Vit D and probiotic combo leads pack to combat rising infertility

According to market research firm Grand View Research, the global fertility supplements market was valued at roughly $2 billion in 2023 and is projected to reach $3.5 billion by 2030. Demand is linked to the rising prevalence of fertility challenges, which the Centers for Disease Control attributes to factors such as delayed childbearing, lifestyle choices and environmental exposures.

Common conditions affecting infertility include PCOS, endometriosis, fallopian tube issues, uterine problems, ovulation disorders, low sperm count, hormonal imbalances, thyroid disease, celiac disease and genetics.

A quick search on Amazon returns a selection of hundreds of fertility supplements, many of which contain a vitamin complex, omega-3 fish oil, folic acid, biotin, coenzyme Q10 and myoinositol. This aligns with Grand View Research’s data which identifies selenium, zinc, folic acid, vitamin C, vitamin B6, coenzyme Q10, and myo-inositol as some of the most in-demand synthetic ingredients.

In the UK, the Human Fertilisation and Embryology Authority reports that nearly three quarters (73%) of people undergoing fertility treatments (such as in-vitro fertilization) are using complementary therapies (such as supplements and emerging technologies) in an effort to improve fertility outcomes.

Despite the high demand and an ever-growing number of new products coming to market, the efficacy of fertility supplements is often questioned due to conflicting research, unproven claims and regulatory warnings about ineffective products. In 2019, the Center for Science in the Public Interest (CSPI) published a report that investigated 39 fertility supplements. It concluded that there was no evidence that any of the products improved the odds of conception.

Official guidance on fertility supplements is also limited. For example, in its latest guidance, the World Health Organization did not make any specific recommendations for or against the use of vitamins, minerals or other supplement ingredients for infertility.

What the science says

To inform new evidence-based recommendations for complementary therapies, public health policies and clinical guidelines, a recent review and meta-analysis assessed the effectiveness of different nutritional supplements in female infertility across 30 studies involving nearly 4,000 participants.

They reported that a number of dietary supplement ingredients—including vitamin D, probiotics, coenzyme Q10, curcumin and astaxanthin—can regulate the ovarian environment and enhance pregnancy outcomes in infertile women.

According to their findings, the combination of probiotics and vitamin D exhibited a particularly significant increase in clinical pregnancy rates, opening up new research avenues and opportunities for evidence-based recommendations.

Meanwhile, popular fertility supplement ingredients such as folic acid and myo-inositol were not found to significantly improve clinical pregnancy rates or fertilization rates.

“Some nutritional supplements may help improve reproductive outcomes, but the evidence for safety remains uncertain due to limited and heterogeneous data,” the researchers from Chengdu University of Traditional Chinese Medicine wrote in Reproductive Biology and Endocrinology.

“Particularly, the combination of vitamin D and other nutritional supplements, as well as the intake of coenzyme Q10, astaxanthin or curcumin, was more effective compared to other nutritional supplements. The results should be considered with circumspection, given the lack of direct comparative studies for most nutritional supplements.”

Combining vitamin D and probiotics for pregnancy outcomes

Despite folic acid being a popular supplement for women trying to conceive, the review reported that it did not significantly increase pregnancy rates or fertilization rates when taken alone or with myo-inositol. However, it is important to note that folic acid is typically recommended for the prevention of neurological defects rather than assisting with conception. L-arginine, melatonin, vitamin C and selenium were also found to be ineffective.

Vitamin D, on the other hand, was found to significantly enhance pregnancy rates in infertile women. This effect was observed both when vitamin D was taken alone or in combination with vitamin E or a probiotic, with the latter showing a particularly strong effect.

The mechanisms responsible for this effect are likely to be independent but complimentary, according to Ana Nunes, business unit director at Spanish probiotic product manufacturer Zinereo Pharma.

“The network meta-analysis highlights a potential benefit when vitamin D is taken alongside a probiotic,” she said. “In the study by Badihi et al., this combination was associated with improved outcomes in a very specific population of women with recurrent implantation failure and thin endometrium.”

“In this trial, the probiotic was administered vaginally, while vitamin D was taken orally as a separate supplement,” she added. “This means that the observed benefit does not depend on a combined formulation; it simply reflects the parallel use of two independent interventions that may act through complementary mechanisms.”

Vitamin D is well recognized for its role in reproductive health. Research shows that it may regulate hormones which affect reproductive maturation, improve the uterine lining’s readiness for embryo implantation and inhibit inflammation.

Probiotics, on the other hand, have only recently begun to be explored in the context of fertility, but there is a growing scientific consensus that the vaginal, endometrial and seminal microbiomes play a significant role in reproductive health, according to Nunes.

“Several studies have shown that imbalances in the reproductive microbiota are associated with reduced implantation rates, recurrent pregnancy loss and poorer IVF outcomes,” she said. “Conversely, a Lactobacillus-dominant, low-inflammation environment is associated with higher clinical pregnancy and live-birth rates.”

This finding led Zinereo Pharma to launch a patented Ligilactobacillus salivarius strain, marketed as Fertibiome, which has been shown to correct dysbiosis and restore Lactobacillus dominance, improving pregnancy and birth rates.

Fertibiome is one of a number of biotic fertility solutions which have come to market in the last few years, following a wave of new research highlighting the link between fertility and the microbiome.

However, the review did not find any statistically significant improvements when probiotics were taken on their own. Nunes suggests this may be due toheterogeneity in study methodologies which limits comparability across studies.

“Multiple recent reviews highlight the urgent need for standardized definitions of reproductive dysbiosis and harmonized methods for sampling and analyzing the vaginal and endometrial microbiome,” Nunes said. “Evidence linking microbiome composition with reproductive success is growing rapidly, but heterogeneity in methodologies limits comparability across studies.

“Better-designed mechanistic research is also required to clarify how restoring eubiosis supports endometrial receptivity, an association suggested by several indexed reviews in the last two years.”

Increasing ATP production to support fertility

Coenzyme Q10 was also shown to improve clinical pregnancy rates. This vitamin-like compound exists in two forms: ubiquinone (the oxidized form) and ubiquinol (the reduced form), with the latter more readily absorbed by the body.

Ubiquinol plays a pivotal role in ATP production—a process cells use to create adenosine triphosphate (ATP), the body’s main energy currency. It also acts as an antioxidant, protecting the body from reactive oxygen species and mitochondria from dysfunction, according to Fillip Van Hulle, general manager at Kaneka Nutrients Europe, which manufactures and supplies a patented ubiquinol ingredient.

“In the reproductive system, ubiquinol aids in the production of healthy sperm and eggs, as it supports the energy-demanding processes of cell division, DNA replication and fertilization,” he said. “By maintaining optimal mitochondrial health, ubiquinol ensures that the reproductive cells have abundant energy reserves, which can help promote fertility and reproductive success.”

The review also found that the combination of vitamin D and coenzyme Q10 significantly improved pregnancy rates compared to routine treatment, such as ovarian stimulation protocols.

The researchers suggest the combination therefore produces a synergistic effect, possibly by improving oocyte quality, endometrial receptivity or reducing oxidative stress, which are key factors for successful pregnancy.

“This finding suggests that there may be a potential avenue for improving fertility outcomes beyond standard treatment,” they wrote.

Antioxidants to support the follicular environment

Supplementation with astaxanthin also appeared to increase the number of mature oocytes (eggs) and good-quality embryos. This is likely due to astaxanthin’s antioxidant properties, which can reduce oxidative stress and inflammation, improving the follicular environment.

“Astaxanthin’s antioxidant properties help neutralize reactive oxygen species, preserving meiotic spindles, DNA and mitochondrial membranes, which are key factors for oocyte competence,” said Susan Hamrahi, scientific communications specialist at astaxanthin ingredient supplier AstaReal.

“By stabilizing meiotic structures and chromosomal alignment, astaxanthin may support the structural integrity needed for developmentally competent oocytes. It also activates the Nrf2 antioxidant pathway in granulosa cells, enhancing endogenous defenses and which may help maintain granulosa–oocyte signaling critical for maturation.”

Although these effects have been shown in multiple studies, the researchers on the review noted that the efficacy of astaxanthin in treating infertility has been investigated in relatively few studies, suggesting a need for further clinical research in this area to confirm whether the observed biochemical changes translate into improved pregnancy rates.

Commenting on the existing body of research, Megha Marwah, assistant general manager at AstaReal India, said that while existing studies provide compelling mechanistic evidence for astaxanthin’s role in supporting oocyte quality, neutralizing free radicals and maintaining early embryonic development, clinical research in this area remains limited.

“Observed improvements in the number of mature oocytes and high-quality embryos are promising, but consistent effects on live birth and pregnancy rates have yet to be firmly established,” she said.

Another antioxidant also showed promise for infertility. Curcumin demonstrated a substantial increase in the number of eggs retrieved, and a notable rise in the fertilization rate. It also showed the most pronounced effect for increasing the number of mature eggs retrieved from follicles.

In mice, curcumin has been shown to promote the proliferation and differentiation of granulosa cells (a type of ovarian cell) and the growth of oocytes. In-vitro treatment of human ovarian tissues with curcumin has also been shown to promote the survival and development of small human ovarian follicles, which could protect immature eggs during the growth process.

However, similarly to astaxanthin, the number of studies exploring curcumin for pregnant women is small, and the exact mechanism of action is unclear, suggesting the need for more research in this area.

In fact, the authors of the network meta-analysis suggested that more clinical trials are needed for each ingredient included in the review, given that the evidence for safety is uncertain due to limited and heterogeneous data.

“Further RCTs are needed to examine the effectiveness of these supplements and related mechanisms, and to report more safety-related outcomes,” they concluded.

Source: Reproductive Biology and Endocrinology. doi: 10.1186/s12958-025-01466-0. “Efficacy and safety of nutritional supplements in female infertility: a network meta-analysis.” Authors: J. Du, et al.