Obesity and fertility

On a global scale, there are more people who are obese than underweight. This finding occurs in every region worldwide with the exception of parts of sub-Saharan Africa and Asia. Previously, obesity and overweight were considered problems nearly exclusive to high-income countries; however, the prevalence of these health problems is now rising in low- and middle- income countries. Moreover, obesity and overweight are health issues which are more prevalent in urban areas compared to rural areas. It has also been shown that the risk of infertility amongst obese women due to disrupted ovulation is 2.7%. This increased risk persists for those who are classified as class 2 and 3 obese. == Women ==

Higher weights have been shown to impair fertility by inhibiting reproductive hormones. Obesity disrupts normal endocrine function, leading to irregularities in ovulation, endometrial development, and embryo development. Adipocytes (fat cells) secrete proteins and signaling molecules known as adipokines. Certain adipokines have been implicated in reducing fertility in women. Hormonal disruption In women with non-disrupted reproduction function, they hypothalamic-pituitary-ovarian (HPO) axis facilitates proper ovulation and egg implantation. Through producing gonadotropic and steroid hormones, the HPO is responsible for follicular and oocyte development. However, the regulatory functions of the HPO can be disrupted due to the up or down regulation of certain hormones in the setting of obesity. Insulin One such disruptor of proper HPO function is insulin. Obesity, particularly the presence of visceral fat (fat around the abdomen), is associated with an increased risk of insulin resistance. Insulin resistance refers to cell's reduced sensitivity to insulin, leading to the reduced ability to uptake glucose from the blood and high levels of circulation insulin. The elevated blood insulin levels can disrupt gonadotropin release. Insulin has been shown to increase androgen production, leading to hyperandrogenism. These androgens are converted to estrogen which exert negative feedback on the HPO, leading to down regulation of the HPO and limiting gonadotropin production. These reduced levels of adiponectin have also been associated with insulin resistance. Due to leptin's interaction with the hypothalamus to decrease appetite, therefore a mutation in the obese gene would result in an increased appetite, leading to obesity. Leptin has been found to be linked to the HPG axis as it can induce the release of gonadotrophin-releasing hormone (GnRH) by the hypothalamus and subsequently follicle stimulating hormone (FSH) and leutinising hormone (LH) by the anterior pituitary. Many women who have PCOS are also obese, and it is estimated that the prevalence of obesity in women with PCOS is 35 - 63%. PCOS diagnosis is defined by the Rotterdam criteria of having at least two of the following: polycystic ovaries, hyperandrogenism, and ovulatory dysfunction. Polycystic ovaries can be viewed by the ultrasound, and it will show multiple, small cysts in the ovaries. Some symptoms that people may experience with PCOS are irregular periods, acne, infertility, and excessive hair growth. PCOS is associated with excess levels of male hormones (androgens) or hyperandrogenism. Studies have shown that hyperandrogenism could be caused by a reaction between ovarian theca cells and reactive oxygen species. Hyperandrogenism in women results in menstrual abnormalities, insulin resistance, and ovarian dysfunction in the body. Currently, therapy is aimed at improving insulin resistance so that hyperinsulinemia is reduced and ovulatory features in women are improved. According to recent studies, insulin-sensitiser drugs are the main type of therapy for women with irregular cycles that want to improve their fertility, although weight loss is normally the first step in overweight women with PCOS. Stigma Apart from biological factors, social factors, such a stigma in health care environments, can limit care and desirable health outcomes. In health care settings, overweight and obese women experience weight-related stigma. Surveys have demonstrated that health care workers view overweight and obese individuals as more lazy, less intelligent, and more self-indulgent than individuals with smaller body sizes. These attitudes may limit overweight and obese women's ability to receive high-quality care or limit their desire to become connected to care due to disrespectful treatment by providers. This stigma and reluctance to provide high quality care has been suggested to exacerbate problems of infertility in those who are overweight or obese. Due to the perceived biological associations between excess body fat and infertility, overweight and obese women's inability to conceive can be pre-judged by health care providers. Women who are overweight and obese report that their infertility is attributed solely to their excess body weight and that providers may be unwilling to treat infertility in women who are overweight and obese until they lose weight. Of note, no formal guidelines exist from the American Society for Reproductive Medicine or the Society for Assisted Reproductive Technology that dictate when women should receive fertility treatment based on weight. Rates of mood disorders are even higher among women who are treated via in vitro fertilization (IVF) and increase further upon IVF failure. Mood disorders, as well as medications used to treat mood disorders, can exacerbate hormonal and menstrual dysfunction, worsening outcomes of infertility management. == Men ==

Numerous studies show the association between obesity in men and infertility. In the developed world, the temporal trend for the reduction in sperm parameters (sperm count, motility, morphology, volume, fructose level, and pH) reflects the increasing prevalence of obesity. The reproductive potential of men who are obese can be attributed to changes in hormone levels which regulate spermatogenesis, increased temperatures in the testicles, the accumulation of environmental toxins in adipose tissue, and increased levels of oxidative stress as well as a higher incidence of erectile dysfunction. This affects the quantity and quality of a man's sperm. Obese men have increased risk of oligozoospemia, having fewer than 15 million sperm per millilitre of semen, and far fewer motile sperm than men of lower weight. Sperm with high amounts of damaged DNA are significantly more common in obese men than in normal weight men. Ejaculate volume is also affected. Altered male hormones can also lead to erectile dysfunction which is the major cause of infertility in obese men. Increased Temperatures in Testicles Gonadal heat can rise with an increase in fat or adipose tissue in the scrotum. Thus, obesity may contribute to altered production and parameters of sperm due to an increase of heat in the testicles. Other studies report sleep apnea decreases the quality of sex and increases the likelihood of erectile dysfunction. The collection of all of these factors may contribute to the overall decrease in fertility. Metabolic Syndrome Metabolic syndrome is a dysfunction of energy utilization and storage. It is diagnosed based on having at least three of the following criteria: high fasting blood glucose levels, high triglyceride levels, low high density cholesterol (HDL) levels, high blood pressure, and abdominal obesity. Metabolic syndrome has been associated with harmful effects with fertility. People with metabolic syndrome can have high insulin levels (hyperinsulinemia) and high blood glucose levels (hyperglycemia ) decreasing sperm quantity and quality, which can increase infertility. Research demonstrates that metals and chemicals present in air, water, food, and health/beauty products are associated with a reduction in fertility and have potential to cause infertility in males via decreasing sperm count and function. Men who consumed fruits and vegetables with high levels of pesticide residues had a lower total sperm count as well as a lower percentage of morphologically normal sperm. Moreover, a United States study which enrolled 501 participants found a significant association between infertility and blood lead levels in men. == Management ==

Female Preventing or treating obesity in women has a positive effect on fertility rates. As simple as modifying lifestyle choices in order to lose weight could lead to a recovery in fertility decline. Taken into consideration firstly must be the weight of the individual before investigating further into complications surrounding fertility. Initially, treatment should proceed for obesity, then if complications still arise with infertility then progression onto ART is required. Women with PCOS Management for obese women with PCOS follows a relatively step-wise approach, but can be individualized based on the person and their unique needs. Weight loss is normally the first option for overweight women with PCOS. Multiple studies have illustrated the marked improvement in endocrine profile, menstrual cycle, rate of ovulation, and likelihood of healthy pregnancy amongst women who have lost weight. The amount of weight lost does not need to be drastic in order for women to reap the aforementioned benefits; indeed, with even only a 5% decrease in total body weight can lead to increased insulin-sensitivity and ovulation restoration. Thus, for overweight women with anovulation and PCOS, lifestyle modifications are important, and are very often an integral part of the treatment plan to relieve PCOS symptoms. These lifestyle modifications may include increased exercise and a diverse diet composed of fruits, vegetables, low-fat products, and lean meats. Following weight loss are insulin-sensitizing drugs. This class of drugs is the main therapy for women who experience irregular cycles, and want to improve their fertility. One example of an insulin-sensitizing drug is Metformin, which works by inhibiting the liver's production of glucose. The decrease in available glucose leads to less insulin secretion, and thereby increases insulin-sensitivity in cells. A systematic review of Metformin illustrated that it benefits women with PCOS in a myriad of ways: decreasing body insulin concentrations, lowering androgen levels, aiding in ovulation, and increasing positive reproductive outcomes. Even for women looking to utilize medications, weight loss should be encouraged to increase the likelihood of ovulation and ovarian response. In the United Kingdom, weight loss is advised for overweight women with PCOS, preferably to a body mass index of less than 30, before initiating drugs for ovarian stimulation. Another study on Metformin is more lenient, and suggests that women with obesity and PCOS should defer treatment with Metformin until achieving a body mass index of 35 or less. Treatment monitoring is more difficult in obese women because the ovaries become more difficult to see on ultrasound scans, potentially leading to oversight of multiple ovulations and pregnancies. Additionally, drugs like Metformin may be less effective in women with anovulation and extreme obesity, although this situation may simply justify a higher dose to be efficacious. Bariatric surgery - procedures that target the stomach and intestines for weight loss - is another option for obese women with PCOS. A small study of 17 women with PCOS revealed that a vast majority improved upon undergoing either biliopancreatic diversion or laparoscopic bypass. Additionally, other metabolic parameters - including insulin sensitivity and blood pressure - also improved in these women. Male Obesity in males leads to negative repercussions in fertility, sperm function, and overall health of the offspring. Fortunately, the effects of obesity on male fertility can be reversed, with either weight loss or testosterone therapy. Bariatric surgery is another option to improve sexual function in overweight men. In a randomized trial, bariatric surgery reduced BMI significantly more than lifestyle modifications, and ultimately led to a reversal in both erectile dysfunction and hypogonadism. Testosterone therapy may improve hormone imbalances and treat erectile dysfunction. the efficacy of these agents remains controversial, with particular concerns about the cardiovascular safety profile. Aromatase inhibitors - such as Letrozole - can be used in place of testosterone to overcome reduced testosterone levels commonly found in obese men. However, aromatase inhibitors are not without their own risks as well; there are concerns surrounding long-term aromatase inhibitor therapy due to its effect on bone health. == Animals ==

Cattle It is common practise for body condition scoring to be used in domesticated animals to assess the fatness of an animal and is often used by vets and livestock handlers to determine whether the animal need more or less energy. Both a low and a high score can reduce an animal's fertility. Cattle that are over-conditioned are also more insulin resistant compared to their leaner counterparts. As demonstrated in mice, insulin resistance is a factor in poor fertility as it has an effect on oocyte development. This in turn means that less oocytes are suitable for fertilisation and fertility is impaired. Another reason for decrease in fertility is to do with leptin. Leptin is a hormone which production is increased in obese animals. In cows, leptin can inhibit thecal cells from producing adrostenediol and progesterone. Androstenediol is important in fertility as it is the precursor to oestrogen. Without oestrogen production, the balance of hormones is affected and there is no LH surge which is required for ovulation. Domestic Fowl Domestic fowl has previously been researched on and it was found that by over feeding but not force feeding the male birds, there was no effect on fertility. However, more recently a study has shown that obesity induced by force feeding can affect the number of spermatozoa and their motility in the male birds. It was also found that in two of the three birds, there was a decrease in testosterone and an increase in LH which suggests the pathway of why there might be reduced spermatozoa. == References ==