It has been suggested that oxidative damage may lead to damage to gametes (sperm and eggs), which in turn may affect future fertilization and embryo development. The specific mechanism may be related to altered chromosomal epigenetic patterns and altered chromatin agglutination status, among others. A good one-carbon cycle and glutathione synthesis in the body can cope well with oxidative damage. However, some people may have abnormalities or defects in the enzymes of these two pathways and are not able to perform antioxidant defense well, so one of the manifestations is infertility. Scientists studying the one-carbon cycle, glutathione synthesis and antioxidant defense system have identified some essential substances, including vitamins B2, B3, B6, B9, B12, chelated zinc and cysteine. They configured them into a dose of a nutritional supplement and studied 88 couples with a history of multiple failed assisted reproductive technology treatments in which the male partner had a sperm DNA fragmentation index and/or a sperm nuclear decondensation index greater than 20%, and found that supplementation with this supplement resulted in significant improvements in both of these indicators in the male partner’s sperm, and encouraging clinical outcomes: 18 couples (21% ) conceived spontaneously and gave birth to children. The remaining 66 couples were re-treated with assisted reproductive technology and 22 couples had clinical pregnancies, 15 of which resulted in births. The overall clinical pregnancy rate was 47.6% and the live birth rate was 39.3%. A later study in a group of infertile couples in the presence of a female factor found that the supplement also improved oxidative damage in female infertility. Of course, the report also noted that the relatively small sample size may not be convincing enough, and that some of the infertile couples involved in the study may have been accompanied by metabolic disease. So why not just use an oral antioxidant? Some studies have shown that some antioxidants are too strong and, in addition to neutralizing oxidative reactions, may put cells in a state of reductive stress, which would also damage cells and be detrimental to further gamete maturation. So how can we determine if our antioxidant defense system is normal? First, let’s talk briefly about its mechanisms. There are many different enzymes involved in the one-carbon cycle and glutathione synthesis, and the genes corresponding to the enzymes may be abnormal or defective, resulting in abnormal function or loss of function of the enzymes, which in turn affects the antioxidant defense of the cells. However, it has been found that some people can still perform antioxidant defense better despite having abnormal or defective enzymes. The reason for this is because of the supplementation of dietary sources of nutrition, such as folic acid, which, after consuming the right amount of folic acid, no longer needs the corresponding enzymes to function to synthesize folic acid, so when the enzymes become weak or non-functional, the reduced form of folic acid from food can still complete this pathway. We can know that there is no need to look up the relevant genes, because there are too many genes involved to make a definite judgment even if we do. Among them, homocysteine is one of the products of these two pathways, and if hyperhomocysteinemia is present, it may indicate abnormalities in the antioxidant defense system, so it is simpler and more feasible to check serum homocysteine. Since the antioxidant defense system is so important, how did those with enzyme deficiencies survive until now? This is the result of the interaction of genes, environment and dietary habits. Scientists have found that people with a defective enzyme, MTHFR, have cells that cannot synthesize reduced folic acid, so the antioxidant defense is theoretically diminished. These people have a Mediterranean diet, which is rich in soluble, reduced-state folate such as lettuce, beans, tomatoes, and broccoli, i.e., they get their antioxidant defense from food, so they are not affected by the enzyme defect. But if they change their Mediterranean diet, the clinical symptoms of enzyme deficiency will manifest themselves. As another example, meat is richer in vitamin B12 and zinc, and long-term vegetarians develop hyperhomocysteinemia, despite adequate folic acid supplementation, suggesting a weakened antioxidant defense. Long-term vegetarians also have a higher incidence of infertility and sterility. As you can see, the richer and more diverse the food intake, the better our antioxidant defense system functions. Some of you reading this may think of buying a lot of these vitamins or trace elements to take. But it is important to be careful not to overconsume. It is likely that different products contain the same ingredients and it is easy to overdose when used at the same time. And overconsumption of these vitamins or trace elements may be counterproductive. For example, excessive intake of folic acid may lead to metabolic disorders, immune system disorders, and even tumors. As you can see, the best way to get all the nutrients you need is from a balanced and comprehensive diet. Oxidative damage is more dangerous and may lead to reduced fertility of eggs or sperm, abnormal fertilization or reduced potential for future embryonic development. Oral antioxidant therapy is sometimes too strong, especially when used in excess, and can lead to environmental imbalances in the body. Current research has found that supplementation with vitamins B2, B3, B6, B9, B12, chelated zinc, and cysteine may have beneficial effects on antioxidant defenses. However, it is still difficult to assess whether there is a deficiency in the antioxidant defense system and genetic screening is difficult; primary screening using blood homocysteine may be considered. Abuse of folic acid, etc. is harmful to health and it is recommended that it should not be overused and should be supplemented with more dietary intake. There is no one suitable supplement for all people, and a balanced diet is the best way to ensure that the antioxidant defense system is working properly. A vegetarian or high protein diet can lead to an imbalance in the internal environment. As you can see, a balanced and comprehensive diet is very important for infertile couples, as it is likely to improve the quality of eggs and sperm, improving pregnancy outcomes and giving you a healthy baby!