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WHO states that obesity poses one of the greatest threats to humanity as it has adverse effects on nearly every bodily system, causing complications in cardiovascular health, diabetes mellitus, oncology, and reproductive health. We not only discuss how obesity can impair fertility but also offer strategies for restoring reproductive function in individuals who are obese.
The adipose tissue is a complete endocrine organ
In the past, adipose tissue was considered a passive substance that simply stored and released energy as needed. However, recent clinical studies have revealed that adipose tissue is actually a fully functioning endocrine organ. It continuously produces adipokines such as adiponectin and leptin, which have an impact on the nervous, immune, and reproductive systems.
Abnormal levels of adipokines have been found in obese individuals, leading to various disorders including infertility. Additionally, adipose tissue synthesizes sex steroids, and an excess of fat in the body can cause hormonal imbalances and reduced fertility in both men and women.
Infertility in obese women: causes and effects
Reproductive health disorders affect 40-50% of women who are obese, and one in three women with a BMI above 30 experiences infertility problems.
Obese women often experience hyperestrogenism, which is characterized by an increase in estrogens within the body. Estrogens, responsible for female beauty, youth, and fertility, are synthesized from androgens with the aid of a specific enzyme called aromatase.
Estrogen hormone synthesis occurs in the ovaries, adrenal glands, and adipose tissue as androgen is converted into estrogen. However, excess weight can enhance aromatase activity, leading to an overabundance of estrogen.
Elevated estrogen levels lead to accelerated replication of adipose tissue cells, perpetuating the cycle of weight gain and hyperestrogenism.
Estrogens have a strong correlation with the hormones produced by the anterior pituitary gland, specifically follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH stimulates the growth and maturation of ovarian follicles, while LH triggers ovulation.
Typically, the pinnacle of LH coincides with follicular maturation: once the LH level reaches its peak, it causes the follicle to rupture, allowing the egg to enter the fallopian tube and be fertilized by sperm. However, when estrogen levels are elevated, an early LH surge occurs, which interferes with ovulation.
A high estrogen level can cause uncontrolled cell division, including the reproductive organs. It can, for example, lead to endometrial hyperplasia.
The endometrium is composed of several layers. The functional (surface) layer is where fertilized eggs are implanted, and pregnancy begins. An overgrowth of endometrial cells prevents the eggs from being implanted, leading to a failed pregnancy.
Due to hyperestrogenism, women experience delays in menstruation, which are replaced by prolonged menstruation, the formation of hormone-dependent tumors in the ovaries, and disruption of the normal cervix structure. Furthermore, excess estrogen can increase the risk of cancer.
An increase in the size and mass of adipose cells, fat accumulation in liver and heart tissues, and free fatty acids in the body are among the effects of obesity. The secretion of adipokines affects metabolic processes. The level of adiponectin, which increases tissue sensitivity to insulin – declines. All of this leads to insulin resistance and hyperinsulinemia.
It is important to note that insulin resistance does not affect all organs. For instance, the ovaries remain sensitive to insulin, and a pathological process begins in them in conjunction with hyperinsulinemia. By acting through their receptors, insulin and IGF-I (a protein with a similar function to insulin) increase the activity of androgen synthesis cells in the ovary, resulting in hyperandrogenism.
Having an excessive amount of androgen in the body can lead to abnormal organ function as well as diseases of the reproductive system. A frequent complication of hyperandrogenism is polycystic ovary syndrome, which causes poor ovulation or abnormal ovulation.
The high levels of leptin in obese women also destroy female fertility. There are leptin receptors in the ovaries, so it can affect their function. When leptin levels are high, ovulation is disturbed and the maturation of the dominant follicle slows down.
Obesity and infertility in men
Infertility rates increase by 20% for overweight men, by 36% for obese men, according to clinical studies.
Testosterone is the main male sex hormone. It is produced in the testicles and is responsible for producing sperm. With obesity, testosterone levels decrease for several reasons:
- Excess fat in the male body accelerates the transformation of testosterone into estradiol, a hormone from the estrogen family.
- In obese men, insulin resistance and hyperinsulinemia occur, resulting in a decrease in the liver’s production of SHBG (a protein that binds sex hormones), which results in elevated levels of estradiol.
- The concentration of leptin increases in obese men.
In clinical studies, excess estradiol and leptin inhibit testosterone production.
It has been observed in obese men that their sperm volume, concentration, and total number decrease significantly from the norm. Additionally, they have decreased sperm motility, which means they are not able to move in a straight line, which is essential for egg fertilization.
There is a 3.8-fold greater chance that obese men will have damaged sperm DNA than overweight or normal-weight men because obesity disrupts sperm DNA synthesis.
As a result of obesity, men’s scrotums become fattier, causing their testicles to overheat. A testicle can function normally at 34-35°C. Overheating disrupts sperm formation processes, which lowers sperm motility. Surgical removal of excess fat from the scrotum improves sperm counts, according to studies.
Men who are obese are likely to suffer from sleep apnea, a condition in which their breath is suspended for more than 10 seconds during sleep. In addition to negatively affecting male fertility, sleep apnea affects testosterone levels directly. Sleep apnea disrupts the deep stages of sleep, which are when this hormone is produced.
Several studies have shown that obesity is characterized by an inflammatory state in the body, caused by adipocytes continuously releasing inflammatory factors and causing oxidative stress. There are a number of diseases and disorders that can result from this, including sex hormone imbalance and reproductive organ cancer.
Among the most serious diseases of the male reproductive system is prostate cancer, which often leads to infertility and death.
Approximately 9 million men were evaluated by the World Cancer Research Foundation in a large-scale meta-analysis. According to the analysis, obesity increases the risk of prostate cancer and complicates its treatment. Systemic inflammation in obesity accelerates cancer cell growth, slows down their death, and makes tumors insensitive to chemotherapy.
Effects of obesity on assisted reproductive technologies in women and men
In assisted reproductive technologies (IVF, ICSI), obesity is an adverse prognosis. According to a meta-analysis of 6,500 IVF-ICSI cycles, obese women are less likely to succeed in implantation, pregnancy, and birth than women of normal weight.
According to studies, an obese woman has a 2.5 times greater risk of miscarriage compared to someone who is unweight, both with a natural and an artificial conception. It may be due to impaired decidua formation.
The decidua is a functional layer of the endometrium modified during pregnancy, which plays an important role in the implantation of the embryo, formation of the placenta, and nourishing and protecting the fetus. Its malformation causes miscarriage.
It is common for ART to cause complications such as ovarian hyperstimulation syndrome (OHSS). It occurs when hormones are introduced into the female body that stimulate superovulation. Due to this, the ovaries produce too much sex hormone, which damages the endothelium, increases vascular permeability, and allows fluid to flow from the vascular system into body cavities. OHSS can cause kidney failure, thrombosis, and respiratory disorders.
Researchers at Belgorod State University analyzed 671 IVF cycles and found that obese women are more likely to suffer from ovarian hyperstimulation syndrome than women who are normal weight. Young age and high levels of prolactin are also risk factors for OHSS, according to the researchers.
Researchers at the University of Adelaide conducted a study involving 305 couples going through an ART cycle. All couples were divided into 4 groups based on the father’s BMI. The sperm count in the ejaculate was much higher in men with normal weight than it was in men with excessive weight.
Among the couples with a man with a BMI greater than 35, ICSI was required more frequently. Classical IVF was not prescribed for any couple whose man had a BMI greater than 35.
A standard IVF procedure combines sperm and oocytes in a test tube, and fertilization occurs independently. During ICSI, the embryologist selects the most active sperm and injects it into the cytoplasm of the egg to increase fertilization chances. If a man has problems with the number and motility of sperm, ICSI is used.
Research was also conducted on the effect of paternal BMI on embryonic development and live births.
In normal-weight subjects, more embryos reach blastocyst stage than in obese subjects. From normal-weight fathers, children are born 2-4 times more often than from obese fathers.
Among obese infertility patients, weight loss is considered the gold standard
The modern medical field offers a wide range of methods to treat infertility, including hormone therapy, gene therapy, and surgery for reproductive organ anomalies.
In obesity, weight loss is the “gold standard” treatment. If a person does not lose weight, no treatment will work.
Compared to normal women, obese women do not respond well to infertility treatments. They require higher dosages of hormonal agents, and longer treatments with drugs to stimulate ovulation.
In clinical studies, weight loss significantly improves the fertility of women. Weight loss helps restore women’s normal cycles, aids in ovulation, improves endocrine function, which also affects reproduction.
With weight loss in men, testosterone levels increase, estradiol levels decrease, and sperm volume, count, and concentration increase.
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