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The increasing survival rates of cancer patients  have encouraged many specialists to focus on the irreversible consequences of chemotherapy and radiotherapy. Chemotherapy and radiotherapy treatment for cancer or other pathologies have resulted in improved survival rates, but these treatments may also lead to sterility . The increasing success of oncological treatments means it is now even more crucial to implement procedures aimed at preserving fertility.
Similar to cancer patients, there are some non-oncological conditions currently treated with gonadotoxic agents, such as patients with autoimmune disorders or some chromosomal abnormalities that can lead to ovarian failure. There are also other situations where a woman may benefit from fertility preservation procedures, such as women with severe or recurrent endometriosis or women who electively postpone conception .
Survival rates after cancer have increased significantly in recent decades; however, these treatments also have drawbacks, and patients (or parents in the case of children) must be informed of the long-term side effects of oncological treatments and the possible options for preserving the fertility of these patients. It is important to set out clearly the possible risks of developing ovarian failure or azoospermia with oncological treatments. These will depend on the age of the patients and on the type, dose and duration of chemotherapy, and on the field, dose and duration of radiotherapy.
Despite the various advances and the increasing success rates of assisted conception treatment, implantation continues to be a rate limiting step. For implantation to occur a blastocyst must attach to and invade the endometrium and as such both the embryo and endometrium are considered critical to the process of implantation. However, there are other factors to consider. Many conditions of the uterine cavity may influence the ability of the embryo to implant such as uterine submucosal fibroids and endometrial polyps, which are well recognized to exert an adverse effect. In addition, an embryo’s implantation potential may be affected by sperm and oocyte quality. Iatrogenic factors such as laboratory conditions and embryo transfer technique play an important role in successful implantation, hence this chapter will focus on the embryo transfer procedure. This is the final step in the treatment cycle, the culmination of both clinicians’ and embryologists’ efforts and a day of great hope for the patients. The importance of the embryo transfer procedure is not to be underestimated. This chapter will highlight the importance to clinicians of not adopting a “one-size-fits-all” approach when planning embryo transfer. It is incumbent on reproductive medicine specialists to focus on the embryo transfer procedure, try to preempt any potential issues that may adversely affect success rates and adopt an individualized plan for embryo transfer when necessary.
This chapter focuses on amniotic fluid-derived stem cells (AFSCs) isolated from the amniotic fluid and placental membranes, discussing their properties and potential clinical applications. The highly multipotent differentiation potential of AFSCs opens the possibility of the cell type being utilized to treat a wide range of diseases through the generation of replacement cells in the laboratory. The ability to use AFSCs to generate large numbers of osteocytes, myocytes, adipocytes, endothelial cells, hepatocytes, chondrocytes, and neurons provides a valuable tool for the development of novel cell therapies. In pre-clinical studies, AFSCs have shown efficacy in the treatment of bone defects, heart disease, kidney disease, neural degeneration, lung disease, and blood disorders. Future applications of AFSCs include the treatment of diabetes, the generation of a living-skin equivalent, for muscle regeneration, as a novel drug delivery system, as well as anti-inflammatory applications for graft vs. host disease.
This chapter describes the existing knowledge regarding the ideal molecular profile of sperm cells, in order to define the model to be mimicked when stem cells are employed in order to create male gametes. Sperm production is defective in a significant proportion of males aiming at fatherhood. Interestingly, there are a significant proportion of infertile males presenting normal sperm counts, thus diagnosed as having idiopathic infertility. To date, there are a lot of studies concerning DNA analysis of human spermatozoa suggesting that the determination of DNA fragmentation levels can be a parameter of semen quality, directly implicated in male fertility. Sperm membrane lipid composition is of special interest, given their involvement in fertilization, capacitation, spermatozoa, and oocyte interaction. The future vision shows the possibility to create sperm cells from adult stem cells, with all the requirements to succeed fulfilled, thus guaranteeing a safe and successful use.
This chapter reviews the sexually dimorphic nature of meiosis in mammalian species, since many aspects of recombination depend on whether the gamete is proceeding through spermatogenesis or oogenesis. Since meiotic recombination occurs at prophase during fetal development in mammalian females, few investigations of human recombination have focused on this stage. Linkage disequilibrium (LD) analysis provides a powerful tool for the generation of high resolution genetic maps. LD mapping does not require analysis of multiple generations in a family. Rather it is a simple assessment of haplotype blocks among different individuals. Fortunately, with improvements in immunostaining techniques and the increasing availability of antibodies capable of detecting meiosis-acting proteins, it has now become possible to analyze the processes of pairing, synapsis, and recombination in human fetal oocytes. Advances in mapping methodology have led to the generation of high-resolution male and female genetic maps.
This chapter presents recent advances in the study of cell reprogramming within the broader context of organ regeneration research in certain animal models. It summarizes current approaches to investigate reprogramming, dedifferentiation, and transdifferentiation, and discusses the mechanisms that underlie the erasure of epigenetic memory during cellular reprogramming. Dedifferentiation entails a stable change in cell fate (reprogramming) so that the resulting cell type represents earlier steps in the cell's developmental history, either molecularly or functionally. The term lineage conversion or transdifferentiation is used to describe changes in cell fate that do not involve a gain in cell potency. Comparing how natural instances of cell reprogramming and their experimental counterparts are regulated will surely identify commonalities, but also context-specific differences. In addition to bettering our understanding of fascinating biological phenomena, research on induced reprogramming to pluripotency and direct cell fate conversion is likely to have profound biomedical implications.
This chapter reviews molecular mechanisms that control germline formation through a complex cascade of gene activation. In mammals, primordial germ cells (PGCs) are derived from the proximal epiblast during early embryogenesis. Interestingly, although both FRAGILIS and STELLA are differentially expressed in PGCs, neither appears to be essential for PGC specification. In general, migration of PGCs from primitive streak to genital ridges is believed to be governed by chemotactic cytokines, cell surface receptors, and cell adhesion factors. Until the colonization of the genital ridges, XX and XY PGCs are indistinguishable in terms of morphology and behavior. Mammalian male sex determination is initiated by sex-determining region Y (SRY) expression in XY genital ridges, which triggers Sertoli cell differentiation in supporting cell precursors. Germ-cell colonization of the gonads is followed by sex determination. Expression of sex-specific genes in somatic tissues initiates molecular events that lead to testis or ovary development.
Stem cell science has the potential to impact human reproductive medicine significantly – cutting edge technologies allow the production and regeneration of viable gametes from human stem cells offering potential to preciously infertile patients. Written by leading experts in the field Stem Cells in Reproductive Medicine brings together chapters on the genetics and epigenetics of both the male and female gametes as well as advice on the production and regeneration of gene cells in men and women, trophoblasts and endometrium from human embryonic and adult stem cells. Although focussing mainly on the practical elements of the use of stem cells in reproductive medicine, the book also contains a section on new developments in stem cell research. The book is essential reading for reproductive medicine clinicians, gynecologists and embryologists who want to keep abreast of practical developments in this rapidly developing field.
This chapter addresses the controversies surrounding the impact and surgical management of hydrosalpinges and uterine leiomyoma on in vitro fertilization (IVF) cycle outcome. Evidence accumulated over the last 15 years suggests that either unilateral or bilateral hydrosalpinges may exert deleterious effects on IVF cycle outcome. Hydrosalpinx fluid may have a direct embryotoxic effect and may also inhibit fertilization. This deleterious effect may be mediated by the presence of inflammatory cytokines present within hydrosalpinx fluid. Several groups have reported that only large hydrosalpinges, visible on ultrasound, resulted in reduced implantation and pregnancy rates. The impact of uterine leiomyomata specifically on the outcome of assisted reproductive technologies has been evaluated with conflicting results. Evaluation of the uterine cavity by hysteroscopy or sonohysterography should be a routine part of the pre-cycle evaluation. The accuracy of routine ultrasound evaluation and hysterosalpingography is more limited.
This chapter focuses on female fertility preservation procedures because of their complexity and peculiarities. Ovarian failure leads to the impossibility of childbearing apart from other problems related to the menopause, such as vasomotor, skeletal or cardiovascular alterations. Early menopause and infertility are two of the main consequences for patients treated with gonadotoxic agents. Gonadotoxicity, a decrease in ovarian activity, depends on several factors, including the age of the patient; the initial status of the ovaries; the treatment applied and cumulative doses; and the type of agent used. Ovarian tissue freezing for later autotransplantation is alternative for fertility preservation in women with oncological or non-oncological diseases. Any patient with a high risk of premature ovarian failure is a possible candidate for fertility preservation. Oocyte and ovarian tissue cryopreservation are useful as they overcome some of the disadvantages, ethical concerns and legal restrictions related to embryo cryopreservation.