samuel J. Ohlander
    • 2
  • Jake S. Jacob
    • 1
  • Tina M. Griffin
    • 3
  • Larry I. Lipshultz
    • 4
    • 5
  • Alexander W. Pastuszak
    • 4
    • 5
    • 6
  1. 1.Baylor College of MedicineHoustonUSA
  2. 2.Department of UrologyUniversity of Illinois Hospital and Health Sciences System at Chicago College of MedicineChicagoUSA
  3. 3.Library of Health SciencesUniversity of Illinois at ChicagoChicagoUSA
  4. 4.Scott Department of UrologyBaylor College of MedicineHoustonUSA
  5. 5.Center for Reproductive MedicineBaylor College of MedicineHoustonUSA
  6. 6.Center for Reproductive Medicine, Scott Department of UrologyBaylor College of MedicineHoustonUSA

Personalised recommendations