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This application helps to propose an appropriate fertility therapy method and to find the most suitable clinic worldwide based on the price, duration and legislative options of the treatment in various countries.

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Toxin exposure treatments

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MACS  technique eliminates apoptotic sperms and may be indicated prior to ICSI, in order to guarantee that the injected spermatozoa are not damaged at a molecular level. Alternatively it could be combined with PICSI.

The externalization of the phospholipid phosphatidylserine (PS) to the sperm plasma membrane is a characteristic feature of the apoptotic phenomenon that occurs early during the process of sperm cell death. This basic knowledge has prompted investigators to develop a magnetic-based selection system for sperm cells that can separate early apoptotic from non-apoptotic germ cells (MACS).

Human sperm quality is defined by the classical parameters, concentration, motility and morphology, according to standard WHO diagnostic semen analysis. Nevertheless, hidden anomalies affecting spermatozoa membranes and causing apoptosis are present. Such features are not routinely detected in ejaculated spermatozoa but they have been proven to have a negative impact on ART outcome. Indeed, successful assisted reproduction is mainly dependent on the quality of the sperm plasma membrane, requiring normal integrity and function to provide motility, acrosome reaction, and fertilization. Spermatozoa with impaired membrane integrity occur more frequently in infertile men, partly explaining suboptimal results in assisted medical procreation. However, striking modifications of sperm plasma membrane occur physiologically in ejaculated sperm. During capacitation, there is a lipid remodelling of the sperm plasma membrane due to phospholipids translocation that lead to externalization of phosphatidylserine (EPS) and phosphatidylethanolamine, and to an albumin mediated efflux of cholesterol resulting in an increase in membrane fluidity.

Externalization of phosphatidylserine (EPS) on ejaculated mature spermatozoa is either the result of a plasma membrane modification because of capacitation and/or acrosome reaction or the sign of an early apoptotic phenotype. Apoptosis in ejaculated sperm is the result of a spermatogenetic failure, thus an abortive apoptotic process that started before ejaculation. 

Annexin V binding to spermatozoa characterizes modified sperm plasma membrane. MACS Technology uses annexin V-conjugated superparamagnetic microbeads (50 nm) to separate nonapoptotic spermatozoa from those with deteriorated plasma membranes with EPS. The spermatozoa/microbeads suspension is loaded on a separation MS column (specialized columns for MACS techniques) containing iron balls, which is fitted in a miniMACS separator (magnet), attached to a multistand. The fraction with intact membranes that passed through the column is labeled as MACS -negative fraction, depleted in phosphatidylserine (PS), whereas the fraction composed of apoptotic or deteriorated PS-positive membranes spermatozoa is retained in the separation column and labeled as MACS -positive fraction. After the column is removed from the magnetic field, the retained fraction is eluted using annexin V-binding buffer.

The positive fraction (called like this due to the fact that the spermatozoa stay retained in the magnetic columns because of their damaged DNA) will allow us to recover a negative fraction (made up of spermatozoa with unharmed DNA), with optimal sperm characteristics to be able to proceed. In other words, the spermatozoa passing through the magnetic columns without being retained will prove to have an unharmed DNA and, therefore, they will be eligible to be used.

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How can Toxin exposure affect fertility

Both men and women can be exposed to chemicals and other materials that may be detrimental to their reproductive health while on the job. Heavy metals and pesticides have many negative side effects, particularly for those who work around them. Men working in agricultural regions and greenhouses which use pesticides have higher concentrations of common pesticides in their urine, overall reduced semen parameters, oligozoospermia, lower sperm counts, and sperm concentrations decreased by as much as 60%. Organic solvents may also prove detrimental. Men who work with these substances often experience indirect consequences with their female partner having decreased implantation rates. Welding is another possible source of occupational exposure, and plays a role in reduced reproductive health. There are also consequences for working in factories that manufacture chemicals and heavy metals. Factories that produce batteries where workers are exposed to lead may have negative impacts on reproductive capabilities, including asthenospermia and teratospermia. Lead compounds are considered to be toxic for reproduction given their adverse effects on the normal intellectual and psychomotor development of human babies and children. Hobbies, while not often associated with excessive amounts of exposure, may be just as damaging as manufacturing. Gardeners may be in contact with pesticides; crafters making jewelry, ceramics, and even stained glass may come in contact with lead; painters may also come in contact with lead-based paints. Whether it is manufacture or hobby, using any kind of heavy metal or pesticide likely will result in some exposure, and possibly reduce fertility.

Female Infertility

One well known group of substances which are toxic for reproduction are teratogens – substances which cause birth defects – of which (S)-thalidomide is possibly the most notorious. Another group of substances which has received much attention (and some controversy) as possibly toxic for reproduction are the so-called endocrine disruptors. Bisphenol A (BPA), an Endocrine disrupting chemicals (EDC) widely used as an industrial chemical. The European and US Food and Drug Administrations concluded that the current BPA levels may have no risk to the general population. However, basic scientists contested that the entire population may suffer adverse health effects from current BPA levels.

BPA can interfere with endocrine function of hypothalamic-pituitary axis, such as by changing gonadotropin-releasing hormones (GnRH) secretion in hypothalamus and promoting pituitary proliferation. Such actions affect puberty, ovulation and may even result in infertility. Ovary, uterus and other reproductive organs are also targets of BPA. BPA exposure impairs the structure and functions of female reproductive system in different times of life cycle and may contribute to infertility. BPA affects reproduction-related gene expression and epigenetic modification that are closely associated with infertility. The detrimental effects on reproduction may be lifelong and transgenerational.

Male Infertility

Occupational activities involving exposure to specific chemicals or expositions to toxicants may impair male reproductive health and cause infertility in humans. Chemicals could adversely affect male reproductive system by, either disrupting the gonadal endocrine axis or, the spermatogenesis process. Any of those mechanisms would result in poor semen quality. Recent studies suggest that sperm DNA integrity may be altered by environmental exposure to some toxic chemicals. DNA fragmentation may be an excellent marker for exposure to potential reproductive toxicants and a diagnostic tool for male infertility.

Taking care of a current fertility problem may provide better fertility in the future. 

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