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Uterine fibroids may cause infertility, depending on their size and their location . The mechanisms linking uterine fibroids and infertility are numerous: uterine cavity distortion according to the FIGO classification; impaired endometrial and myometrial blood supply; increased uterine contractility; hormonal, paracrine and molecular changes; impaired endometrial receptivity and gene expression (decrease in homeobox 10 [HOXA-10] expression); and thicker capsule. The effect on infertility of fibroids distorting the cavity is easy to understand. We will also review the influence of non-cavity-distorting intramural fibroids.
Endometriosis is a benign estrogen-dependent gynecological disease, known to occur in 7–10% of women of childbearing age [1, 2]. This percentage may rise to 30–50% if only women presenting with pelvic pain and infertility are taken into account . The condition is histopathologically defined as the presence of endometrial tissue (glands and stroma) in ectopic locations outside the uterine cavity. It is now widely recognized that three different forms of endometriosis can occur in the pelvis, namely peritoneal endometriosis, ovarian endometriosis, and deep endometriotic nodules of the rectovaginal septum, each with its own pathogenesis .
Although the clinical presentation of endometriosis includes dysmenorrhea (painful menstruation), dyspareunia (painful sexual intercourse), and chronic pelvic pain, infertility is still regarded as the biggest concern for endometriosis patients [5, 6]. The presence of intraovarian endometriomas in particular can cause follicle loss, diminishing the ovarian reserve and consequently leading to infertility [7, 8].
Fertility preservation is now recognized as the most essential quality of life issue in young cancer survivors. Since the last decade several strategies to preserve fertility in women have been developed and applied clinically (although some are still experimental). Ovarian tissue cryobanking is currently perceived as a promising technology for fertility preservation which draws enormous attention not only from scientific communities but also from the general public. Ovarian tissue cryopreservation followed by transplantation has proven to be very successful not only in many animals but also in humans. Indeed, we have accumulated enough data since 2004 that ovarian transplantation can restore fertility in women. As of 2018, approximately 130 healthy babies have been born worldwide after transplantation of frozen-thawed ovarian tissue [1–9].
The first live birth to occur after ovarian-tissue transplantation between two genetically different sisters was reported in 2011. Since this is an acceptable practice with monozygotic twins, there is no apparent reason to refrain from using it with genetically different sisters, especially if one of the sisters previously received bone marrow from the other, leading to complete chimerism (HLA compatibility) between donor and recipient, thus obviating the need for immunosuppressive treatment. This approach allows for natural conception, which could be important on moral, ethical or religious grounds.
Successful live births after transplantation of frozen-thawed human ovarian tissue have been observed since the first report in 2004 . Up to 2017, approximately 130 live births have been achieved . Currently, this procedure is performed for children, adolescents, and young adults with cancer in many countries.
The standard method of ovarian tissue cryopreservation is slow freezing, but rapid freezing (also called “vitrification”) has increasingly been reported as an alternate cryopreservation method in recent years. The present article reviews recent findings with regard to techniques for vitrification of ovarian tissue.
During fetal life, 100–2000 primordial germ cells enter a massive proliferation process and, by mid-gestation, there are several million potential oocytes. However, most (85 per cent) of them are lost prior to birth  (Figure 6.1).
The use of gonadotropin-releasing hormone agonists (GnRHa) for prevention of chemotherapy-induced gonadotoxicity remains controversial. With the initial dose of GnRHa, the pituitary gland releases endogenous gonadotropins. This initial follicle stimulating hormone (FSH) release stimulates the ovary. After continued GnRHa exposure, further FSH release is prevented. Gonadotropin-releasing hormone analogues can be administered in many formulations with different durations of action. The most common side effects of GnRH analogues are related to the subsequent estrogen deprivation. Vasomotor symptoms, hot flushes, night sweats, vaginal dryness and headaches can occur. Cotherapy of a GnRHa during chemotherapy has been under investigation since the mid 1990s. If prolonged GnRHa administration decreases ovarian blood flow, then less chemotherapy may reach the ovary. Direct effects of GnRHa or FSH on ovarian tissue may influence ovarian response to chemotherapy. For GnRHa to be of benefit to fertility preservation, they would likely need to spare both oocyte quantity and quality.
Cryopreservation of male and female gametes has been long established, and nowadays low-temperature storage of human spermatozoa is a routine technique in assisted reproduction. The vitrification method uses no specially developed cooling program; it does not need to apply permeable cryoprotectants; it is much faster, simpler and cheaper; and it can also provide a high recovery of motile spermatozoa after warming as effective protection of spermatozoa against cryodamage. Higher concentrations of cryoprotectants are needed for extracellular than for intracellular vitrification. The success of Luyet's vitrification technique was supported by Shaffner applying the technique to frog spermatozoa after vitrification of fowl sperm. The advantage of programmable or non-programmable conventional slow freezing is the ability to simultaneously preserve a relatively large volume of diluted ejaculate or prepared spermatozoa. Long-term storage of frozen cells and tissues remains elusive in both theoretical and routine cryobiology, and future investigation applying nanotechnology is needed.
The ovaries are very sensitive to cytotoxic treatment, especially to alkylating agents. It is clear that high doses of alkylating agents, irradiation, and advancing age all increase the risk of gonadal damage. This chapter presents the oncological indications for ovarian tissue cryopreservation. Cryopreservation of oocytes can be performed in postpubertal patients who are able to undergo a stimulation cycle, but the effectiveness of this technique is still low, with delivery rates from 1 to 5% for frozen-thawed oocytes using the slow-cooling techniques. The main drawback of ovarian tissue cryopreservation followed by avascular transplantation is that the graft is completely dependent on neovascularization and, as a result, a large proportion of follicles are lost during the initial ischemia occurring after transplantation. Reducing the ischemic interval between transplantation and revascularization is, therefore, essential to maintaining the follicular reserve and extending the lifespan and function of the graft.
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