Fertility Supplements: What the Evidence Shows

31 October 2024, by SANUSq Research team
13 min reading time

Smiling couple holding their newborn baby in a bright, airy room

The market for fertility supplements is large, the promises are bold and the people it sells to are often at their most hopeful and most anxious. Only one supplement has truly solid evidence behind it when you are trying for a baby, and it is rarely the one on the front of the box. Here is how the rest compare.

Written by SANUSq Research Team | Medically reviewed by Dr Ajay Kumar, MD
Published: 31 October 2024 | Updated: 31 October 2024

The one well-established supplement: folic acid

Let's start with the part that isn't in doubt, even though it concerns the pregnancy that follows rather than fertility itself.

Folic acid supplementation increases maternal folate status, and low maternal folate status is a recognised risk factor for neural tube defects, such as spina bifida, in the developing baby. That is why health services across Europe and beyond advise women who could become pregnant to take 400 µg of folic acid a day before conception and through the first 12 weeks of pregnancy. Some women, for example those with a previous pregnancy affected by a neural tube defect, diabetes or certain medicines, are advised by their doctor to take a higher dose.

A Cochrane review by De-Regil et al. (2015), pooling five trials in 7,391 women, found that daily folic acid taken around conception, alone or with other vitamins and minerals, was linked to a much lower risk of neural tube defects (risk ratio 0.31, high-quality evidence). The effect was similar at 400 µg a day and at higher doses. The review found no clear effect on other birth defects and no difference in miscarriage rates.

Timing is the key detail. The neural tube closes in the first weeks after conception, often before a woman knows she is pregnant. So the usual advice is to start folic acid when you stop contraception, not when you get a positive test. It is the one supplement with firmly established value when planning a pregnancy, and it happens to be cheap, simple and rarely the focus of marketing.

Coenzyme Q10: a real lead with a narrow scope

Coenzyme Q10 (CoQ10) is often promoted for egg quality. There is genuine research interest here, but the most quoted trial needs to be read carefully.

In a randomised trial, Xu et al. (2018) gave CoQ10 for 60 days before IVF/ICSI to women under 35 with poor ovarian reserve, compared with no pre-treatment. Of 169 women analysed, those taking CoQ10 had more eggs retrieved, a higher fertilisation rate and more high-quality embryos. Clinical pregnancy and live birth rates tended to be higher but the difference was not statistically significant, and the authors said more work is needed on those outcomes.

This finding concerns a specific group, younger women with diminished ovarian reserve going through IVF, under a supervised protocol. It tells us nothing about a healthy woman who has been trying to conceive naturally for a few months, and it does not make CoQ10 a treatment for infertility. If you are having fertility treatment, it is a reasonable question to put to your clinic, which can weigh it against your own situation.

Fertility supplements: how the other candidates compare

Supplements for female fertility

Vitamin D comes up often. Low levels are common, and correcting a documented deficiency is sensible in its own right, but an effect on the chances of conceiving has not been shown. Inositol is studied in polycystic ovary syndrome (PCOS), where research has looked at metabolic markers and ovulation. That is a specific situation that belongs under medical supervision, and the evidence on births is still uncertain.

A Cochrane review of inositol by Showell et al. (2018), covering 13 trials in 1,472 women with PCOS, judged the evidence to be of low to very low quality. The authors were uncertain whether myo-inositol improves live birth or clinical pregnancy rates in women with PCOS undergoing IVF, and noted that live birth and side effects were poorly reported.

Antioxidant blends for women follow a similar pattern: plenty of small trials, low confidence in the overall result.

The Cochrane review of antioxidants for female subfertility by Showell et al. (2020) included 63 trials in 7,760 women and rated the evidence low to very low quality. The authors were uncertain whether antioxidants improve live birth rates and concluded that there is limited evidence in support of oral antioxidants for subfertile women.

Multivitamin formulas sold for fertility have not shown a benefit beyond the folic acid they contain.

Supplements for male fertility

For men, antioxidants such as zinc, selenium, vitamins C and E, and CoQ10 have been reported to change some semen parameters in a number of trials. Zinc contributes to normal fertility and reproduction, and selenium contributes to normal spermatogenesis, so an adequate intake of both matters. The question that counts, though, is whether taking extra leads to more babies, and that remains unanswered.

The Cochrane review of antioxidants for male subfertility by de Ligny et al. (2022), covering 90 studies and 10,303 men, found only very low-certainty evidence that antioxidants might increase live birth rates. When studies at high risk of bias were removed, there was no evidence of an increase. The authors advise that, overall, the current evidence is inconclusive.

The largest single trial so far, by Schisterman et al. (2020), randomised 2,370 men from couples planning infertility treatment to 5 mg folic acid plus 30 mg zinc daily or placebo for six months. Live birth rates were almost identical (34% versus 35%), most semen measures did not differ, sperm DNA fragmentation was slightly higher and stomach upsets were more common in the supplement group.

This is a textbook example of the gap between a marker and an outcome. A change in a semen test can be measured quickly; a live birth takes a large, long trial to assess, and that is where the promises often fall short.

What matters more than any supplement

A handful of factors have much better-established effects on the chances of conceiving:

Age. It can't be changed, but it should shape how soon you seek advice.
Smoking. It affects the fertility of both partners, and stopping is the single most worthwhile step.
Weight. Both a high body weight and being underweight can disrupt ovulation.
Alcohol. Cutting down is advisable for both partners.
Heat. Testicles work best slightly cooler than the body, so very hot baths and laptops on the lap are worth avoiding.
Timing. Knowing your fertile window is the most underused tool of all. Sex in the days leading up to ovulation counts for more than how often you have sex overall.

Why this market promises so much

Three features make fertility an easy place for bold claims. First, most couples conceive without help: around eight in ten within a year, and many of the rest during the second year. Any product started during that wait will tend to take the credit for a pregnancy that would often have happened anyway.

In a prospective German study of 346 women timing intercourse with natural family planning methods, Gnoth et al. (2003) found that the cumulative chance of conceiving was 38% after one cycle, 68% after three, 81% after six and 92% after 12. The authors concluded that most couples conceive within six cycles of well-timed intercourse.

Second, the emotional stakes are high, which makes price feel secondary and comparison hard. Third, it is easy to move the goalposts: a change in a semen test or a hormone level can be shown quickly, while a live birth needs time and a large trial.

None of this means you shouldn't try anything. It simply makes sense to decide in advance on a time limit, a budget and what would make you stop, and never to let supplements delay seeing a doctor.

When to see a doctor

The usual guidance is to see your GP after a year of regular unprotected sex without a pregnancy, or after six months if the woman is over 35. Go sooner if periods are very irregular or absent, if either partner has had pelvic or testicular surgery or problems, or if endometriosis or another relevant condition is known. Seeing a doctor commits you to nothing. A few simple tests often point the way quickly, and some causes respond well when they are found early. Time matters here, which is the best reason not to spend it working through one supplement after another. Your GP can refer you to a fertility specialist if needed.

How to read a fertility supplement label

Three checks are worth making:

The folic acid dose. This is the ingredient with real evidence, so check that it matches the standard 400 µg rather than a token amount.
Vitamin A. In pregnancy, high doses of vitamin A in the form of retinol can harm the developing baby. Avoid supplements containing retinol, don't combine several products, and avoid liver and liver products such as pâté.
The length of the ingredient list. Twenty ingredients at tiny doses is a marketing argument, not nutrition.

Herbal products deserve particular care. Many have not been tested for safety in pregnancy, and some can interact with fertility medicines. Check with your doctor, fertility clinic or pharmacist before taking any herbal remedy while trying to conceive or once you are pregnant.

One last point for both partners: supplements add to your diet; they don't replace it. A varied diet, decent sleep and regular physical activity belong to the same plan, and they cost nothing.

Frequently asked questions

Which fertility supplement actually has evidence behind it?

Folic acid. Folic acid supplementation increases maternal folate status, and the standard advice is 400 µg a day before conception and for the first 12 weeks of pregnancy. Its value relates to the pregnancy that follows rather than to fertility itself.

Does CoQ10 improve fertility?

One randomised trial found better ovarian response and embryo quality in younger women with poor ovarian reserve having IVF, but no significant difference in pregnancy or live birth rates. The result can't be applied to natural conception, so discuss it with your fertility clinic if it interests you.

Do antioxidants help male fertility?

Several trials report changes in semen test results. Whether this leads to more live births has not been established, and the largest trial of folic acid and zinc in men found no difference in live births. Zinc contributes to normal fertility and reproduction, and selenium contributes to normal spermatogenesis, which is why an adequate intake matters.

When should I start taking folic acid?

When you stop using contraception, not when you find out you are pregnant. The baby's neural tube forms in the first weeks of pregnancy, often before the pregnancy is known.

What makes the biggest difference when trying to conceive?

Age, not smoking, a weight that is neither too high nor too low, cutting down on alcohol and knowing your fertile window. Sex in the days before ovulation counts for more than frequency overall.

When should we see a doctor about trying for a baby?

After a year of regular unprotected sex without a pregnancy, after six months if the woman is over 35, and sooner if periods are very irregular or there is a relevant medical history in either partner. A few simple tests often clarify things quickly.

References

De-Regil LM, Peña-Rosas JP, Fernández-Gaxiola AC, Rayco-Solon P. Effects and safety of periconceptional oral folate supplementation for preventing birth defects. Cochrane Database of Systematic Reviews. 2015;2015(12):CD007950. PMID 26662928
Xu Y, Nisenblat V, Lu C, et al. Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in low-prognosis young women with decreased ovarian reserve: a randomized controlled trial. Reproductive Biology and Endocrinology. 2018;16(1):29. PMID 29587861
Showell MG, Mackenzie-Proctor R, Jordan V, Hodgson R, Farquhar C. Inositol for subfertile women with polycystic ovary syndrome. Cochrane Database of Systematic Reviews. 2018;12(12):CD012378. PMID 30570133
Showell MG, Mackenzie-Proctor R, Jordan V, Hart RJ. Antioxidants for female subfertility. Cochrane Database of Systematic Reviews. 2020;8(8):CD007807. PMID 32851663
de Ligny W, Smits RM, Mackenzie-Proctor R, et al. Antioxidants for male subfertility. Cochrane Database of Systematic Reviews. 2022;5(5):CD007411. PMID 35506389
Schisterman EF, Sjaarda LA, Clemons T, et al. Effect of folic acid and zinc supplementation in men on semen quality and live birth among couples undergoing infertility treatment: a randomized clinical trial. JAMA. 2020;323(1):35–48. PMID 31910279
Gnoth C, Godehardt D, Godehardt E, Frank-Herrmann P, Freundl G. Time to pregnancy: results of the German prospective study and impact on the management of infertility. Human Reproduction. 2003;18(9):1959–1966. PMID 12923157

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