Antioxidants and oocyte maturation: rethinking their potential in IVF

In the field of in vitro fertilization (IVF), one of the most commonly used indicators to evaluate a cycle has traditionally been the number of oocytes retrieved, but this metric doesn’t always reflect the true reproductive potential. A significant portion of these oocytes—around 20%—do not reach full maturation by the time of follicular puncture, and are typically discarded in clinical practice.

Far from being irrelevant, these immature oocytes represent a clinical opportunity. Recent research by IVI, presented at the 42nd Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE), is offering new strategies to improve their quality and open up fresh possibilities within assisted reproduction treatments.

Table of Contents

Can oocyte quality be optimized?

Optimizing the quality of available oocytes is one of the main challenges in reproductive medicine, especially in patients with a low ovarian response, where each oocyte can spell the difference between a successful and a failed treatment.

“For years, we thought immature oocytes had chromosomal abnormalities, but today we know these oocytes are genetically normal. The difference lies in their internal functioning,” explains Dr. Marga Esbert, the research coordinator at the IVF laboratory at IVI Barcelona.

This shift in focus has driven research toward more complex aspects of cell biology, including gene expression, energy metabolism, and the conditions under which oocyte maturation occurs, both within the ovary and in the laboratory.

Analyzing each oocyte: the value of single-cell sequencing

A key advance in this field has been the application of single-cell RNA sequencing. This technology allows us to study each oocyte individually, overcoming the limitations of previous analyses, which were based on cell groups and yielded less precise results.

Thanks to this methodology, it has been possible to observe in great detail how gene expression evolves during the maturation process. In particular, natural maturation has been compared with in vitro maturation, revealing crucial information about the differences between the two.

The results indicate that oocytes that complete maturation in the laboratory retain the fundamental mechanisms of meiosis intact. In other words, at the nuclear level, the process unfolds properly. Differences emerge in other cellular components, however, particularly in the cytoplasm.

The role of the cytoplasm

The most significant differences between naturally matured oocytes and those matured in vitro are linked to three key factors: oxidative stress, mitochondrial function, and the organization of the cellular environment.

Mitochondria play a crucial role in this context, as they are responsible for generating the energy needed to complete oocyte maturation and support early embryonic development. Any disruption to this energy system can directly impact the viability of the oocyte.

When there’s an energy imbalance, oxidative stress rises, potentially damaging cell structures and compromising the oocyte’s potential. Under physiological conditions, the oocyte develops surrounded by support cells within the ovary that help maintain this balance. However, during in vitro maturation, this protective environment disappears, exposing the oocyte to less favorable conditions.

Are antioxidants the solution?

This deeper understanding leads to a clear hypothesis: if the main problem lies in oxidative stress and mitochondrial dysfunction, could the quality of oocytes be improved by modulating their environment during in vitro maturation?

To answer this question, researchers have evaluated antioxidant supplementation in laboratory-matured oocytes. The compounds used include resveratrol, melatonin, and coenzyme Q10, all known for their ability to protect cells from oxidative damage.

The results obtained are particularly relevant. Adding antioxidants not only regulates gene expression in the oocyte, but also enhances cellular pathways involved in defending against oxidative stress, and optimizes key metabolic processes.

One of the most significant findings is that these treated oocytes exhibit a molecular profile resembling that of naturally matured oocytes, suggesting a partial recovery of their biological functionality.

Impact on patients and clinical practice

Although these results are still in the research phase, their clinical implications are broad and promising.

In patients with low ovarian reserve, where the number of retrieved oocytes is limited, improving the quality of those currently discarded could significantly increase the chances of success.

In cases where multiple stimulation cycles are not possible—such as with cancer patients—making the most of every available oocyte is crucial.

This approach allows us to rethink the role of immature oocytes, which are no longer seen as disposable material, but rather as a potential source of viable embryos.

From research to the clinic: next steps

Despite the interest in these findings, their impact on specific clinical outcomes still needs to be validated. Future studies will need to determine whether the improvements observed at the molecular level translate into real benefits, such as:

higher fertilization rates
improved embryonic development
a higher proportion of euploid embryos
higher pregnancy rates

Conclusions

Overall, this advancement reflects an evolution in how IVF is understood. The focus is no longer solely on the number of oocytes obtained, but also on their quality and the conditions that shape their development.

The ability to address factors like oxidative stress brings a new level of precision to treatments, making it possible to design more personalized strategies tailored to each patient’s needs.

In this context, antioxidants are emerging as a tool with great potential to improve oocyte maturation and contribute to more efficient IVF, optimizing the available biological resources to the fullest.