scholarly journals The matrisome contributes to the increased rigidity of the bovine ovarian cortex and provides a source of new bioengineering tools to investigate ovarian biology

2021 ◽  
Author(s):  
Nathaniel FC Henning ◽  
Monica M Laronda
Keyword(s):  
Fertility Restoration ◽  
Ovarian Tissue ◽  
Oocyte Retrieval ◽  
Biochemical Properties ◽  
Ovarian Tissue Cryopreservation ◽  
Native Form ◽  
Adolescent Cancer ◽  
Ovarian Cortex ◽  
3D Printed ◽  
Bovine Ovary

The gonadotoxic effects of some cancers significantly increase the risk of developing infertility and cessation of ovary hormones (premature ovarian insufficiency, POI). Fertility preservation in the form of ovarian tissue cryopreservation (OTC) is offered to pediatric and adolescent cancer patients who cannot undergo oocyte retrieval and egg cryopreservation. The cryopreserved ovarian tissue can be transplanted back and has been found to restore fertility in 20 - 40% of transplants and restore hormone function for an average of 3 to 5 years. However, some individuals have primary or metastatic disease within their ovarian tissue and would not be able to transplant it back in its native form. Therefore, there is a need for additional methods for hormone and fertility restoration that would support a safe transplant with increased successful livebirths and long-term hormone restoration. To support this goal, we sought to understand the contribution of the ovarian microenvironment to its physical and biochemical properties to inform bioprosthetic ovary scaffolds that would support isolated follicles. Using atomic force microscopy (AFM), we determined that the bovine ovarian cortex was significantly more rigid than the medulla. To determine if this difference in rigidity was maintained in isolated matrisome proteins from bovine ovarian compartments, we cast, and 3D printed hydrogels created from decellularized bovine ovarian cortex and medulla slices. The cast gels and 3D printed bioprosthetic ovary scaffolds from the cortex was still significantly more rigid than the medulla biomaterials. To expand our bioengineering toolbox that will aide in the investigation of how biochemical and physical cues may affect folliculogenesis, we sought to confirm the concentration of matrisome proteins in bovine ovarian compartments. The matrisome proteins, COL1, FN, EMILIN1 and AGRN were more abundant in the bovine ovarian cortex than the medulla. Whereas VTN was more abundant in the medulla than the cortex and COL4 was present in similar amounts within both compartments. Finally, we removed proteins of interest, EMILIN1 and AGRN, from decellularized bovine ovarian cortex materials and confirmed that this specifically depleted these proteins without affecting the rigidity of cast or 3D printed hydrogels. Taken together our results indicate the existence of a rigidity gradient in the bovine ovary, that this rigidity gradient is maintained in resulting engineered materials strongly implicating a role for matrisome proteins in contributing to the physical properties of the bovine ovary. By establishing additional engineering tools, we will continue to explore mechanisms behind matrisome-follicle interactions.

scholarly journals Function of Cryopreserved Cat Ovarian Tissue after Autotransplantation

Animals ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 1065 ◽  
Author(s):  
Janice M. V. Vilela ◽  
Ellen C. R. Leonel ◽  
Liudimila P. Gonçalves ◽  
Raísa E. G. Paiva ◽  
Rodrigo S. Amaral ◽  
...  
Keyword(s):  
Subcutaneous Tissue ◽  
Ovarian Tissue ◽  
Fibrous Tissue ◽  
Ovarian Tissue Cryopreservation ◽  
Post Transplantation ◽  
Fresh Tissue ◽  
Tissue Samples ◽  
Antral Follicles ◽  
Ovarian Cortex ◽  
Tissue Cryopreservation

The aim of this study was to assess a slow-freezing protocol of cat ovarian tissue cryopreservation using autotransplantation. Four adult queens were ovariohysterectomized and the ovaries were fragmented and cryopreserved. After one week, the grafts were thawed and autografted to the subcutaneous tissue of the dorsal neck of each queen, then randomly removed after 7, 14, 28, 49, and 63 days after transplantation. Percentages of morphologically normal primordial and growing follicles (MNFs) were 88% and 97%, respectively, in fresh tissue samples (fresh controls), and 74% and 100%, respectively, immediately after thawing (cryo D0). No MNFs were found after 49 days of transplantation. In both fresh control and cryo D0 fragments, granulosa cells were frequently in proliferation. Two morphologically normal antral follicles were detected in one queen on Day 28 post-transplantation. Connective tissue fibers increased, suggesting replacement of active ovarian cortex by fibrous tissue. Tissue vascularization was observed at 7 days after grafting, and wide blood vessels were clearly visible on Days 49 and 63. In conclusion, although follicular survival was low after cryopreservation and grafting of cat ovarian tissue, follicles were able to develop up to the antral stage, which is an encouraging outcome.

Ovarian tissue cryopreservation and transplantation in patients with central nervous system tumours

2021 ◽  
Author(s):  
Thu Yen Thi Nguyen ◽  
Luciana Cacciottola ◽  
Alessandra Camboni ◽  
Joachim Ravau ◽  
Michel De Vos ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cancer Cells ◽  
Ovarian Tissue ◽  
Neuron Specific Enolase ◽  
Ovarian Tissue Cryopreservation ◽  
Malignant Cells ◽  
Ovarian Cortex ◽  
Cns Tumours ◽  
Tissue Cryopreservation

Abstract STUDY QUESTION Is there a possibility of reseeding cancer cells potentially present in frozen ovarian tissue from patients with central nervous system (CNS) tumours? SUMMARY ANSWER Malignancy reseeding in cryopreserved ovarian tissue from 20 patients with CNS tumours was not detected by histology, immunohistochemistry (IHC), molecular biology or xenotransplantation. WHAT IS KNOWN ALREADY Ovarian metastasis potential has been documented in patients with leukaemia, borderline ovarian tumours, advanced breast cancer and Ewing sarcoma. However, data on the safety of transplanting frozen-thawed ovarian tissue from cancer patients with CNS tumours are still lacking. STUDY DESIGN, SIZE, DURATION This prospective experimental study was conducted in an academic gynaecology research laboratory using cryopreserved ovarian cortex from 20 patients suffering from CNS tumours. Long-term (5 months) xenografting was performed in immunodeficient mice. PARTICIPANTS/MATERIALS, SETTING, METHODS Subjects enrolled in the study were suffering from one of six types of CNS tumours including medulloblastoma, ependymoma, primitive neuroectodermal tumours, astrocytoma, glioblastoma and germinoma. The presence of malignant cells was investigated with disease-specific markers for each patient in cryopreserved and xenografted ovarian tissue by histology, IHC via expression of neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), and reverse transcription droplet digital polymerase chain reaction (RT-ddPCR) for quantification of GFAP and ENO2 gene amplification. MAIN RESULTS AND THE ROLE OF CHANCE Serial sections of cryopreserved and xenografted ovarian tissue from 20 patients showed no malignant cells by histology. All samples were negative for NSE and GFAP, although these neural markers were expressed extensively in the patients’ primary tumours. Analysis by RT-ddPCR revealed no cancer cells detected in cryopreserved and xenografted ovarian fragments from subjects with astrocytoma, ependymoma, glioblastoma or medulloblastoma. Taken together, the study found no evidence of malignancy seeding in frozen-thawed and xenotransplanted ovarian tissue from patients affected by CNS cancers. LIMITATIONS, REASONS FOR CAUTION This analysis cannot guarantee complete elimination of disseminated disease from all cryopreserved ovarian cortex, since we are unable to examine the fragments used for transplantation. WIDER IMPLICATIONS OF THE FINDINGS This is the first study to be conducted in patients with CNS cancers undergoing ovarian tissue cryopreservation and transplantation, and clearly demonstrates no tumour seeding in their frozen-thawed and xenografted tissue. This information is vital for doctors to provide patients with meaningful and accurate advice on the possibilities and risks of ovarian tissue reimplantation. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique–the Excellence of Science (FNRS–EOS), number 30443682 awarded to M.-M.D. and T.Y.T.N., FNRS grant number 5/4/150/5 and FNRS-PDR Convention grant number T.0077.14 awarded to M.-M.D., grant 2018-042 from the Foundation Against Cancer awarded to A.C., and private donations (Ferrero, de Spoelberch). The authors declare no competing financial interests. TRIAL REGISTRATION NUMBER N/A.

scholarly journals Technologies for the Production of Fertilizable Mammalian Oocytes

2019 ◽  
Vol 9 (8) ◽  
pp. 1536 ◽  
Author(s):  
Gianna Rossi ◽  
Valentina Di Nisio ◽  
Guido Macchiarelli ◽  
Stefania Annarita Nottola ◽  
Iman Halvaei ◽  
...  
Keyword(s):  
Ovarian Tissue ◽  
Reproductive Potential ◽  
Oocyte Retrieval ◽  
Ovarian Tissue Cryopreservation ◽  
Embryo Freezing ◽  
Realistic Possibility ◽  
Developmental Capacity ◽  
New Ideas

Women affected by ovarian pathologies or with cancer can usually preserve fertility by egg/embryo freezing. When oocyte retrieval is not feasible, the only option available is ovarian tissue cryopreservation and transplantation. The culture of follicles isolated from fresh or cryopreserved ovaries is considered still experimental, although this procedure is considered safer, because the risk of unintentional spreading of cancer cells eventually present in cryopreserved tissue is avoided. Animal and human small follicles can be cultured in vitro, but standardized protocols able to produce in vitro grown oocytes with the same developmental capacity of in vivo grown oocytes are not available yet. In fact, the different sizes of follicles and oocytes, the hormonal differences existing between mono- (e.g., human, goat, cow, and sheep) and poly-ovulatory (rodents and pig) species, and the incomplete identification of the mechanisms regulating the oocyte–follicle and follicle–ovary interrelationships affect the outcome of in vitro culture. From all these attempts, however, new ideas arise, and the goal of assuring the preservation of female reproductive potential appears a more realistic possibility. This review surveys and discusses advances and challenges of these technologies that, starting from a simple attempt, are now approaching the biosynthesis of a functional engineered ovary.

scholarly journals Restoring Fertility in Cancer Survivors: Ovarian Tissue Cryopreservation or Assisted Reproduction Technique

2017 ◽  
Vol 8 (1) ◽  
pp. 24-31
Author(s):  
PS Divyashree ◽  
Khushboo Priya
Keyword(s):  
Cancer Survivors ◽  
Assisted Reproduction ◽  
Fertility Restoration ◽  
Ovarian Tissue ◽  
Ovarian Tissue Cryopreservation ◽  
Embryo Cryopreservation ◽  
Assisted Reproduction Technique ◽  
Advantages And Disadvantages ◽  
The Status ◽  
Tissue Cryopreservation

ABSTRACT Fertility restoration in cancer patients is gaining a very important role in the field of reproductive medicine, due to the rising incidence of cancer as well as its early detection and improved survival rate. The two options for achieving this aim are ovarian tissue cryopreservation (OTC) and assisted reproductive treatment (ART) through oocyte or embryo cryopreservation after IVF. However, both these have some advantages and disadvantages over each other. OTC is still in experimental phase but is growing faster as an important part of fertility restoration. ART is time tested method which can be relied upon to a great extent, but there are some situations where ART cannot meet the expectations. This review is an overview of the pros and cons of both these options and the status of these methods in the present scenario of fertility preservation. How to cite this article Priya K, Divyashree PS. Restoring Fertility in Cancer Survivors: Ovarian Tissue Cryopreservation or Assisted Reproduction Technique. Int J Infertil Fetal Med 2017;8(1):24-31.

Fertility preservation in borderline ovarian tumor patients and survivors

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Marine Poulain ◽  
Jessica Vandame ◽  
Chloé Tran ◽  
Sonia Koutchinsky ◽  
Paul Pirtea ◽  
...  
Keyword(s):  
Fertility Preservation ◽  
Ovarian Tissue ◽  
Conservative Surgery ◽  
Reproductive Technologies ◽  
Minimal Invasive ◽  
Oocyte Cryopreservation ◽  
Ovarian Tissue Cryopreservation ◽  
Ovarian Cortex ◽  
Estrogen Exposure ◽  
Future Fertility

AbstractBorderline ovarian tumors (BOTs) represent around 15% of all epithelial ovarian cancer. Around one third of those patients is under 40 and has not completed childbearing when the tumor is diagnosed. Cancer survivors are more and more concerned about their future fertility since a large proportion of those with BOTs are young. Whatever the tumor stage, information regarding future fertility after treatment and fertility preservation (FP) options must be delivered to all patients before treatment. A multidisciplinary team will discuss and propose personalized treatment and FP strategies. Nowadays, the FP options offered to patients with BOT are the followings: i) minimal invasive conservative surgery, ii) oocyte cryopreservation after controlled ovarian stimulation (COS) or in vitro maturation (IVM) and iii) ovarian tissue cryopreservation. Generally, the most common strategy to preserve future fertility is represented by minimal invasive conservative surgery. However, with the remarkable success and evolution of assisted reproductive technologies (ART) – notably progress and efficiency in COS and oocyte vitrification – have led to offer another potential approach for FP consisting in oocyte cryopreservation. Several COS protocols, such as random start or dual stimulation associating tamoxifen or aromatase inhibitors with gonadotropins provide similar results when compared to standard protocols while providing safety by minimizing the risk of high estrogen exposure. When COS is contraindicated, oocyte cryopreservation can still be possible throw IVM. Even though, oocyte competence after IVM is lower than that obtained after COS. A less used approach is cryopreservation of ovarian tissue, consisting in freezing ovarian cortex fragments for a future thawing and graft. Some concerns and limitations regard the ovarian cortex graft and the risk of reintroducing malignant cells once performed. Nonetheless, the latter it is the only option in prepubertal patients.

scholarly journals Slow Freezing Versus Vitrification of Mouse Ovaries: from Ex Vivo Analyses to Successful Pregnancies after Auto-Transplantation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Carmen Terren ◽  
Maïté Fransolet ◽  
Marie Ancion ◽  
Michelle Nisolle ◽  
Carine Munaut
Keyword(s):  
Ex Vivo ◽  
Fertility Restoration ◽  
Ovarian Tissue ◽  
Reference Method ◽  
Slow Freezing ◽  
Ovarian Tissue Cryopreservation ◽  
Freezing Damage ◽  
Specific Proteins

AbstractSlow freezing (SF) is the reference method for ovarian tissue cryopreservation. Vitrification (VT) constitutes an alternative but controversial method. This study compares SF and VT (open [VTo] and closed [VTc] systems) in terms of freezing damage and fertility restoration ability. In vitro analyses of C57Bl/6 SF or VTo-ovaries, immediately after thawing/warming or after culture (cult), revealed that event though follicular density was similar between all groups, nuclear density was decreased in VTo-ovaries compared to CT-ovaries (CT = 0.50 ± 0.012, SF = 0.41 ± 0.03 and VTo = 0.29 ± 0.044, p < 0.01). Apoptosis was higher in VTo-cult ovaries compared to SF-cult ovaries (p < 0.001) whereas follicular Bmp15 and Amh gene expression levels were decreased in the ovaries after culture, mostly after VTo (p < 0.001). Natural mating after auto-transplantation of SF, VTo and VTc-ovaries revealed that most mice recovered their oestrous cycle. Fertility was only restored with SF and VTo ovaries (SF: 68%; VTo: 63%; VTc: 0%; p < 0.001). Mice auto-transplanted with SF and VTo-ovaries achieved the highest number of pregnancies. In conclusion, in vitro, no differences between SF and VTo were evident immediately after thawing/warming but VTo ovaries displayed alterations in apoptosis and follicular specific proteins after culture. In vivo, SF and VTo ovary auto-transplantation fully restored fertility whereas with VTc-ovary auto-transplantation no pregnancies were achieved.

scholarly journals Establishment of the ovarian tissue cryopreservation protocol on bovine model

2016 ◽  
Vol 19 (2) ◽  
pp. 24-32
Author(s):  
Dung Thi Phuong Nguyen ◽  
Lan Thi Thu Nguyen ◽  
Quang Nhat Nguyen ◽  
Tuong Manh Ho ◽  
Loc Minh Tai Nguyen ◽  
...  
Keyword(s):  
Ovarian Function ◽  
Ovarian Tissue ◽  
Neutral Red ◽  
Slow Freezing ◽  
Ovarian Tissue Cryopreservation ◽  
Control Group ◽  
Ovarian Cortex ◽  
Group 2 ◽  
Tissue Cryopreservation ◽  
Cryopreservation Protocol

Ovarian tissue cryopreservation is a suitable method for fertility preservation on women receiving treatment that may threaten the ovarian function and subsequent fertility. The whole ovarian or a part of ovarian can be cryopreserved for future use. This study was aimed to establish ovarian tissue cryopreservation protocols on bovine model for human application in Vietnam. In this method, bovine ovarians were collected from a slaughterhouse and kept at 4 oC up to a maximum of 12 hours before doing experiments. The ovarian cortex was cut into pieces of 10x10x1 mm. These pieces were randomly divided into 3 groups: (1) fresh species (control group), (2) species were freezed by slow-freezing method and (3) pieces were freezed by vitrification. After thawing, ovarian cortex pieces were treated with Collagenase Ia for the follicle isolation. The isolated follicles then were stained with Neutral Red. The rate of viable follicles was used as the outcome measure to assess the efficiency of the cryopreservation protocol. In results, the rates of viable follicles were 72.46 ± 6.11 % and 59.09 ± 7.08 % after slow-freezing and vitrification comparing to the control group, respectively. This was the first study which successfully established a protocol of ovarian tissue cryopreservation on bovine model in Vietnam. The protocol should be improved for further application to human treatment in the near future.

scholarly journals A challenge of fertility preservation in the setting of cervical cancer - a clinical case

2021 ◽  
pp. 28-32
Author(s):  
I. E. Dmitrieva ◽  
Y. O. Martirosyan ◽  
L. G. Dzhanashvili ◽  
V. O. Dementyeva ◽  
L. V. Adamyan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Fertility Preservation ◽  
Ovarian Stimulation ◽  
Clinical Case ◽  
Ovarian Tissue ◽  
Oocyte Retrieval ◽  
Ovarian Tissue Cryopreservation ◽  
Embryo Cryopreservation ◽  
Ovarian Transposition

The issue of fertility preservation in patients with cervical cancer is getting more and more common considering the improved effectiveness of early diagnosis and treatment of cancer. There is a number of evidence-based tactics available to the patients with diagnosed cervical cancer. These tactics have been proved effective and include methods such as ovarian transposition; oocyte, embryo and ovarian tissue cryopreservation. Nonetheless, there are no existing medical algorithms to define the priority of actions that should be taken in such cases of restricted time. The objective of this clinical case report is to highlight an existing concern towards the decision-making process regarding fertility preservation in patients with cervical cancer.In this paper we report a clinical case of fertility preservation tactics in a patient undergone ovarian transposition. We pay attention to particular features of the controlled ovarian stimulation (COS) and oocyte retrieval process typical for such patients. The article discusses the subject of COS and oocyte retrieval effectiveness compared to patients who did not undergo ovarian transposition. The 35-year old patient presented 9 month after ovarian transposition to perform oocyte cryopreservation. As a result of COS 3 oocytes were aspirated, compared to 20 oocytes in another patient of comparable age and medical history, but with no ovarian transposition performed.Regarding particular conditions constraining ovarian stimulation and oocyte retrieval after ovarian transposition, we recommend to consider the possibility of performing oocyte/embryo cryopreservation before ovarian transposition in patients with cervical cancer. Prioritizing oocyte and embryo cryopreservation in case of having sufficient time before treatment could significantly improve possibilities of achieving genetically related offspring in a long-term perspective.

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