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Background <p>Infertility represents a prevalent condition affecting the reproductive system. It has a global incidence of approximately 17.5%. Nutritional supplements are increasingly used as complementary therapy for female infertility, though their efficacy remains controversial. This study aimed to systematically assess the effectiveness of various nutritional supplements in female infertility through a network meta-analysis (NMA).</p> Methods <p>The Web of Science, Cochrane Library, EMBASE, and PubMed, and databases were retrieved for relevant English articles on the effectiveness of nutritional supplements in female infertility up to April 17, 2025. The quality of articles was assessed via the Cochrane Risk of Bias tool 2.0. The GEMTC package in R software was employed to compare the results via a Bayesian NMA. The mean difference (MD) or risk ratio (RR) and 95% credible interval (CrI) served as effect size indicators. The effectiveness of interventions was evaluated via the surface under the cumulative ranking curve to the total area (SUCRA). The evidence’s confidence was evaluated via the confidence in network meta-analysis (CINeMA). <i>P</i> &lt; 0.05 indicated statistical significance. Funnel plots were created via Stata 18.0 to assess the publication bias.</p> Results <p>This NMA included 30 studies with 3,977 patients. The results revealed that compared to alternative interventions, the combination of probiotics and vitamin D exhibited the most significant increase in the clinical pregnancy rate (RR = 1.29, 95% CrI = 1.1, 1.52; CINeMA: Low certainty). Curcumin alone demonstrated a substantial increase in both the number (No.) of oocytes retrieved (MD = 6.96, 95% CrI = 3.23, 10.71; CINeMA: Very low certainty) and the fertilization rate (MD = 9.02, 95% CrI = 2.98, 15.07; CINeMA: Low certainty). Astaxanthin alone resulted in a notable increase in the No. of good-quality embryos (MD = 1.17, 95% CrI = 0.19, 2.16; CINeMA: Very low certainty). Curcumin intake showed the greatest effect on the increase in MII (MD = 6.35, 95% CrI = 3.31, 9.41; CINeMA: Very low certainty). The assessment of adverse events indicated that no interventions were significantly linked to miscarriage.</p> Conclusions <p>Nutritional supplements can play a crucial role in regulating the ovarian environment and enhancing pregnancy outcomes for infertile women. The combination of vitamin D with other nutritional supplements, as well as the intake of coenzyme Q10, astaxanthin, or curcumin, was more effective than other nutritional supplements.</p> Trial registration <p>Its protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD420251052361.</p>

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Efficacy and safety of nutritional supplements in female infertility: a network meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月18日

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  • Jihang Du,
  • Jia Liu,
  • Qianxue Liu,
  • Chaoliang Li,
  • Hao Zhu,
  • Ran Ji,
  • Ziyu Shang,
  • Xiaoyan Zheng,
  • Jie Yang

摘要

Background

Infertility represents a prevalent condition affecting the reproductive system. It has a global incidence of approximately 17.5%. Nutritional supplements are increasingly used as complementary therapy for female infertility, though their efficacy remains controversial. This study aimed to systematically assess the effectiveness of various nutritional supplements in female infertility through a network meta-analysis (NMA).

Methods

The Web of Science, Cochrane Library, EMBASE, and PubMed, and databases were retrieved for relevant English articles on the effectiveness of nutritional supplements in female infertility up to April 17, 2025. The quality of articles was assessed via the Cochrane Risk of Bias tool 2.0. The GEMTC package in R software was employed to compare the results via a Bayesian NMA. The mean difference (MD) or risk ratio (RR) and 95% credible interval (CrI) served as effect size indicators. The effectiveness of interventions was evaluated via the surface under the cumulative ranking curve to the total area (SUCRA). The evidence’s confidence was evaluated via the confidence in network meta-analysis (CINeMA). P < 0.05 indicated statistical significance. Funnel plots were created via Stata 18.0 to assess the publication bias.

Results

This NMA included 30 studies with 3,977 patients. The results revealed that compared to alternative interventions, the combination of probiotics and vitamin D exhibited the most significant increase in the clinical pregnancy rate (RR = 1.29, 95% CrI = 1.1, 1.52; CINeMA: Low certainty). Curcumin alone demonstrated a substantial increase in both the number (No.) of oocytes retrieved (MD = 6.96, 95% CrI = 3.23, 10.71; CINeMA: Very low certainty) and the fertilization rate (MD = 9.02, 95% CrI = 2.98, 15.07; CINeMA: Low certainty). Astaxanthin alone resulted in a notable increase in the No. of good-quality embryos (MD = 1.17, 95% CrI = 0.19, 2.16; CINeMA: Very low certainty). Curcumin intake showed the greatest effect on the increase in MII (MD = 6.35, 95% CrI = 3.31, 9.41; CINeMA: Very low certainty). The assessment of adverse events indicated that no interventions were significantly linked to miscarriage.

Conclusions

Nutritional supplements can play a crucial role in regulating the ovarian environment and enhancing pregnancy outcomes for infertile women. The combination of vitamin D with other nutritional supplements, as well as the intake of coenzyme Q10, astaxanthin, or curcumin, was more effective than other nutritional supplements.

Trial registration

Its protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD420251052361.