scholarly journals Female Fertility Preservation through Stem Cell-based Ovarian Tissue Reconstitution In Vitro and Ovarian Regeneration In Vivo

2019 ◽  
Vol 13 ◽  
pp. 117955811984800 ◽  
Author(s):  
Taichi Akahori ◽  
Dori C Woods ◽  
Jonathan L Tilly

Historically, approaches designed to offer women diagnosed with cancer the prospects of having a genetically matched child after completion of their cytotoxic treatments focused on the existing oocyte population as the sole resource available for clinical management of infertility. In this regard, elective oocyte and embryo cryopreservation, as well as autologous ovarian cortical tissue grafting posttreatment, have gained widespread support as options for young girls and reproductive-age women who are faced with cancer to consider. In addition, the use of ovarian protective therapies, including gonadotropin-releasing hormone agonists and sphingosine-1-phosphate analogs, has been put forth as an alternative way to preserve fertility by shielding existing oocytes in the ovaries in vivo from the side-effect damage caused by radiotherapy and many chemotherapeutic regimens. This viewpoint changed with the publication of now numerous reports that adult ovaries of many mammalian species, including humans, contain a rare population of oocyte-producing germ cells—referred to as female germline or oogonial stem cells (OSCs). This new line of study has fueled research into the prospects of generating new oocytes, rather than working with existing oocytes, as a novel approach to sustain or restore fertility in female cancer survivors. Here, we overview the history of work from laboratories around the world focused on improving our understanding of the biology of OSCs and how these cells may be used to reconstitute “artificial” ovarian tissue in vitro or to regenerate damaged ovarian tissue in vivo as future fertility-preservation options.

2020 ◽  
pp. 54-62
Author(s):  
Taisiia Yurchuk ◽  
Maryna Petrushko ◽  
Barry Fuller ◽  
Anatoliy Goltsev

Increased incidence of global recorded cancer, unforeseen circumstances in assisted reproductive technology, a pandemic situation, and surgical interventions which can cause impairment of the reproductive system all necessitate urgent fertility preservation. Unfortunately, the application of successfully developed methods for oocyte and embryo cryopreservation is not possible in some situations because of contraindications for inducing superovulation, inability to delay other treatments, or in the case of prepubertal patients; in these cases, cryopreservation of ovarian tissue may be an alternative method. Despite current achievements in ovarian tissue low-temperature preservation, only 130 children have been born using this method. Further development of this technique and methods for in vitro maturation of immature oocytes, following their cryopreservation and use in assisted reproductive technology, as well as a differentiated approach for the selection of mature oocytes obtained without preliminary superovulation are needed. This review outlines the modern achievements and future prospects of female fertility preservation in emergency situations by cryopreservation of oocytes with different quality and maturity states.


2020 ◽  
Vol 21 (20) ◽  
pp. 7792
Author(s):  
Hyun-Woong Cho ◽  
Sanghoon Lee ◽  
Kyung-Jin Min ◽  
Jin Hwa Hong ◽  
Jae Yun Song ◽  
...  

Due to improvements in chemotherapeutic agents, cancer treatment efficacy and cancer patient survival rates have greatly improved, but unfortunately gonadal damage remains a major complication. Gonadotoxic chemotherapy, including alkylating agents during reproductive age, can lead to iatrogenic premature ovarian insufficiency (POI), and loss of fertility. In recent years, the demand for fertility preservation has increased dramatically among female cancer patients. Currently, embryo and oocyte cryopreservation are the only established options for fertility preservation in women. However, there is growing evidence for other experimental techniques including ovarian tissue cryopreservation, oocyte in vitro maturation, artificial ovaries, stem cell technologies, and ovarian suppression. To prevent fertility loss in women with cancer, individualized fertility preservation options including established and experimental techniques that take into consideration the patient’s age, marital status, chemotherapy regimen, and the possibility of treatment delay should be provided. In addition, effective multidisciplinary oncofertility strategies that involve a highly skilled and experienced oncofertility team consisting of medical oncologists, gynecologists, reproductive biologists, surgical oncologists, patient care coordinators, and research scientists are necessary to provide cancer patients with high-quality care.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Chung-Hoon Kim ◽  
Gyun-Ho Jeon

With improved survival rates among cancer patients, fertility preservation is now being recognized as an issue of great importance. There are currently several methods of fertility preservation available in female cancer patients and the options and techniques via assisted reproduction and cryopreservation are increasing, but some are still experimental and continues to be evaluated. The established means of preserving fertility include embryo cryopreservation, gonadal shielding during radiation therapy, ovarian transposition, conservative gynecologic surgery such as radical trachelectomy, donor embryos/oocytes, gestational surrogacy, and adoption. The experimental methods include oocyte cryopreservation, ovarian cryopreservation and transplantation, in vitro maturation, and ovarian suppression. With advances in methods for the preservation of fertility, providing information about risk of infertility and possible options of fertility preservation to all young patients with cancer, and discussing future fertility with them should be also considered as one of the important parts of consultation at the time of cancer diagnosis.


Zygote ◽  
2016 ◽  
Vol 24 (5) ◽  
pp. 635-653 ◽  
Author(s):  
M.A. Filatov ◽  
Y.V. Khramova ◽  
M.V. Kiseleva ◽  
I.V. Malinova ◽  
E.V. Komarova ◽  
...  

SummaryIn the present review, the main strategies of female fertility preservation are covered. Procedures of fertility preservation are necessary for women who suffer from diseases whose treatment requires the use of aggressive therapies, such as chemotherapy and radiotherapy. These kinds of therapy negatively influence the health of gametes and their progenitors. The most commonly used method of female fertility preservation is ovarian tissue cryopreservation, followed by the retransplantation of thawed tissue. Another approach to female fertility preservation that has been actively developed lately is the ovarian tissuein vitroculture. The principal methods, advantages and drawbacks of these two strategies are discussed in this article.


1973 ◽  
Vol 71 (3_Suppla) ◽  
pp. S5-S27 ◽  
Author(s):  
Sardul S. Guraya

ABSTRACT The interstitial gland cells of the mammalian ovary originate from the theca interna and surrounding stromal elements of degenerating follicles and are simultaneously vascularized, and hypertrophied (or luteinized). They form a specific feature of the mammalian ovary, and are invariably present in the ovaries of young and adult mammals. The interstitial gland cells show several variations in their amount and distribution in different mammals. They also show cycles of abundance and differentiation correlated with the reproductive age and ovarian cycles. The interstitial gland cells possess the cytological, histochemical and biochemical features of well-established steroid-secreting cells. These features are: a) abundant diffuse lipids (lipoproteins) in the cytoplasm, which apparently derive from the abundant ultrastructural agranular endoplasmic reticulum; b) well-developed cell organelles, especially the pleomorphic mitochondria with complex system of internal cristae that are predominantly tubular; c) the development of diffuse lipoproteins (or membranes of smooth reticulum), closely accompanied by the appearance of enzyme activities indicative of the biosynthesis of steroid hormones; d) under certain physiological situations, stored lipid droplets in the cytoplasm, which consist of phospholipids, triglycerides, and cholesterol and/or its esters; and e) the capacity to form steroid hormones in biochemical experiments in vitro and in vivo. The physiological significance of these various features, which do not show any appreciable development in the compressed, relatively embryonic stromal elements of the general ovarian stroma, has been discussed in relation to steroid hormone synthesis in the interstitial gland cells. In general, the results of the cytological, histochemical and biochemical studies agree well with each other and are compatible with their endocrine function. After stimulation with endogenous gonadotrophins, the interstitial gland cells undergo conspicuous cytological, histochemical and biochemical changes, which have been correlated to the accelerated production of steroid hormones. The formation of androgenic steroids seems to be the principal product of interstitial gland cells; in some mammalian species, oestrogens and progestins are also formed. Further comparative studies on the interstitial gland cells in different mammalian species are suggested to determine the nature and physiological significance of their steroid secretions under different physiological situations. Interstitial gland cells of different mammals show several variations with regard to their permanency, apparently depending on some gonadotrophic stimulation. After persisting for some time, they gradually lose their cytoplasm and lipids, and ultimately revert to the relatively embryonic, compressed stromal tissue from which they are originally derived. This cytoplasmic change is closely accompanied by the loss of blood vascularity, which may be providing the gonadotrophic hormone and other nutrient substances to the functional interstitial gland cells. Some interstitial gland cells show degenerative cytoplasmic changes, and ultimately become refractory to gonadotrophic stimulation.


2021 ◽  
Vol 2 (1) ◽  
pp. 59-68
Author(s):  
Briet D Bjarkadottir ◽  
Charlotte A Walker ◽  
Muhammad Fatum ◽  
Sheila Lane ◽  
Suzannah A Williams

In vitro follicle growth is a potential fertility preservation method for patients for whom current methods are contraindicated. Currently, this method has only been successful using fresh ovarian tissue. Since many patients who may benefit from this treatment currently have cryopreserved ovarian tissue in storage, optimising in vitro follicle growth (IVG) for cryopreserved-thawed tissue is critical. This study sought to improve the first step of IVG by comparing different short-term culture systems for cryopreserved-thawed human ovarian tissue, in order to yield a higher number of healthy multilayer follicles. We compared two commonly used culture media (αMEM and McCoy’s 5A), and three plate conditions (300 µL, 1 mL on a polycarbonate membrane and 1 mL in a gas-permeable plate) on the health and development of follicles after 6 days of culture. A total of 5797 follicles from three post-pubertal patients (aged 21.3 ± 2.3 years) were analysed across six different culture conditions and non-cultured control. All culture systems supported follicle development and there was no difference in developmental progression between the different conditions tested. Differences in follicle morphology were evident with follicles cultured in low volume conditions having significantly greater odds of being graded as morphologically normal compared to other conditions. Furthermore, culture in a low volume of αMEM resulted in the highest proportion of morphologically normal primary and multilayer follicles (23.8% compared to 6.3-19.9% depending on condition). We, therefore, recommend culturing cryopreserved human ovarian tissue in a low volume of αMEM to support follicle health and development. Lay summary Ovaries contain a large number of follicles, each containing an immature egg and other important cells. Cancer treatments can lead to long-lasting negative side effects to the ovaries including the destruction of follicles, resulting in infertility. One strategy to preserve fertility is freezing of ovaries or ovarian tissue in girls and women undergoing cancer treatment. The long-term aim is to thaw and grow their ovarian tissue in the laboratory to obtain mature eggs, which can then be fertilised. In this study, we compared six different methods of growing previously frozen human ovarian tissue in order to best support follicle growth and health. We found that using the lowest amount of αMEM medium (a specific type of nutrient-rich growth solution) resulted in the highest proportion of healthy follicles. Improving the methods used to grow ovarian tissue, particularly frozen tissue, is important for future fertility preservation.


2015 ◽  
Vol 04 (03) ◽  
pp. 134-139 ◽  
Author(s):  
Virender Suhag ◽  
B. S. Sunita ◽  
Arti Sarin ◽  
A. K. Singh ◽  
Dashottar S.

AbstractInfertility can arise as a consequence of treatment of oncological conditions. The parallel and continued improvement in both the management of oncology and fertility cases in recent times has brought to the forefront the potential for fertility preservation in patients being treated for cancer. Many survivors will maintain their reproductive potential after the successful completion of treatment for cancer. However total body irradiation, radiation to the gonads, and certain high dose chemotherapy regimens can place women at risk for acute ovarian failure or premature menopause and men at risk for temporary or permanent azoospermia. Providing information about risk of infertility and possible interventions to maintain reproductive potential are critical for the adolescent and young adult population at the time of diagnosis. There are established means of preserving fertility before cancer treatment; specifically, sperm cryopreservation for men and in vitro fertilization and embryo cryopreservation for women. Several innovative techniques are being actively investigated, including oocyte and ovarian follicle cryopreservation, ovarian tissue transplantation, and in vitro follicle maturation, which may expand the number of fertility preservation choices for young cancer patients. Fertility preservation may also require some modification of cancer therapy; thus, patients’ wishes regarding future fertility and available fertility preservation alternatives should be discussed before initiation of therapy.


Reproduction ◽  
2018 ◽  
Vol 156 (1) ◽  
pp. F11-F27 ◽  
Author(s):  
Benjamin Fisch ◽  
Ronit Abir

Anti-cancer therapy, particularly chemotherapy, damages ovarian follicles and promotes ovarian failure. The only pharmacological means for protecting the ovaries from chemotherapy-induced injury is gonadotrophin-releasing hormone agonist, but its efficiency remains controversial; ovarian transposition is used to shield the ovary from radiation when indicated. Until the late 1990s, the only option for fertility preservation and restoration in women with cancer was embryo cryopreservation. The development of other assisted reproductive technologies such as mature oocyte cryopreservation andin vitromaturation of oocytes has contributed to fertility preservation. Treatment regimens to obtain mature oocytes/embryos have been modified to overcome various limitations of conventional ovarian stimulation protocols. In the last decades, several centres have begun cryopreserving ovarian samples containing primordial follicles from young patients before anti-cancer therapy. The first live birth following implantation of cryopreserved-thawed ovarian tissue was reported in 2004; since then, the number has risen to more than 130. Nowadays, ovarian tissue cryopreservation can be combined within vitromaturation and vitrification of oocytes. The use of cryopreserved oocytes eliminates the risk posed by ovarian implantation of reseeding the cancer. Novel methods for enhancing follicular survival after implantation are presently being studied. In addition, researchers are currently investigating agents for ovarian protection. It is expected that the risk of reimplantation of malignant cells with ovarian grafts will be overcome with the putative development of an artificial ovary and an efficient follicle class- and species-dependentin vitrosystem for culturing primordial follicles.


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