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Effectiveness of Nutritional Therapies in Male Factor Infertility Treatment: A Systematic Review and Network Meta-analysis

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Abstract

Background

Nutritional therapies are effective alternative treatments for male infertility or subfertility. These are cost-effective and easily implementable, unlike other advanced invasive treatments. Even moderate improvements in sperm quality could improve spontaneous pregnancy.

Objective

We aimed to compare the effectiveness of all nutritional therapies in male infertility/subfertility treatment and ranked their efficacy based on type and etiology. We intend to aid clinicians with an evidence-based approach to affordable and safer initial infertility treatment for those who mainly do not wish to have other advanced invasive treatments or could not afford or have access to them.

Methods

We included 69 studies with 94 individual study arms identified from bibliographic databases and registries. We included studies in adult men with proven infertility or subfertility that investigated nutritional or dietary supplement therapies compared with control or placebo and at least reported on a sperm parameter. We undertook a network meta-analysis and performed a pairwise meta-analysis on all sperm parameter outcomes and meta-regression. No language or date restriction was imposed. A systematic article search was concluded on August 29, 2022.

Results

Our network meta-analysis is the first to compare all dietary interventions in a single analysis, sub-grouped by intervention type and type of infertility. l-Carnitine with micronutrients, antioxidants, and several traditional herbal supplements showed statistically and clinically significant improvement in sperm quality. Meta-regression identified that improvement in the sperm count, motility and morphology translated into increased pregnancy rates (p < 0.001; p < 0.001; p < 0.002, respectively). In particular, l-carnitine with micronutrient therapy (risk ratio [RR]: 3.60, 95% CI 1.86, 6.98, p = 0.0002), followed by zinc (RR 5.39, 95% CI 1.26, 23.04, p = 0.02), significantly improved pregnancy rates. Men with oligozoospermia (RR 4.89), followed by oligoasthenozoospermia (RR 4.20) and asthenoteratozoospermia (RR 3.53), showed a significant increase in pregnancy rates.

Conclusion

We ranked nutritional therapies for their ability to improve sperm quality in men with infertility. Nutritional therapies, particularly l-carnitine alone or combined with micronutrients, significantly improved sperm parameters and pregnancy rates even under severe conditions. We believe these affordable solutions may be valuable for people without access to or who do not wish to undergo more invasive and costly fertility treatments.

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Acknowledgements

We would like to acknowledge Elena Smertina for translating several articles from Russian into English and Sima Haee for translating articles from Farsi into English. We want to thank the University of Canberra library staff for prompt, thorough, cheerful, and professional assistance. We would like to thank our reviewers for extremely thorough, detailed, and helpful feedback on our manuscript.

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Authors and Affiliations

  1. Institute of Reproductive Health/Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hang Kong Road, Wuhan, 430030, China

    Mohammad Ishraq Zafar & Honggang Li

  2. Reproductive Medicine Center, Fourth Affiliated Hospital Zhejiang University School of Medicine, Yiwu, China

    Mohammad Ishraq Zafar

  3. Department of Science and Technology, University of Canberra, Bruce 2617, Canberra, Australia

    Kerry E. Mills

  4. TruDataRx, White River Junction, Vermont, USA

    Kerry E. Mills & Charles D. Baird

  5. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China

    Huahua Jiang

  6. Wuhan Huake Reproductive Hospital, Wuhan, China

    Honggang Li

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Correspondence to Kerry E. Mills or Honggang Li.

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Author contributors

MIZ, KEM, and HL designed the study and defined the inclusion and exclusion criteria; MIZ and KEM designed the study search; MIZ and KEM did abstract and full-text inclusion and exclusion; HJ and KEM extracted data from studies and cross-checked; CDB designed the network meta-analysis approach, undertook all network meta-analysis and sensitivity analyses for the networks; KEM did pairwise meta-analysis and meta-regression; MIZ, KEM, and CDB wrote the manuscript; HL provided critical feedback on the manuscript.

Conflict of interest/competing interest

 MIZ, KEM, CBD, HJ and HL have no conflicts to declare.

Funding

The study was supported by two grants to MI Zafar: the Research Fund for Young International Scientists from the National Natural Science Foundation Fund (Grant number 82150410456) and a research fund from the Postdoctoral Science Foundation, P.R. China (Grant number 2019M662636).

Role of the funder/sponsor

The funding bodies are public entities; they had no role in the study conception, design, conduct, or result interpretation and publication of the manuscript.

Data availability

All data and network meta-analysis are available at https://github.com/trucharles/fertility. The meta-analyses themselves are available upon request to the authors.

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Code availability

The code used in this study is available at https://github.com/trucharles/fertility.

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Zafar, M.I., Mills, K.E., Baird, C.D. et al. Effectiveness of Nutritional Therapies in Male Factor Infertility Treatment: A Systematic Review and Network Meta-analysis. Drugs 83, 531–546 (2023). https://doi.org/10.1007/s40265-023-01853-0

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