Couples trying to conceive are bombarded with supplement recommendations. Scroll through any fertility forum and you’ll find confident claims about CoQ10, vitamin D, and a dozen other compounds that supposedly hold the key to conception. Some of these recommendations are grounded in solid clinical data. Others are riding waves of hype with remarkably little behind them.
Here’s what the peer-reviewed evidence actually supports, where it falls short, and what deserves healthy skepticism.
Why Micronutrient Status Matters for Conception
Reproduction is one of the most energy-demanding biological processes the human body undertakes. Oocyte maturation, sperm production, implantation, and early embryonic development all depend on adequate micronutrient availability. Deficiencies don’t just affect general health; they directly compromise the cellular machinery of fertility.
This is true for both partners. Spermatogenesis takes roughly 74 days, and sperm cells are highly vulnerable to oxidative damage throughout that cycle. Oocytes, which resume meiosis just before ovulation, require enormous mitochondrial energy output to divide correctly. When the raw materials are missing, these processes falter.
The question isn’t whether nutrition matters for fertility. It clearly does. The question is which specific supplements have earned their place through clinical evidence, and which are coasting on biological plausibility alone.
Supplements With Strong Clinical Evidence
Folate: More Than Neural Tube Prevention
Most people associate folate with preventing neural tube defects, and that alone justifies supplementation before conception. But the fertility data extends beyond birth defect prevention. In the EARTH (Environment and Reproductive Health) prospective cohort study, women with higher supplemental folate intake had significantly higher live birth rates following assisted reproduction [1]. Separate data from the same research group found that higher folate intake was associated with modestly greater ovarian reserve as measured by antral follicle count [2].
The form of folate matters. Standard folic acid requires enzymatic conversion via MTHFR to become biologically active 5-methyltetrahydrofolate. An estimated 10-15% of the population carries MTHFR variants (particularly C677T homozygosity) that impair this conversion. For these individuals, supplementing with methylfolate (5-MTHF) bypasses the bottleneck entirely. This isn’t fringe science; it’s straightforward pharmacogenomics, and clinicians should be screening for it.
CoQ10: The Mitochondrial Case Is Compelling
Coenzyme Q10 has accumulated some of the strongest interventional data in fertility supplementation. A 2018 randomized controlled trial (n=169) demonstrated that 60 days of CoQ10 pretreatment in young women with poor ovarian reserve led to significantly higher oocyte retrieval numbers, improved fertilization rates (67.5% vs. controls), and more high-quality embryos. Women receiving CoQ10 were also far less likely to have embryo transfers cancelled due to poor embryo development (8.3% vs. 22.9%, p=0.04) [3]. A 2024 systematic review and meta-analysis of CoQ10 pretreatment for diminished ovarian reserve confirmed these benefits across multiple trials [4].
The mechanism is straightforward: CoQ10 is essential for mitochondrial electron transport and ATP generation. Oocytes contain more mitochondria than any other human cell, and mitochondrial dysfunction is a primary driver of age-related egg quality decline. CoQ10 supplementation directly addresses this energy deficit.
Vitamin D: Deficiency Correction Matters
A systematic review and meta-analysis of 11 cohort studies (2,700 women) published in Human Reproduction found that vitamin D-replete women undergoing assisted reproduction had 33% higher odds of live birth compared to those with deficient or insufficient levels (OR 1.33, 95% CI: 1.08-1.65) [5]. A subsequent meta-analysis of supplementation trials found that moderate daily vitamin D dosing improved clinical pregnancy rates in infertile women with documented deficiency [6].
The critical distinction: these benefits appear to be about correcting deficiency, not about mega-dosing. Women with adequate vitamin D levels don’t seem to gain additional benefit from supplementation. Testing 25-hydroxyvitamin D levels before starting supplementation is the rational approach.
Omega-3 Fatty Acids: Emerging but Credible
Omega-3 data has matured in recent years. A 2022 prospective cohort study of women attempting natural conception found that omega-3 supplementation was associated with improved fecundability [7]. In the IVF context, women with higher serum omega-3 levels had improved treatment outcomes in the EARTH study [8]. A 2024 systematic review and meta-analysis across multiple trials concluded that omega-3 intake significantly improved pregnancy and fertilization rates [9].
The biological rationale centers on prostaglandin modulation and anti-inflammatory effects on the endometrium. DHA specifically plays a role in membrane fluidity, which affects both oocyte quality and endometrial receptivity during the implantation window.
Male Fertility: Zinc, Selenium, and L-Carnitine
Male factor infertility accounts for roughly 40-50% of all infertility cases, yet it receives a fraction of the supplement attention directed at women. The evidence here is actually quite strong.
A comprehensive 2018 meta-analysis of RCTs found that selenium increased sperm concentration by 3.9 million/mL and motility by 3.3%, zinc improved motility by 7.0%, and L-carnitine was the standout for progressive motility improvement at 7.5% [10]. A 2022 network meta-analysis across 18 RCTs confirmed these findings, ranking CoQ10 highest for sperm concentration improvement and carnitine highest for motility [11].
These aren’t marginal effects. For men with borderline parameters, the difference between subfertile and normal semen analysis values often comes down to exactly these magnitudes of improvement.
Common Mistakes
Timing errors are the most frequent problem. CoQ10 takes at least 60 days to influence oocyte quality, consistent with the follicular development timeline. Starting it two weeks before an IVF cycle accomplishes nothing. Sperm-targeted supplements need a minimum of 74 days to affect the current crop of developing sperm. Planning three months ahead is the minimum for either partner.
Form selection matters beyond folate. CoQ10 as ubiquinol has superior bioavailability compared to ubiquinone, particularly in individuals over 35 whose endogenous conversion capacity declines. Selenium as selenomethionine is better absorbed than selenite.
Supplement-drug interactions are under-discussed. High-dose vitamin E can interfere with gonadotropin medications used in IVF stimulation protocols. Excessive antioxidant supplementation during certain phases of IVF may theoretically counteract the controlled oxidative stress that triggers ovulation. Patients undergoing fertility treatment should disclose all supplements to their reproductive endocrinologist.
What’s Overhyped
DHEA
DHEA for diminished ovarian reserve generated enormous excitement based on early uncontrolled studies. The reality is sobering. A 2023 meta-analysis that specifically isolated RCTs from the larger body of observational data found that DHEA treatment did not significantly improve live birth rates in women with diminished ovarian reserve or poor ovarian response undergoing IVF/ICSI [12]. The positive results in earlier literature were largely driven by non-randomized studies with significant bias. DHEA remains widely prescribed in fertility clinics, but the RCT evidence does not support the enthusiasm.
Myo-Inositol: Context-Dependent
Myo-inositol occupies an unusual position. For women with PCOS, it does improve metabolic and hormonal profiles, reducing hyperandrogenism and improving insulin sensitivity [13]. These are real effects. But the 2018 Cochrane systematic review was blunt in its assessment: the evidence that myo-inositol improves live birth rates or clinical pregnancy rates in subfertile women with PCOS undergoing IVF was rated as “very low quality,” and the reviewers stated they were “uncertain” whether it actually improves these outcomes [14].
Myo-inositol is reasonable as metabolic support in PCOS. Selling it as a fertility treatment for the general population is a stretch the data doesn’t support.
Royal Jelly
Human clinical evidence for royal jelly and fertility is virtually nonexistent. The few studies that appear in literature searches are animal studies or uncontrolled human observations with sample sizes too small to draw conclusions. It belongs firmly in the “interesting biology, no clinical proof” category.
Practical Guidance
Start supplementation at least three months before attempting conception, for both partners. This aligns with the biological timelines of both oogenesis and spermatogenesis.
For women: folate (as methylfolate for MTHFR carriers or folic acid for others), CoQ10, vitamin D (after testing), and omega-3 DHA have the strongest evidentiary basis.
For men with suboptimal semen parameters: CoQ10, L-carnitine, zinc, and selenium are supported by meta-analyses of RCTs.
Get baseline blood work. Vitamin D supplementation without knowing your starting level is guessing. The same applies to other micronutrients where testing is available.
Work with a clinician who understands both the evidence and its limits. The gap between “this supplement shows promise in RCTs” and “this supplement will get you pregnant” is wide, and navigating it requires individualized medical judgment.
Author Bio
Mary is a Supplement Research Specialist at supplements.org. Her work focuses on reviewing clinical data and meta-analyses to help consumers understand ingredient safety and efficacy in the reproductive health space.
Medical Disclaimer: The information provided in this article is for educational and informational purposes only and is not intended as medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or the use of dietary supplements. Never disregard professional medical advice or delay in seeking it because of something you have read in this article. Statements regarding dietary supplements have not been evaluated by relevant local health authorities (such as the FDA in the US or similar regulatory bodies elsewhere) and are not intended to diagnose, treat, cure, or prevent any disease.
