Fertility

Allegory to the fertility of Valeriano Salvatierra at the Museo del Prado (Madrid)

Fertility is the ability of a living being to produce numerous offspring. This is the result of the interaction of several factors, both biological: age, state of health, the functioning of the endocrine system, as well as cultural, prescriptions regarding sex and marriage, the sexual division of labor, the type and rhythm occupation, which makes it vary spectacularly between different situations.

Human fertility has historically been a culturally significant issue. As children are a crucial source of labor in agrarian or subsistence economy societies, the ability to provide the family nucleus with numerous offspring was a highly valued trait in women, and in many traditions the husband was authorized to annul the marriage. marriage to a barren wife. Male sterility, with a similar frequency, remained unknown for a long time, attributing responsibility for reproduction only to women, as part of the bias towards the dignity of women generally since ancient times.

In sociology, the fertility rate, measured as the number of children per woman, has been used as a reliable estimator for the natural growth of the population.

Preservation of fertility in humans

In the case of patients with serious pathologies (such as cancer) who are subjected to aggressive treatments to achieve remission of the disease (radiotherapy, chemotherapy), a frequent side effect is the loss of reproductive capacity, due to the destruction of the tissues that produce gametes, sperm or eggs. Therefore, a growing concern in these patients is the possibility of preserving their fertility, to maintain their reproductive capacity after the disease has been overcome. In the male case, the simplest solution is sperm cryopreservation, a perfectly developed technique that allows the patient to maintain reproductive capacity, although using assisted reproduction techniques. In the female case, the situation is more complex, due to the lower rate of egg production per cycle, the difficulty of extracting them, and the greater complication in cryopreservation techniques.

In recent decades the incidence of cancer has increased, but in parallel the survival rate has greatly improved: for example, in the last 25 years, the 5-year relative survival rate for all types of cancer has risen from 56% to 64% in female patients, so fertility preservation needs also increase. Breast cancer is the most common tumor in Western women (accounting for 65% of all tumors and 99% of cancer-related deaths), while Hodgkin's disease (HD) is the most common solid tumor in adolescents. For this reason, patients with these two types of cancer are possibly the most likely to resort to fertility preservation techniques.

Fertility preservation options for women include:

cryopreservation of embryos

for this, it is necessary to obtain eggs from the woman, fertilize them through in vitro fertilization (IVF) and freeze the embryos for their subsequent implantation in the woman's uterus; In this case, either the woman has a stable partner or an anonymous donor must be used, which can be inconvenient. This is the most frequently used method, with a 40% success rate.

cryopreservation of ovarian tissue

removing and freezing ovarian tissue from the woman for reimplantation after cancer treatment; in this case the main potential complications are the cryopreservation procedure (which does not appear to be the limiting factor), and the risk of ischemic damage, although techniques to reduce such complications are being successfully developed. Development-wise, researchers are still working on the best way to connect the implanted ovarian tissue to the blood supply, although some children have already been born using this technique, which is the most promising in the case of young girls with fertility problems.

ovarian deletion

hormone treatments to protect ovarian tissue during chemotherapy or radiation therapy.

ovarian transposition

repositioning of the ovaries through surgery, to move them away from the area of exposure to radiotherapy.

Conservative gynecological surgery

for example, removal of the cervix by surgery, but maintenance of the uterus.

A final technique that has been developed is oocyte vitrification, which can be used in clinical situations where other options are feasible. Although hundreds of children have been born after egg vitrification, the clinical pregnancy rate per donation cycle is 48.8%. However, this rate is expected to improve considerably in the coming years.

The choice between the different options depends on several parameters: the type and time at which cancer therapy should be started, the type of cancer, the patient's age and the patient's relationship situation.

Relation between alcohol and fertility

Alcohol is one of the most widely consumed substances. There are more and more studies linking alcohol consumption with decreased fertility in both men and women.

In men, according to a study by the University of Southern Denmark, it has been shown that the concentration of semen and the number of spermatozoa decrease as the consumption of alcoholic beverages increases. This is reflected with consumptions as moderate as 5 units of alcohol per week. In more severe cases, a decrease in libido, impotence and testicular atrophy could even occur.

Women, as a general rule, are more susceptible to the deleterious effect of alcohol (because they have a faster gastrointestinal absorption, a slower metabolization through the alcohol dehydrogenase enzyme, as well as the expression of said enzyme in less quantity in women). It is estimated that a daily consumption of 2-3 alcoholic beverages (140g per week) in women multiplies the risk of infertility by 1.6. It is also related to ovulation problems (since the hormonal regulation that leads to the achievement of a normal ovarian cycle can be altered), with a higher abortion rate and worse perinatal prognosis if consumption continues (premature births, low birth weight). birth, fetal death and the so-called fetal alcohol syndrome).

Studies on the results of assisted reproduction treatments have observed that the results of the treatment are worse the more recent the consumption. Thus, couples who are going to start assisted reproduction treatment must stop drinking alcohol at least 3-6 months before any procedure.

Eating disorders and fertility

Eating disorders are psychological and medical illnesses that can negatively affect reproductive health. According to data from the Association for the Fight against Bulimia and Anorexia (ALUBA) published in 2010, although these diseases have a higher incidence in adolescence, the age of onset is increasingly younger and in recent years the cases have tripled of these disorders among young men.

In women, the most frequent infertility problems associated with eating disorders are:

• Threat
• Irregular menstrual cycles
• Enough egg quality
• Ovarian disorders or problems
• Inappropriate or unfavourable uterine environment
• Spontaneous abortions

It should be noted that the reproductive system is very sensitive to the physiological stress that eating disorders can entail. Once the ideal weight is recovered, amenorrhea can persist in some cases because it is not always enough for the body to recover all of its reproductive functions. However, in general, when people stop restricting caloric intake, menstruation normalizes and they can even achieve a spontaneous pregnancy. In the case of men, obesity can also cause erectile dysfunction and a decrease in the frequency of sexual intercourse. We can affirm that ten extra kilos in men increase their infertility problems by 10%. In addition, high-fat food raises testicular temperature and damages male germ cells.

Therefore, having a good diet has a positive influence on fertility. In fact, adherence to anti-inflammatory diets such as the Mediterranean diet (specifically, a higher intake of n-3 monounsaturated and polyunsaturated fatty acids, flavonoids, and a lower intake of red and processed meat) improves fertility, assisted reproductive technology (ART) success and sperm quality in men. Ultimately, the integration of anti-inflammatory dietary patterns as adjunctive low-risk fertility treatments may partially or fully improve fertility and reduce the need for prolonged or intensive pharmacological or surgical interventions.

Sports and fertility

The effect of sport on fertility depends both on the biological sex of the person and on the type of sporting activity and its intensity. In men, the sports that most affect fertility are:

• Motor sports: in different studies high scrotal temperatures are observed that produce altered and even inhibited spermatogenesis, as well as a reduced sperm count. This does not have to be strictly related to a substantial impact on fertility. Cycling is highlighted, as it is one of the most problematic activities for fertility due to the mechanical impact that occurs when sitting on the saddle, overheating gonadal and wearing tight clothing. All of this has been associated with abnormal sperm morphology and reduced motility.
• Athleticism: Running a minimum average distance of 108 km/week for 12 months has been associated with reductions in several parameters of the semen, as well as the concentration and motility of the sperm and the number of round cells. Below these values of distance and time, there are no modifications. There can be a recovery period where the values become normal, and can reach the initial figures.
• Montañismo: short exposure (5 days) to hypoxia combined with exercise did not significantly alter the parameters of the sperm, but produces a marked reduction in the motility of the same.

In women, clinical trials conducted to date suggest that regular physical activity positively affects female fertility and the health of offspring, although this effect appears to depend on exercise intensity. Furthermore, high-intensity exercise with exhaustion was associated with a 2-fold increased risk of fertility problems compared with low-intensity exercise. In women who perform high-intensity exercise, menstrual irregularities occur, with a higher prevalence of amenorrhea, anovulation, and luteal phase deficiency. However, low or moderate intensity exercise seems to show beneficial effects on pregnancy, which could be due to differential expression of endometrial proteins. For all these reasons, moderate intensity exercise could be suggested to improve female fertility. Therefore, it can be stated that in both sexes performing high-intensity sports produces negative consequences, while performing sports of medium or low intensity produces positive consequences for fertility.

Anabolic androgenic drugs and fertility

In athletes who abuse anabolic androgenic drugs (AAS), low or normal concentrations of gonadotropins and low concentrations of testosterone are usually observed.

In men by immunohistochemical findings, articles suggest that there is decreased steroidogenesis in testicular tissue, a specific impairment of end-stage spermatogenesis, with a lack of advanced forms of spermatids. After discontinuation of ASA administration, Leydig cells tend to proliferate, always remaining below regular counts. In addition, sperm analysis using the fluorescent in situ hybridization (FISH) technique revealed disomies of the XY sex chromosomes and of chromosomes 1 and 9. This is caused by abnormalities in the meiotic process and genetic damage due to the intake of these substances.. It is relevant to affirm that this process cannot be reversed by not administering this type of substance, being able to recover part of the decreased values, but never the initial values.

In women, ASA intake suppresses the release of gonadotropins from the pituitary gland through a negative feedback mechanism, either directly at the pituitary gland or indirectly by suppressing hypothalamic release of GnRH. This results in decreased serum levels of LH and FSH. Likewise, phenotypic characteristics such as hirsutism, decreased breast size or clitoral hypertrophy are observed.

Stress and fertility

There are numerous investigations that have shown that stress can promote long-term changes in multiple neurochemical systems, since it influences the reactions of various neuroendocrine axes such as the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-gonadal axis (HPG) or the sympathetic-adrenal-medullary system. They produce allostatic overload, that is, a change in the stability of important physiological systems with negative consequences for the release of sex hormones that can affect fertility.

Stress mainly affects women since it has been proven in different studies that most of them plan their fertility very meticulously as they do with their work objectives, lifestyle, contracting marriage, rigorous planning of the exact day you can get pregnant, etc. The inability to fulfill these social expectations can constitute a source of stress and tension that results in the deterioration of the woman's quality of life, directly affecting her fertility.

Despite these positions, in general, research is not conclusive when it comes to determining a causal relationship between stress and infertility, one of the reasons for this controversy being the heterogeneity of the criteria. However, they all support the following idea: "Although infertility causes stress, stress does not necessarily cause infertility."

Radiation and fertility

Ionizing radiation is radiation with sufficient energy to ionize matter, extracting electrons from their states bound to the atom. It mostly affects the female sex. An example of this type of radiation is radiotherapy, a technique used to eliminate certain types of tumors. In this therapy, the tumor and surrounding healthy tissues are irradiated, causing genetic damage in the cells included in this section. In some tissues, the damage is reversible, but in others, for example the ovary, despite the presence of genetic damage repair machinery, this damage is progressive and permanent. Mammalian oocytes have the enzymatic damage repair capacity to cope with and correct DNA modifications, although their role in repairing radiation-induced genomic damage remains unclear. This can cause:

• Deficient production of ovarian hormones
• Uterin dysfunction due to inadequate exposure of estrogen
• Premature menopause
• Infertility.
• Vascularization of altered uterine
• Decrease in volume and uterine elasticity
• Fibrosis and necrosis of myometrium
• Atrophy and endometrial insufficiency.

All of this depends on the age of the patient (the younger the patient is at the time of radiation, the greater the damage), the exposure dose, the exposure time and finally the associated chemotherapy. Children of cancer survivors were more likely to be premature and weigh less than 2,500 g, while the risk of birth defects or death was not increased. Several studies have demonstrated an increased risk of adverse pregnancy and neonatal outcomes associated with a history of abdominal irradiation. Non-ionizing radiation is defined as that wave or particle that is not capable of removing electrons from the matter that it illuminates, producing, at most, electronic excitations. These affect a greater proportion of men. In them, the use of mobile phones negatively affects semen quality by decreasing sperm count, motility, viability and morphology, which could contribute to male infertility. Furthermore, microwave exposure disrupts the seminiferous tubules and reduces the Leydig cell population and therefore the serum testosterone concentration. Many in vitro and in vivo studies demonstrated that non-ionizing radiation induced genotoxic single- and double-stranded DNA breaks, micronucleus formation, changes in gene expression, cell proliferation, and apoptosis. This all depends on the duration of exposure, the distance to the radiation source, the power density and the depth of penetration.

In women the effect of non-ionizing radiation is not yet well understood, but appears to be correlated with higher rates of miscarriage and birth defects

Oncological diseases and fertility

Cancer treatments aim to kill rapidly dividing cells in the body. However, although cancer cells stand out for it, they are not the only ones in our body that do so. An example of cells in our body that are affected, therefore, are sperm and their germ cells. In the case of women, the ovarian follicles (sacs where the eggs are found) are damaged and the body's normal production of hormones is disturbed. The infertility produced by these treatments in some cases is temporary, while it lasts, but it can also be irreversible. For all this, the preservation of fertility in reproductive age is especially important.