Antioxidants in female infertility

WRITTEN BY: HASINI SANDEEPA RANASINGHE CLASS OF 2024

Antioxidants are like tiny superheroes, swooping in to rescue faltering fertility, when in reality, they are merely diligent assistants in the complex symphony of reproductive well-being, offering support but not miracles.

Antioxidants are chemical substance that inhibits oxidation or slow down the damage that caused by oxygen to organisms. Vitamin C or E are antioxidants that potentially remove damaging oxidising agents in a living organism. Female infertility is a condition woman who is in reproductive stage failure to achieve pregnancy after 12 months or more after unprotected sexual intercourse, affecting 48 million couples worldwide nowadays.

In female reproduction oxidative stress plays a major role in ovulation, endometrium decidualization, menstruation, oocyte fertilization, and development and implantation of an embryo in the uterus. The physiological concentration of reactive forms of oxygen and nitrogen as redox signal molecules regulate the menstrual cycle, trigger and regulate the length of individual phases of the menstrual cycle.

Low level of reactive oxygens have a significant signaling role in ovulation and in the endometrium of the uterus (decidualization, healing after the menstrual phase without scarring), and thus in fertility. It stimulates energy production, angiogenesis,and regulates the inflammatory response in the female menstrual cycle.

Recent research has found that the decline in female fertility is modulated by pathological oxidation stress. It may trigger many disorders of female reproduction which could lead to gynecological diseases and to infertility.

Therefore, antioxidants are crucial for proper female reproductive function. It acts in the metabolism of oocytes, in endometrium maturation via the activation of antioxidant signaling pathways and in the hormonal regulation of vascular action.

Disruption in redox signaling pathways in females can lead to the development and progression of gynecological, immunological, and hormonal disorders that lead to subfertility and infertility.

One of the main tools for improving the female fertility rate is to decrease/normalize OS conditions to the physiologically desirable level and create a reproductive-friendly microenvironment via the right lifestyle and supplementation of antioxidants.

For successful implantation requires elevated ovarian hormones in secretory phase of the menstrual cycle. This process occurs under specific physiological levels of reactive nitrogen and oxygen species related to the signals for interaction in the decidualized uterine endometrium, which is later exposed to extensive changes in oxygen tension during fertilization and pregnancy.

Ovulation, oocyte maturation, ovarian steroidogenesis, luteolysis, luteal maintenance in pregnancy , the development of follicles and blastocysts, and blastocyst implantation as well as embryo development are regulated via reactive oxygen and nitrogen species which fulfill the role of signaling.

In Vitro experiments have clearly emphasized , that deficiency of ovarian glutathione accelerates antral follicles atresia, which leads to high sensitivity of antral follicles to oxidative Stress. It is the same for the process of fertilization and embryonic development. Recent studies have been found that higher ROS (Reactive Oxygen Species) values in women with unexplained infertility, when compared with their fertile counterpart. The natural accumulation of Free radicals with age can very well explain the poorer quality of oocytes encountered in females of advanced age.

Recent research relives that oxidative stress could be the key factor for the pathogenesis and progression of the endometriosis in female which lead to infertility. Due to the linkage of endometriosis with retrograde menstruation , the peritoneal iron overload impairs the functionality of protective immune cells, rather than simply implantation of shaded endometrium. In metabolism of hemoglobin , iron is released which considered as a toxic substance, that will trigger a series of reactions that ultimately generate free radicals which are toxic to the sperm and impair its motility, in addition can arrest embryo development, which explains the infertility in patients with early-stage endometriosis. If more free radicals are generated in endometriosis, toxically it may be effect on oocyte.

In polycystic ovarian syndrome, insulin resistance is encountered in approximately 50% - 70% in patients with PCOS. Deficiency of antioxidants is the responsible for reducing the sensitivity of insulin receptors. As a result, compensatory hyperinsulinemia which augments luteinizing hormone, subsequently androgen production is increased either via its own receptors or via insulin growth factor

Administration of vitamin C to women with a luteal phase defect increased the level of progesterone in serum and the pregnancy rate. Due to increased oxidation stress during the fertilization process and oocyte maturation, antioxidants are crucial for the proper functioning of female reproduction.

So, imbalance between excess of reactive oxygen species and lack of antioxidants could negatively affect female fertility. Normally, the selected naturally occurring antioxidants show improvement in the endometrial thickness of the uterine lining which is very important for the successful implantation of the embryo. Supplementing with antioxidants during the treatment of infertility might get a good prognosis of assisted reproduction techniques. Some antioxidants are promising in preventing pre-eclampsia and preterm birth. The administration of antioxidants to patients with reproductive disorders such as PCOS, endometriosis, or functional hypothalamic amenorrhea improved the course of the diseases.

However, not all antioxidants are recommended for pregnant women.