Comprehensive review combines research on use of supplements for female infertility

A new study performed an “umbrella review” on the use of supplements for improving female infertility, finding that while studies show improvements in pregnancy outcomes, the quality of the data is low and “insufficient to recommend nutrient supplementation.”

Many women take antioxidant supplements to improve egg quality, but it’s unclear if this truly has a benefit on pregnancy or live birth rates.

This post is a summary of a study by Pandey et al. (2025), who conducted an “umbrella review” to provide an overview of the evidence for supplements in improving female infertility. They included 4 meta-analyses in their review:

• Unanyan et al. (2022), which included 35 RCTs investigating the use of inositol in PCOS patients (clinical pregnancy rates only).
• Meng et al. (2023), which included 9 RCTs investigating vitamin D (clinical pregnancy rates only).
• Devi et al. (2020), which included 15 RCTs investigating the use of N-acetyl-cysteine (NAC) (clinical pregnancy rates only).
• Showell et al. (2020), which included 63 RCTs investigating a variety of supplements (live birth and clinical pregnancy rates). This meta-analysis is the latest Cochrane review on the use of supplements, which I reviewed in my post Impact of supplements on live birth and pregnancy rates in women: a meta-analysis. This single meta-analysis represents the majority of the data seen in this umbrella review, with additional data for inositol, vitamin D and NAC coming from the other three meta-analyses. This meta-analysis was given a “high” confidence rating, while the other three were given a “critically low” rating (due to a variety of reasons, such as lacking justification for excluding studies, risk of bias, inappropriate meta-analytical methods, etc.).

All studies compared supplements to a placebo and/or no treatment. The following supplements were included in the studies:

• Inositol
• N-acetylcysteine (NAC)
• Vitamin D
• L-arginine
• L-carnitine
• Coenzyme Q10 (CoQ10)
• Melatonin
• Vitamin B complex
• Vitamin C
• Vitamin E
• Multiple supplements

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Supplements improve live birth rates

Of the 4 meta-analyses included in this umbrella review, only the Showell et al. (2020) study included studies that measured live birth rates. I have already reviewed this meta-analysis in the past (link), so I’ll keep it brief!

Overall impact. Based on 13 RCTs and 1,227 participants, the odds of live birth increased 1.81 times in women who used supplements compared to those who didn’t, or used a placebo (27.8% vs 19.0%, odds ratio [95%] CI: 1.81 [1.36-2.43]). The quality of evidence was very low.

When they looked at the individual supplements and their impact on live birth rates:

• The odds of live birth increased 3.00 times in women taking NAC (odds ratio [95%] CI: 3.00 [1.05-8.60]). This was based on a single study.
• The odds of live birth increased 2.59 times for women taking multiple supplements (odds ratio [95%] CI: 2.59 [1.52-4.40]). This was based on 3 studies, and included vitacap, seidivid or multiple micronutrients. The quality of evidence was very low.
• No difference in live births for women taking L-arginine, CoQ10, vitamin D, vitamin B, vitamin E or melatonin.

Supplements improve clinical pregnancy rates

Again, much of this data is from the Showell et al. (2020) study, which I’m briefly summarizing below:

• The odds of clinical pregnancy increased 1.66 times in women taking melatonin (26.1% vs 19.1%, odds ratio [95%] CI: 1.66 [1.12-2.47]). This was based on 7 studies. The quality of evidence was very low.
• The odds of clinical pregnancy increased 11.14 times in women taking L-carnitine (36.0% vs 4.4%, odds ratio [95%] CI: 11.14 [5.70-21.81]). This was based on 2 studies, and both these RCTs involved the use of clomiphene with or without metformin. The quality of evidence was very low.
• The odds of clinical pregnancy increased 2.49 times in women taking CoQ10 (28.4% vs 14%, odds ratio [95%] CI: 2.49 [1.50-4.13]). This was based on 4 studies. The quality of evidence was very low.
• There was no difference in clinical pregnancy in women taking vitamin E, vitamin C, L-arginine or vitamin B.

The data for inositol, NAC and vitamin D was based on the other 3 meta-analyses:

• The chance of clinical pregnancy increased 1.52 times in women with PCOS taking myo-inositol vs metformin (relative risk [95%] CI: 1.52 [1.05-2.18]). This was based on 2 studies. The quality of evidence was low.
• For NAC, they did two analyses based on whether the control was no treatment (2 studies, moderate quality of evidence) or placebo (8 studies, very low quality of evidence). The odds of clinical pregnancy increased 2.15 times in women taking NAC vs no treatment (odds ratio [95%] CI: 2.15 [1.01-4.60]) and 2.14 times in women taking NAC vs placebo (odds ratio [95%] CI: 2.14 [1.05-4.37]).
• The chance of clinical pregnancy increased 1.49 times in women taking vitamin D vs placebo (odds ratio [95%] CI: 1.49 [1.05-2.11]). This was based on 9 studies. The quality of evidence was very low.

No adverse effects with supplements

• In general, adverse effects were poorly reported.
• For NAC, vitamin D and multiple supplements, there was no difference in miscarriage rates or multiple pregnancy rates (low to very low quality of evidence).
• Multiple supplements had no impact on ectopic pregnancy rates (low quality of evidence).

Conclusions

For live birth rates, the researchers found that NAC and multiple (combined) supplements* showed increases, while L-arginine, CoQ10, vitamin D, vitamin B, vitamin E and melatonin didn’t.

* The authors note that for studies looking at multiple supplements, “the products and ingredients varied, including the dosages, making it difficult to draw valid conclusions or offer general recommendations.”

For pregnancy rates, the researchers found that melatonin, L-carnitine, CoQ10, myo-inositol (in PCOS patients), NAC and vitamin D showed increases, while vitamin E, vitamin C, L-arginine and vitamin B didn’t.

While adverse effects were poorly reported, the available data showed that supplements had no impact on miscarriages, multiples or ectopic pregnancies.

Most of the studies included were rated as very low quality, and the authors stress the need for more high-quality RCTs to improve confidence in the results. Future studies should standardize supplement doses, types and administration duration.

I think this is an important point to emphasize: There is little consistency in how these supplement studies are done, and part of the problem is with the supplement industry itself. Since supplements aren’t regulated like prescription drugs, manufacturers can impose their own quality standards, leading to supplements with inaccurate doses or contaminants. It’s important that supplements are verified by an independent lab that’s separated from the manufacturer/brand, like USP or NSF International. You can read more in my post The problem with supplements.

The authors conclude that while supplements appear to be safe, “the available evidence is currently insufficient to recommend nutrient supplementation to improve female infertility due to the very low quality of evidence.”

As mentioned, the bulk of this umbrella review was from the Showell et al. (2020) study, which contains more information not discussed here in my post Impact of supplements on live birth and pregnancy rates in women: a meta-analysis. For more background on supplements for egg quality, check my post Improving egg quality with supplements.

Reference

Pandey C, Maunder A, Liu J, Vaddiparthi V, Costello MF, Bahri-Khomami M, Mousa A, Ee C. The Role of Nutrient Supplements in Female Infertility: An Umbrella Review and Hierarchical Evidence Synthesis. Nutrients. 2024 Dec 27;17(1):57. doi: 10.3390/nu17010057. PMID: 39796491; PMCID: PMC11722770.

 

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About Embryoman

Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.

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