A systematic review and meta-analysis examining the effect of micronutrients on fertility and aneuploidy (an abnormal chromosome number) rates has been published in the journal Reproductive Biomedicine Online. Specifically, they assessed single-nutrient-only studies, including both randomized trials and in vitro analyses, of 66 micronutrients primarily derived from a WHO database (an important caveat, as some relevant nutrients were not included). After an initial screening of over 500 records, only 11 studies were assessed for eligibility, only 5 were included in the review, and only 2 nutrients were evaluated.
Among the inclusion criteria that eliminated many studies for consideration were the following: women with a 46 XX karyotype seeking fertility treatment, single micronutrient use only (no combinations), and random assignment to parallel arms (no cross-over studies). According to this strict criterion, the 5 remaining studies (3 clinical trials and 2 in vitro) evaluated only resveratrol and CoQ10 and included a total of 326 women in clinical trials. This included 24 women of advanced maternal age (AMA, often defined as age 35+), 133 women with polycystic ovary syndrome (PCOS), and 169 women with poor ovarian response (POR, decreased ovarian response to IVF). The in vitro studies used either resveratrol or CoQ10 in the in vitro maturation media, and reported oocyte maturation rate.
The meta-analysis found that CoQ10 increased live birth rates and oocyte retrieval in women diagnosed with PCOS (OR 2.28) and increased the pregnancy rate in women diagnosed with either POR (OR 2.2) or PCOS (OR 13.26). CoQ10 supplementation significantly increased the clinical pregnancy rate (39.24% vs. 14.04%) among women undergoing fertility treatment, with some distinctions. CoQ10 significantly increased clinical pregnancy rates among women diagnosed with POR (who were not of AMA), 31.58% vs. 17.2%, and also dramatically among women with clomiphene-citrate-resistant PCOS (also not AMA), 48.57% vs. 6.35%. The effect among women of AMA but without a diagnosis of PCOS was not significant (33.33% vs. 26.67%). No effect was found on miscarriage rate, though it was only reported in one trial among women not of AMA but with POR, so the effect in other populations is not clear. CoQ10 also increased the oocyte maturation rate (OR 2.73), and among women of AMA, reduced oocyte (69% reduction) and chromosome aneuploidy (43% reduction) rates. The only study that evaluated resveratrol was in vitro, and the authors of the meta-analysis (but not the original paper) found no significant effect.
While this meta-analysis suggests CoQ10 may be the only nutrient worth considering to help enhance fertility, as mentioned above, the included studies were restricted to single nutrients and a predefined list, which may leave some important gaps.
For example, myo-inositol was not on the authors’ list of micronutrients, and yet it has some encouraging data for its use. Supplementation with myo-inositol is recommended (in a joint position statement from several expert groups) to both women with and without PCOS seeking IVF therapy prior to ovarian stimulation, as it “may affect gonadotropin use and duration, oocyte and embryo quality, fertilization, and clinical pregnancy rates.” Often recommended to improve insulin sensitivity in women with PCOS (by increasing cellular glucose uptake via the GLUT-4 pathway), it also enhances FSH activity as a second messenger, likely driving improved fertility.
Similarly, DHEA was not included in the meta-analysis, despite published randomized controlled trials in women undergoing IVF reporting the appropriate outcomes. It was not among the 66 micronutrients on the WHO list, which appears to be the reason it was excluded from the analysis. Yet in a randomized, double-blind clinical trial, women aged 36 to 40 who received 75 mg DHEA each day during treatment and the prior eight weeks had a significantly higher live birth rate (41.5% vs. 23.2%) and lower miscarriage rate (0 vs. 8.9%). A 2025 systematic review and meta-analysis of randomized controlled trials published in the Journal of Ovarian Research found that DHEA significantly increased endometrial thickness in women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. DHEA was also associated with a 34% significantly higher clinical pregnancy rate, and improved quality of oocyte and embryos, oocytes fertilized, as well as transferred and high-quality embryos. Notably, the authors also concluded that the limited sample size and methodological issues warrant additional trials of DHEA.
N-acetylcysteine was not included on the WHO list of nutrients and was therefore excluded from this recent meta-analysis. Yet NAC has been used in combination with clomiphene citrate (CC), and in one randomized and double-blind placebo-controlled trial that enrolled 180 women with PCOS, participants who received 1.2 g NAC per day in addition to CC had a significantly higher number of follicles, greater endometrial thickness, and both ovulation and pregnancy rates than women who received only CC. In a more recent randomized and controlled trial with 200 women of AMA, NAC was found to improve oocyte quality by increasing glutathione content, and to improve the sensitivity of the ovaries to exogenous gonadotropins.
Overall, this recent meta-analysis highlights the broad benefits of CoQ10 for women undergoing fertility treatments, though it seems to have overlooked a number of other relevant interventions. Additionally, while single-use studies can be helpful in clinical research, these compounds have complementary mechanisms of action that have the potential to be more potent when used together.
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