The Advances in Infertility Treatment in the Last 20 Years - Research Paper Example

Introduction In the recent past, the need for fertility preservation in various es of patients has led to the development of methods of fertility treatment. The need for female fertility preservation is borne out of many reasons; for example, according to the practice Committee of American Society for Reproductive Medicine (2006), more than 600,000 women in the United States are diagnosed with some form of cancer every year. In 2001 alone, approximately 625,000 women were diagnosed with different forms of invasive cancer. The treatment methods for cancer patients requires intensive chemotherapy, radiotherapy, and bone marrow transplants, all of which have been proven to be detrimental to the reproductive systems. Despite the success rates of these methods in treating cancer, the chemical agents and the radiation to which the patients are exposed to often lead to ovarian failure, which lead to infertility. With this increasing risk of infertility due to cancer, the option of preserving fertility is increasingly becoming popular. The other reason for preserving fertility is due to social reasons, for example, some patients prefer to delay motherhood. With the reasons stated above, the medical world has been necessitated to develop some means of preserving fertility. The preservation of female genetics has seen tremendous advancement over the past two decades, since the practice has been around since as early as 1985. This progress has been mainly due to research done on humans, cows and mice, and has resulted in two main methods (Eggan et al, 2006). The use of cryopreservation has seen numerous advances from the previous techniques that did not guarantee success, to the current methods being used. This paper will discuss the two main methods of oocyte and embryo cryopreservation; slow freezing, and vitrification. The first method, slow freezing, has been around for many years, and vitrification is a relatively new technique. Vitrification is divided into embryo and oocyte vitrification, both of which will be discussed in this section. The expected advances in the field of fertility preservation will as lobe discussed. To counter the effects of cancer treatment methods, embryo cryopreservation is one of the methods of preserving fertility among affected females (Gajda and Smorag, 2009). However, chemotherapy of cancer patients is usually initiated immediately after diagnosis of the cancer, and since oocyte harvesting usually takes a long time, embryo freezing is affected. Apart from breast cancer, chemotherapy is initiated after diagnosis, which eliminates the possibility of oocyte harvesting. Even with breast cancer, the potential effects of high oestrogen levels on the tumor eliminates the possibility of oocyte harvesting (Saragusty and Arav, 2011). These factors mean that most females of reproductive age do not have the option of preserving fertility using embryo cryopreservation. However, the cryopreservation of ovarian tissue is an available mechanism for fertility preservation for cancer patients. Oocyte Cryopreservation Oocyte cryopreservation is a method that can be used to preserve female fertility since it does not require the sue of surgical methods. The history of successful oocyte preservation and subsequent birth dates back to 1985, after which more than 100 births have been recorded (Thomas and Wook, 2011). However, the pregnancy rates for this method have been very low, perhaps due to low oocyte survival rates, low fertilization rates, and inadequate development of the embryos (Singh, Kunj and Puram, 2009; Johnston et al, 2005). The freezing process also introduces hardening of the zona pellucida, which hampers the fertilization process by preventing the entry of the sperm. Oocyte freezing is usually affected by several factors, with the main factor being chilling injury (Almodin, et al 2010). Research indicates that chilling injury affects the embryonic membrane, microtubules, and the zona pellucida, and introduces chromosome abnormalities in the embryo. To prove this factor, it has been observed that in the second meiotic spindle, the microtubules are usually disrupted or disassembled. This chilling injury is usually caused by tubulin depolimerization, especially in mouse oocytes, which had abnormal spindles after exposure to cryopreservation (Tao and De Valle, 2008). The spindle assembly of the human oocyte is also affected by chilling injury. The effects of chilling injury have been reduced in human embryos by the use of rapid cooling techniques in the transition phase and by the use of substances proven to stabilize the plasma membrane (Fuku, Xia and Downey, 1995). Cryopreservation of the oocyte is usually done in two main ways; slow freezing and vitrification, both of which have been shown to produce tremendous positive results (Cobo and Diaz, 2011). The first process; slow freezing gives adequate results, since the method uses cryoprotectants. The main issue with the process of slow freezing of the oocyte is the exposure time to cryoprotectants, which means that the cooling rate should be optimized. This means that the cooling rate should be slow enough to allow the oocyte to dehydrate and avoid freezing at the cellular level. However, the rate should also be fast enough to avoid the toxic nature of the cryoprotectants (Vajta, 2000; Kuleshova et al, 1999). Therefore, the use of slow freezing and rapid thawing have been proven to minimize the formation of ice which leads to structural damage (Best, 2010). Despite the time consuming nature of slow freezing, it is still the standard operating procedure in most IVF centers. The human oocytes are protected against freezing effects by using different solutes that improve the survival rates of the oocytes. The second method for oocyte cryopreservation is the use of vitrification, which refers to ultra rapid freezing methods (Kuwayama et al, 2005; Luvoni, Pellizzari and Battocchio, 1997). This method is rapidly catching up as the method of choice for fertility preservation. This method uses high concentrations of cryoprotectant solutes to rapidly cool the oocyte without forming ice crystals. This method also helps to reduce the thermal stress to which the oocytes are subjected to, which reduces the possibility of chilling injury to the oocyte. Therefore, since vitrification is a major improvement on slow freezing, systems have been improved to increase the cooling rate of the oocytes. The occurrence of human pregnancies and subsequent births from vitrified oocytes offered a major breakthrough for vitrification. However, little is known of the potential effects of the vitrification process, and despite the progress made, skepticism remains attached to the procedure. These potential effects arise from the use of high concentrations of cryoprotectants, which are usually associated with higher levels of toxicity and injuries to the oocytes. The use of less toxic cryoprotectants, combination of more that one cryoprotectant, and other methods are currently used to reduce these injuries. Ovarian Tissue Cryopreservation The cryopreservation of mature oocytes posses a lot of challenges, challenges that can be overcome with the use of ovarian tissue (Wood, Shaw and Trounson, 1997). As already mentioned, the damage to which oocytes are exposed to pose the major challenge to cryopreservation, which necessitates the use of immature oocytes in primordial follicles. These follicles, found in the ovarian cortex, are less sensitive to cryopreservation damage because of their size, few organelles, lack of pellucida, and undifferentiation. The use of ovarian cortex tissue cryopreservation has been suggested as an alternative to the cryopreservation of oocytes and ovulation induction. The ovarian cortex tissue contains primordial and primary follicles, which can be used for the fertilization process. In this process, viable follicles usually survive the process of freezing and thawing of the ovaries, which can be sued as a means of preserving the fertility of patients at risk of ovarian failure. The process of ovarian tissue cryopreservation is also divided into slow freezing and vitrification, since the freezing and thawing process has the potential to damage the ovarian tissue. This damage is resultant from the formation of intracellular ice and the toxic nature of the cryoprotectants used in the process. The slow freezing process of ovarian tissue starts with the incubation of the ovarian tissue in ethylene glycol and sucrose for twenty to thirty minutes. The ovarian tissue is then cooled to -7 degrees Celsius, seeded, and further cooled to -40 degrees Celsius at a slower rate. The temperature is then allowed to free fall to -100 degrees Celsius before the ovarian tissue is stored in liquid nitrogen (Isachenko, 2003). Then thawing process is done at 37 degrees Celsius, after which the tissue is passed through lower concentrations of cryoprotectant solutes. Conversely, the vitrification process usually involves rapid cooling of the ovarian tissue, where the solution is directly converted from the an aqueous phase to the amorphous solid state. This ensures that the tissue is not exposed to the ice crystalline state where tissue damage is likely to occur. The rapid cooling process is used in the presence of cryoprotectant solutions, which ensures that the tissue is not exposed to the possibility of crystallization. After the preservation of the ovarian tissue, the grafting process has to be done to transfer the tissue to the potential parent (Newton et al, 1996). The grafting process is usually divided into four parts, with the first process being orthotopic autografting. In this process, the ovarian tissue is grafted into the normal production site, which ensures that pregnancy continues without further medical assistance (Radford et al, 2001). Ovarian transplantation has been in use since as early as 1906, though orthotopic transplantation has been preformed only in animals. The use of this method has achieved recent success, with the successful birth of an infant from cryopreserved ovarian tissue. The second method is the use of heterotropic autografting, which is usually accompanied by in vitro fertilization. This process provides the possibility of pregnancy to patients who have previously undergone chemotherapy or radiotherapy. The other two methods of transfer are xenografting and in vitro maturation of primordial follicles (Lee et al, 2004). However, the transfer of ovarian tissue posses the risk of reseeding cancer to the patient, since the tissue was previously harvested from cancerous patients. Despite the fact that ovarian involvement is highly unlikely in cancer patients, metastasis of ovarian tissue with tissue is still possible. This posses the risk of transferring cancerous cells to the recipient of the ovarian tissue. This indicates the importance of detection of metastasis in ovarian tissue before the cryopreservation process, which eliminates the risk of reseeding the cancer tissue. The use of cryopreservation techniques is also faced by ethical and legal issues, as is the case with most reproductive techniques. Some of the issues include clinical indications, offspring welfare issues of experimental nature, and time limits for preservation. However, the two methods discussed above, oocyte and embryo preservation are commonly used, especially with people who want to preserve their progeny. The current development in treatment of infertility can be improved in the future through the use of different methods (Kovacs, 2002). The first method to be discussed is the generation of artificial gametes from stem cells (Nagy, 2005). This area of specialization is still relatively new, with studies being done to determine its viability (Kovacs, 2002). The potential effects of this type of research have tremendous impacts on the treatment of infertility, since it would be possible to achieve fertility in humans. In the recent past, many researchers have proposed the possibility of creation of viable gametes, egg and sperm cells, from embryonic stem cells (Nayernia, Lee and Drusenheimer, 2006; Nayernia and Jaroszynski, 2004). Previously, researchers have used these embryonic stem cells to generate different types of tissues in mammals. Some of the tissues generated include brain and liver cells, without any breakthrough in the production of artificial gametes. Previously, the production of gamete cells was done by letting the stem cells differentiate naturally, however, recent studies have focused on identifying the precise way of differentiating stem cells into gametes. These researchers were mainly conducted on mice, which indicate that advancement could provide a way of using it in human cell research (Nayernia, Nolte and Michelmann, 2006). A recent breakthrough in this area was achieved by a professor in the University of Newcastle, who managed to create sperm cells from a female human embryo. This breakthrough suggests that in the near future, it would be possible to eliminate the need for male participation in the reproduction process, which would lead to the possibilities of single sex couples to get offspring. The first breakthrough in this study was in 2006, when the professor used sperm derived from male embryonic stem cells to achieve fertilization. The process resulted in the birth of seven mice, six of which survived to adulthood, albeit with different health problems. The success of this method motivated the professor to apply for permission to turn female bone marrow into sperm, which would mean that the method would be made more practical (Newson and Smajdor, 2005). The implications of this research for single sex couples is tremendous, since it means that the sperm cells created from a female human can be sued to fertilize the eggs of another female partner. Previous achievements of the professor include the development of a form of sperm cells from stem cells from men. This achievement has now been dup0licated with the possibility of repeating it using female stem cells. However, skepticism has been attached to this research, since it is known that only male progeny possess the Y chromosome, which is essential for making sperm (Lacham-Kaplan, Daniels and Trounson, 2001). This is to be achieved if the professor is able to make the developed sperm cells to undergo meiosis. Other studies with the same implications include the development of sperm and eggs from male mouse embryonic cells, which implies that male humans have the ability to reproduce without female capacity. Initial breakthroughs in this field were achieved through the use of simple science, where the researchers used standard cell culture conditions, but at higher densities. This resulted in the formation of cell aggregates similar to ovaries, and could produce eggs (Kang et al, 2009). The produced cells have strikingly similar characteristics to real gametes, since they have the ability to undergo meiosis and profess specific genes at appropriate times. The formation of sperm from stem cells follows a different path from the formation of female gametes, since the cultured embryonic cells formed clusters called embryoid bodies, which contained primordial germ cells (Hubner et al, 2003). The researchers proved that the cells had indeed become spermatocytes by exposing them to an agent that stimulates gametes to divide, but causes embryoid cells to stop dividing. The produced cells then divided according to expectation (Lavagnolli and Kerki, 2010). This research is also complemented by other researchers who successfully developed immature sperm, which developed into blastocysts. These blastocysts maintained their expected male to female ratios and contained the expected chromosome composition (Johnstone et al, 2005). The potential impacts of this type of research is unprecedented, since the gametes developed from this method develop and exist normally, implying that the human stem cells can be cultured in the same way (Teifer, 2005; Lokman and Moore, 2010). In this manner, researchers would be able to create a renewable source of gametes. This would help in the development of research embryos and stem cells. Currently, the unavailability of research gametes is a serious detriment to research, since the eggs used far exceed the stem cells produced from the studies. This research could also lead to the increased understanding of genomic imprinting, which refers to the chemical suppressors on individual chromosomes affecting gene expression (Geijsen, 2004). The gene expression in every offspring is acquired from either the mother or mother of an individual; however, the use of reproductive cloning would hamper this. This means that the developed cells do not have previous imprinting, meaning that the chromosomes do not have optimal gene imprints. However, cloned offspring have minimal defects; therefore, the imprints are corrected in the offspring. The other development expected in the fertility field is the development and use of the artificial womb, which is expected to create a lot of ethical debates. According to Lupton (1997), the creation of the artificial womb would lead to myriad benefits including the normal development of extremely premature fetuses, and the benefit to be derived from barren women. However, the artificial womb would also lead to a lot of legal and ethical debates, debates that the law is not equipped to handle. Some of the challenges include the right of persons to use the artificial womb, and the redefinition of the term parent. Research into the development of the artificial womb has received recent success, with the development of the first prototype in 1997 by a Japanese professor (Toyooka, 2003). The research team compiled by the professor managed to sustain goat fetuses for several days (Pak et al, 2002). The artificial womb was made of a clear plastic tank filled with artificial amniotic fluid, and an artificial placenta attached to the tank to facilitate the delivery of nutrients and the expulsion of waste from the womb. The professor expressed his optimism that the artificial womb would one day be able to sustain human life. Other researchers have developed different approaches to the research, for example, a professor in Cornell University managed to grow cells from the endometrium in a biodegradable scaffold. The growth was complete when a fully grown uterus grew, then the scaffold broke down. The Professor attached human embryos to the resultant artificial womb, where they survived for several days. However, the embryo had to be destroyed after several days since existing regulation place a cap on the maximum time in which experiments can be conducted on human embryo. There have been a number of similar studies into artificial wombs, though the controversy generated has reached sizable proportions (Bulleti et al, 1988). Though some people hail the development of artificial wombs as a significant medical breakthrough, the ethical and legal constraints are still many. The artificial wombs could be used to help infertile women, help in the medical care of premature babies, and help in the development of scientific research. However, the legal constraints faced by the development of artificial wombs include the time constraints faced by the researchers, as well as the legal definitions of the baby and parents. The use of the artificial womb would help in furthering the fertility process, since the fetus would be able to develop in relative safety (Bulleti et al, 2011). As already stated, an extremely premature fetus would be incubated in an artificial womb, a process that would save the life of the fetus. In other cases, it can be argued that the artificial womb could be safer that the natural womb, since the risk of diseases and habits engaged in by the natural parent are drastically reduced (Kaczor, 2005). For example, the risk of ill health faced by a baby because of the habits of the mother is reduced, for example, drug taking, stress, and inadequate nutrition. However, the ethical debate can extend to this safety factor, for example, if the artificial wombs are really proven safe, employees and insurance companies would require mothers to use them. The ethical debate surrounding the development of the artificial womb is also centered on the natural development of the fetus, since research suggests that the environment in which the baby grows influences that child’s future development. In this case, it is arguable that the baby would not be able to form some sort of bond with the birth mother. However, the potential effects of the artificial womb on the issue of fertility are widespread, since mothers with damaged wombs would be able to reproduce. In this case, the flip side is the issue of abortion, where the main argument is the reluctance of the mother to carry the progeny to term. In this case, the potential mothers usually argue the right not to carry the fetus to full term. However, with the introduction of the artificial womb, regulations can be amended to allow mothers not to carry the baby to term, but instead, would be forced to use the artificial womb. The development of the artificial womb would also be accompanied by the development of the machines to help babies develop fully, which would ensure the medical care of fetuses and babies (Greenspan et al, 1997; Hammell, Forrest, and Barett, 2008). The recent past has witnessed a number of advances in the field of fertility preservation, and with the development of increased ways to preserve gametes; many people can be assured of fertility. As stated above, the main reason why the preservation of gametes is done is because of cancer patients and individuals who prefer to get their progeny at a later stage in life. In this case, the methods discussed above can be of a lot of help. The use of gamete cryopreservation can be used for a number of reasons, for example, it is known that famous individuals have had their gametes cryopreserved to assure future progeny. This ensures that the individuals are assured of offspring at a future time. The use of oocyte and ovarian tissue cryopreservation is a field that has been achieved successfully, though some of the methods have not been perfected. One of the major ethical issues to consider in this area is the fact that the progeny are not assured of natural development. However, the future field, the development of gametes from stem cells and the development of an artificial womb are the ones faced by the biggest ethical dilemmas. For example, the perfection of research into the production of gametes from stem cells would mean that same sex couples would be able to reproduce without the need for opposite-sex partners (Mertes and Pennings, 2010). 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